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

OBJECTIVE To investigate the effect of pharmaceutical services guided by root cause analysis （RCA） in a problem-oriented manner combined with knowledge-attitude-practice （KAP） theory on reducing the incidence of protocol violations of investigational medicinal products in pediatric clinical trials. METHODS A total of 617 participants from 69 drug clinical trial projects conducted in our hospital from January 2016 to December 2020 were selected as the control group， and 868 participants from 72 drug clinical trial projects from January 2022 to December 2025 as the observation group. RCA was performed on the protocol violations of investigational medicinal product in the control group to identify the types and underlying causes. The control group received routine pharmaceutical services for drug clinical trials， while the observation group was provided with precision pharmaceutical services from the three dimensions of knowledge， attitude and practice on the basis of routine pharmaceutical services， according to the root causes identified by RCA. The occurrence of investigational medicinal products protocol violations was compared between the two groups. RESULTS The total incidence of protocol violations of investigational medicinal products， as well as the incidences of minor and major protocol violations， were all significantly lower in the observation group than in the control group （ P ＜0.001）. The main types of protocol violations in both groups included missed/under-/over-dosing of medications， non-adherence to administration time， failure to adjust dosage as required， and combined medication/vaccination in violation of the protocol. Regarding the responsible subjects of protocol violations， the incidences of protocol violations attributed to participants and their guardians as well as investigators and accidental factors were significantly lower in the observation group than in the control group （ P ＜0.001， P ＜0.001， P ＝0.025）. However， there were no statistically significant differences in the incidences of protocol violations caused by sponsor-related reasons between the two groups （ P ＞0.05）. CONCLUSIONS Pharmaceutical services led by pharmacists， based on problem-oriented RCA and combined with KAP theory， can effectively reduce the protocol violations of investigational medicinal products rate in pediatric clinical trials， thereby safeguarding the safety and rights of study participants.

Esophageal cancer （EC） is a highly prevalent malignant tumor in China. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， as one of the key oncogenic pathways， can promote the cell cycle progression， proliferation， migration， and invasion， induce chemoresistance， and inhibit apoptosis and autophagy of EC cells. Traditional Chinese medicine （TCM）， with the advantages of targeting multiple points with multiple components to delay cancer progression， can target the PI3K/Akt signaling pathway for EC treatment. This article preliminarily discusses the molecular mechanism and role of the PI3K/Akt signaling pathway in EC and elaborates on the specific targets and efficacy of TCM in treating EC through intervention in the PI3K/Akt signaling pathway in the past five years. TCM materials and extracts inhibiting the PI3K/Akt signaling pathway in EC include Borneolum， spore powder of Ganoderma lucidum without spore coat， extract of Celastrus orbiculatus， root extract of Taraxacum， and Bruceae Fructus oil emulsion. TCM active ingredients exerting the effect include flavonoids， terpenoids， saponins， phenols， polysaccharides， alkaloids， and other compounds. TCM compound prescriptions with such effect include Qige San， Huqi San， Xuanfu Daizhetang， Tongyoutang and its decomposed prescriptions， Liujunzi Tang， and Xishenzhi Formula. In addition， TCM injections such as Compound Kushen Injection and Kang'ai injection also inhibit the PI3K/Akt signaling pathway in EC. This paper summarizes the role of the PI3K/Akt signaling pathway in EC and the TCM interventions， aiming to provide reference for the research and clinical application of new drugs for EC.

