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

ObjectiveTo investigate the regulatory effect of icariin （ICA） on transforming growth factor-β₁ （TGF-β₁）/Smad pathway in bone microvascular endothelial cells （BMECs） and the effect on autophagy in BMECs. MethodsBMECs were isolated and cultured， and the cell types were identified by immunofluorescence. Cells were divided into the control group， model group （0.1 g·L^-1 methyl prednisolone）， ICA group （0.1 g·L^-1 methyl prednisolone +1×10^-5 mol·L^-1 ICA）， and TGF-β inhibitor group （0.1 g·L^-1 methyl prednisolone +1×10^-5 mol·L^-1 ICA +1×10^-5 mol·L^-1 LY2157299）. Transmission electron microscopy was used to observe the ultrastructure and autophagosome number of BMECs. Autophagy double-standard adenovirus was used to monitor the confocal autophagy flow generation of each cell. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the gene and protein expression of autophagy in the TGF-β₁/ Smad pathway. ResultsAfter cell separation culture， platelet endothelial cell adhesion molecule （CD31） and von willebrand factor （vWF） immunofluorescence identified BMECs. Transmission electron microscopy showed that the cell membrane was damaged， and the nucleus was pyknotic and broken in the model group. Compared with the model group， the ICA group had complete cell membranes， clear structures， with autophagy-lysosome sparsely distributed. The confocal photo showed that BMECs had autophagosomes and autophagy-lysosomes， and the autophagy expression of the ICA group was similar to that of the blank group. Compared with the blank group， in the model group and the LY2157299 group， autophagosomes and autophagy-lysosomes were barely seen in the autophagy flow. Compared with the blank group， the mRNA and protein expressions of autophagy effector protein 1 （Beclin1） and microtubule-associated protein 1 light chain 3B （LC3B） in the model group were significantly decreased （P<0.01）， and those of ubiquitin-binding protein （p62） were significantly increased （P<0.01）. The mRNA expression of TGF-β₁， Smad homolog 2 （Smad2）， and Smad homolog 3 （Smad3） decreased （P<0.05， P<0.01）. The protein expressions of TGF-β₁， p-Smad2， and p-Smad3 were significantly decreased （P<0.01）. Compared with those of the model group， the mRNA and protein expression of Beclin1 and LC3B in BMECs of the ICA group increased （P<0.01）， and those of p62 significantly reduced （P<0.01）. The mRNA expression of TGF-β₁， Smad2， and Smad3 increased significantly （P<0.01）. The protein expression of TGF-β₁， p-Smad2， and p-Smad3 increased significantly （P<0.01）. Compared with those in the model group， the mRNA and protein expressions of Beclin1， LC3B， and p62 in the inhibitor group were not statistically significant. The expression of key genes and proteins of the TGF-β₁ pathway in the inhibitor group was not statistically significant. ConclusionICA can promote glucocorticoid-induced autophagy expression of BMECs， and its mechanism may be related to activating the TGF-β₁/Smad signaling pathway.

Steroid-induced osteonecrosis of the femoral head （SONFH） is a severe musculoskeletal disorder often induced by the prolonged or excessive use of glucocorticoids. Characterized by ischemia of bone cells， necrosis， and trabecular fractures， SONFH is accompanied by pain， femoral head collapse， and joint dysfunction， which can lead to disability in severe cases. The pathogenesis of SONFH involves hormone-induced osteoblast apoptosis， bone microvascular endothelial cell （BMEC） apoptosis， oxidative stress， and inflammatory responses. The phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway plays a pivotal role in the development of the disease. Modulating the PI3K/Akt signaling pathway can promote Akt phosphorylation， thereby stimulating the osteogenic differentiation of bone marrow mesenchymal stem cells and osteoblasts， promoting angiogenesis in BMECs， and inhibiting osteoclastogenesis. The research on the treatment of SONFH with traditional Chinese medicine （TCM） has gained increasing attention. Recent studies have shown that TCM monomers and compounds have potential therapeutic effect on SONFH by intervening in the PI3K/Akt signaling pathway. These studies not only provide a scientific basis for the application of TCM in the treatment of SONFH but also offer new ideas for the development of new therapeutic strategies. This review summarized the progress in Chinese and international research on the PI3K/Akt signaling pathway in SONFH over the past five years. It involved the composition and transmission mechanisms of the signaling pathway， as well as its regulatory effects on osteoblasts， mesenchymal stem cells， osteoclasts， BMECs， and other cells. Additionally， the review explored the TCM understanding of SONFH and the application of TCM monomers and compounds in the intervention of the PI3K/Akt pathway. By systematically analyzing and organizing these research findings， this article aimed to provide references and point out directions for the clinical prevention and treatment of SONFH and promote further development of TCM in this field. With in-depth research on the PI3K/Akt pathway and the modern application of TCM， it is expected to bring safer and more effective treatment options for patients with SONFH.

