OBJECTIVE: To explore the clinical, genetic, therapeutic and prognostic characteristics of two children with Lesch-Nyhan syndrome (LNS) in order to enhance understanding of this disease and formulate more effective therapeutic strategies. METHODS: Clinical data were collected from two children clinically diagnosed with LNS who were treated at Anhui Provincial Children's Hospital from April 2023 to January 2024. Data were retrospectively collected and included clinical manifestations (symptoms, signs, laboratory and imaging findings), treatment course, and results of follow-up. Peripheral venous blood samples were obtained from child 1 and his parents. Whole-exome sequencing (WES) was performed. Candidate variants were validated by Sanger sequencing. Standard bioinformatic analysis of the raw WES data was conducted, including quality control, alignment, variant calling, and annotation. Candidate pathogenic variants were filtered using population frequency databases (e.g., gnomAD), disease databases (e.g., OMIM, ClinVar), and multiple in silico pathogenicity prediction tools (e.g., SIFT, PolyPhen-2, CADD). Phenotype matching was integrated using Human Phenotype Ontology (HPO) terms. Pathogenicity classification of variants was performed according to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants (2015). This study was approved by the Medical Ethics Committee of Anhui Children's Hospital, Children's Hospital of Fudan University (Ethics No.: EYLL-2014-027). RESULTS: Child 1, a 4-year-old boy, had presented with developmental delay for over 3 years, accompanied by abnormal postures and involuntary lip-biting. Physical examination revealed limb dystonia, anxious expression, lower lip damage, and communication difficulties. Laboratory tests showed hyperuricemia and renal stones. Genetic testing identified a hemizygote variant of the HPRT1 gene, c.135G>T (p.Arg45Ser), inherited from an asymptomatic carrier mother, which confirmed the diagnosis of LNS. This variant was absent from population databases (gnomAD, 1000 Genomes, dbSNP). Protein function prediction tools consistently indicated it as a pathogenic or likely pathogenic variant (SIFT, PolyPhen-2, CADD, and REVEL scores all reached pathogenic thresholds). Protein structural modeling revealed that the variant may disrupt the hydrogen-bonding network compromising the tetramer stability. ACMG classification designated it as likely pathogenic (PM1+PM2_Supporting+PM5+PP3). The patient was treated with benhaxol hydrochloride, baclofen, and clonazepam to improve his neurological symptoms, in addition with treatment with febuxostat from the Nephrology Department to manage his purine metabolism. After one year of follow-up, the patient's abnormal posture showed slight improvement, self-injurious behavior persisted but was managed with protective gloves, blood uric acid levels normalized, and renal stones decreased. Case 2, a 13-year-old boy, was hospitalized to the Nephrology Department due to urinary tract infection. Following successful control of the infection, his limb dystonia has worsened, leading to his transfer to the Neurology Ward. The patient had a history of delayed motor and language development, abnormal postures, and lip-biting self-injurious behavior, with elevated blood uric acid levels, leading to the diagnosis of LNS. His parents had declined genetic testing due to financial constraints. Following discharge, the patient did not adhere to the prescribed medication regimen or attend scheduled outpatient visits. The patient had died by the time of the 4-month follow-up contact. CONCLUSION Variants of the HPRT1 gene probably underlay the LNS in the two children, and the HPRT1 is the only known pathogenic gene for LNS. Early genetic diagnosis, strict adherence to multidisciplinary comprehensive treatment, and intensive intervention for self-injurious behaviors are crucial for improving the quality of life and prolonging the survival of children with LNS.
Humans ; Male ; Lesch-Nyhan Syndrome/diagnosis* ; Exome Sequencing ; Child, Preschool ; Phenotype ; Infant ; Child ; Female ; Retrospective Studies ; Mutation

