Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) cause a severe neurodevelopmental disorder, yet the impact of truncating mutations remains unclear. Here, we introduce the Cdkl5^492stop mouse model, mimicking C-terminal truncating mutations in patients. 492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors, alongside other behavioral deficits. After creating cell lines with various Cdkl5 truncating mutations, we found that these mutations are regulated by the nonsense-mediated RNA decay pathway. Most truncating mutations result in CDKL5 protein loss, leading to multiple disease phenotypes, and offering new insights into the pathogenesis of CDKL5 disorder.
Animals ; Disease Models, Animal ; Mice ; Protein Serine-Threonine Kinases/deficiency* ; Mutation/genetics* ; Epileptic Syndromes/genetics* ; Humans ; Dendritic Spines/pathology* ; Spasms, Infantile/genetics* ; Male ; Seizures/genetics* ; Mice, Inbred C57BL

OBJECTIVES: To investigate the application value of targeted next-generation sequencing (tNGS) in the etiological diagnosis of moderate to severe respiratory distress syndrome (RDS) in neonates. METHODS: A prospective randomized controlled trial was conducted, enrolling 81 term and late-preterm neonates with moderate to severe RDS admitted to Fujian Children's Hospital between December 2023 and December 2024. Patients were randomly assigned to the conventional microbiological test (CMT) group (n=42) or the tNGS group (n=39). For routine pathogen detection, bronchoalveolar lavage fluid was obtained via bronchoscopy, and lower respiratory tract specimens were collected via the endotracheal tube; all specimens underwent culture, and some specimens additionally underwent polymerase chain reaction or antigen testing. In the tNGS group, tNGS was performed in addition to routine pathogen detection on the same specimen types. The detection rate of pathogens, the detection rate of co-infections, and the duration of antibiotic use were compared between the two groups. RESULTS: The pathogen detection rate in the tNGS group (18/39, 46%) was significantly higher than that in the CMT group (8/42, 19%) (P=0.009). The co-infection detection rate was 13% (5/39) in the tNGS group, while no co-infections were identified in the CMT group (P=0.024). Regarding treatment, the duration of antibiotic use in the tNGS group was shorter than that in the CMT group [(12±4) days vs (15±5) days, P=0.003]. CONCLUSIONS tNGS significantly improves the pathogen detection rate in neonates with moderate to severe RDS and offers advantages in the rapid identification of co-infections and reduction of antibiotic treatment duration, suggesting it has clinical utility and potential for wider adoption.
Humans ; Prospective Studies ; Infant, Newborn ; Female ; Respiratory Distress Syndrome, Newborn/etiology* ; Male ; High-Throughput Nucleotide Sequencing/methods*

Objective To investigate the therapeutic effects of focused ultrasound and ATP-infrared bioeffect for non-neoplastic epithelial disorders of the vulva(NNEDV),aiming to provide references for the clinical study and selection of individualized treatment plans of NNEDV patients.Methods The clinical data of 278 NNEDV patients attending the gynecology department of some hospital from May 2020 to December 2023 were retrospectively analyzed,who were divided into an observation group receiving focused ultrasound treatment and a control group receiving ATP-infrared bioeffect treatment with the single random grouping mmethod.The observation group enrolled in 143 patients including 84 cases of lichen simplex chronicus(LSC)and 59 cases of vulvar lichen sclerosus(VLS),and the control group had 135 patients including 71 LSC cases and 64 VLS cases.Comparisons were carried out in terms of the therapeutic effect and safety in the two groups,the efficacy for LSC and VLS between and within the two groups,and the clinical symptom scores and the quality of life scores before and after treatment of the two groups.SPSS 23.0 software was used for statistical analysis.Results The two groups had no significant differences in response rate and recurrence rate(P>0.05),while the observation group had the cure rate higher and the complication rate higher than those of the control group(P<0.05).In the observation group,the overall response rates for LSC and VLS were not significantly different(P>0.05);in the control group,the overall response rate for LSC was higher than that for VLS significantly(P<0.05).The cure rate for LSC in the observation group was higher than that in the control group,with the differences being statistically significant(P<0.05);the two groups had no significant differences in the cure rate for VLS(P>0.05).The two groups had significant differences in the skin color socre,vitiligo area scoring index and skin elasticity one month,three months and six months after treatment(P<0.05),with the differences being statistically significant in the tissue structure score three months and six months after treatment(P<0.05);there were no significant differences found between the two groups in the pruritus score one month,three months and six months after treatment and in tissue structure score one month after treatment(P>0.05).In the two groups the differences were all statistically significant in the quality of life score three and six months after treatment(P<0.05);the two groups had significant differences in the quality of life score before and after treatment(P>0.05).Conclusion Focused ultrasound and ATP-infrared bioeffect are both effective for NNEDV.Focused ultrasound gains advantages in restoring the color and tissue structure of vulvar skin,and the physical therapy is the first choice for NNEDV that has failed drug therapy and risks for recurrence and canceration;ATP-infrared bioeffect with a low complication rate can be used for the patients with mild symptoms,cracked skin inflammation or those unable to tolerate ultrasound.[Chinese Medical Equipment Journal,2025,46(6):59-64]

