Achondroplasia (ACH) is a common inherited skeletal dysplasia (inherited dwarfism) that compromises quality of life across the lifespan. In 2021, vosoritide became the first approved precision therapy for ACH and is now available in more than 40 countries. Compared with prior symptomatic measures, vosoritide has demonstrated favorable efficacy and a reassuring safety profile. Nevertheless, existing international ACH guidelines largely emphasize complication management and symptomatic care, and there is no unified consensus on pharmacologic therapy. To address this gap, an international expert group developed the International Consensus Guidelines for the Implementation and Monitoring of Vosoritide Therapy in Patients with Achondroplasia providing systematic recommendations that span the continuum of care - from initial patient contact and pre-treatment assessment to medication counseling, injection training, and long-term outcome monitoring. These recommendations complement and refine current management and nursing protocols for individuals with ACH and offer practical guidance for clinicians across diverse regions. This article highlights key elements of the guideline to provide evidence-based support and clinical direction for healthcare professionals in China treating children with ACH using vosoritide.
Humans ; Achondroplasia/drug therapy* ; Consensus ; Practice Guidelines as Topic ; Child

AIM:This study aims to investigate the functions of interleukin-6(IL-6)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway in adenomyosis(ADM),and to assess the therapeutic potential of JAK2 inhibitor AG490.METHODS:(1)Neonatal female mice were randomly divided into 2 groups:control group and ADM group.An ADM mice model was established by tamoxifen.Additionally,Western blot was employed to detect the expression of IL-6/JAK2/STAT3 signaling pathway-related proteins.(2)Human endometrial adenocarcinoma Ishikawa cells were treated with AG490,and Western blot was performed to evaluate the expression of the proteins related to IL-6/JAK2/STAT3 signaling pathway,epithelial-mesenchymal transition(EMT),cell migration and cell proliferation.Besides,wound-healing and Transwell assays were carried out to investigate the cell migration and inva-sion.Colony formation and EdU assays were employed to investigate the cell proliferation,and flow cytometry analysis was performed to investigate the cell apoptosis.(3)The ADM mice were randomly divided into 2 groups:ADM group and AG490 group.The expression of IL-6/JAK2/STAT3 signaling pathway-related proteins in uterine tissues was detected by Western blot.Besides,Western blot and immunohistochemistry were employed to detect the expression of the proteins re-lated to cell EMT,migration and proliferation.Cell apoptosis in uterine tissues was detected by TUNEL assay.RE-SULTS:(1)The expression of IL-6/JAK2/STAT3 signaling pathway-related proteins exhibited an increasing trend in ADM mice(P<0.05).(2)Treatment with AG490 significantly suppressed the expression of IL-6/JAK2/STAT3 signaling pathway-related proteins in Ishikawa cells(P<0.05).The protein level of E-cadherin showed an increasing trend(P<0.01),while the expression levels of N-cadherin,vimentin and Slug showed a decreasing trend(P<0.05)in Ishikawa cells after AG490 treatment.Besides,the expression of MMP-2 and MMP-9 was down-regulated(P<0.05),and the capa-bilities of cell migration and invasion were suppressed in AG490-treated Ishikawa cells(P<0.05).The expression levels of Bcl-2 and cyclin D1 exhibited a decreasing trend(P<0.05),and the expression level of Bax increased(P<0.05)in Ishikawa cells after treatment with AG490.Additionally,AG490 inhibited Ishikawa cell proliferation,and enhanced the cell apoptosis(P<0.01).(3)The p-JAK2/JAK ratio and the IL-6 expression exhibited a decreasing trend in AG490 group(P<0.01).Moreover,the expression of E-cadherin was up-regulated(P<0.05),while the expression of N-cadherin,vi-mentin,Snail,Slug and Twist was down-regulated(P<0.05)in ADM mice after treatment with AG490.Compared with ADM group,the expression of MMP-2 and MMP-9 decreased in AG490 group(P<0.05),alongside the down-regulated Bcl-2/Bax ratio and PCNA expression(P<0.01).Besides,the cell apoptosis was enhanced by AG490.CONCLUSION:The IL-6/JAK2/STAT3 signaling pathway is aberrantly activated in ADM and facilitates endometrial cell EMT,prolifera-tion,invasion and migration.Additionally,AG490 inhibits the progression of ADM by blocking the IL-6/JAK2/STAT3 sig-naling pathway.

