OBJECTIVE:To compare the efficacy of laser ablation combined with photodynamic therapy (LA-PDT) versus PDT alone in the treatment of cervical intraepithelial neoplasia grade 2/3 (CIN2/3). METHODS:Patients diagnosed with CIN2/3 were enrolled and allocated to either the LA-PDT or the PDT group based on patients' choice. Pathological regression and human papillomavirus (HPV) clearance were compared at 12-month follow-up between the two groups. RESULTS:A total of 77 patients in the LA-PDT group and 68 patients in the PDT group completed follow-up. Baseline characteristics showed no significant differences between the two groups. At the 12-month follow-up, both the pathological complete remission rate and HPV clearance rate were significantly higher in the LA-PDT group compared to the PDT group (98.7%vs. 86.4%, P < 0.05; 92.3% vs. 86.4%, P < 0.05). Univariate and multivariate analyses indicated that the pre-treatment pathology of CIN3 was an independent risk factor for both lesion persistence and HPV persistence. Among the 111 patients with CIN2, the pathological complete remission rate was 98.2% and the HPV clearance rate was 95.5%. Among the 33 patients with CIN3, both the pathological complete remission rate and HPV clearance rate were significantly higher in the LA-PDT group than in the PDT group (94.1%vs. 56.3%, P < 0.05; 76.5% vs. 37.5%, P < 0.05). CONCLUSION:LA-PDT for CIN2/3 demonstrates high efficacy and potentially saves time and economic costs. The combined therapy shows significant advantages over PDT alone, particularly for patients with CIN3.

BACKGROUND:Vanishing White Matter disease (VWM) is a rare autosomal recessive leukoencephalopathy caused by biallelic variants in any of the five subunits of eukaryotic initiation factor 2B (EIF2B1-5), with varied clinical manifestations, including progressive neurological deterioration, cerebellar ataxia, and white matter abnormalities on MRI. Early and accurate diagnosis is crucial for medical interventions and genetic counseling. METHODS:We aimed to characterize the prevalence and spectrum of pathogenic variants of VWM in the Chinese population through Genetic screening for VWM mutations in 36,820 Chinese newborns from 31 hospitals across 14 provinces using next-generation sequencing. Pathogenic and likely pathogenic variants were identified and classified according to ACMG guidelines. Prevalence rates and variant spectra were analyzed. RESULTS:Among screened newborns, 114 carriers with 36 distinct pathogenic and likely pathogenic variants were identified, including 18 novel variants. The overall carrier frequency was 1 in 323. EIF2B2 showed the highest carrier frequency (1 in 498), with c.254 T > A/p.Val85Glu being a hotspot variant (61/74 carriers, 82.4%). The estimated prevalence rate of VWM in China was 1.12/1,000,000. CONCLUSIONS:This large-scale screening provides valuable insights into the genetic landscape of VWM in the Chinese population, contributing to improved genetic counseling, early diagnosis, and management strategies. These findings contribute to enhancing the understanding and management of VWM in China.

Platelets, derived from megakaryocytes (MKs), are crucial for blood clotting. Identifying genes that regulate MK development and platelet production could advance treatments for blood disorders. We found that KxDL motif-containing 1 (Kxd1) knockout (KO) mice exhibited doubled platelet counts without impairment of individual platelet function. Kxd1-KO mice showed enhanced MK progenitor differentiation and rapid polyploid MK formation in vivo and in vitro. Mechanistically, KXD1 deficiency increased TSPAN14 levels by disrupting its endolysosomal trafficking, thus activating the ADAM10-Notch axis to drive MK polyploidization. In platelet/MK-specific Tspan14-KO mice, TSPAN14 deficiency impaired MK polyploidization and maturation. Our findings reveal that KXD1 is a key negative regulator of Notch signaling, controlling megakaryopoiesis mediated by TSPAN14. The KXD1-TSPAN14 axis is a promising therapeutic target for platelet disorders, including thrombocytopenia and myeloproliferative neoplasms, and as an interventional pathway for platelet production in transfusion medicine.