Objective To develop and validate a fast Monte Carlo(MC)-based patient-specific quality assurance(PSQA)tool using the treatment log files that is suitable to be used in the online adaptive radiotherapy for pencil beam scanning proton therapy(PBSPT-ART).Methods The proposed tool first used the delivery log file of a PBSPT plan to reversely reconstruct the PBSPT(rPBSPT)plan,and then used an in-house developed graphic processing unit(GPU)-accelerated virtual particle MC(VPMC)dose engine to calculate the dose distribution of the rPBSPT plan.The rPBSPT dose calculated by VPMC was then compared to the rPBSPT dose calculated by another independent MC dose engine(MCsquare),using 3D gamma analysis to verify the accuracy of VPMC calculation.As a demonstration of the feasibility of developed log file-based PSQA,the VPMC calculated dose of the rPBSPT plan was compared to the pre-delivery second check dose of the corresponding PBSPT plan calculated by MCsquare,using 3D gamma analysis.3D gamma analysis employes a criterion of 2 mm/2%/10%.Twenty patients with different disease sites were representatively selected to validate the efficiency and accuracy of the tool.Results The average calculation time of a rPBSPT plan by VPMC was(5.88±4.00)s in the accuracy verification.Compared to MCsquare,the passing rate of the 3D gamma analysis was 99.47%±0.72%.In the proposed PSQA tool demonstration,the passing rate of comparing the VPMC calculated rPBSPT dose to MCsquare calculated second check dose of the corresponding PBSPT plan was 98.91%±0.92%.Conclusion The accuracy and efficiency of the tool can meet the requirements of PSQA in the online PBSPT-ART workflow.

Objective:This study aims to explore the risk factors of Multi-center Investigator-Initiated Clinical Trials (MIITs), and provide a basis for developing study management strategies.Methods:The original draft of MIIT risk evaluation factors was determined through literature analysis and internal discussions of the research group. Thirty five experts were consulted using the Delphi method, and then the MIIT risk evaluation elements were finally determined. Analytic Hierarchy Process (AHP) was used to calculate the weights of each index.Results:The recovery rates of both rounds of expert consultation were 100%, and the degree of expert authority was 0.856. The study ultimately formed an MIIT risk evaluation framework consisting of three first-class indexes, twelve second-class indexes, and thirty-eight third-class indexes. The weight values of the first-class indexes (start-up period, implementation period, and summary period) were 0.209 8, 0.710 6, and 0.079 6, respectively. Meanwhile, the weight values of the second-class indexes and third-class indexes were determined.Conclusions:Exploring the risk evaluation factors of MIIT provides valuable insights into identifying critical risk points, which, in turn, contributes to enhancing MIIT management efficiency, research progress, and quality.

