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 prepare a variety of quality control(QC)materials for SARS-CoV-2 variants as an addition to the conven-tional SARS-CoV-2 nucleic acid QC products for the laboratory detection of mutant strains by optimizing the preparation and purification process of MS2 phage virus-like particle(VLP)technique,and evaluate their performances.Methods The typical mutation sequence fragments or full length S genes were designed and synthesized according to the genomic information of SARS-CoV-2 variants.Then,they were inserted into the downstream of maturase gene,coat protein and the pac-site of MS2 phage to construct a series of recombi-nant expression vectors.After induced by the prokaryotic expression system,the VLP products were purified through the polyethylenei-mine precipitation,ultrafiltration,nuclease digestion,and gel filtration chromatography.The obtained VLP were validated by the nucle-ic acid electrophoresis,protein electrophoresis,protein concentration determination,and fluorescence PCR,and their performances such as nucleic acid residue and stability were also evaluated.Results A total of 10 kinds of VLP containing the targeted sequences of the gene to be tested were prepared.The length of the foreign sequence wrapped in them ranged from 297 bp to 3 822 bp,which could be combined into a variety of QC materials for the mutation detection of different SARS-CoV-2 variants.The prepared VLP QC materials could not be effectively amplified without nucleic acid extraction or reverse transcription steps during the routine nucleic acid detection.The simulated QC samples remained stable after repeated freeze-thaw cycles.They could be stored stably for 2 months at 25 ℃ and 4 weeks at 37 ℃.Conclusion The established preparation and combined purification process of VLP QC materials can encapsulate vari-ous exogenous nucleic acid sequences with different lengths into the viral coat protein to form VLP,with high production efficiency.The VLP QC products prepared by the above process have stable performance and almost no residual exogenous nucleic acid,which can ef-fectively meet clinical requirements and ensure the quality of laboratory testing.

Excessive ionizing radiation can disrupt the molecular structures of organisms,leading to health issues such as acute radiation syndrome and cancer,posing serious threats to human health.The development of radioprotective drugs holds significant importance for mitigating ionizing radiation damage and safeguarding public health,yet its research process faces multidimensional ethical challenges.This paper systematically explores the ethical issues involved in the full lifecycle of radioprotective drug development,focusing on the ethical particularities of animal experimentation,ethical dilemmas in human trials,data privacy and security risks,as well as challenges in managing conflicts of interest.Targeted solutions are proposed,including strengthening ethical review mechanisms,promoting interdisciplinary collaboration,constructing data security management systems,and establishing conflict-of-interest mediation mechanisms.These comprehensive measures aim to build a scientifically rigorous ethical framework for radioprotective drug research,fostering sustainable development in this field.

Objective:To investigate the clinicopathological features, immunohistochemical characteristics, and differential diagnosis of low-grade adenosquamous carcinoma of the breast arising from benign sclerosing lesions.Methods:Twelve cases of low-grade adenosquamous carcinoma arising from benign sclerosing lesions of the breast were collected, which were diagnosed from January 2010 to December 2023 at the Seventh Medical Center of the Chinese People′s Liberation Army General Hospital. Their clinical manifestations, histopathological morphology, and immunohistochemical characteristics were analyzed and related literatures were reviewed.Results:All the 12 patients were females with a median age of 42 years (21-60 years). Five of the 12 cases had coexisting complex sclerosing lesions, 5 with sclerosing adenosis, 1 with sclerosing intraductal papilloma, and 1 with ductal adenoma. Microscopically, low-grade adenosquamous carcinoma grew infiltratively in multinodular and sclerosing lesions. The carcinomatous component was characterized by small irregular glandular structures, tubular formations, solid nests, clusters, or a single tumor cell. The epithelium showed varying degrees of squamous differentiation. The carcinoma was surrounded by fibroadenomatoid and desmoplastic lesions. The invasive neoplastic component typically infiltrated normal breast structures, and might infiltrate nerves and adipose tissue. There were lymphocytic aggregates commonly seen at the periphery. By immunohistochemistry, the tumor cells of all 12 cases showed diffuse and strong immunopositivity for CK5/6; negative expression of ER, PR and HER2; and variable expression of myoepithelial markers such as SMA, calponin, SMMHC and others. There was varied staining pattern of tumor cells for p63. CK8/18 (or CK7) was variably positive or negative. The proliferative index measured by Ki-67 was low.Conclusions:Low-grade adenosquamous carcinoma of the breast is a rare variant, which is found to coexist with other benign sclerosing lesions and can be easily missed and/or misdiagnosed. Their invasive growth pattern, presence of sweat duct-like structures and immunophenotypic profile are key features for appropriate diagnosis.

Prostate cancer is one of the most common male urological malignancies,in which bone metastasis of desmo-plasia-resistant prostate cancer is an important stage in the progression of the disease,which seriously affects the quality of life and survival of patients.With the development of nuclide therapy technology in recent years,223-Ra,as a new type of alpha-targeted therapy,has shown good efficacy in the treatment of desmoplasia-resistant prostate cancer bone metastasis.The purpose of this pa-per is to review the characteristics,mechanism of action,treatment,and the main research results of its treatment of desmoplasia-resistant prostate cancer bone metastasis,and provide a comprehensive review of the clinical application of 223-Ra in the treatment of desmoplasia-resistant prostate cancer bone metastasis for the clinical application of 223-Ra in prostate cancer bone metastasis.