Kaposiform hemangioendothelioma (KHE) is a rare borderline vascular tumor that occurs primarily during infancy and childhood. The tumor typically originates in the skin and exhibits invasive growth into deeper tissues, often manifesting as a firm, poorly defined purplish-red mass. Cases of KHE involving visceral organs, including the bone, retroperitoneum, or mediastinum, have also been reported; however, their clinical features are often nonspecific, which may lead to delayed diagnosis. Importantly, these tumors are frequently associated with Kasabach-Merritt phenomenon, a consumptive coagulopathy that represents a major cause of mortality in KHE. Furthermore, tumor location, size, and clinical response to pharmacotherapy are closely associated with patient prognosis. Therefore, early recognition and timely treatment of KHE are essential. This article aims to review the epidemiology, etiology, clinical manifestations, diagnosis, and management of KHE.

Uncontrollable traumatic bleeding caused by surgery or traffic accidents is an important factor leading to high mortality rates. Therefore, there is an urgent hemostatic materials with fast, effective, and safe to achieve rapid hemostasis. Traditional hemostatic materials have limited effect in deep irregular tissues or massive bleeding scenes, while exocrine hydrogel can break through limitations by quickly stopping bleeding and reducing secondary injury. The gelatin time of an injectable 10 % oxidized sodium alginate-10 % gelatin (OSA-G) hydrogel was 8 s. Platelet-rich plasma exosomes (PRP-Exo) from the autologous biological macromolecule play a crucial role in blood coagulation and hemostasis. The OSA-G hydrogel loaded with PRP-Exo exhibited superior effects on proliferation and angiogenesis in vitro. The APTT and thromboelastography of the OSA-G-EXO group were significantly reduced, indicating the occurrence of intrinsic coagulation pathways and the blood was in a hypercoagulable state and promoting hemostasis. Meanwhile, it has been confirmed in the rat tail-cutting model and the liver bleeding model that the hemostasis time is approximately 30 s, promoting skin healing in the skin wound model. By providing a controlled environment for coagulopathy or anticoagulant-treated patients, it shows a good clinical application prospect.

Cutaneous nodular fasciitis (cNF) is a rare, benign myofibroblastic proliferation commonly misdiagnosed as a malignancy due to its rapid growth and histological features. We reviewed 15 paediatric patients with cNF, highlighting clinical, histological and molecular characteristics. The patients' median age was 6 years, and there was a predilection for cNF in the head and neck region. Histologically, cNF showed plump spindle cells and myxoid stromal changes. USP6 rearrangement, particularly MYH9-USP6 fusion, was present in the majority of patients. Spontaneous resolution was observed in nonsurgically managed cases. Accurate diagnosis by screening for USP6 rearrangement is essential to avoid overtreatment. This study underscores the benign nature of cNF and the importance of conservative management, especially in cosmetically sensitive areas.

BackgroundPropranolol for infantile hemangiomas (IHs) is effective and relatively safe. However, propranolol has different formulations and there is no consensus on the optimal formulation for IHs. The propranolol oral solution was not used in China until 2022.ObjectiveTo evaluate the efficacy and safety of propranolol tablets and an oral solution in infants with high-risk IH.MethodsA retrospective cohort study was conducted involving 234 consecutive patients with a clinical diagnosis of high-risk IH who were treated with propranolol between August 2018 and February 2023 (propranolol tablets, 168 patients; propranolol oral solution, 66 patients). All patients were assessed in the hospital at the initiation of treatment and in the outpatient setting during treatment. The Hemangioma Activity and Severity Index was used to monitor the clinical activity of the hemangioma after propranolol treatment.ResultsBased on the Hemangioma Activity and Severity Index, 66.52% and 69.15% improvement occurred in the propranolol tablet and oral solution groups, respectively. 23.21% of patients in the propranolol tablet group and 42.42% in the oral solution group achieved >75% score improvement (X2 = 8.557; P = 0.003). Adverse reactions occurred in 34 (20.24%) and 11 patients (16.67%) in the propranolol tablet and oral solution groups, respectively. The most common adverse reaction in the propranolol tablet group was liver function abnormalities due to mild elevation of liver enzymes (X2 = 4.09; P = 0.045).ConclusionBoth propranolol tablets and oral solution had positive efficacy in patients with high-risk IHs, but more patients in the propranolol oral solution group achieve >75% score improvement compared to the propranolol tablet group. No life-threatening adverse reactions occurred in either group but liver function abnormalities were more likely to occur in patients treated with propranolol tablets.