Objective Taking into account the physical and mental characteristics of patients with COPD,we develop and implement a lung rehabilitation education game software,aiming to explore more effective health education practices for COPD.Methods Drawing on the Health Belief Model theory,the game content was developed by semi-structured interviews,brainstorming sessions,and expert consultations,and it was implemented via a WeChat mini program.Patients with COPD from the respiratory department of a tertiary general hospital of Luzhou city between March and October 2023 were conveniently selected as the study subjects.Among them,40 patients from July to October 2023 were designated as an experimental group,and another 40 from March to June 2023 constituted a control group.The experimental group was provided with routine health education combined with pulmonary rehabilitation games,whereas the control group received standard health education.After the intervention,the researchers compared the COPD knowledge questionnaire scores and pulmonary rehabilitation adherence between the 2 groups,and assessed the satisfaction of both patients and nurses with the software.Results No sample detachment.The score of the COPD knowledge questionnaire in the experimental group was higher than that in the control group,and the difference was statistically significant(Z=5.361,P＜0.001).The proportion of patients in the experimental group with good adherence to pulmonary rehabilitation(85％)was significantly higher than it in the control group(25％),(x2=29.091,P＜0.001).The patients'overall satisfaction rate with the game was 95％,with operational effectiveness receiving the highest satisfaction rating at 97％.Conclusion The pulmonary rehabilitation education game for patients with COPD can improve their knowledge of COPD,enhance their compliance with pulmonary rehabilitation.Patients have high satisfaction with the software.The software enriches the clinical health education methods,which can be used in clinical practice.

Objective Taking into account the physical and mental characteristics of patients with COPD,we develop and implement a lung rehabilitation education game software,aiming to explore more effective health education practices for COPD.Methods Drawing on the Health Belief Model theory,the game content was developed by semi-structured interviews,brainstorming sessions,and expert consultations,and it was implemented via a WeChat mini program.Patients with COPD from the respiratory department of a tertiary general hospital of Luzhou city between March and October 2023 were conveniently selected as the study subjects.Among them,40 patients from July to October 2023 were designated as an experimental group,and another 40 from March to June 2023 constituted a control group.The experimental group was provided with routine health education combined with pulmonary rehabilitation games,whereas the control group received standard health education.After the intervention,the researchers compared the COPD knowledge questionnaire scores and pulmonary rehabilitation adherence between the 2 groups,and assessed the satisfaction of both patients and nurses with the software.Results No sample detachment.The score of the COPD knowledge questionnaire in the experimental group was higher than that in the control group,and the difference was statistically significant(Z=5.361,P＜0.001).The proportion of patients in the experimental group with good adherence to pulmonary rehabilitation(85％)was significantly higher than it in the control group(25％),(x2=29.091,P＜0.001).The patients'overall satisfaction rate with the game was 95％,with operational effectiveness receiving the highest satisfaction rating at 97％.Conclusion The pulmonary rehabilitation education game for patients with COPD can improve their knowledge of COPD,enhance their compliance with pulmonary rehabilitation.Patients have high satisfaction with the software.The software enriches the clinical health education methods,which can be used in clinical practice.