Objective:To explore the correlative factors for insomnia severity in chronic insomnia patients using MemTrax memory test.Methods:Two hundred and twenty-two chronic insomnia patients (insomnia≥3 days per week with a duration≥3 months) recruited from Center for Preventive Treatment of Diseases, Guangdong Provincial Hospital of Chinese Medicine or through in-hospital advertisements from April 2024 to September 2024 were chosen. Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep quality over the last month; according to PSQI score, these patients were divided into mild insomnia group (scores of 7-10), moderate insomnia group (scores of 11-15) and severe insomnia group (scores of 16-21). MemTrax memory test was used to record the picture recognition accuracy and picture recognition reaction time, and MemTrax comprehensive index (MTx-Cp) was calculated; Patients' Health Questionnaire (PHQ-9), and Generalized Anxiety Disorder-7 scale(GAD-7) were used to evaluate the depression and anxiety status of these patients in recent 2 weeks. The clinical data, MemTrax test results, PHQ-9 and GAD-7 scores of patients with different degrees of chronic insomnia were compared. Spearman rank correlation analysis was used to investigate the correlation between insomnia severity and clinical data such as cognitive memory function in chronic insomnia patients.Results:Among the 220 chronic insomnia patients, 54 had mild insomnia, 111 had moderate insomnia, and 55 had severe insomnia. Severe insomnia patients had significantly higher percentages of those>50 years old and those using hypnotics compared with mild insomnia patients and moderate insomnia patients ( P<0.05). Compared with the mild insomnia patients and moderate insomnia patients, the severe insomnia patients exhibited significantly lower picture recognition accuracy (90%[86%, 94%], 88%[82%, 94%], 84%[78%, 92%]), significantly lower MTx-Cp (88.55±18.67, 84.41±20.93, 76.69±17.43), and significantly higher PHQ-9 score (9[6, 11], 9[6, 15], 12[8, 16], P<0.05). Moreover, severe insomnia patients had significantly longer picture recognition reaction time and higher GAD-7 score than mild insomnia patients (1.11[1.03, 1.24] s vs. 1.04[0.90, 1.15] s; 7[5, 13] vs. 6[3, 9], P<0.05). Spearman rank correlation analysis showed that insomnia severity in chronic insomnia patients was positively correlated with age, PHQ-9 score, GAD-7 score, and picture recognition reaction time, and negatively correlated with picture recognition accuracy and MTx-Cp ( P<0.05). Conclusion:Insomnia severity in patients with chronic insomnia is correlated with age, cognitive memory function, depression and anxiety.

Extramammary Paget disease (EMPD) is an intraepidermal adenocarcinoma that predominantly occurs in apocrine gland-rich regions such as the vulva and perianal area. It commonly presents clinically as erythematous and pruritic plaques. The disease is categorized into primary and secondary types: the former often arises from abnormal differentiation of epidermal or adnexal cells, while the latter is frequently associated with underlying malignancies of the gastrointestinal or genitourinary tracts. Differentiation between the two subtypes relies on immunohistochemical markers and endoscopic examinations. This article provides a systematic review of recent advances in the epidemiology, pathogenesis, diagnosis, and treatment of EMPD. Epidemiological studies indicate variations in incidence influenced by geographic region and gender. Research on pathogenesis has revealed potential driver mutations in genes such as ERBB2 and PIK3CA. In terms of diagnosis, the combined use of immunohistochemical markers plays a crucial role in subtype classification and differential diagnosis. Regarding treatment, Mohs micrographic surgery is the preferred option for localized lesions, while photodynamic therapy, imiquimod, and radiotherapy are applicable in selected cases. For metastatic disease, targeted therapies against HER2 and the PIK3CA/AKT pathway offer promising new directions. Comprehensive and individualized treatment strategies are essential for improving patient prognosis.