BACKGROUND:Studies have shown that disorders of mineral metabolism may be responsible for premature aging and that the kl/FGF23 axis plays an important role in mineral metabolism.OBJECTIVE:To explore the effect of long-term endurance exercise on the kl/FGF23 axis in naturally aging mice,and to observe the impact of long-term endurance exercise on calcium and phosphorus metabolism,so as to provide a reference for the influence of long-term endurance exercise on natural aging.METHODS:Twenty-two 5-week-old SPF male balb/c mice were randomly divided into three groups:young and quiet control group,natural aging quiet group and natural aging exercise group.Mice in the young and quiet control group were then killed immediately.Mice in the natural aging quiet group were raised normally until 60 weeks of age.Mice in the natural aging exercise group were subjected to adaptive exercise for 1 week,followed by the maximum running speed test.The official exercise speed was set at 70％of the maximum running speed,and exercise was performed on Mondays,Wednesdays,and Fridays for 50 minutes each.Maximum running speed was retested at 8-week intervals to adjust the official exercise speed until the age of 60 weeks.(3)Enzyme-linked immunoassay was used to measure the levels of femoral fibroblast growth factor 23,renal fibroblast growth factor receptor 1,1α-hydroxylase,and serum 1,25(OH)2D3.RESULTS AND CONCLUSION:(1)Compared with the young and quiet control group,serum calcium and phosphorus levels in natural aging quiet group had no significant changes(P＞0.05),but bone calcium and phosphorus levels were significantly reduced(P＜0.01).Compared with the natural aging quiet group,the serum phosphorus level was significantly reduced(P＜0.05),the serum calcium level did not change(P＞0.05),and bone calcium and phosphorus levels were significantly increased in the natural aging exercise group(P＜0.05).(2)Compared with the young and quiet control group,the level of fibroblast growth factor 23 in the femur of the natural aging quiet group was significantly increased(P＜0.05).Compared with the natural aging quiet group,the level of fibroblast growth factor 23 in the femur of the natural aging exercise group was reduced,but it was not statistically significant(P＞0.05).(3)Compared with the young and quiet control group,the renal Klotho protein expression,the renal fibroblast growth factor receptor 1,1α-hydroxylase,and serum 1,25(OH)2 D3 levels in the natural aging quiet group were significantly decreased(P＜0.05,P＜0.01).Compared with the natural aging quiet group,the levels of the above-mentioned indicators were significantly increased in the natural aging exercise group(P＜0.05,P＜0.01).To conclude,long-term endurance exercise can regulate Klotho protein and fibroblast growth factor 23 through the kl/FGF23 axis,thereby affecting the expression of 1α-hydroxylase and the level of 1,25(OH)2D3,and further regulating the body's calcium and phosphorus metabolism,especially phosphate metabolism.This indicates that long-term endurance exercise can delay the natural aging of the body through the kl/FGF23 axis.

BACKGROUND:Studies have shown that disorders of mineral metabolism may be responsible for premature aging and that the kl/FGF23 axis plays an important role in mineral metabolism.OBJECTIVE:To explore the effect of long-term endurance exercise on the kl/FGF23 axis in naturally aging mice,and to observe the impact of long-term endurance exercise on calcium and phosphorus metabolism,so as to provide a reference for the influence of long-term endurance exercise on natural aging.METHODS:Twenty-two 5-week-old SPF male balb/c mice were randomly divided into three groups:young and quiet control group,natural aging quiet group and natural aging exercise group.Mice in the young and quiet control group were then killed immediately.Mice in the natural aging quiet group were raised normally until 60 weeks of age.Mice in the natural aging exercise group were subjected to adaptive exercise for 1 week,followed by the maximum running speed test.The official exercise speed was set at 70％of the maximum running speed,and exercise was performed on Mondays,Wednesdays,and Fridays for 50 minutes each.Maximum running speed was retested at 8-week intervals to adjust the official exercise speed until the age of 60 weeks.(3)Enzyme-linked immunoassay was used to measure the levels of femoral fibroblast growth factor 23,renal fibroblast growth factor receptor 1,1α-hydroxylase,and serum 1,25(OH)2D3.RESULTS AND CONCLUSION:(1)Compared with the young and quiet control group,serum calcium and phosphorus levels in natural aging quiet group had no significant changes(P＞0.05),but bone calcium and phosphorus levels were significantly reduced(P＜0.01).Compared with the natural aging quiet group,the serum phosphorus level was significantly reduced(P＜0.05),the serum calcium level did not change(P＞0.05),and bone calcium and phosphorus levels were significantly increased in the natural aging exercise group(P＜0.05).(2)Compared with the young and quiet control group,the level of fibroblast growth factor 23 in the femur of the natural aging quiet group was significantly increased(P＜0.05).Compared with the natural aging quiet group,the level of fibroblast growth factor 23 in the femur of the natural aging exercise group was reduced,but it was not statistically significant(P＞0.05).(3)Compared with the young and quiet control group,the renal Klotho protein expression,the renal fibroblast growth factor receptor 1,1α-hydroxylase,and serum 1,25(OH)2 D3 levels in the natural aging quiet group were significantly decreased(P＜0.05,P＜0.01).Compared with the natural aging quiet group,the levels of the above-mentioned indicators were significantly increased in the natural aging exercise group(P＜0.05,P＜0.01).To conclude,long-term endurance exercise can regulate Klotho protein and fibroblast growth factor 23 through the kl/FGF23 axis,thereby affecting the expression of 1α-hydroxylase and the level of 1,25(OH)2D3,and further regulating the body's calcium and phosphorus metabolism,especially phosphate metabolism.This indicates that long-term endurance exercise can delay the natural aging of the body through the kl/FGF23 axis.