Objective To investigate the effect and mechanism of dexmedetomidine(Dex)in alleviating sevoflurane(Sev)-induced cognitive dysfunction in neonatal rats via the Janus kinase 2/signal transducer and activators of transcription 3(JAK2/STAT3)signaling pathway.Methods A total of 50 neonatal Sprague-Dawley(SD)rats were randomly divided into control group,model group,Dex group,AG490 group,and Colivelin group,with 10 rats in each group.Except for control group,the rats in the other four groups were used to construct a model of cognitive dysfunction in neonatal rats by inhaling Sev.Before modeling,Dex group was intraperitoneally injected with 20 μg/kg Dex;AG490 group was intraperitoneally injected with 20 μg/kg Dex and 1 mg/kg AG490;Colivelin group was intraperitoneally injected with 20 μg/kg Dex,1 mg/kg AG490,and 1 mg/kg Colivelin;control group and model group were intraperitoneally injected with an equal doses of physiological saline.The novel object recognition test and step-down test were used to detect the cognitive,learning,and memory functions of neonatal rats.TUNEL method was used to detect the cell apoptosis rate in the hippocampus.Rhodamine 123 staining was used to detect the mitochondrial membrane potential in the hippocampus.ELISA method was used to detect the levels of malondialdehyde(MDA)and superoxide dismutase(SOD)in the hippocampus.DHE probe method was used to detect the intracellular reactive oxygen species(ROS)content.qRT-PCR was used to detect the mRNA expression levels of phosphorylated JAK2(p-JAK2),phosphorylated STAT3(p-STAT3),Synapsin-I,brain-derived neurotrophic factor(BDNF),B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X protein(Bax).Western Blotting was used to detect the protein expression levels of p-JAK2,p-STAT3,JAK2,and STAT3 in the hippocampus.Results Compared with control group,model group showed cognitive and memory impairment,significantly increased apoptosis rate,increased levels of ROS and MDA,decreased SOD level,decreased mRNA expression levels of p-JAK2,p-STAT3,Synapsin-I,BDNF,and Bcl-2,increased Bax mRNA expression level,decreased ratios of p-JAK2/JAK2 and p-STAT3/STAT3,and decreased mitochondrial membrane potential in the hippocampus(P<0.05).Compared with model group,Dex,AG490,and Colivelin groups showed significantly improved cognitive and memory impairment,significantly decreased apoptosis rate,decreased levels of ROS and MDA,increased SOD level,increased mRNA expression levels of p-JAK2,p-STAT3,Synapsin-I,BDNF,and Bcl-2,decreased Bax mRNA level,increased ratios of p-JAK2/JAK2 and p-STAT3/STAT3,and increased mitochondrial membrane potential in the hippocampus(P<0.05).Compared with Dex group,AG490 and Colivelin groups exhibited cognitive and memory impairment,significantly increased apoptosis rate,increased levels of ROS and MDA,decreased SOD level,decreased mRNA expression levels of p-JAK2 and p-STAT3,Synapsin-I,BDNF,and Bcl-2,increased Bax mRNA expression level,decreased ratios of p-JAK2/JAK2 and p-STAT3/STAT3,and decreased mitochondrial membrane potential in the hippocampus(P<0.05).Compared with AG490 group,Colivelin group showed significantly improved cognitive and memory impairment,significantly decreased apoptosis rate,decreased levels of ROS and MDA,increased SOD level,decreased mRNA expression levels of p-JAK2 and p-STAT3,Synapsin-I,BDNF,and Bcl-2,increased Bax mRNA expression level,decreased ratios of p-JAK2/JAK2 and p-STAT3/STAT3,and increased mitochondrial membrane potential in the hippocampus,with statistically significant differences(P<0.05).Conclusion Dex can inhibit the oxidative stress in the hippocampus of brain tissue in Sev-induced neonatal rats and improve their cognitive,learning,and memory impairment,which may be related to the activation of JAK2/STAT3 signaling pathway.

This paper summarizes the progress of theoretical research and practice of One Health in China,and discusses the paradigm of One Health governance to improve the prevention and control of infectious diseases in China and the world,and provide an example for the improvement of the public health system.In particular,China has long history to apply the concept of One Health in the national schistosomiasis control programmes and patriotic health campaigns,which were not only focusing on human health,but also emphasizing the sustainable development of animal health and ecological environment.At the same time,the application of tools such as system dynamics model,eDNA technology,One Health economic assessment and global One Health index(GOHI)in the field of disease control and environmental health provides technical support for the concept of One Health.Despite the challenges of practical application of these tools,the One Health concept will play a greater role in providing sustainable solutions for human-animal-environmental health by strengthening interdisciplinary collaboration,improving standardization protocols and promoting inter-national cooperation.