Significance Port-wine stains (PWS) are challenging vascular malformations with significant cosmetic and psychosocial implications, especially in young children. Early and effective treatment is crucial to minimize long-term impact. Approach A 2-year-old boy presented with PWS involving the right cheek, forehead, and periocular area. Ophthalmologic evaluation ruled out glaucoma and Sturge-Weber syndrome. The patient underwent photodynamic therapy (PDT) using a photosensitizing agent and targeted light activation. Results After the first PDT session, the lesion demonstrated 50% resolution. Following a second treatment, near-complete clearance of the PWS was achieved. The outcomes were cosmetically satisfactory, with no adverse effects or recurrence observed to date. Conclusions PDT proved to be a safe and effective treatment for pediatric PWS, achieving substantial lesion clearance with minimal side effects. This case underscores the potential of PDT as a valuable therapeutic option for early intervention in PWS, warranting further investigation and protocol optimization.

ObjectiveThis study investigates the epidemiological trends of childhood type 1 diabetes (T1D) in China and establishes predictive models to estimate future disease burden.MethodsTemporal trend analyses were performed using data from the Global Burden of Disease (GBD) database, stratified by age and sex. Joinpoint regression analysis was applied to evaluate changes in incidence and mortality rates from 1990 to 2021, complemented by autoregressive integrated moving average (ARIMA) and exponential smoothing state space (ETS) models to project disease trends through 2040.ResultsThe results indicate a rising trend in the incidence of childhood T1D among Chinese children aged 0-14 years, alongside an overall decline in mortality, reflecting an epidemiological pattern characterized by low incidence yet non-negligible mortality. Notably, infants < 1 year of age have shown increasing mortality rates in recent years. Projections indicate that both incidence and mortality in this age group will continue to increase through 2040. Additionally, incidence among children 1 year of age also expected to persist on an upward trajectory. Sex-based disparities were evident, with girls bearing a higher disease burden than boys, as indicated by elevated incidence, mortality and underdiagnosis rates.ConclusionThese findings necessitate enhanced public health and clinical management strategies for childhood T1D in China, specifically targeting underdiagnosis reduction, incidence rate stabilization, and mortality rate improvement.

Albinism is a heterogeneous inherited disorder with at least 21 known causative genes. Clinically, interpreting the potential digenic or oligogenic effects of the variants is a big challenge. We identified digenic mutations in a Chinese individual with oculocutaneous albinism, carrying a loss-of-function mutation in the Cl- (chloride) channel gene OCA2 (c.808-3C>G) and an unreported gain-of-function mutation in the Na+/Ca2+ channel gene TPCN2 (p.Ala24Val), which was confirmed by patch-clamp analysis. We further demonstrated that Cl- bilaterally modulated TPC2 activity by patch clamping: cytosolic high Cl- inhibited but luminal high Cl- enhanced TPC2 channel activity. Using CRISPR/Cas9-mediated knockout cell models and knockin mouse models, we confirmed that OCA2 modulated TPC2 activity by influencing melanosomal pH and pigment production. Mice mimicking double heterozygotes for the OCA2 loss-of-function p.Val443Ile and the TPCN2 gain-of-function p.Arg210Cys exhibited synergistic hypopigmentation in both fur and retina, phenocopying the albinism patient with digenic loss-of-function OCA2 and gain-of-function TPCN2 heterozygous mutations. This study provides experimental evidence supporting an oligogenic mode of inheritance in albinism, pinpoints melanosomal ion homeostasis as a key pathogenic mechanism and potential therapeutic target, and establishes a generalized research framework for elucidating gene-gene interactions in heterogeneous inherited disorders, especially for the channelopathies.