With the accelerating trend of population aging, the number of elderly patients with lung cancer continues to rise, and the disease burden is becoming increasingly heavy. The clinical management of these patients faces severe challenges due to their decreased physiological reserve, complex comorbidities, and significant individual heterogeneity. Consequently, under traditional diagnosis and treatment models, doctors often struggle to identify the individualized risks of elderly patients in a timely and comprehensive manner, which can easily lead to decision biases such as undertreatment or overtreatment. In view of this, this study advocates for the establishment of an umbrella decision-making model specifically tailored for elderly lung cancer patients. Grounded in a multidisciplinary team (MDT) platform, this model deeply integrates oncological indicators with the comprehensive geriatric assessment (CGA) system. By holistically considering multidimensional variables including tumor burden, organ function, frailty index, cognitive status, and social support, the model establishes an operational mechanism characterized by "single entry, precise stratification, and targeted selection". Accordingly, patients can be scientifically triaged into distinct intervention tiers, such as active surveillance, minimally invasive surgery, drug therapy, radiotherapy, and best supportive care, thereby achieving real-time alignment between treatment intensity and patient fitness. This article elaborates on the construction logic and key operational procedures of this novel decision-making framework, aiming to guide clinical practice beyond the limitations of a tumor-centric perspective toward a holistic, dynamic, whole-course management strategy. This transition seeks to ensure optimal quality of life and clinical net benefit for elderly patients alongside survival prolongation.

[Objective] To investigate the infection status and characteristics of HEV among voluntary blood donors in Ningbo, and to provide a basis for improving the blood screening strategy. [Methods] A total of 12 227 blood samples from voluntary blood donors in Ningbo from June 2022 to May 2023 were tested for HEV serology, enzymology, and nucleic acid testing. Furthermore, HEV gene sequencing was performed for genotyping analysis, and donors with reactive nucleic acid testing results were followed up to confirm their infection status. [Results] The reactivity rate of HEV Ag, anti-HEV IgM and anti-HEV IgG was 0.098%, 0.899% and 29.198%, respectively. There was no difference in the reactivity of anti-HEV IgM and anti-HEV IgG between genders, donation frequencies and donation types (P>0.05). The reactivity rate increased significantly with age (P<0.05). The rate of ALT disqualification (ALT>50U/L) was significantly higher than that in non-reactive samples (P<0.05). The HEV Ag reactivity rate (0.098%) was not correlated with gender, donation frequency, donation type or age. One HEV RNA positive case was found, with a positive rate of 0.008%(1/12 227). It was confirmed to be hepatitis E virus genotype 3 by sequencing analysis. Apart from HEV Ag reactivity, all other blood safety screening items were non-reactive, suggesting this case might be in the acute infection phase. The follow-up results showed that all indicators of the donor's previous blood donation were non-reactive. [Conclusion] Pre-donation ALT detection can reduce the risk of transfusion-transmitted HEV (TT-HEV) to a certain extent, and the effective way to prevent TT-HEV is to detect HEV RNA and serology of donor blood.