Objective:To explore the clinical, genetic, and therapeutic prognostic characteristics of two pediatric cases of Lesch-Nyhan syndrome (LNS) in order to enhance understanding of this disease and investigate more effective treatment strategies.Methods:Clinical data were collected from two children clinically diagnosed with LNS who were treated at Anhui Provincial Children′s Hospital from April 2023 to January 2024. Data were collected retrospectively and included clinical manifestations (symptoms, signs, laboratory and imaging findings), treatment course, and follow-up results. Peripheral venous blood samples (2 mL each) were obtained from children 1 and his parents. Whole-exome sequencing (WES) was performed. Candidate variants were validated by Sanger sequencing to confirm the genetic etiology.Standard bioinformatic analysis of the raw WES data was conducted, including quality control, alignment, variant calling, and annotation. Candidate pathogenic variants were filtered using population frequency databases (e.g., gnomAD), disease databases (e.g., OMIM, ClinVar), and multiple in silico pathogenicity prediction tools (e.g., SIFT, PolyPhen-2, CADD). Phenotype matching was integrated using Human Phenotype Ontology (HPO) terms. Pathogenicity classification of variants was performed according to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants (2015). This study was approved by the Medical Ethics Committee of Anhui Children′s Hospital, Children′s Hospital of Fudan University (Approval No.: EYLL-2014-027).Results:Case 1, a 4-year-old boy presented with "developmental delay for over 3 years, accompanied by abnormal postures and involuntary lip-biting". Physical examination revealed limb dystonia, anxious expression, lower lip damage, and communication difficulties. Laboratory tests showed hyperuricemia and renal stones. Genetic testing identified a hemizygote variant in the HPRT1 gene, c. 135G>T (p.Arg45Ser), inherited from an asymptomatic carrier mother, confirming the diagnosis of LNS. This variant was absent from population databases (gnomAD, 1000 Genomes, dbSNP). Protein function prediction tools consistently indicated pathogenic or likely pathogenic variant (SIFT, PolyPhen-2, CADD, and REVEL scores all reached pathogenic thresholds). Protein structural modeling revealed that the mutation disrupts the hydrogen-bonding network, compromising tetramer stability. ACMG classification designated it as likely pathogenic (PM1 + PM2_Supporting + PM5 + PP3). The patient was treated with benhaxol hydrochloride, baclofen, and clonazepam to improve neurological symptoms, and also received treatment with febuxostat in the nephrology department to manage purine metabolism. After one year of follow-up, the patient′s abnormal posture showed slight improvement, self-injurious behavior persisted but was managed with protective gloves, blood uric acid levels normalized, and renal stones decreased. Case 2, a 13-year-old boy was hospitalized in the nephrology department due to a urinary tract infection. Following successful infection treatment, his limb dystonia worsened, leading to his transfer to the neurology ward. The patient had a history of delayed motor and language development, abnormal postures, and lip-biting self-injurious behavior, with elevated blood uric acid levels, leading to an LNS diagnosis. The parents declined genetic testing due to financial constraints. Following discharge, the patient did not adhere to the prescribed medication regimen or attend scheduled outpatient visits. The patient had died by the time of the 4-month follow-up contact. Conclusion:HPRT1 gene variants are the genetic cause of LNS in children, and the HPRT1 gene is the only known pathogenic gene for LNS. Early genetic diagnosis, strict adherence to multidisciplinary comprehensive treatment, and intensive intervention for self-injurious behaviors are crucial for improving the quality of life and prolonging survival in children with LNS.

The anti-inflammatory phytochemical investigation of the leaves of Illicium dunnianum (I. dunnianum) resulted in the isolation of five pairs of new lignans (1-5), and 7 known analogs (6-12). The separation of enantiomer mixtures 1-5 to 1a/1b-5a/5b was achieved using a chiral column with acetonitrile-water mixtures as eluents. The planar structures of 1-2 were previously undescribed, and the chiral separation and absolute configurations of 3-5 were reported for the first time. Their structures were determined through comprehensive spectroscopic data analysis [nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass (HR-ESI-MS), infrared (IR), and ultraviolet (UV)] and quantum chemistry calculations (ECD). The new isolates were evaluated by measuring their inhibitory effect on NO in lipopolysaccharide (LPS)-stimulated BV-2 cells. Compounds 1a, 3a, 3b, and 5a demonstrated partial inhibition of NO production in a concentration-dependent manner. Western blot and real-time polymerase chain reaction (PCR) assays revealed that 1a down-regulated the messenger ribonucleic acid (mRNA) levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), COX-2, and iNOS and the protein expressions of COX-2 and iNOS. This research provides guidance and evidence for the further development and utilization of I. dunnianum.
Lignans/isolation & purification* ; Plant Leaves/chemistry* ; Anti-Inflammatory Agents/isolation & purification* ; Mice ; Animals ; Molecular Structure ; Plant Extracts/pharmacology* ; Illicium/chemistry* ; Cyclooxygenase 2/immunology* ; Interleukin-6/immunology* ; Nitric Oxide/metabolism* ; Cell Line ; Tumor Necrosis Factor-alpha/immunology* ; Nitric Oxide Synthase Type II/immunology* ; Lipopolysaccharides