Background:Kaposiform hemangioendothelioma (KHE) is a rare but aggressive vascular tumor, potentially life-threatening when associated with Kasabach-Merritt phenomenon (KMP). Oral sirolimus is effective but may cause systemic adverse effects in infants. Oral propranolol offers a safer alternative in early infancy, but its efficacy may plateau over time. Sequential topical sirolimus may enhance outcomes while minimizing systemic toxicity. Objective:To evaluate the additive therapeutic effect and safety of topical sirolimus in KHE patients with suboptimal response after oral propranolol. Methods:This retrospective study included five pediatric patients with cutaneous KHE treated at Beijing Children's Hospital from October 2018 to October 2022. All had received oral propranolol for ≥24 months and showed therapeutic plateau (tumor shrinkage ≤70%). They were subsequently treated with 0.1% topical sirolimus ointment twice daily for at least six months and followed for one year. Efficacy was assessed by Visual Analog Scale (VAS), Doppler ultrasound, and a four-grade evaluation system; safety was monitored throughout. Results:All patients showed significant improvement within 6-12 months (mean: 9.6 months), achieving Grade III or IV response. Doppler imaging revealed reduced or absent blood flow signals, and lesions nearly regressed in some cases. Symptoms such as pain and localized hyperthermia resolved, and skin appearance normalized. Two patients experienced mild local irritation; no systemic adverse effects or recurrences were observed. Conclusion:Sequential topical sirolimus following oral propranolol offers a safe and effective treatment strategy for KHE, especially after therapeutic plateau. It enhances efficacy, avoids systemic toxicity, and may accelerate lesion regression. Further large-scale studies are warranted to optimize individualized treatment protocols.

Background:The package insert is a key reference and legal basis for clinical medication. However, in the field of rare diseases, advances in diagnosis and treatment often outpace updates to drug labels, resulting in widespread off-label drug use-a practice that is particularly common and often unavoidable in pediatric populations. Inappropriate off-label use, however, carries significant clinical and safety risks. Methods:Under the guidance of the Rare Disease Expert Committee of the Guangdong Pharmaceutical Association, a multidisciplinary panel of experts from clinical medicine, pharmacy, and related specialties developed the "Expert consensus on the off-label use of drugs for pediatric rare diseases in China (2025 edition)". The consensus integrates available evidence, clinical experience, evidence quality, and medication safety profiles, and was finalized after several rounds of rigorous iterative review. Results:The consensus presents 73 recommendations on off-label drug use across 21 rare diseases, organized in a tabular format for clarity and ease of reference. Conclusions:This consensus aims to standardize the management of off-label drug use in pediatric rare diseases. It supports medical institutions in developing off-label drug formularies, promotes rational drug use, and helps address the diagnostic and therapeutic needs of pediatric rare disease patients. Furthermore, it contributes to the establishment of a structured evaluation and management framework for off-label drug use in this clinical context.

Oculocutaneous albinism type 1, caused by mutations in the tyrosinase gene TYR gene, is the most common form of albinism worldwide. Owing to the variants of uncertain significance (VUSs) classified by the American College of Medical Genetics and Genomics guidelines, patients who carry these VUSs do not receive a definitive molecular diagnosis. To clarify the pathogenicity of the VUS variants, we conducted multiplexed assays of variant effect to reclassify the TYR VUS variants. Protein expression, melanin production, enzyme activity, and subcellular localization were applied to 46 selected variants: 27 VUSs from 1243 patients with albinism, 14 pathogenic/likely pathogenic, and 5 benign/likely benign control variants. Odds of pathogenicity values were calculated as recommended by Brnich et al (2019). By conducting multiplexed assays of variant effect, PS3_moderate or PS3_supporting evidence was applied. By following the American College of Medical Genetics and Genomics guidelines, 25 of 27 VUSs were reclassified as likely pathogenic, and 3 of 11 likely pathogenic variants were reclassified as pathogenic. Therefore, 19 of 20 (95%) previously undiagnosed patients had a molecular diagnosis of oculocutaneous albinism type 1. In addition, the pathogenic mechanisms of TYR have been elucidated and categorized. These comprehensive multiplexed assays of variant effect provide a robust approach for curating TYR VUS. This study advocates multiplexed assays of variant effect for validating an accurate genotype-phenotype relationship.