Objective To prepare a variety of quality control(QC)materials for SARS-CoV-2 variants as an addition to the conven-tional SARS-CoV-2 nucleic acid QC products for the laboratory detection of mutant strains by optimizing the preparation and purification process of MS2 phage virus-like particle(VLP)technique,and evaluate their performances.Methods The typical mutation sequence fragments or full length S genes were designed and synthesized according to the genomic information of SARS-CoV-2 variants.Then,they were inserted into the downstream of maturase gene,coat protein and the pac-site of MS2 phage to construct a series of recombi-nant expression vectors.After induced by the prokaryotic expression system,the VLP products were purified through the polyethylenei-mine precipitation,ultrafiltration,nuclease digestion,and gel filtration chromatography.The obtained VLP were validated by the nucle-ic acid electrophoresis,protein electrophoresis,protein concentration determination,and fluorescence PCR,and their performances such as nucleic acid residue and stability were also evaluated.Results A total of 10 kinds of VLP containing the targeted sequences of the gene to be tested were prepared.The length of the foreign sequence wrapped in them ranged from 297 bp to 3 822 bp,which could be combined into a variety of QC materials for the mutation detection of different SARS-CoV-2 variants.The prepared VLP QC materials could not be effectively amplified without nucleic acid extraction or reverse transcription steps during the routine nucleic acid detection.The simulated QC samples remained stable after repeated freeze-thaw cycles.They could be stored stably for 2 months at 25 ℃ and 4 weeks at 37 ℃.Conclusion The established preparation and combined purification process of VLP QC materials can encapsulate vari-ous exogenous nucleic acid sequences with different lengths into the viral coat protein to form VLP,with high production efficiency.The VLP QC products prepared by the above process have stable performance and almost no residual exogenous nucleic acid,which can ef-fectively meet clinical requirements and ensure the quality of laboratory testing.

Objective:To investigate the clinicopathological features, immunohistochemical characteristics, and differential diagnosis of low-grade adenosquamous carcinoma of the breast arising from benign sclerosing lesions.Methods:Twelve cases of low-grade adenosquamous carcinoma arising from benign sclerosing lesions of the breast were collected, which were diagnosed from January 2010 to December 2023 at the Seventh Medical Center of the Chinese People′s Liberation Army General Hospital. Their clinical manifestations, histopathological morphology, and immunohistochemical characteristics were analyzed and related literatures were reviewed.Results:All the 12 patients were females with a median age of 42 years (21-60 years). Five of the 12 cases had coexisting complex sclerosing lesions, 5 with sclerosing adenosis, 1 with sclerosing intraductal papilloma, and 1 with ductal adenoma. Microscopically, low-grade adenosquamous carcinoma grew infiltratively in multinodular and sclerosing lesions. The carcinomatous component was characterized by small irregular glandular structures, tubular formations, solid nests, clusters, or a single tumor cell. The epithelium showed varying degrees of squamous differentiation. The carcinoma was surrounded by fibroadenomatoid and desmoplastic lesions. The invasive neoplastic component typically infiltrated normal breast structures, and might infiltrate nerves and adipose tissue. There were lymphocytic aggregates commonly seen at the periphery. By immunohistochemistry, the tumor cells of all 12 cases showed diffuse and strong immunopositivity for CK5/6; negative expression of ER, PR and HER2; and variable expression of myoepithelial markers such as SMA, calponin, SMMHC and others. There was varied staining pattern of tumor cells for p63. CK8/18 (or CK7) was variably positive or negative. The proliferative index measured by Ki-67 was low.Conclusions:Low-grade adenosquamous carcinoma of the breast is a rare variant, which is found to coexist with other benign sclerosing lesions and can be easily missed and/or misdiagnosed. Their invasive growth pattern, presence of sweat duct-like structures and immunophenotypic profile are key features for appropriate diagnosis.

Prostate cancer is one of the most common male urological malignancies,in which bone metastasis of desmo-plasia-resistant prostate cancer is an important stage in the progression of the disease,which seriously affects the quality of life and survival of patients.With the development of nuclide therapy technology in recent years,223-Ra,as a new type of alpha-targeted therapy,has shown good efficacy in the treatment of desmoplasia-resistant prostate cancer bone metastasis.The purpose of this pa-per is to review the characteristics,mechanism of action,treatment,and the main research results of its treatment of desmoplasia-resistant prostate cancer bone metastasis,and provide a comprehensive review of the clinical application of 223-Ra in the treatment of desmoplasia-resistant prostate cancer bone metastasis for the clinical application of 223-Ra in prostate cancer bone metastasis.

