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 investigate the effect and preliminary mechanism of hypervirulent Klebsiella pneumoniae (hvKP) on the immune response to sepsis induced by liver abscess in mice. Methods:C57BL/6 mice were intraperitoneally injected with hvKP strain NTUH-K2044 or classical Klebsiella pneumoniae (cKP) strain HS11286 suspension to prepare the model of sepsis. The survivals rates of mice within 24 h were recorded. HE staining was used to observed the inflammatory cell infiltration in mouse liver tissues. The levels of neutrophil marker lymphocyte antigen 6G (Ly6G) in mouse liver tissues were detected by immunohistochemistry. The activity of reactive oxygen species (ROS) in mouse liver macrophages and peripheral blood monocytes was measured by ROS assay kit. The activation of p105/p50 and p65 in NF-κB signaling pathway in mouse liver macrophages and peripheral blood monocytes was detected by Western blot. The expression of IL-1β, IL-6 and TNF-α at mRNA and protein levels in mouse liver macrophages and peripheral blood monocytes were detected by qRT-PCR and ELISA, respectively. One-way analysis of variance and t test were used for statistical analysis. Results:Compared with cKP, hvKP infection could induce C57BL/6 mice to develop obvious liver abscess with massive inflammatory cell infiltration. Moreover, the level of Ly6G in liver tissues was significantly higher in hvKP-infected mice than in cKP-infected mice ( P<0.000 1), but the survival rate of hvKP-infected mice was significantly lower than that of cKP-infected mice ( P<0.000 1). hvKP significantly promoted the ROS activity ( P<0.000 1) and enhanced the phosphorylation of p105/p50 and p65 in NF-κB signaling pathway in mouse liver macrophages and peripheral blood monocytes as compared with cKP ( P<0.001). The expression of IL-1β, IL-6 and TNF-α at mRNA and protein levels in mouse liver macrophages and peripheral blood monocytes were significantly higher in hvKP-infected mice than in cKP-infected mice ( P<0.001). Conclusion:hvKP can promote the development of liver abscess and induce sepsis in mice.

Objective:To investigate the role of TcpC, a virulence factor of uropathogenic Escherichia coli (UPEC), in inhibiting the formation of neutrophil extracellular traps (NETs) in mouse bone marrow neutrophils, and to analyze its pathogenic mechanism. Methods:C57BL/6 mice were injected with either wild-type (CFT073 wt) or tcpc gene-knockout UPEC CFT073(CFT073 Δ tcpc) to establish a mouse model of cystitis. Mice were sacrificed 3 d post-infection, and their bladders were collected to observe gross pathological changes. Hematoxylin-eosin (HE) staining was used to assess histopathological changes in bladder tissues, and immunohistochemistry was performed to localize TcpC in bladder tissues. Bacterial loads in urine samples were quantified using the ten-fold dilution method, and the presence of tcpc gene in genomic DNA from bladder or urine samples was confirmed by PCR. The expression of TcpC at mRNA and protein levels in mouse bone marrow nuetrophils infected with CFT073 wt was detected by qRT-PCR and Western blot. The effects of UPEC infection on expression of NETs-related proteins and the production of pro-inflammatory factors in mouse bone marrow neutrophils were analyzed by Western blot and ELISA, respectively. Reactive oxygen species(ROS) level and bacterial viability in mouse bone marrow nuetrophils were measured using ROS and bacterial viability detection kits. Results:Compared to the CFT073 Δ tcpc group, the bladder of CFT073 wt group mice exhibited significant enlargement, extensive inflammatory cell infiltration, and the presence of TcpC in bladder tissue. The bacterial load in the urine of CFT073 wt -infected mice was significantly higher than that in the CFT073 Δ tcpc group ( P<0.01). PCR confirmed the presence of the tcpc gene in bladder and urine samples from CFT073 wt-infected mice. Increased expression of TcpC at both mRNA and protein levels was observed in CFT073 wt-infected mouse bone marrow neutrophils. CFT073 wt infection inhibited the mRNA and protein expression of NETs-related proteins and reduced the production of pro-inflammatory factors in mouse bone marrow neutrophils. TcpC suppressed ROS level and promoted the survival of CFT073 wt in mouse bone marrow neutrophils. Conclusions:TcpC enhances the pathogenicity of UPEC CFT073 by inhibiting the formation and activation of NETs in mouse bone marrow neutrophils. This study provides new insights into the pathogenic mechanisms of UPEC and the immune evasion strategies of other pathogenic bacteria, as well as potential targets for clinical prevention and treatment of UPEC-induced urinary tract infections.