Objective:To analyze the clinical characteristics，laboratory tests，endoscopic features，treatment，and follow-up of peptic ulcers caused by eosinophilic gastrointestinal disorders（EGIDs）in children，with the aim of improving the level of understanding，diagnosis and treatment of EGIDs in children with the onset of peptic ulcers.Methods:A retrospective analysis was conducted on children admitted to the Department of Gastroenterology，Capital Center for Children's Health，Capital Medical University from January 1st，2019 to October 31st，2023，who underwent complete endoscopic examination. The first examination showed the presence of peptic ulcers（gastric or duodenal ulcers）under the endoscope，and were ultimately diagnosed with peptic ulcers caused by EGIDs through examination and follow-up. The clinical characteristics，laboratory tests，endoscopic results，and treatment follow-up were analyzed.Results:Thirty-five children were EGIDs，22 males and 13 females.Twenty-two cases（62.9%）had abdominal pain as the main symptom.Laboratory tests：17 cases（48.6%）showed a decrease in hemoglobin，15 cases（42.9%）showed an increase in eosinophil count，20 cases（57.1%）tested gastro positive for food allergen specific IgE，and 17 cases（48.6%）showed thickening of the intestinal wall on gastrointestinal ultrasound. Endoscopic features：8 cases（22.9%）showed gastric antral ulcers，including 7 cases（20.0%）with multiple gastric antral ulcers，and 25 cases（71.4%）showed duodenal bulb ulcers.There were 15 cases（42.9%）showed huge ulcers，and 14 cases（40.0%）were located in the duodenal bulb. Comparison of clinical characteristics between children with EGIDs（EGIDs group）and those with peptic ulcers caused by Helicobacter pylori infection（Hp group）：the first clinical symptom in both groups was mainly abdominal pain，but the incidence rate in the EGIDs group was lower（62.9% vs 93.5%），and the weigth for length Z score in the EGIDs group was lower［0（-1.6，0.8）vs 1.1（0，1.9）］，with statistical significance（all P<0.05）. Comparison of laboratory tests：the EGIDs group showed a statistically significant difference in hemoglobin levels［120（101，124）g/L vs 130（100，138）g/L］，eosinophil count［0.28（0.13，0.71）× 10 9/L vs 0.16（0.08，0.22）×10 9/L］，a positive rate of food allergen specific IgE detection（57.1% vs 32.3%），and a positive rate of intestinal wall thickening detected by gastrointestinal ultrasound（48.6% vs 16.1%）compared with the Hp group（all P<0.05）. Comparison of endoscopic examinations：multiple ulcers in the gastric antrum were more common in the EGIDs group than in the Hp group（20.0% vs 0），and the difference was statistically significant（ P<0.05）. Conclusion:For children with peptic ulcers with onset of abdominal pain，with anemia or malnutrition，or multiple ulcers in the gastric antrum and huge ulcers in the duodenal bulb detected by endoscopy，it is recommended to perform multi site biopsies to help diagnose EGIDs early.

Objective To propose a whole-life cycle management model for valvular heart disease (VHD), systematically elucidate its underlying logic and implementation pathways, and concurrently review and analyze its preliminary application outcomes. Methods Since 2020, West China Hospital of Sichuan University has established a management system encompassing "assessment-decision-intervention-follow-up", including: (1) a risk-stratified, tiered management pathway; (2) six core functions ("promotion, screening, prevention, diagnosis, treatment, and rehabilitation") coordinated by disease-specific managers; (3) an intelligent decision support information platform; and (4) a collaborative network of multidisciplinary teams and regional academic alliances. To evaluate the effectiveness of this management model, we retrospectively included three cohorts: (1) the population screened by echocardiography from 2020 to 2024, analyzing the detection rate of aortic valve disease and risk stratification; (2) patients enrolled in the whole-life cycle management from April 2021 to December 2024, assessing follow-up outcomes, hospital satisfaction, and changes in quality of life; (3) patients who underwent transcatheter aortic valve replacement (TAVR) from January 2022 to January 2024, evaluating the one-year all-cause mortality rate, perioperative complications, and improvements in New York Heart Association (NYHA) classification. Results Between 2020 and 2024, a total of 583 874 individuals underwent echocardiographic screening. A total of 48 089 patients with aortic valve disease were identified, including 3 401 (7.1%) high-risk patients, 18 657 (38.8%) moderate-risk patients, and 26 031 (54.1%) low-risk patients. Among them, 2 417 patients were enrolled in whole-life cycle management. Patient satisfaction scores showed a yearly increase, rising from 73.89 points before 2020 to 93.74 points in 2024. The 1-year mortality rate in the TAVR cohort decreased to 5.3%, significantly lower than the 8.2% observed under early standard management between 2014 and 2019 (P<0.01). Conclusion Through process optimization and resource integration, the VHD whole-life cycle management model has demonstrated significant effectiveness in standardizing diagnostic and follow-up procedures, enhancing patient satisfaction and quality of life, and reducing mortality. These outcomes highlight its practical value for broader implementation in China.