Objective:To investigate the role of YTHDF2 in cervical lesions and its potential molecular mechanism.Methods:Gene expression data of cervical tissue were obtained from the GEO database to analyze the expression of YTHDF2 mRNA and perform pathway enrichment analysis. Patients with cervical lesions diagnosed by thinprep cytologic test in Gynecological Outpatient Department of Maternal and Child Health Hospital in Jiexiu, Shanxi Province, were selected as the research subjects. Data of cervical lesions and cervical exfoliated cells were collected. HPV infection status was detected by flow-through hybridization, and the expression of YTHDF2 mRNA was detected by reverse transcription real-time polymerase chain reaction. The expression of YTHDF2 in cervical lesions and the mediating role of HPV infection in the relationship between YTHDF2 and squamous intraepithelial lesion (SIL) were evaluated. YTHDF2-related genes were screened from multiple datasets in the GEO and ENCORI databases, and their expression, immune infiltration, and survival analysis were performed to assess the association between YTHDF2 and prognosis. Results:Compared with normal cervical tissue, YTHDF2 was highly expressed in cervical lesion tissue ( P<0.05). A total of 3 672 differentially expressed genes were screened from the dataset GSE49339. Gene Ontology analysis showed that YTHDF2 was mainly involved in transcription regulation. Kyoto Encyclopedia of Genes and Genomes analysis showed that YTHDF2 might be related to HPV infection and other signaling pathways. In the mediation analysis, χ2 test results showed that the expression level of YTHDF2 was significantly different among groups ( χ2=22.47, P<0.001). Trend χ2 test further showed that the expression level of YTHDF2 was upregulated with the degree of cervical precancerous lesions (trend χ2=10.26, P=0.001). Multivariate logistic regression analysis indicated that high YTHDF2 expression increased the risk of low-grade squamous intraepithelial lesions ( OR=3.15, 95% CI: 1.93-5.15) and high-grade squamous intraepithelial lesions ( OR=1.85, 95% CI: 1.01-3.39). Mediation effect analysis revealed a partial mediating effect of HPV infection between YTHDF2 and SIL, accounting for 32.02% of the total effect. Twelve YTHDF2 related genes were screened by the intersection of multiple datasets. The immune infiltration analysis results showed that YTHDF2 and related genes KLF4, E2F3 and HOXC6 were associated with immune infiltration (all P<0.05). Multivariate Cox proportional hazard regression model analysis showed that low expression of KLF4 ( HR=0.53, 95% CI: 0.30-0.94) and high expression of RHOB ( HR=1.80, 95% CI: 1.04-3.13) were risk factors for the prognosis of cervical cancer. Conclusion:YTHDF2 is highly expressed in cervical lesions and may have been involved in the regulation of HPV infection-related pathways and its downstream related genes are related to immune infiltration and prognosis of cervical cancer, providing a theoretical basis for the study of mechanisms related to cervical lesions.

Aim To investigate the effect of exosomes derived from bone marrod-derived mesenchymal stem cells(BMSCs)on dexamethasone-induced C2C12 muscular canal atrophy.Methods(1)C57BL/6J mouse bone marrow mesenchymal stem cells were isola-ted and cultured by whole bone marrow adhesion meth-od.(2)Extraction and identification of BMSCs EXOs were performed.(3)Myogenic differentiation of C2C12 cells was carried out.(4)The successfully differentia-ted myotubes were divided into the control group(cul-tured in 2％equine serum medium for 48 h),dexam-ethasone group(dexamethasone,DEX,10 μmol·L-1 concentration of DEX interfered with myotubes for 48 h),and exosomes group(exosomes,EXOs,interfered with myotubes for 48 h),exosome inhibitor group(exo-somes extracted from BMSCs after 10 μm GW4869 in-tervention,interfered with myotubes for 48 h).48 h later,the morphology and diameter of muscle tubes were observed and measured by microscope.Cell via-bility of each group was detected by CCK-8 method.The expression levels of atrogin-1 and MuRF-1,myo-genic differentiation antigen(MYOD)in each group were detected by Western blot.Results BMSCs were long spusiform,and BMSCS-EXOS showed a circular bilayer structure under transmission electron microsco-py,with a diameter of about 200 nm.CD9,CD63 and CD81 were highly expressed.Compared with the con-trol group,cell activity in DEX group decreased(P＜0.01),diameter of myotubes decreased(P＜0.01),expressions of atrogin-1(P＜0.05)and MuRF-1(P＜0.01)were significantly up-regulated,and expression of MYOD(P＜0.01)was significantly down-regula-ted.Compared with the DEX group,cell activity in the BMSCs-EXOs group increased(P＜0.01),diameter of myotubes increased(P＜0.01),expressions of atrogin-1(P＜0.05)and MuRF-1(P＜0.01)were signifi-cantly down-regulated,and expression of MYOD(P＜0.01)was up-regulated.Compared with the BMSCs-EXOs group,cell activity of the BMSCs-EXOs(GW4869)group decreased(P＜0.05),diameter of myotubes decreased(P＜0.01),expressions of atrog-in-1(P＜0.05)and MuRF-1(P＜0.05)were up-regulated,and expression of MYOD(P＜0.01)was down-regulated.Conclusion Bone marrow mesen-chymal stem cell-derived exosomes(BM-MSCs-EXOs)inhibit dexamethasone-induced C2C12 muscle tube at-rophy.