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

Microorganisms are closely associated with human health, and their pathogenicity is a key factor in various infectious diseases, particularly in dentistry, where they contribute to common conditions such as dental caries, periodontitis, and oral mucosal diseases. Accurate and rapid microbial detection is crucial for early diagnosis, targeted therapy, and disease prevention. Conventional methods, including bacterial culture and molecular biological assays, offer specificity but are limited by long detection cycles, complex procedures, and dependence on laboratory conditions. Terahertz (THz) spectroscopy has emerged as a promising tool in microbial detection due to its non-ionizing nature, high sensitivity, and specific responses to water molecules and biomacromolecules. Integrating THz time-domain spectroscopy, near-field imaging, and metamaterial-enhanced techniques, studies have demonstrated the ability of this approach to effectively distinguish bacteria, fungi, and yeast, differentiate gram-positive and gram-negative bacteria, and even assess bacterial viability. Machine learning has further enhanced feature extraction and classification accuracy, and THz-based methods have shown notable advantages in multi-class microbial identification, detection of antibiotic-resistant strains, and quantitative analysis of microbial concentrations. However, current THz technologies are still constrained by strong water absorption, limited penetration depth, and the lack of standardized spectral databases. Future efforts should focus on mitigating water background interference, improving detection in complex samples, and establishing unified microbial spectral standards. This review systematically summarizes the latest advances of THz technologies in microbial detection, analyzes their mechanisms, advantages, and translational challenges, and proposes directions for future research.

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.

BACKGROUND:It has also been confirmed that ferroptosis is closely related to a variety of musculoskeletal diseases,such as rheumatoid arthritis,osteosarcoma,and osteoporosis.The pathophysiological mechanisms of ferroptosis and osteoporosis need to be further studied and elucidated to broaden our understanding of iron metabolism and osteoporosis.It will provide research ideas for the future elucidation of new mechanisms of osteoporosis and the development of new technologies and drugs for the treatment of osteoporosis. OBJECTIVE:To provide an overview of the current status of research on ferroptosis in osteoporosis,to provide a new direction for future research on the specific molecular mechanisms of osteoporosis,and to provide more effective and better options for osteoporosis treatment strategies. METHODS:The first author used the computer to search the literature published from 2000 to 2024 in CNKI,WanFang,VIP,and PubMed databases with search terms"ferroptosis,iron metabolism,osteoporosis,osteoblast,osteoclast,bone metabolism,signal pathway,musculoskeletal,review"in Chinese and English.A total of 68 articles were finally included according to the selection criteria. RESULTS AND CONCLUSION:(1)Ferroptosis is a new type of cell death discovered in recent years,which is usually accompanied by a large amount of iron accumulation and lipid peroxidation during cell death,and its occurrence is iron-dependent.This is distinctly different from several types of cell death that are currently being hotly studied(e.g.,cellular pyroptosis,necrotic apoptosis,cuproptosis,and autophagy).(2)Intracellular iron homeostasis is manifested as a balance between iron uptake,export,utilization,and storage.The body's iron regulatory system includes systemic and intracellular regulation.The main factor of systemic regulation is hepcidin produced by hepatic secretion,and cellular regulation depends on the iron regulatory protein/iron response element system.Of course,intracellular iron homeostasis can be controlled by other factors,such as hypoxia,cytokines,and hormones.(3)Lipid peroxidation causes oxidative damage to biological membranes(plasma membrane and internal organelle membranes),lipoproteins,and other lipid-containing molecules.Polyunsaturated fatty acid-containing phospholipids are important targets of lipid peroxidation.Free polyunsaturated fatty acid is an important substrate for lipid oxidation and can bind to the phospholipid bilayer,leading to over-oxidation and thus triggering lipid apoptosis.(4)Several studies have shown that osteoblasts are overloaded with iron in different ways,resulting in the accumulation of unstable ferrous iron and the generation of reactive oxygen species and lipid peroxides,causing ferroptosis of osteoblasts and ultimately a decrease in bone formation,affecting bone homeostasis and the development of osteoporosis.(5)Osteoclasts are large multinucleated cells formed by the fusion of mononuclear macrophage cell lines or bone marrow mesenchymal stem cells induced by nuclear factor-κB ligand receptor activator,and they have the function of bone resorption.Iron ions can promote osteoclast differentiation and bone resorption through the production of intracellular lipid reactive oxygen species,while iron chelators can inhibit osteoclast formation in vitro and thus affect the occurrence and development of osteoporosis.