AIM:This study aims to investigate the functions of interleukin-6(IL-6)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway in adenomyosis(ADM),and to assess the therapeutic potential of JAK2 inhibitor AG490.METHODS:(1)Neonatal female mice were randomly divided into 2 groups:control group and ADM group.An ADM mice model was established by tamoxifen.Additionally,Western blot was employed to detect the expression of IL-6/JAK2/STAT3 signaling pathway-related proteins.(2)Human endometrial adenocarcinoma Ishikawa cells were treated with AG490,and Western blot was performed to evaluate the expression of the proteins related to IL-6/JAK2/STAT3 signaling pathway,epithelial-mesenchymal transition(EMT),cell migration and cell proliferation.Besides,wound-healing and Transwell assays were carried out to investigate the cell migration and inva-sion.Colony formation and EdU assays were employed to investigate the cell proliferation,and flow cytometry analysis was performed to investigate the cell apoptosis.(3)The ADM mice were randomly divided into 2 groups:ADM group and AG490 group.The expression of IL-6/JAK2/STAT3 signaling pathway-related proteins in uterine tissues was detected by Western blot.Besides,Western blot and immunohistochemistry were employed to detect the expression of the proteins re-lated to cell EMT,migration and proliferation.Cell apoptosis in uterine tissues was detected by TUNEL assay.RE-SULTS:(1)The expression of IL-6/JAK2/STAT3 signaling pathway-related proteins exhibited an increasing trend in ADM mice(P<0.05).(2)Treatment with AG490 significantly suppressed the expression of IL-6/JAK2/STAT3 signaling pathway-related proteins in Ishikawa cells(P<0.05).The protein level of E-cadherin showed an increasing trend(P<0.01),while the expression levels of N-cadherin,vimentin and Slug showed a decreasing trend(P<0.05)in Ishikawa cells after AG490 treatment.Besides,the expression of MMP-2 and MMP-9 was down-regulated(P<0.05),and the capa-bilities of cell migration and invasion were suppressed in AG490-treated Ishikawa cells(P<0.05).The expression levels of Bcl-2 and cyclin D1 exhibited a decreasing trend(P<0.05),and the expression level of Bax increased(P<0.05)in Ishikawa cells after treatment with AG490.Additionally,AG490 inhibited Ishikawa cell proliferation,and enhanced the cell apoptosis(P<0.01).(3)The p-JAK2/JAK ratio and the IL-6 expression exhibited a decreasing trend in AG490 group(P<0.01).Moreover,the expression of E-cadherin was up-regulated(P<0.05),while the expression of N-cadherin,vi-mentin,Snail,Slug and Twist was down-regulated(P<0.05)in ADM mice after treatment with AG490.Compared with ADM group,the expression of MMP-2 and MMP-9 decreased in AG490 group(P<0.05),alongside the down-regulated Bcl-2/Bax ratio and PCNA expression(P<0.01).Besides,the cell apoptosis was enhanced by AG490.CONCLUSION:The IL-6/JAK2/STAT3 signaling pathway is aberrantly activated in ADM and facilitates endometrial cell EMT,prolifera-tion,invasion and migration.Additionally,AG490 inhibits the progression of ADM by blocking the IL-6/JAK2/STAT3 sig-naling pathway.

