OBJECTIVE: To summarize the clinical and genetic characteristics of a child with 46,XX Ovotesticular disorder of sex development (46,XX OTDSD) due to copy number variation of SOX3 gene. METHODS: A 46,XX male patient presented at the Capital Center for Children's Health, Capital Medical University in November 2024 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were taken from the child and his parents and subjected to trio whole-genome sequencing. Skewed X-chromosome inactivation was tested in the child and his mother. A literature review was carried out on 46,XX males associated with mutations of the SOX3 gene. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: SHERLL2025056). RESULTS: The 10-year-old boy presented with hypospadias and cryptorchidism at birth. Chromosome analysis at one year and a half revealed a 46,XX karyotype. Gonadal biopsy showed testicular tissue, while ultrasound at the age of 10 detected ovotesticular tissue. Whole-genome sequencing identified a 660 kb duplication in the Xq27.1 region, which was derived from his mother. X-chromosome inactivation testing showed random inactivation in the child and mild non-random inactivation in the mother. Literature review has found 11 publications involving 15 patients (including our case), among whom 14 had a male social gender. They had primarily presented with hypospadias at birth but had no significant endocrine abnormalities. Most patients had experienced testicular failure after puberty. SOX3 related 46,XX males are mainly caused by de novo duplications, although a few maternal carriers had been discovered. CONCLUSION Duplication of the SOX3 gene probably underlay the pathogenesis is this 46,XX male. Individuals with 46,XX SRY negative male phenotypes should be routinely screened for SOX3 gene variants. Structural variations of the SOX3 gene can lead to complete or partial sex reversal in 46,XX individuals with minimal impact on intellectual and motor development, as well as other endocrine hormones.
Child ; Humans ; Male ; 46, XX Disorders of Sex Development/genetics* ; DNA Copy Number Variations ; Gene Duplication ; Phenotype ; SOXB1 Transcription Factors/genetics*

In the context of the modernization of traditional Chinese medicine （TCM）， the inheritance of the experiences of famous doctors faces significant challenges due to its complex nonlinear characteristics and dynamic evolution. There are still issues in the current inheritance system， such as the homogenization of talent cultivation models， lack of standardized mentoring practices， and monotonous evaluation method， which hinder the systematic inheritance and innovative development of famous doctors' experiences. Based on a systematic review of the current state of artificial intelligence （AI）-assisted inheritance of famous doctors' experiences， this study explores innovative pathways for deep integration of modern information technologies with famous doctors' experiences from key dimensions， including data authenticity assurance， interdisciplinary collaboration mechanisms， and the establishment of dynamic inheritance standards. It proposes a paradigm shift in the inheritance of TCM famous doctors' experiences in the AI era， aiming to build a new TCM inheritance system of "digital intelligence empowerment and cross-disciplinary innovation"， providing theoretical support and practical pathways for the inheritance of famous doctors' experiences in TCM.