A second-order calibration method combined with excitation-emission matrix(EEM)fluorescence spectroscopy was presented for simultaneous quantitative analysis of two anti-hypertensive drugs,metolazone(MET)and valsartan(VAL),in human serum and urine,and the quantitative results were compared with the results obtained by zero-and first-order calibration methods.The results indicated that the methods based on zero-and first-order calibration were inadequate for accurately quantifying the components of interest in cases where severe spectral overlap and unknown interferences coexisted.However,it was possible to obtain satisfactory results with the second-order calibration method based on alternating normalization-weighted error(ANWE)algorithm because of its strong"mathematical separation",even when the fluorescence spectra of the target analytes and unknown interferents considerably overlapped.Correlation coefficients for both analytes were greater than 0.99,with mean recoveries of 104.9%±5.7%and 107.8%±9.2%for MET and VAL in human serum,and 103.7%±8.9%and 94.7%±3.8%in human urine,respectively.In addition,the sensitivity,selectivity,limit of detection,limit of quantification,repeatability,and reproducibility of the proposed second-order calibration method were thoroughly examined.All results indicated that the established method was capable of achieving simultaneous and accurate quantification of MET and VAL in human body fluids,which was expected to be applied to analysis of both drugs in clinical settings.

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.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

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 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.

OBJECTIVES: To explore the status and risk factors of neuropsychological development in small for gestational age (SGA) infants at corrected 12-24 months of age. METHODS: Clinical data were retrospectively collected for 754 SGA infants at corrected ages 12-24 months in Shenzhen Bao'an Women and Children's Hospital between April 2018 and December 2023. Developmental quotient (DQ) levels were analyzed. According to the presence of global developmental delay (GDD), participants were divided into a GDD group (71 cases) and a control group (683 cases), and the incidence and influencing factors of GDD were investigated. RESULTS: In the high-risk preterm SGA group, the total DQ and DQ in all domains were lower than in the full-term SGA group (P<0.017). The overall incidence of GDD was 9.4% (71/754) and increased with decreasing gestational age (P<0.017). Compared with the control group, the GDD group had higher proportions of males; low-risk and high-risk preterm birth; mothers with less than a bachelor's degree; multiple birth; neonatal hypoglycemia; neonatal pneumonia; neonatal respiratory distress syndrome; bronchopulmonary dysplasia; and, at corrected 12-24 months, low body weight, growth retardation, and microcephaly. The length of neonatal hospital stay was longer in the GDD group than in the control group (P<0.05). The weight-for-age Z score, length-for-age Z score, and head circumference-for-age Z score at birth and at corrected 12-24 months were lower in the GDD group than in the control group (P<0.05). Multivariable logistic regression showed that male sex and maternal education below a bachelor's degree were independent risk factors for GDD in SGA infants (P<0.05). CONCLUSIONS Neuropsychological development in preterm SGA infants is comparatively delayed; male SGA infants born to mothers with less than a bachelor's degree should receive priority attention.
Humans ; Female ; Male ; Infant, Small for Gestational Age/psychology* ; Risk Factors ; Infant ; Retrospective Studies ; Child Development ; Developmental Disabilities/epidemiology* ; Infant, Newborn ; Child, Preschool

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.