Objective To analyze the epidemiological characteristics and spatial-temporal clustering trend of scarlet fever in Nantong from 2009 to 2023, and to provide a scientific basis for scarlet fever prevention and control. Methods The incidence data of scarlet fever in Nantong from 2009 to 2023 were analyzed. Descriptive analysis, seasonal index method and Joinpoint 5.2.0 software were used to analyze epidemiological characteristics. Spatial-temporal clustering was assessed with SaTScan 10.2.5 software. Results The average annual incidence of scarlet fever in Nantong from 2009 to 2023 was 6.54/100 000. The overall morbidity rate of scarlet fever in Nantong had an increasing trend from 2009 to 2019 with an average annual percentage change of 14.55% (t=3.36，P<0.05). The cases mainly occurred during late spring to early summer and late autumn to early winter. Students, preschool children and scattered children were the main scarlet fever population. The average annual incidence of males was significantly higher than that of females (χ²=7.00, P<0.05). Rugao City, Chongchuan District and Tongzhou District were identified as high-incidence areas, accounting for 76.51% of all reported cases. Spatial-temporal scan analysis indicated that Rugao City and Chongchuan District were primary cluster areas, spanning from 2015 to 2021 (RR=3.77, LLR=1 308.07, P<0.05). Conclusion The number of reported cases of scarlet fever in Nantong City from 2009 to 2023 shows epidemic and spatial clustering, mainly concentrated in the central urban area and adjacent counties (cities). It is necessary to strengthen health education and disease surveillance in high-incidence areas, as well as in key institutions and key populations before epidemic peaks.

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*

Medical parasitology, as a course bridging basic medical sciences and clinical medicine, has an important disciplinary value in the medical education system. This study investigated the composition of parasitology teachers from multiple medical colleges and universities across China. The results showed that there was a significant difference in the proportion of teachers with clinical medicine background knowledge, and there was common dilemma that there were insufficient clinical medicine knowledge reserves among teachers in some medical colleges and universities, who encountered severe teaching challenges. Based on this issue, this study constructed a basic-clinical medicine collaborative problem-based learning (PBL) teaching model. This model integrated theoretical teaching, case analyses, and experimental operations, and combined transdisciplinary team building and multidimensional teacher training, which significantly improved the clinical teaching capability among parasitology teachers, and effectively compensated the impact of insufficient clinical medicine knowledge reserves on teaching. Following teaching reform, students' scores significantly improved, and their case analysis capability enhanced. This study provides a practical path to address the shortage of clinical medicine background knowledge among parasitology teachers, which facilitates the progress of educational reform of medical parasitology and improvement of teaching quality.

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.

Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

Pan vascular disease （PVD） is a systemic vascular disorder that has become the leading cause of death among the Chinese residents， and there is currently a lack of effective systemic treatment options. Clinical practice has found that the traditional Chinese medicine （TCM） method of kidney tonification can effectively intervene in PVD and target key pathological mechanisms of PVD recognized in Western medicine. Accordingly， this paper conducts research from the following three aspects： First， it clarifies that immune dysregulation， metabolic disorders， and genetic susceptibility constitute the core pathological mechanisms of PVD in Western medicine. Typical pathological manifestations include progressive vascular endothelial injury， lipid deposition， and plaque formation， ultimately leading to multi-organ damage and dysfunction. PVD activates pathways such as the NOD-like receptor thermal protein domain-associated protein 3 （NLRP3） inflammasome， triggering immune dysregulation； it also induces disorders of mitochondrial energy metabolism， water-salt metabolism， and hormonal metabolism， synergizing with genetic susceptibility factors （e.g.， apolipoprotein E gene） to accelerate vascular homeostasis imbalance. Second， this study analyzes the intrinsic relationship between the TCM theory of "kidney deficiency" and the "immune-metabolic-genetic" axis， revealing the theoretical basis for kidney tonification in intervening PVD. The kidney stores essence， governs bones， and produces marrow， which is related to the generation and differentiation of immune cells. It regulates Qi transformation and governs water， overseeing material and energy metabolism. The kidney is the root of congenital essence and governs reproduction， closely related to genetic mechanisms. Third， by integrating modern clinical research， this study elaborates on the unique advantages and clinical value of kidney tonification in targeting the "immune-metabolic-genetic" axis of heart， brain， and kidney organs. Traditional kidney-tonifying formulas and their active ingredients improve immune-inflammatory responses， enhance material and energy metabolism homeostasis， and modulate epigenetic pathways through multiple pathways， targeting various pathways to intervene in PVD. This study systematically elucidates the scientific connotation of kidney tonification in treating PVD， providing theoretical support and practical guidance for integrated TCM-Western medicine approaches and contributing to innovation and improvement in diagnostic and treatment strategies for PVD.