Atherosclerosis (AS), the primary pathological contributor to cardiovascular diseases (CVDs), has increasingly affected younger populations due to modern dietary habits and sedentary lifestyles. Current diagnostic modalities, including ultrasound, MRI, and CT, primarily identify advanced lesions and inadequately evaluate plaque vulnerability, thereby hindering early detection. Conventional treatments, which involve long-term medications associated with side effects such as hepatic injury and surgical interventions that carry risks of restenosis and hemorrhage, underscore the urgent need for non-invasive, cost-effective early diagnostic methods and targeted therapies. Gut microbiota metabolites are pivotal in AS pathogenesis, with trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs) serving as functionally opposing biomarkers. TMAO is produced when gut bacteria, specifically Firmicutes and Proteobacteria, metabolize dietary choline and carnitine into trimethylamine (TMA), which the liver subsequently converts to TMAO via flavin-containing monooxygenase 3 (FMO3); TMAO is then excreted in urine. Variability in TMAO levels is influenced by marine food consumption and FMO3 modulation, which can be affected by genetics, age, and diet. Mechanistically, TMAO exacerbates AS by disrupting cholesterol metabolism, inducing endothelial dysfunction through the elevation of reactive oxygen species (ROS) and pro-inflammatory cytokines such as IL-6, and reducing nitric oxide levels. Additionally, TMAO activates NF-κB and NLRP3 pathways while enhancing platelet reactivity. Clinically, elevated TMAO levels correlate with early AS and serve as predictors of mortality in patients with stable coronary artery disease (CAD) and acute coronary syndrome (ACS), as well as major adverse cardiovascular events (MACE) in stroke patients. Conversely, SCFAs—namely acetate, propionate, and butyrate—are produced by gut bacteria such as Akkermansia muciniphila and Faecalibacterium prausnitzii through the fermentation of dietary fiber. These metabolites exert anti-AS effects: acetate aids in maintaining metabolic homeostasis; propionate protects endothelial function and reduces plaque area; and butyrate fortifies intestinal barriers while suppressing inflammation. Furthermore, SCFAs cross-regulate bile acid metabolism, thereby influencing TMAO levels, and antagonize the pro-inflammatory and lipid-disrupting effects of TMAO. The use of TMAO and SCFAs as standalone biomarkers is constrained by limitations. TMAO lacks specificity, while SCFA levels fluctuate based on gut microbiota and dietary intake. Traditional AS risk assessment tools, which include clinical indicators, imaging techniques, and single biomarkers such as CRP, LDL-C, and ASCVD scores, overlook gut metabolism and demonstrate inadequate performance in younger populations. This review advocates for an “antagonistic-complementary” combined strategy: utilizing acetate and TMAO for early AS, propionate and TMAO for progressive AS, and butyrate and TMAO for advanced AS, addressing endothelial dysfunction, lipid deposition, and plaque stability/thrombosis risk, respectively. For clinical application, standardization of detection methods is crucial; liquid chromatography-mass spectrometry (LC-MS) is the gold standard, necessitating a unified sample pretreatment protocol, such as extraction with 1% formic acid in methanol. Additionally, dried blood spots (DBS) facilitate non-invasive testing, provided that dietary controls are implemented prior to detection, including a 12-hour fast and avoidance of high-choline and high-fiber foods. Existing challenges encompass the absence of standardized systems, limited large-scale validation, and ambiguous interactions with conditions such as hypertension. The authors’ team has previously established connections between gut metabolites and AS, including the reduction of TMAO as a preventive measure for AS, thereby reinforcing this proposed strategy. Future research should prioritize standardization, the development of machine learning-optimized models, validation of interventions, and the exploration of multi-omics-based “gut microbiota-metabolite-vascular” networks. In conclusion, the combined detection of TMAO and SCFAs offers a novel framework for AS risk assessment, facilitating early diagnosis and targeted interventions while enhancing the integration of gut metabolism into cardiovascular disease management.

Atherosclerosis (AS), the primary pathological contributor to cardiovascular diseases (CVDs), has increasingly affected younger populations due to modern dietary habits and sedentary lifestyles. Current diagnostic modalities, including ultrasound, MRI, and CT, primarily identify advanced lesions and inadequately evaluate plaque vulnerability, thereby hindering early detection. Conventional treatments, which involve long-term medications associated with side effects such as hepatic injury and surgical interventions that carry risks of restenosis and hemorrhage, underscore the urgent need for non-invasive, cost-effective early diagnostic methods and targeted therapies. Gut microbiota metabolites are pivotal in AS pathogenesis, with trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs) serving as functionally opposing biomarkers. TMAO is produced when gut bacteria, specifically Firmicutes and Proteobacteria, metabolize dietary choline and carnitine into trimethylamine (TMA), which the liver subsequently converts to TMAO via flavin-containing monooxygenase 3 (FMO3); TMAO is then excreted in urine. Variability in TMAO levels is influenced by marine food consumption and FMO3 modulation, which can be affected by genetics, age, and diet. Mechanistically, TMAO exacerbates AS by disrupting cholesterol metabolism, inducing endothelial dysfunction through the elevation of reactive oxygen species (ROS) and pro-inflammatory cytokines such as IL-6, and reducing nitric oxide levels. Additionally, TMAO activates NF-κB and NLRP3 pathways while enhancing platelet reactivity. Clinically, elevated TMAO levels correlate with early AS and serve as predictors of mortality in patients with stable coronary artery disease (CAD) and acute coronary syndrome (ACS), as well as major adverse cardiovascular events (MACE) in stroke patients. Conversely, SCFAs—namely acetate, propionate, and butyrate—are produced by gut bacteria such as Akkermansia muciniphila and Faecalibacterium prausnitzii through the fermentation of dietary fiber. These metabolites exert anti-AS effects: acetate aids in maintaining metabolic homeostasis; propionate protects endothelial function and reduces plaque area; and butyrate fortifies intestinal barriers while suppressing inflammation. Furthermore, SCFAs cross-regulate bile acid metabolism, thereby influencing TMAO levels, and antagonize the pro-inflammatory and lipid-disrupting effects of TMAO. The use of TMAO and SCFAs as standalone biomarkers is constrained by limitations. TMAO lacks specificity, while SCFA levels fluctuate based on gut microbiota and dietary intake. Traditional AS risk assessment tools, which include clinical indicators, imaging techniques, and single biomarkers such as CRP, LDL-C, and ASCVD scores, overlook gut metabolism and demonstrate inadequate performance in younger populations. This review advocates for an “antagonistic-complementary” combined strategy: utilizing acetate and TMAO for early AS, propionate and TMAO for progressive AS, and butyrate and TMAO for advanced AS, addressing endothelial dysfunction, lipid deposition, and plaque stability/thrombosis risk, respectively. For clinical application, standardization of detection methods is crucial; liquid chromatography-mass spectrometry (LC-MS) is the gold standard, necessitating a unified sample pretreatment protocol, such as extraction with 1% formic acid in methanol. Additionally, dried blood spots (DBS) facilitate non-invasive testing, provided that dietary controls are implemented prior to detection, including a 12-hour fast and avoidance of high-choline and high-fiber foods. Existing challenges encompass the absence of standardized systems, limited large-scale validation, and ambiguous interactions with conditions such as hypertension. The authors’ team has previously established connections between gut metabolites and AS, including the reduction of TMAO as a preventive measure for AS, thereby reinforcing this proposed strategy. Future research should prioritize standardization, the development of machine learning-optimized models, validation of interventions, and the exploration of multi-omics-based “gut microbiota-metabolite-vascular” networks. In conclusion, the combined detection of TMAO and SCFAs offers a novel framework for AS risk assessment, facilitating early diagnosis and targeted interventions while enhancing the integration of gut metabolism into cardiovascular disease management.