Radiation-induced thrombocytopenia(RIT)faces a perplexing challenge in the clinical treatment of cancer patients,and current therapeutic approaches are inadequate in the clinical settings.In this research,oxy-matrine,a new molecule capable of healing RIT was screened out,and the underlying regulatory mecha-nism associated with magakaryocyte(MK)differentiation and thrombopoiesis was demonstrated.The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro.The ability to induce thrombopoiesis was subsequently demonstrated in Tg(cd41:enhanced green fluorescent protein(eGFP))zebrafish and RIT model mice.In addition,we carried out network pharmacological pre-diction,drug affinity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)analyses to explore the potential targets of oxymatrine.Moreover,the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,Western blot(WB),and immunofluorescence.Oxymatrine markedly promoted MK differentiation and maturation in vitro.Moreover,oxymatrine induced thrombopoiesis in Tg(cd41:eGFP)zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice.Mechanistically,oxymatrine directly binds to toll-like receptor 2(TLR2)and further regulates the downstream pathway stimulator of interferon genes(STING)/nuclear factor-kappaB(NF-κB),which can be blocked by C29 and C-176,which are specific inhibitors of TLR2 and STING,respectively.Taken together,we demonstrated that oxymatrine,a novel TLR2 agonist,plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis,suggesting that oxymatrine is a promising candidate for RIT therapy.

[Purpose]To analyze the trends of brain tumor incidence and age of onset in cancer registration areas of Jiangsu Province from 2009 to 2019.[Methods]The incidence data of brain tumors from 2009 to 2019 were obtained from 16 national cancer registration areas of Jiangsu Province.The crude incidence rate,age-standardized incidence rate by Chinese standard popula-tion(ASIRC),average age of onset,standardized age-specific incidence rate,and annual average percentage change(AAPC)by sexes and regions were calculated.[Results]The incidence rate of brain tumor in Jiangsu Province from 2009 to 2019 showed an increasing trend(AAPC=4.12％,95％CI:3.31％～4.95％),and the increase in female(AAPC=5.79％,95％CI:4.44％～7.15％)was higher than that in male(AAPC=2.31％,95％CI:1.66％～2.97％);and the increase in urban areas(AAPC=4.84％,95％CI:3.52％～6.18％)was higher than that in rural areas(AAPC=3.04％,95％CI:2.12％～3.98％).The ASIRC also showed an increasing trend(AAPC=2.14％,95％CI:1.27％～3.02％).Birth cohort analysis showed that within the same age group,the incidence rate of brain tumors increased with increasing birth years.The average age of onset for crude incidence showed a delaying trend of 0.43 years old per year(t=7.09,P＜0.001);that for ASIRC was 0.20 years old per year(t=3.33,P=0.009).The proportion of patients in the age group of 60 years old and above increased from 35.79％in 2009 to 44.18％in 2019.[Conclusion]The incidence of brain tumor in cancer registration areas of Jiangsu Province showed an increasing trend from 2009 to 2019 with a delaying trend of average age of onset.

Objective:To explore the application of full-thickness advancement flap of upper abdominal wall in breast-conserving surgery for lower quadrant breast cancer.Methods:This is a retrospective case series study. The clinic data of 25 lower quadrant breast cancer patients who underwent a breast-conserving surgery with advancement flap of full-thickness of upper abdominal wall at the Breast Center, Beijing Tongren Hospital, Capital Medical University, from June 2022 to September 2023 were analyzed retrospectively. All patients were female, aged (47.6±5.8) years (range: 38 to 57 years). Tumor staging included stageⅠ in 8 cases, stageⅡA in 13 cases, stageⅡB in 4 cases. The subcutaneous fat thickness of the upper abdominal walls and the volume of wide local excision of the tumor were measured and recorded. The operation time of repairing the breast, the duration of retention of postoperative drainage tubes, postoperative complications, and cosmetic results were recorded.Results:The subcutaneous fat thickness in the upper abdominal walls was (1.7±0.2) cm (range: 1.3 to 2.2 cm), the excision volume of breast-conserving surgery was (70.8±13.6) mm 3 (range: 49 to 97 mm 3), the operation time of repairing the breast was (55.4±5.1) minutes (range: 45 to 65 minutes) and the retention time of the drainage tube was (7.4±0.8) days (range: 6 to 9 days). Cosmetic results: excellent in 12 cases (48.0%), good in 9 cases (36.0%) and fair in 4 cases (16.0%). There was 1 case of postoperative seroma in the donor area, which healed after repositioning the negative pressure drain. Conclusion:In breast-conserving surgery for lower quadrant breast cancer, using a full-thickness abdominal wall advancement flap to repair breast defects is a simple and effective tumor reconstructive technique, yielding good results in achieving postoperative symmetry of the lower quadrant of the breast.