Glutathione(GSH)is a tripeptide containing sulfhydryl groups,which has the function of antioxidant,detoxifying,and immune enhancing effects,and its expression is closely associated with many diseases such as cancer,etc.Therefore,it is of great significance for clinical diagnosis by developing a highly sensitive,simple,and rapid method for detecting GSH.Herein,two-dimensional(2D)Zn-TCPP(Fe)nanosheets employing Zn2+and Fe-bound tetrakis(4-carboxyphenyl)porphyrin ligands were obtained by a surfactant-assisted synthetic method.The 2D Zn-TCPP(Fe)nanosheets exhibited excellent peroxidase-like activity,which allowed the catalysis of the H2O2-initiated oxidation of colorless 3,3',5,5'-tetramethylbenzidine(TMB)to blue oxidized TMB(ox-TMB).In the presence of GSH,GSH underwent a reduction reaction with oxTMB,resulting in the blue color of the solution fading.The proposed colorimetric sensor exhibited favorable sensitivity for GSH in the linear range of 0.1-200 μmol/L with a limit of detection(S/N=3)of 0.042 μmol/L,indicating excellent selectivity.The developed sensor was successfully applied to detect GSH level in the human serum samples with recoveries of 93.0％-107.7％,showing satisfactory results.The developed colorimetric sensor provided a new approach for detecting GSH.

Extramammary Paget disease (EMPD) is an intraepidermal adenocarcinoma that predominantly occurs in apocrine gland-rich regions such as the vulva and perianal area. It commonly presents clinically as erythematous and pruritic plaques. The disease is categorized into primary and secondary types: the former often arises from abnormal differentiation of epidermal or adnexal cells, while the latter is frequently associated with underlying malignancies of the gastrointestinal or genitourinary tracts. Differentiation between the two subtypes relies on immunohistochemical markers and endoscopic examinations. This article provides a systematic review of recent advances in the epidemiology, pathogenesis, diagnosis, and treatment of EMPD. Epidemiological studies indicate variations in incidence influenced by geographic region and gender. Research on pathogenesis has revealed potential driver mutations in genes such as ERBB2 and PIK3CA. In terms of diagnosis, the combined use of immunohistochemical markers plays a crucial role in subtype classification and differential diagnosis. Regarding treatment, Mohs micrographic surgery is the preferred option for localized lesions, while photodynamic therapy, imiquimod, and radiotherapy are applicable in selected cases. For metastatic disease, targeted therapies against HER2 and the PIK3CA/AKT pathway offer promising new directions. Comprehensive and individualized treatment strategies are essential for improving patient prognosis.

BACKGROUND: Prolonged occupational noise exposure poses potential health risks, but its impact on mitochondrial DNA (mtDNA) damage and methylation patterns remains unclear. METHOD: We recruited 306 factory workers, using average binaural high-frequency hearing thresholds from pure-tone audiometry to assess noise exposure. MtDNA damage was evaluated through mitochondrial DNA copy number (mtDNAcn) and lesion rate, and mtDNA methylation changes were identified via pyrophosphate sequencing. RESULTS: There was a reduction in MT-RNR1 methylation of 4.52% (95% CI: -7.43% to -1.62%) among workers with abnormal hearing, whereas changes in the D-loop region were not statistically significant (β = -2.06%, 95% CI: -4.44% to 0.31%). MtDNAcn showed a negative association with MT-RNR1 methylation (β = -0.95, 95% CI: -1.23 to -0.66), while no significant link was found with D-loop methylation (β = -0.05, 95% CI: -0.58 to 0.48). Mediation analysis indicated a significant increase in mtDNAcn by 10.75 units (95% CI: 3.00 to 21.26) in those with abnormal hearing, with MT-RNR1 methylation mediating 35.9% of this effect. CONCLUSIONS These findings suggest that occupational noise exposure may influence compensatory increases in mtDNA content through altered MT-RNR1 methylation.
Humans ; DNA, Mitochondrial ; DNA Methylation ; Male ; Adult ; Noise, Occupational/adverse effects* ; Middle Aged ; Occupational Exposure/adverse effects* ; Biomarkers/blood* ; Female