Objective To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application.Methods and Results Recommendations were formulated based on literature review and expert group discussion,and consensus was reached following expert consultation.The consensus recommendations are comprehensive,covering the entire treatment procedures from preoperative assessment and preparation,surgical operation process,postoperative management and traditional Chinese medicine treatment to individualized treatment planning.The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain,reduced the use of opioid drugs,and significantly improved the quality of life and enhanced immune function of the patients.Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.Conclusion The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy.The combined treatment has a high clinical value with a good safety profile for management of cancer pain.

Objective The experimental method of cervical vestibular evoked myogenic potential(cVEMP)with high retest reliability was designed to verify the accuracy of locating sternocleidomastoid muscle in mice.Methods Three 2-month-old ICR male mice were selected,one of which was dissected to locate the sternocleidomastoid muscle,while the other two were used to design the experimental plan to verify the accuracy of localization.Results The recording electrode positioned on the sternocleidomastoid muscle of mice can repeatedly elicit clear cVEMP waveform.Conclusion The cVEMP waveform with high retest reliability can be measured in both experimental mice,suggesting that the localization of sternocleidomastoid muscle in this research is accurate.

This research aims to construct a stable epithelial cell senescence model for screening and e-valuation of senolytics.We explored the optimal conditions for doxorubicin-induced senescence of non-transformed epithelial cells MCF 10A,including the optimal induction concentration,the optimal inter-vention time,and the optimal senescence duration,and confirmed the feasibility of MCF 10A as an epi-thelial senescence model by multiple ways.The optimal condition for Doxorubicin-induced senescence of MCF 10A cells was treatment with 0.6 μmol/L Doxorubicin for 16 h to achieve the best senescence state on the 8th day.Under the optimal induction conditions,the positive rate of senescence-associated β-gal-actosidase(SA-β-gal)staining in the treated group reached 97％.At the same time,biochemical results of detecting the expression of mRNA,proteins,and immunofluorescence demonstrated that the expression levels of senescence-associated secretory phenotype(SASP),p16,p21 and p53 in the treated group were significantly higher than those in the control cells,and Lamin B1 was significantly decreased(P＜0.001),which were consistent with the specific characteristics of senescence.In summary,an epithelial senescence model was successfully induced in MCF 10A cells by Doxorubicin in this study,which will promote the screening of senolytics for senescent epithelial cells.