Objective:To explore the effect of ezetimibe combined with atorvastatin on the efficacy,blood lipids,ca-rotid ultrasound indicators in patients with coronary heart disease(CHD)and its safety.Methods:This randomized controlled study enrolled 98 CHD patients admitted to 945th Hospital of the PLA Joint Logistic Support Force be-tween June 2021 and June 2023.Patients were divided into intervention group and control group with 49 cases in each group.Patients in the control group was treated with atorvastatin-bascd routine medication comparing to those in intervention group receiving additional ezetimibe,both groups were treated for 90 d.Clinical efficacy,blood lipids,carotid ultrasound indicators,endothelial function indicators,and incidence of adverse reactions were compared between two groups.Results:Compared with patients in the control group,those in the intervention group had significant higher total effective rate(91.83％vs.73.47％,P=0.016).Compared with patients in the control group after treatment,those in intervention group had significant lower levels of low density lipoprotein cho-lesterol(LDL-C)[(2.74±0.61)mmol/L vs.(3.42±0.66)mmol/L],total cholesterol(TC)[(3.80±0.89)mmol/L vs.(4.69±1.02)mmol/L],triglyceride(TG)[(1.79±0.53)mmol/L vs.(2.35±0.62)mmol/L],re-sistance index(RI)[(52.02±6.32)％vs.(57.95±6.02)％],carotid intima-media thickness(IMT)[(0.91±0.17)mm vs.(1.08±0.24)mm],von Willebrand factor(vWF)[(19.03±3.76)mg/L vs.(23.41±4.42)mg/L],angiotensin Ⅱ(Ang Ⅱ)[(45.83±5.87)ng/L vs.(52.87±6.01)ng/L](P＜0.001 all);and significant high-er high density lipoprotein cholesterol(HDL-C)[(1.63±0.32)mmol/L vs.(1.35±0.27)mmol/L],peak systol-ic velocity(PSV)[(47.93±5.26)cm/s vs.(41.32±4.98)cm/s],end-diastolic velocity(EDV)[(36.14±5.10)cm/s vs.(30.73±4.48)cm/s],pulse index(PI)[(85.98±9.03)％vs.(78.42±8.82)％],vascular endothelial growth factor receptor 1(VEGFR1)[(289.14±32.98)ng/L vs.(258.34±29.32)ng/L](P＜0.001 all).There was no significant difference in the incidence of adverse reactions between the two groups(P=0.538).Conclusion:Ezetimibe combined with atorvastatin possesses significant therapeutic effect on CHD patients,which could signifi-cantly reduce blood lipids,improve the carotid blood flow velocity and vascular endothelial function with good safety.

AIM:To investigate the effects of the Qingfei-Jiedu-Huatan formula(QJHF)on damage to the lung vascular endothelial barrier induced by Klebsiella pneumoniae in mice with severe pneumonia,as well as to elucidate its underlying mechanisms.METHODS:Fifty-one C57BL/6J mice were randomly divided into control group(n=6),model group(n=15),QJHF group(n=15),and ceftriaxone sodium(CRO)group(n=15).Severe pneumonia was in-duced in the mice by a single tracheal intubation with 50 μL of 1×1011 CFU/mL Klebsiella pneumoniae on day 0.Six hours after modeling,the mice in QJHF and CRO groups received their respective treatments,while those in control and model groups were administered an equal volume of saline.All mice were sacrificed on day 3 after the end of gavage.Lung histo-pathological changes were assessed using hematoxylin-eosin(HE)staining.Levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and IL-6 in lung tissues were measured by enzyme-linked immunosorbent assay(ELISA).Flow cytometry was used to detect CD11b+Ly6g+cells in bronchoalveolar lavage fluid(BALF).Proteomics and network pharma-cology analyses were conducted to elucidate the mechanisms of drug action.Western blot was conducted to assess the ex-pression levels of vascular endothelial cadherin(VE-cadherin),zonula occludens-1(ZO-1),occludin,vascular endothe-lial growth factor(VEGF),P38 mitogen-activated protein kinase(P38),and phosphorylated P38(p-P38)in lung tis-sues.RESULTS:Treatment with QJHF significantly attenuated the symptoms such as mental status and respiratory dis-tress,reduced mortality,mitigated lung tissue lesions,and decreased levels of IL-6,TNF-α,IL-1β,as well as BALF to-tal protein concentration,total cell count and neutrophil content in a mouse model of severe pneumonia(P＜0.05 or P＜0.01).Additionally,QJHF increased the expression of VE-cadherin,ZO-1 and occludin proteins in lung tissues.Pro-teomic analysis demonstrated that QJHF modulated the expression of 129 proteins in the lung tissues of mice suffering from severe pneumonia.Network pharmacology identified 328 potential targets associated with 14 major bioactive components of QJHF and 1 665 genes related to severe pneumonia,with 125 overlapping genes between the two datasets.The construc-tion of a protein-protein interaction(PPI)network,along with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the regulated proteins and overlapping genes,indicated that QJHF primarily in-fluenced the PI3K-Akt,MAPK and Rap1 signaling pathways,as well as VEGFR.Western blot analysis showed that QJHF significantly inhibited the expression of VEGF and P38 in lung tissues(P＜0.05 or P＜0.01).CONCLUSION:Treatment with QJHF attenuates severe pneumonia in mice,potentially by inhibiting VEGF/P38 signaling to protect the vascular endothelial barrier.