Panvascular diseases refer to systemic vascular lesions with atherosclerosis as its common pathological basis， affecting the vascular networks of multiple organs such as the heart， brain， kidneys， limbs， and large arteries. This concept transcends the limitations of traditional classifications and promotes comprehensive vascular health management through multidisciplinary collaboration. Latent pathogenic factors play a critical role in the pathogenesis of panvascular diseases. They remain dormant within the body until finding an opportunity to manifest， which aligns closely with the characteristics of panvascular diseases， including their early covert progression and subsequent adverse vascular events. According to the ''latent pathogen'' theory， this article elucidates the pathogenesis of panvascular diseases from latent pathogen， vessel damage， and healthy Qi consumption. It posits that the disease onset involves a pathological process progressing from Qi to blood， with endothelial injury serving as the initiating factor. Disease progression encompasses changes from blood to vessels， with inflammatory responses accelerating the disease course. A comprehensive traditional Chinese medicine （TCM） based prevention and treatment system has been developed， dividing the disease course into three stages. In the early stage， pathogenic factors lurk in the vessels， primarily manifesting as abnormal lipid metabolism. In the middle stage， pathogenic factors evolve， leading to inflammatory cascade reactions. In the late stage， pathogenic factors become excessive while positive factors decline， resulting in abnormal energy metabolism. Three core therapeutic approaches-invigorating the spleen and resolving phlegm， activating blood and resolving stasis， and reinforcing healthy Qi and nourishing deficiency-have been established to address key pathological links. In conjunction with modern medical research， the mechanisms of these methods in regulating lipid metabolism， inhibiting inflammatory responses， and modulating energy metabolism to prevent and treat panvascular diseases are explained. It is anticipated that this theoretical framework will enrich the diagnostic and therapeutic thinking in TCM for panvascular diseases and provide a theoretical foundation for constructing TCM-characteristic prevention and treatment plans for panvascular diseases.

Panvascular diseases represent systemic vascular disorders characterized by atherosclerosis as their core pathological feature. Their incidence rates continue to rise， posing significant challenges for clinical management. Based on Traditional Chinese Medicine （TCM） theory of ''positive deficiency phlegm stasis''， this study delved into the pivotal role of mitochondrial homeostasis dysregulation in the pathogenesis and progression of pan-vascular diseases， along with its intrinsic connection to TCM pathogenesis. Mitochondrial homeostasis dysregulation pervades the entire course of these diseases， with mitochondrial oxidative stress serving as the initiating factor. Excessive reactive oxygen species （ROS） trigger endothelial dysfunction， lipid accumulation， and inflammatory initiation. Additionally， the imbalance between mitochondrial autophagy and apoptosis constitutes a pivotal link in disease progression. Excessive or insufficient autophagy may lead to the accumulation of damaged mitochondria and excessive cellular apoptosis， thereby promoting plaque instability. Furthermore， mitochondrial metabolic reprogramming impairs energy supply and function in vascular wall cells， hindering subsequent vascular repair. These pathological processes constitute the microscopic manifestation of the core pathogenesis， which is characterized by ''the intermingle of phlegm and stasis and the deficiency of healthy Qi''. Specifically， the endogenous phlegm-turbidity drives mitochondrial oxidative stress injuries， the mutual entanglement of phlegm and stasis induces an imbalance between mitochondrial autophagy and apoptosis， while deficiency of healthy Qi propels mitochondrial energy metabolism disorders and reprogramming. In view of this， this study proposed to employ phlegm-resolving and turbidity-clearing methods to mitigate mitochondrial oxidative stress injuries， phlegm-resolving and blood-activating methods to regulate mitochondrial autophagy and apoptosis， and spleen-tonifying and kidney-nourishing methods to modulate mitochondrial metabolic reprogramming. This approach can prevent and treat panvascular diseases by multi-target regulation of mitochondrial homeostasis， providing a theoretical framework and therapeutic strategies for the prevention and treatment of panvascular diseases through integrated Chinese and Western medicine.

Liver transplantation is the preferred treatment for end-stage liver disease, but recipients require long-term immunosuppressive therapy to control rejection, which may lead to complications and affect their long-term survival. Immune tolerance refers to the ability of organ transplant recipients to maintain their immune system's tolerance to the graft without relying on long-term immunosuppressants. Immune tolerance is an ideal goal pursued in the field of organ transplantation, which can reduce adverse drug reactions and improve long-term survival rates. Cell therapy has emerged as a promising strategy to induce such tolerance after liver transplantation. Therefore, this article reviews the application progress of cell therapies such as regulatory T cells, regulatory dendritic cells, mesenchymal stem cells, hematopoietic stem cells, etc. in inducing immune tolerance after liver transplantation, in order to provide reference for the clinical application of immune tolerance induction after liver transplantation.