Objective To investigate the relationship between polymorphisms at the rs3093030 and rs5498 loci of the intercellular adhesion molecule-1(ICAM-1)gene in combination with high sensitive C-reactive protein(hs-CRP)and susceptibility to type 2 diabetes mellitus complicated with HTN(T2MH)susceptibility.Methods 200 newly diagnosed T2DM patients,175 T2MH patients and 200 healthy controls from Affiliated Hospital of Guilin Medical University between September 2021 and January 2022.Single nucleotide polymorphisms(SNP)-scan high-throughput technology was used to detect the genotyping of serum rs3093030 and rs5498 polymorphisms in the study subjects and to detect hs-CRP levels in peripheral plasma to analysed and explore the correlation between them and the development of T2MH.Results The peripheral blood hs-CRP expression level of patients in the T2MH group[2.65(1.18,6.50)mg/L]was significantly higher than that in the T2DM group[1.82(0.80,4.48)mg/L]and healthy controls[1.02(0.54,2.29)mg/L],and the differences were statistically significant(Z=-2.729,-7.132,all P<0.001).After population classification by genotype,it was found that compared with healthy controls,rs3093030 CC(Z=-3.912,-5.800),rs5498 AA(Z=-3.293,-4.944)and AG(Z=-3.275,-4.872)genotypes had significantly higher hs-CRP levels.The peripheral blood hs-CRP levels of patients with rs3093030 CT genotype in the T2MH group were significantly higher than that of healthy controls(Z=-3.987),and the differences was statistically significant(all P<0.001),respectively.Meanwhile,regression analysis showed that HS-CRP was a risk factor for both T2MH group and healthy control group(OR=1.181,95%CI=1.095～1.274,P<0.001).Conclusion There is a correlation between ICAM-1 gene rs3093030 and rs5498 polymorphisms combined with hs-CRP levels in peripheral blood and the pathogenesis of T2MH patients.

Objective:To investigate the short-term pulmonary function outcomes in children with congenital diaphragmatic hernia (CDH) following surgery and analyze the influencing factors of poor outcomes.Methods:This study retrospectively enrolled 81 children who had undergone surgery for CDH and were discharged after recovery at the Department of Neonatal Surgery, Children's Hospital of Capital Institute of Pediatrics from January 2020 to June 2023. All children had pulmonary function tests before discharge, 6 months to 2 year after discharge. Changes in the pulmonary function parameters at different time points were compared. Based on the results of the final pulmonary function test after discharge, these patients were categorized into a favorable outcome group (32 cases) with normal pulmonary function and an unfavorable outcome group (49 cases) with pulmonary dysfunction. Clinical data of the two groups were compared using two independent samples t-test, rank-sum test, Chi-square test, or Fisher's exact test. Logistic regression analysis was used to explore the factors influencing pulmonary function outcomes. Results:A total of 81 cured and discharged CDH children were included in this study, comprising 34 males (42.0%) and 47 females (58.0%). The first two pulmonary function tests were performed at a mean postnatal age of (30.1±14.1) d (14-75 d) and (8.3±1.3) months (4 months and 14 d to 12 months), respectively. Pre-discharge pulmonary function tests revealed that 13 cases (16.0%) had nearly normal pulmonary function, while 68 cases (84.0%) showed pulmonary function abnormalities with seven cases of restrictive ventilatory dysfunction, 56 cases of obstructive ventilatory dysfunction, and five cases of mixed ventilatory dysfunction. In the children with abnormal pulmonary function before discharge, their second pulmonary function tests showed that some parameters including tidal volume [(7.49±1.35) ml/kg vs. (8.02±2.21) ml/kg], the ratio of time to peak tidal expiratory flow and expiratory time [(23.21±4.95)% vs. (26.50±5.48)%], the ratio of volume to peak expiratory flow and expiratory volume [(26.41±5.79)% vs. (27.55±5.20)%], respiratory system compliance per kg body weight during single occlusion [(0.93±0.22) ml/(cmH 2O·kg) vs. (0.96±0.25) ml/(cmH 2O·kg), 1 cmH 2O=0.098 kPa], functional residual capacity [(52.18±17.83) ml vs. (126.39±26.73) ml], and respiratory system resistance in single occlusion condition [(0.06±0.02) cmH 2O/(ml·s) vs. (0.05±0.01) cmH 2O/(ml·s)] improved after discharge ( t values were－2.41,－6.14,－7.68,－2.26,－18.94, and 4.87, all P<0.05). Eight children with obstructive ventilatory dysfunction were followed up for two years after surgery, of which three had normal lung function and five still showed mild to moderate obstructive ventilatory dysfunction. Logistic regression analysis indicated that liver herniation, severe pulmonary hypertension (PH), low observed-to-expected lung-to-head ratio (o/e LHR), grade C/D diaphragmatic defect, and prolonged invasive ventilation were risk factors for poor pulmonary outcomes [ OR(95% CI) were 5.655(1.410-22.676), 5.610 (1.589-19.804),4.183 (1.234-14.180) and 1.195(1.074- 1.329), all P<0.05]. Conclusions:Although lung function parameters of CDH patients show certain improvement after surgery, many children still have mild to moderate obstructive ventilatory dysfunction, requiring long-term follow-up. Prenatal and postnatal indicators such as liver herniation, severe PH, and low o/e LHR can predict the pulmonary outcomes of children with CDH.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.