BACKGROUND:Expanded newborn genetic screening can identify a wide range of inherited conditions early in life. However, the prevalence and distribution of pathogenic and likely pathogenic variants in large-scale cohorts remain underexplored in the Chinese population. METHODS:We screened 33,894 newborns using targeted sequencing of 465 genes associated with monogenic disorders. Variants were classified with locally optimized American College of Medical Genetics and Genomics guidelines, focusing on pathogenic and likely pathogenic variants. We analyzed cumulative carrier rates, disease-specific prevalence, and regional differences. RESULTS:Here we show that among 33,894 newborns, 16,687 (49.2%) carry at least one pathogenic/likely pathogenic variant. In total, 22,457 such alleles are detected across 427 (91.8%) genes. Detection rates are higher in the south (52.1%) than in the north (48.5%). On average, each newborn carries 0.7 variants. The most frequent genes (allele frequency >1%) include GJB2 (5.56%), PAH (1.41%), and SLC26A4 (1.30%). The cumulative predicted incidence of 57 inborn errors of metabolism included in newborn tandem mass spectrometry screening is 1/2,177, with PAH, MMACHC, SLC22A5, MMUT and SLC25A13 as the main contributors. Regional analysis reveales significant geographic variation, with three inborn errors of metabolism (e.g., methylmalonic aciduria, phenylketonuria) more common in the north, five disorders (e.g. G6PD deficiency, thalassemia) more common in the south. CONCLUSIONS:This large-scale study highlights the utility of targeted genetic screening for identifying carrier status and early-onset disease risks in newborns. The findings provide a critical foundation for integrating genetic screening into routine newborn care and for optimizing public health strategies.

Experimental DermatologyVolume 33, Issue 3 e15053 LETTER TO THE EDITOR First report of propranolol treating papillary endovascular angioendothelioma, a promising treatment Lu Yu, Lu Yu orcid.org/0000-0003-0169-1459 Department of Dermatology, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, ChinaSearch for more papers by this authorLin Ma, Corresponding Author Lin Ma [email protected] Department of Dermatology, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China Correspondence Lin Ma and Li Wei, Department of Dermatology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China. Email: [email protected] and [email protected]Search for more papers by this authorLi Wei, Corresponding Author Li Wei [email protected] Department of Dermatology, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China Correspondence Lin Ma and Li Wei, Department of Dermatology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China. Email: [email protected] and [email protected]Search for more papers by this author Lu Yu, Lu Yu orcid.org/0000-0003-0169-1459 Department of Dermatology, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, ChinaSearch for more papers by this authorLin Ma, Corresponding Author Lin Ma [email protected] Department of Dermatology, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China Correspondence Lin Ma and Li Wei, Department of Dermatology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China. Email: [email protected] and [email protected]Search for more papers by this authorLi Wei, Corresponding Author Li Wei [email protected] Department of Dermatology, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China Correspondence Lin Ma and Li Wei, Department of Dermatology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China. Email: [email protected] and [email protected]Search for more papers by this author First published: 14 March 2024 https://doi.org/10.1111/exd.15053Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Open Research DATA AVAILABILITY STATEMENT The data that support the findings of this study are available from the corresponding author upon reasonable request. REFERENCES 1Dabska M. Malignant endovascular papillary angioendothelioma of the skin in childhood. Clinicopathologic study of 6 cases. Cancer. 1969; 24(3): 503-510. 10.1002/1097-0142(196909)24:3<503::AID-CNCR2820240311>3.0.CO;2-L CASPubMedWeb of Science®Google Scholar 2Schwartz RA, Dabski C, Dabska M. The Dabska tumor: a thirty-year retrospect. Dermatology. 2000; 201(1): 1-5. 10.1159/000018419 CASPubMedGoogle Scholar 3Li B, Li Y, Tian X-y, Li Z. Unusual multifocal intraosseous papillary intralymphatic angioendothelioma (Dabska tumor) of facial bones: a case report and review of literature. Diagn Pathol. 2013; 8: 160. 10.1186/1746-1596-8-160 PubMedWeb of Science®Google Scholar 4Wang L, Yang Q, Zhou H, Li J. Multiple papillary intralymphatic angioendotheliomas in the spleen. Rev Esp Enferm Dig. 2022; 115: 46-47. Google Scholar 5Storch CH, Hoeger PH. Propranolol for infantile haemangiomas: insights into the molecular mechanisms of action. Br J Dermatol. 2010; 163(2): 269-274. 10.1111/j.1365-2133.2010.09848.x CASPubMedWeb of Science®Google Scholar 6Chow W, Amaya CN, Rains S, Chow M, Dickerson EB, Bryan BA. Growth attenuation of cutaneous Angiosarcoma with propranolol-mediated β-blockade. JAMA Dermatol. 2015; 151(11): 1226-1229. 10.1001/jamadermatol.2015.2554 PubMedWeb of Science®Google Scholar Volume33, Issue3March 2024e15053 ReferencesRelatedInformation