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.

Background Coal workers' pneumoconiosis is a serious occupational disease in China. Exhaled volatile organic compounds (VOCs) can serve as the "breath fingerprint" of internal pathological processes, which provides a theoretical basis for exhaled VOCs to be used as potential non-invasive biomarkers for early diagnosis of coal workers' pneumoconiosis. Objective To screen out the characteristic VOCs and important characteristic VOCs of exhaled air in patients with coal workers' pneumoconiosis, and to explore the potential of these VOCs as biomarkers for early non-invasive diagnosis of the disease. Methods In this study, 27 VOCs in the exhaled breath of 22 patients with stage I coal workers' pneumoconiosis, 77 workers exposed to dust, and 92 healthy controls were quantitatively detected by thermal desorption gas chromatography-mass spectrometry (TD-GC-MS). Substances with P<0.05 in univariate analysis and variable importance projection (VIP) >1 in supervised orthogonal partial least squares discriminant analysis (OPLS-DA) model were selected as the characteristic VOCs for early diagnosis of coal workers' pneumoconiosis. Age was included in the LASSO regression model as a covariate to screen out important characteristic VOCs, and the diagnostic performance was evaluated by receiver operating characteristic (ROC) curve. Spearman correlation was further used to explore the correlation between important characteristic VOCs and clinical lung function indicators. Results Through univariate analysis and OPLS-DA modeling, 8 VOCs were selected, including 2-methylpentane, 3-methylpentane, n-hexane, methylcyclopentane, n-heptane, methylcyclohexane, 4-methyl-2-pentanone, and 2-hexanone, in exhaled breath of patients with coal workers' pneumoconiosis. The concentrations of 4 VOCs, including 3-methylpentane, n-hexane, 4-methyl-2-pentanone, and 2-hexanone, showed a decreasing trend with the increase of dust exposure years. By LASSO regression, the important characteristic VOCs of the coal workers' pneumoconiosis group and the dust exposure group were n-hexane, methylcyclohexane and 4-methyl-2-pentanone, and the important characteristic VOCs of the coal workers' pneumoconiosis group and the healthy group were 2-methyl-pentane and 4-methyl-2-pentanone. The ROC analysis showed that the area under the curve (AUC) of n-hexane, methylcyclohexane, and 4-methyl-2-pentanone were 0.969, 0.909, and 0.956, respectively, and the AUC of combined diagnosis was 0.988 and its Youden index was 0.961, suggesting that these results can serve as a valuable reference for further research on early diagnosis. The Correlation analysis found that there was a positive correlation between n-hexane and lung function indicators in the important characteristic VOCs, indicating that it could indirectly reflect the obstruction of lung function ventilation, further proving that important characteristic VOCs have the potential to monitor lung function decline. Conclusion Three important characteristic VOCs selected in this study have the potential to be used as non-invasive biomarkers for early diagnosis and disease monitoring of coal workers' pneumoconiosis, and are worthy of further study and verification.

The microstructures of pharmaceutical preparations play a pivotal role in determining their critical quality attributes(CQAs),such as drug release,content uniformity,and stability,which greatly impact the safety and efficacy of drugs.Unlike the inherent molecular structures of active pharmaceutical in-gredients(APIs)and excipients,the microstructures of pharmaceutical preparations are developed during the formulation process,presenting unique analytical challenges.In this review,we primarily focus on presenting the research methods used to elucidate the microstructures of pharmaceutical preparations,including X-ray imaging(XRI),scanning electron microscopy(SEM),atomic force microscopy(AFM),Raman spectroscopy,infrared(IR)spectroscopy,and rheometer technology.Subse-quently,we highlight the applications,advantages,and limitations of these methods.Finally,we discuss the current challenges and future perspectives in this field.This review aims to provide a comprehensive reference for understanding the microstructures of pharmaceutical preparations,offering new insights and potential advancements in their development.