Objective:To explore the clinical, genetic, and therapeutic prognostic characteristics of two pediatric cases of Lesch-Nyhan syndrome (LNS) in order to enhance understanding of this disease and investigate more effective treatment strategies.Methods:Clinical data were collected from two children clinically diagnosed with LNS who were treated at Anhui Provincial Children′s Hospital from April 2023 to January 2024. Data were collected retrospectively and included clinical manifestations (symptoms, signs, laboratory and imaging findings), treatment course, and follow-up results. Peripheral venous blood samples (2 mL each) were obtained from children 1 and his parents. Whole-exome sequencing (WES) was performed. Candidate variants were validated by Sanger sequencing to confirm the genetic etiology.Standard bioinformatic analysis of the raw WES data was conducted, including quality control, alignment, variant calling, and annotation. Candidate pathogenic variants were filtered using population frequency databases (e.g., gnomAD), disease databases (e.g., OMIM, ClinVar), and multiple in silico pathogenicity prediction tools (e.g., SIFT, PolyPhen-2, CADD). Phenotype matching was integrated using Human Phenotype Ontology (HPO) terms. Pathogenicity classification of variants was performed according to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants (2015). This study was approved by the Medical Ethics Committee of Anhui Children′s Hospital, Children′s Hospital of Fudan University (Approval No.: EYLL-2014-027).Results:Case 1, a 4-year-old boy presented with "developmental delay for over 3 years, accompanied by abnormal postures and involuntary lip-biting". Physical examination revealed limb dystonia, anxious expression, lower lip damage, and communication difficulties. Laboratory tests showed hyperuricemia and renal stones. Genetic testing identified a hemizygote variant in the HPRT1 gene, c. 135G>T (p.Arg45Ser), inherited from an asymptomatic carrier mother, confirming the diagnosis of LNS. This variant was absent from population databases (gnomAD, 1000 Genomes, dbSNP). Protein function prediction tools consistently indicated pathogenic or likely pathogenic variant (SIFT, PolyPhen-2, CADD, and REVEL scores all reached pathogenic thresholds). Protein structural modeling revealed that the mutation disrupts the hydrogen-bonding network, compromising tetramer stability. ACMG classification designated it as likely pathogenic (PM1 + PM2_Supporting + PM5 + PP3). The patient was treated with benhaxol hydrochloride, baclofen, and clonazepam to improve neurological symptoms, and also received treatment with febuxostat in the nephrology department to manage purine metabolism. After one year of follow-up, the patient′s abnormal posture showed slight improvement, self-injurious behavior persisted but was managed with protective gloves, blood uric acid levels normalized, and renal stones decreased. Case 2, a 13-year-old boy was hospitalized in the nephrology department due to a urinary tract infection. Following successful infection treatment, his limb dystonia worsened, leading to his transfer to the neurology ward. The patient had a history of delayed motor and language development, abnormal postures, and lip-biting self-injurious behavior, with elevated blood uric acid levels, leading to an LNS diagnosis. The parents declined genetic testing due to financial constraints. Following discharge, the patient did not adhere to the prescribed medication regimen or attend scheduled outpatient visits. The patient had died by the time of the 4-month follow-up contact. Conclusion:HPRT1 gene variants are the genetic cause of LNS in children, and the HPRT1 gene is the only known pathogenic gene for LNS. Early genetic diagnosis, strict adherence to multidisciplinary comprehensive treatment, and intensive intervention for self-injurious behaviors are crucial for improving the quality of life and prolonging survival in children with LNS.

Objective:To evaluate the effect of ultrasound-guided internal branch of superior laryngeal nerve(ibSLN) block on the quality of anesthesia recovery in the patients undergoing intracranial tumor surgery.Methods:The data from patients of either gender, aged 18-65 yr, with a body mass index of 18-28 kg/m 2, who underwent intracranial tumor surgery from December 2022 to October 2023, were retrospectively collected. Patients were divided into control group (group C) and ultrasound-guided ibSLN block group (group U). Bilateral ibSLN block was performed with 0.375% ropivacaine hydrochloride 2 ml.The tracheal extubation time, emergence time, development of cardiovascular events within 15 min after extubation, emergence agitation, Ramsay sedation score, Steward recovery score, visual analogue scale scores at 10 min after extubation and development of postoperative sore throat and hoarseness in postanesthesia care unit were recorded. Results:Compared with group C, the incidence of emergence agitation, Ramsay sedation score, visual analogue scale scores and sore throat were significantly decreased, the incidence of hoarseness was increased ( P<0.05), and no significant change was found in the extubation time, emergence time and Steward recovery score in group U( P>0.05). No hypertension, hypotension, tachachycardia and bradycardia were found in two groups. Conclusions:Ultrasound-guided ibSLN block can improve the quality of anesthesia recovery in the patients undergoing intracranial tumor surgery.