Objective: To investigate the effect of self -developed Ye'an Analgetic Decoction/Jiawei Shaoyao Gancao Decoction on Traditional Chinese Medicine (TCM) symptom scores and RLS Severity of patients with restless legs syndrome (RLS). Methods: This was a clinical comparative study. Eighty patients with RLS admitted to Baoding No.1 Central Hospital from January 2022 to December 2022 were randomly divided into observation group and control group(n=40). Patients in the control group were given basic and oral tramadol treatment, while those in the observation group were given self -developed Ye'an Analgetic Decoction/Jiawei Shaoyao Gancao Decoction based on the treatment in the control group. The differences of TCM symptom scores, RLS severity (IRLS), quality of life (QOL-RLS), sleep quality (PSQI) and clinical efficacy between the two groups were compared. Results: Before treatment, no statistically significant differences were observed in the TCM symptom scores, IRLS scores, QOL-RLS scores and PSQI scores between the two groups (p>0.05). After treatment, the above scores decreased significantly in both groups, with a higher degree of decrease in the observation group than in the control group, indicating statistically significant differences (p<0.05). The QOL-RLS scores were significantly higher in the observation group than in the control group, with a statistically significant difference (p<0.05). The overall response rate in the observation group was 95.00%, which was higher than that in the control group (80.00%), with a statistically significant difference (p<0.05). Conclusion: Self -developed Ye'an Analgetic Decoction/Jiawei Shaoyao Gancao Decoction leads to numerous benefits in the treatment of RLS, such as obviously ameliorating patients' clinical symptoms, reducing RLS severity, and improving their quality of life and sleep quality.

SIGNIFICANCE:Inflammatory linear verrucous epidermal nevus (ILVEN) is an uncommon type of epidermal nevus and is refractory to therapy. We report the effectiveness of photodynamic therapy (PDT) for treating ILVEN with claudication in a young girl.ADDITIONAL CONTRIBUTIONS:We thank the patient for granting permission to publish this information.APPROACH:Aminolaevulinic Acid Hydrochloride (ALA) photodynamic therapy (PDT) was applied six times in 1-month interval.RESULTS:Most lesions and pruritus have subsided markedly, with mild scarring and a marked reduction in claudication.CONCLUSIONS:ALA PDT might be an effective and promising treatment for ILVEN in the future.