Objective To develop and validate a fast Monte Carlo(MC)-based patient-specific quality assurance(PSQA)tool using the treatment log files that is suitable to be used in the online adaptive radiotherapy for pencil beam scanning proton therapy(PBSPT-ART).Methods The proposed tool first used the delivery log file of a PBSPT plan to reversely reconstruct the PBSPT(rPBSPT)plan,and then used an in-house developed graphic processing unit(GPU)-accelerated virtual particle MC(VPMC)dose engine to calculate the dose distribution of the rPBSPT plan.The rPBSPT dose calculated by VPMC was then compared to the rPBSPT dose calculated by another independent MC dose engine(MCsquare),using 3D gamma analysis to verify the accuracy of VPMC calculation.As a demonstration of the feasibility of developed log file-based PSQA,the VPMC calculated dose of the rPBSPT plan was compared to the pre-delivery second check dose of the corresponding PBSPT plan calculated by MCsquare,using 3D gamma analysis.3D gamma analysis employes a criterion of 2 mm/2%/10%.Twenty patients with different disease sites were representatively selected to validate the efficiency and accuracy of the tool.Results The average calculation time of a rPBSPT plan by VPMC was(5.88±4.00)s in the accuracy verification.Compared to MCsquare,the passing rate of the 3D gamma analysis was 99.47%±0.72%.In the proposed PSQA tool demonstration,the passing rate of comparing the VPMC calculated rPBSPT dose to MCsquare calculated second check dose of the corresponding PBSPT plan was 98.91%±0.92%.Conclusion The accuracy and efficiency of the tool can meet the requirements of PSQA in the online PBSPT-ART workflow.

Objective To investigate the therapeutic effects of focused ultrasound and ATP-infrared bioeffect for non-neoplastic epithelial disorders of the vulva(NNEDV),aiming to provide references for the clinical study and selection of individualized treatment plans of NNEDV patients.Methods The clinical data of 278 NNEDV patients attending the gynecology department of some hospital from May 2020 to December 2023 were retrospectively analyzed,who were divided into an observation group receiving focused ultrasound treatment and a control group receiving ATP-infrared bioeffect treatment with the single random grouping mmethod.The observation group enrolled in 143 patients including 84 cases of lichen simplex chronicus(LSC)and 59 cases of vulvar lichen sclerosus(VLS),and the control group had 135 patients including 71 LSC cases and 64 VLS cases.Comparisons were carried out in terms of the therapeutic effect and safety in the two groups,the efficacy for LSC and VLS between and within the two groups,and the clinical symptom scores and the quality of life scores before and after treatment of the two groups.SPSS 23.0 software was used for statistical analysis.Results The two groups had no significant differences in response rate and recurrence rate(P>0.05),while the observation group had the cure rate higher and the complication rate higher than those of the control group(P<0.05).In the observation group,the overall response rates for LSC and VLS were not significantly different(P>0.05);in the control group,the overall response rate for LSC was higher than that for VLS significantly(P<0.05).The cure rate for LSC in the observation group was higher than that in the control group,with the differences being statistically significant(P<0.05);the two groups had no significant differences in the cure rate for VLS(P>0.05).The two groups had significant differences in the skin color socre,vitiligo area scoring index and skin elasticity one month,three months and six months after treatment(P<0.05),with the differences being statistically significant in the tissue structure score three months and six months after treatment(P<0.05);there were no significant differences found between the two groups in the pruritus score one month,three months and six months after treatment and in tissue structure score one month after treatment(P>0.05).In the two groups the differences were all statistically significant in the quality of life score three and six months after treatment(P<0.05);the two groups had significant differences in the quality of life score before and after treatment(P>0.05).Conclusion Focused ultrasound and ATP-infrared bioeffect are both effective for NNEDV.Focused ultrasound gains advantages in restoring the color and tissue structure of vulvar skin,and the physical therapy is the first choice for NNEDV that has failed drug therapy and risks for recurrence and canceration;ATP-infrared bioeffect with a low complication rate can be used for the patients with mild symptoms,cracked skin inflammation or those unable to tolerate ultrasound.[Chinese Medical Equipment Journal,2025,46(6):59-64]

This paper summarizes the progress of theoretical research and practice of One Health in China,and discusses the paradigm of One Health governance to improve the prevention and control of infectious diseases in China and the world,and provide an example for the improvement of the public health system.In particular,China has long history to apply the concept of One Health in the national schistosomiasis control programmes and patriotic health campaigns,which were not only focusing on human health,but also emphasizing the sustainable development of animal health and ecological environment.At the same time,the application of tools such as system dynamics model,eDNA technology,One Health economic assessment and global One Health index(GOHI)in the field of disease control and environmental health provides technical support for the concept of One Health.Despite the challenges of practical application of these tools,the One Health concept will play a greater role in providing sustainable solutions for human-animal-environmental health by strengthening interdisciplinary collaboration,improving standardization protocols and promoting inter-national cooperation.