OBJECTIVE Hospital-acquired infections have emerged as an increasingly prominent and hard-to-com-pletely-avoid problem,with their complexity and challenges continuing to intensify.As a major public health con-cern,these hospital-acquired infections pose a serious threat to the safety of individuals within hospitals.Among the various routes of transmission,airborne transmission is one of the most important pathways leading to hospi-tal-acquired infections.A variety pathogenic viruses can attach to infectious respiratory particles produced by hu-man body and spread through these particles.Patients in hospitals,as the primary group releasing respiratory in-fectious particles,have behaviors(such as breathing,coughing,talking,etc.)that are closely related to the trans-mission,dissemination and spread of pathogenic microorganisms.It is generally believed that pathogens re-leased into the air by patients will propagate and spread with air currents,thereby elevating the risk of infection.In order to comprehensively safeguard the safety of healthcare workers and patients,and effectively curb the occur-rence of hospital-acquired infections,it is essential to investigate the impact of pathogen-releasing behaviors on the transmission of pathogenic microorganisms.This paper aims to review the research progress on the impact of pathogen-releasing behaviors of patients on the transmission of respiratory pathogenic microorganisms within healthcare buildings,as well as to provide an outlook for further research directions.

OBJECTIVE Hospital-acquired infections have emerged as an increasingly prominent and hard-to-com-pletely-avoid problem,with their complexity and challenges continuing to intensify.As a major public health con-cern,these hospital-acquired infections pose a serious threat to the safety of individuals within hospitals.Among the various routes of transmission,airborne transmission is one of the most important pathways leading to hospi-tal-acquired infections.A variety pathogenic viruses can attach to infectious respiratory particles produced by hu-man body and spread through these particles.Patients in hospitals,as the primary group releasing respiratory in-fectious particles,have behaviors(such as breathing,coughing,talking,etc.)that are closely related to the trans-mission,dissemination and spread of pathogenic microorganisms.It is generally believed that pathogens re-leased into the air by patients will propagate and spread with air currents,thereby elevating the risk of infection.In order to comprehensively safeguard the safety of healthcare workers and patients,and effectively curb the occur-rence of hospital-acquired infections,it is essential to investigate the impact of pathogen-releasing behaviors on the transmission of pathogenic microorganisms.This paper aims to review the research progress on the impact of pathogen-releasing behaviors of patients on the transmission of respiratory pathogenic microorganisms within healthcare buildings,as well as to provide an outlook for further research directions.

Objective:To investigate the effect and preliminary mechanism of hypervirulent Klebsiella pneumoniae (hvKP) on the immune response to sepsis induced by liver abscess in mice. Methods:C57BL/6 mice were intraperitoneally injected with hvKP strain NTUH-K2044 or classical Klebsiella pneumoniae (cKP) strain HS11286 suspension to prepare the model of sepsis. The survivals rates of mice within 24 h were recorded. HE staining was used to observed the inflammatory cell infiltration in mouse liver tissues. The levels of neutrophil marker lymphocyte antigen 6G (Ly6G) in mouse liver tissues were detected by immunohistochemistry. The activity of reactive oxygen species (ROS) in mouse liver macrophages and peripheral blood monocytes was measured by ROS assay kit. The activation of p105/p50 and p65 in NF-κB signaling pathway in mouse liver macrophages and peripheral blood monocytes was detected by Western blot. The expression of IL-1β, IL-6 and TNF-α at mRNA and protein levels in mouse liver macrophages and peripheral blood monocytes were detected by qRT-PCR and ELISA, respectively. One-way analysis of variance and t test were used for statistical analysis. Results:Compared with cKP, hvKP infection could induce C57BL/6 mice to develop obvious liver abscess with massive inflammatory cell infiltration. Moreover, the level of Ly6G in liver tissues was significantly higher in hvKP-infected mice than in cKP-infected mice ( P<0.000 1), but the survival rate of hvKP-infected mice was significantly lower than that of cKP-infected mice ( P<0.000 1). hvKP significantly promoted the ROS activity ( P<0.000 1) and enhanced the phosphorylation of p105/p50 and p65 in NF-κB signaling pathway in mouse liver macrophages and peripheral blood monocytes as compared with cKP ( P<0.001). The expression of IL-1β, IL-6 and TNF-α at mRNA and protein levels in mouse liver macrophages and peripheral blood monocytes were significantly higher in hvKP-infected mice than in cKP-infected mice ( P<0.001). Conclusion:hvKP can promote the development of liver abscess and induce sepsis in mice.