This study aimed to investigate whether fetal growth trajectories (FGTs) could predict early childhood development, indicate intrauterine metabolic changes, and explore potential optimal and suboptimal FGTs. FGTs were developed by using an unsupervised machine-learning approach. Children’s neurodevelopment, anthropometry, and respiratory outcomes in the first 6 years of life were assessed at different ages. In a subgroup of participants, we conducted a metabolomics analysis of cord blood to reveal the metabolic features of FGTs. We identified 6 FGTs: early decelerating, early decelerating with late catch-up growth, early accelerating, early accelerating with late medium growth, late decelerating, and late accelerating. The early accelerating with late medium growth pattern might be the optimal FGT due to its associations with better psychomotor development, mental development, intelligence quotient, and lung function and a lower risk of behaviour and respiratory problems. Compared with the optimal FGT, early decelerating and late decelerating FGTs were associated with poor neurodevelopment and lung function, while early accelerating FGT was associated with more severe autistic symptoms, poor lung function, and increased risks of overweight/obesity. Metabolic alterations were enriched in amino acid metabolism for early decelerating and late decelerating FGTs, whereas altered metabolites were enriched in lipid metabolism for early accelerating FGT. These findings suggest that FGTs are predictors of early life development and may indicate intrauterine adaptive metabolism. The discovery of optimal and suboptimal FGTs provides potential clues for the early identification and intervention of fetal origin dysplasia or disease, but further research on related mechanisms is still needed.

Importance:Port-wine stain (PWS) is a congenital vascular condition involving dilation of skin capillaries and venules, significantly affecting patients' physical and mental health. Pulsed dye laser (PDL) is widely used for PWS treatment; however, large-scale data on pediatric cases remain limited. This retrospective study aims to investigate the efficacy of laser treatment and its related factors in a large sample. Objective:To assess the clinical efficacy and adverse reactions of 595nm PDL for treating pediatric PWS and to identify factors influencing treatment outcomes. Methods:This retrospective study included 974 pediatric patients with PWS treated at Beijing Children's Hospital from 2003 to 2021. Inclusion criteria required patients to be under 18, with solitary PWS and Fitzpatrick skin types II-IV. Treatment efficacy was evaluated using standardized photographs taken before and after treatment, with outcomes categorized by Achauer's clearance criteria. Ridit analysis assessed the impact of variables such as gender, age, lesion location, and treatment frequency on outcomes. Results:The overall efficacy rate was 65.3%, higher in females (69.7%) than males (59.7%). Adolescents had the highest efficacy (100%) due to better compliance. Limb lesions responded best (87.5%), followed by neck (75.0%), trunk (66.7%), and head/face (63.0%). Smaller lesions (≤3 cm²) achieved 76.8% efficacy. Efficacy rose with sessions, reaching 84.0% after three. The mandibular branch (V3) had the highest trigeminal efficacy (68.5%). Adverse reactions (4.31%) included pigmentation changes (2.87%), hypopigmentation (1.03%), and minimal scarring (0.41%). Conclusion:The efficacy of 595nm PDL for treating PWS in children is influenced by gender, age, lesion location, size, and the number of treatment sessions. PDL is an effective treatment for pediatric PWS with minimal adverse reactions.

Objective: To identify genetic variants associated with Stanford A thoracic aortic aneurysm and dissection (ATAAD) using whole-exome sequencing (WES) and analyze positive mutation rates among patients of different onset ages. Methods: WES was performed on 62 sporadic Chinese ATAAD patients (51-74 years old), and then grouped based on onset age together with 73 previously reported TAAD patients (19-50 years old): <= 35, 36-45, 46-55, and >55 years. The proportion of patients with pathogenic/likely pathogenic (P/LP) variants in TAAD causal genes was compared across groups. Results: The average onset age of the 62 patients was 57.66 years. Eight P/LP variants were identified (two novel, six previously described) in five known TAAD causal genes (FBN1, SMAD3, TGFBR2, TGFB2, and MYLK) in eight individuals. P/LP variant positive rates among patients across age groups were: 22.73% for <= 35 years, 32% for 36-45 years, 15.52% for 46-55 years, and 3.33% for >55 years. Significant differences (p = 0.0077) were observed between 36-45 and >55 years group. Conclusions: ATAAD patients aged 36-45 years old at diagnosis had a higher chance of having a P/LP variant and patients >55 years old had the lowest P/LP diagnostic rate. Therefore, gene screening in ATAAD patients <= 55 years old is key to improved diagnostic rate.