【Objective】 To establish an information management platform for provincial rare blood group bank to achieve the interconnection and sharing of data such as rare blood group types, donor information and blood inventory, so as to enhance the supply security of rare blood group blood. 【Methods】 The information barriers of rare blood group management in each business link and among blood stations in Zhejiang province were analyzed using fishbone diagram. Data modeling technology was introduced based on the unified blood collection and supply business system and blood cloud platform of Zhejiang, the database view of rare blood group donors and rare blood group was constructed through demand analysis and model design, and a unified query platform was developed to achieve the sharing of rare blood group information. 【Results】 The system integrated, retrievaled and displayed rare blood type information, achieving the interconnection of information among various business links and blood stations within blood banks. Up to now, in addition to RhD negative blood group, there were 8 types of rare red blood cells in the bank, covering 7 blood group systems, 289 rare blood group donors and 216 units of frozen red blood cells of rare blood group. 【Conclusion】 The information system based on data modeling can improve the overall efficiency and collaboration of the system, and reduce the workload of system development and operation. It can provide reference for standardized data management and application, and also provide a model for establishing and improving of a national rare blood group information network.

ObjectiveTo study the anti-inflammatory effects of Blumea balsamifera （L.） DC oil （BBO） based on nuclear factor kappa-B （NF-κB） nonclassical and arachidonic acid （AA） pathway. MethodsEffects of BBO on the production of slow reacting substance of anaphylaxis （SRS-A） were detected by the ileal smooth muscle method. The contents of prostaglandin E₂ （PGE₂） and leukotriene B₄ （LTB₄） in lipopolysaccharides （LPS） -induced macrophages were detected by ELISA kit. The expression of COX-2， 5-LOX， FLAP and RelB were detected by qRT-PCR. Western blot was performed to detect the effects of BBO on the level of NF-κB nonclassical pathway proteins TNF receptor associated factor 3 （TRAF3）， TNF receptor associated factor 2 （TRAF2）， NF-κB-inducing kinase （NIK）， p100 and RelB. ResultsThe contractile tension of guinea pig ileum was reduced （P<0.001）， and the SRS-A production inhibition rate reached 65.34% at 1mg·mL^-1 BBO concentration. Compared with LPS group， BBO reduced the concentrations of PGE₂ （P<0.05） and LTB₄ （P<0.05）_， and decreased the expressions of COX-2 （P<0.05）， 5-LOX （P<0.05） and FLAP （P<0.05） in AA pathway at concentrations of 40-80 μg·mL^-1. Moreover， 40-80 μg·mL^-1 BBO decreased the concentrations of TRAF3 （P<0.05）， TRAF2 （P<0.05）， and NIK （P<0.05）， and further inhibited the phosphorylation of p100 （P<0.05）， as well as the level of the transcription factor RelB in genes （P<0.05） and proteins （P<0.05） in nonclassical NF-κB pathway， whereas BBO did not cause such changes. ConclusionBBO may potentially exert its anti-inflammatory effects by suppressing the regulatory proteins TRAF3 and TRAF2 and the transcription factor RelB in NF-κB nonclassical pathway. The inhibitory action extending to the induction kinase function of NIK， further hindering the phosphorylation of p100 and its binding with the transcription factor RelB. Consequently， downstream elements in the AA pathway， including the pivotal rate-limiting enzymes COX-2， 5-LOX and FLAP， were altered. This modulation influences the levels of inflammatory mediators such as PGE₂ and LTB₄.

Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.