Objective:To investigate the role of TcpC, a virulence factor of uropathogenic Escherichia coli (UPEC), in inhibiting the formation of neutrophil extracellular traps (NETs) in mouse bone marrow neutrophils, and to analyze its pathogenic mechanism. Methods:C57BL/6 mice were injected with either wild-type (CFT073 wt) or tcpc gene-knockout UPEC CFT073(CFT073 Δ tcpc) to establish a mouse model of cystitis. Mice were sacrificed 3 d post-infection, and their bladders were collected to observe gross pathological changes. Hematoxylin-eosin (HE) staining was used to assess histopathological changes in bladder tissues, and immunohistochemistry was performed to localize TcpC in bladder tissues. Bacterial loads in urine samples were quantified using the ten-fold dilution method, and the presence of tcpc gene in genomic DNA from bladder or urine samples was confirmed by PCR. The expression of TcpC at mRNA and protein levels in mouse bone marrow nuetrophils infected with CFT073 wt was detected by qRT-PCR and Western blot. The effects of UPEC infection on expression of NETs-related proteins and the production of pro-inflammatory factors in mouse bone marrow neutrophils were analyzed by Western blot and ELISA, respectively. Reactive oxygen species(ROS) level and bacterial viability in mouse bone marrow nuetrophils were measured using ROS and bacterial viability detection kits. Results:Compared to the CFT073 Δ tcpc group, the bladder of CFT073 wt group mice exhibited significant enlargement, extensive inflammatory cell infiltration, and the presence of TcpC in bladder tissue. The bacterial load in the urine of CFT073 wt -infected mice was significantly higher than that in the CFT073 Δ tcpc group ( P<0.01). PCR confirmed the presence of the tcpc gene in bladder and urine samples from CFT073 wt-infected mice. Increased expression of TcpC at both mRNA and protein levels was observed in CFT073 wt-infected mouse bone marrow neutrophils. CFT073 wt infection inhibited the mRNA and protein expression of NETs-related proteins and reduced the production of pro-inflammatory factors in mouse bone marrow neutrophils. TcpC suppressed ROS level and promoted the survival of CFT073 wt in mouse bone marrow neutrophils. Conclusions:TcpC enhances the pathogenicity of UPEC CFT073 by inhibiting the formation and activation of NETs in mouse bone marrow neutrophils. This study provides new insights into the pathogenic mechanisms of UPEC and the immune evasion strategies of other pathogenic bacteria, as well as potential targets for clinical prevention and treatment of UPEC-induced urinary tract infections.

OBJECTIVE To analyze the differences in gait features between patients with cardiovascular and cerebrovascular dis-eases and normal people,and to explore new objective features of traditional Chinese medicine(TCM)whole-body inspection.METHODS A monocular camera was used to collect frontal walking videos of subjects,and the diagnosis results of TCM practitioners were used as disease annotation data;a deep learning model was used to estimate the three-dimensional coordinates of key points;the gait features were defined and calculated based on the three-dimensional coordinates of key points of the lower limbs;differences in gait features among people with cardiovascular and cerebrovascular diseases were collected and verified.RESULTS The three-di-mensional coordinates of key points of the lower limbs were automatically extracted and 8 types of TCM gait features were calculated:step width,stride length,foot lift height,limb angle,left and right hip joint angles,and left and right knee joint angles.It was found that there were significant differences in the features between people with cardiovascular and cerebrovascular diseases and healthy peo-ple(P<0.05).CONCLUSION The TCM inspection gait extracted by this study can effectively distinguish patients with cardiovas-cular and cerebrovascular diseases from healthy people,expands the research scope of TCM whole-body inspection,and provides new ideas for the early detection and prevention of cardiovascular and cerebrovascular diseases.

OBJECTIVE To analyze the differences in gait features between patients with cardiovascular and cerebrovascular dis-eases and normal people,and to explore new objective features of traditional Chinese medicine(TCM)whole-body inspection.METHODS A monocular camera was used to collect frontal walking videos of subjects,and the diagnosis results of TCM practitioners were used as disease annotation data;a deep learning model was used to estimate the three-dimensional coordinates of key points;the gait features were defined and calculated based on the three-dimensional coordinates of key points of the lower limbs;differences in gait features among people with cardiovascular and cerebrovascular diseases were collected and verified.RESULTS The three-di-mensional coordinates of key points of the lower limbs were automatically extracted and 8 types of TCM gait features were calculated:step width,stride length,foot lift height,limb angle,left and right hip joint angles,and left and right knee joint angles.It was found that there were significant differences in the features between people with cardiovascular and cerebrovascular diseases and healthy peo-ple(P<0.05).CONCLUSION The TCM inspection gait extracted by this study can effectively distinguish patients with cardiovas-cular and cerebrovascular diseases from healthy people,expands the research scope of TCM whole-body inspection,and provides new ideas for the early detection and prevention of cardiovascular and cerebrovascular diseases.

Objective:To investigate the efficacy of Sishen pill compound combined with mesalazine in the treatment of mild to moderate ulcerative colitis and its effect on the circadian rhythm of symptoms. Methods:A total of 136 patients with mild to moderate ulcerative colitis who received treatment in Hospital of Chengdu University of Traditional Chinese Medicine from January 2018 to December 2020 were included in this prospective randomized controlled trial. These patients were divided into a treatment group ( n = 68) and a control group ( n = 68). The treatment group was treated with Sishen pill compound combined with mesalazine. The control group was treated with mesalazine alone. All patients were treated for 12 weeks. Clinical efficacy, as well as morning abdominal pain grade, morning diarrhea score, fecal trait score, Mayo score, hemoglobin, and hypersensitive C-reactive protein pre- and post-treatment, were compared between the two groups. Results:Total response rate in the treatment group was significantly higher than that in the control group [91.18% (62/68) vs. 72.06% (49/68), χ2 = 8.28, P < 0.05]. After treatment, morning diarrhea score, morning abdominal pain score, fecal trait score, Mayo score, hemoglobin, and hypersensitive C-reactive protein in the treatment group were (0.47 ± 0.56) points, (0.53 ± 0.56) points, (3.01 ± 0.72) points, (7.13 ± 1.38) points, (108.04 ± 12.21) g/L, (4.00 ± 2.19) mg/L, respectively, and they were (0.84 ± 0.56) points, (1.12 ± 0.56) points, (4.40 ± 0.76) points, (3.25 ± 1.44) points, (102.15 ± 12.61) g/L, and (6.07 ± 3.66) mg/L respectively in the control group. There were significant differences in these indexes between the treatment and control groups ( t = 3.59, 5.95, 10.06, 9.62, 2.78, 3.99, all P < 0.05). Conclusion:Sishen pill compound combined with mesalazine can effectively reduce clinical symptoms of active ulcerative colitis, increase hemoglobin level, decrease C-reactive protein level, improve the efficiency of treatment, reduce symptoms and the number of diarrhea rhythms, and improve stool symptoms of mild to moderate ulcerative colitis patients.