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 study the clinical efficacy of Professor Li Bingmao's Tongfu Xiere Quyu Shuli Prescription in the treatment of patients with functional dyspepsia(FD)of spleen and stomach damp-heat and qi stagnation and blood stasis type.METH-ODS A total of 206 patients with functional dyspepsia of spleen and stomach damp-heat and qi stagnation and blood stasis type diag-nosed by Hengshui People's Hospital were included in the study and randomly divided into a study group and a control group with 103 cases in each group.During the treatment,3 cases dropped out in each group.The control group adopted the conventional Western medicine treatment plan for functional dyspepsia(mosapride+rabeprazole),and the study group took Tongfu Xiere Quyu Shuli Pre-scription on the basis of the treatment of the control group.The treatment course of both groups was 4 weeks.The traditional Chinese medicine(TCM)syndrome scores,psychological status[self-rating anxiety scale(SAS),self-rating depression scale(SDS),and quality of life[Nepean dyspepsia life quality index(NDLQI)of the two groups of patients before and after treatment were observed and the clinical efficacy was evaluated;serum motilin(MTL),ghrelin,gastrin(GAS),corticotropin-releasing hormone(CRH)and pep-sinogen(PG Ⅰ,PG Ⅱ)were measured by enzyme-linked immunosorbent assay;changes in gastric motility indexes were analyzed by electrogastrogram analyzer;changes in intestinal flora were detected by instillation method.The occurrence of adverse reactions in the two groups of patients was monitored during treatment.RESULTS After treatment,the TCM syndrome scores of the two groups were significantly reduced(P<0.05,P<0.01),and the score in the study group was lower than that in the control group(P<0.01).The total effective rate of the study group was significantly higher than that in the control group(P<0.01).After treatment,the expression levels of MTL,Ghrelin,GAS,PG Ⅰ and PG Ⅱ in the two groups increased,and CRH decreased,and the improvement degree of the study group was better than that of the control group(P<0.01).After treatment,the main frequency and slow wave percentage of the electrogastrogram increased in the two groups,and the study group was better than that of the control group(P<0.01).After treat-ment,the number of bifidobacteria and lactobacilli in the two groups increased,and the number in the study group was greater than that in the control group,while the number of enterobacteria,enterococci and yeast decreased,and the number in the study group was less than that in the control group(P<0.01).There was no significant difference in adverse reactions between the two groups(P>0.05).CONCLUSION Tongfu Xiere Quyu Shuli Prescription is effective in the treatment of FD patients with spleen and stomach damp-heat syndrome,and can improve FD clinical symptoms,quality of life,anxiety and depression symptoms,regulate gastrointesti-nal hormone expression levels,gastric motility and intestinal flora expression,and does not increase adverse reactions,and is safe and reliable.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

The Chinese medicine Zha Gui,the senior manager of traditional Chinese medicine dispensing,plays an important role and key function in the"front store and back factory"Chinese medicine pharmacy.Inheriting the valuable experience and excellent culture of Chinese medicine Zha Gui is of great academic value and practical significance in clarifying the development of the discipline of traditional Chinese medicine,standardizing the technical operation of traditional Chinese medicine preparation,and promoting the"living inheritance"of the old pharmacist's skills.At the start of the new era and opening up to new thinking,this paper examined the rise of old Chinese medicine stores and Chinese medicine Zha Gui,analyzed the post responsibility,inheritance path and future development of Chinese medicine Zha Gui,and put forward the strategy of cultivating high-quality Chinese medicine Zha Gui talents,aiming at cultivating compound innovative talents in the traditional Chinese medicine industry in line with the needs of the contemporary society.

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.

ObjectiveTo investigate the effect of icariin （ICA） on steroid-induced ferroptosis in bone microvascular endothelial cells （BMECs）. MethodsRat BMECs were selected and treated with 500 mg·L^-1 hydrocortisone for 1.5 h to establish a ferroptosis model of BMECs. The experimental cells were divided into a blank group， hormone group （500 mg·L^-1 hydrocortisone）， ICA group （500 mg·L^-1 hydrocortisone + 34 mg·L^-1 ICA）， and ferroptosis agonist group （500 mg·L^-1 hydrocortisone + 34 mg·L^-1 ICA + 2.7 mg·L^-1 erastin）. Cell viability was detected by CCK-8. The levels of ferrous ion， glutathione （GSH）， malondialdehyde （MDA）， superoxide dismutase （SOD）， and reactive oxygen species （ROS） were detected by related kit species. The ferroptosis-related proteins， such as glutathione peroxidase 4（GPX4）， ferritin light chain （FTL）， and transferrin receptor protein1 （sTfR） were detected by Western blot， as well as autophagy-related proteins including microtubule-associated protein 1 light chain 3B （LC3B）， Beclin1， B-cell lymphoma-2 （Bcl-2）， and Caspase-3. Results500 mg·L^-1 hydrocortisone intervention for 1.5 h could effectively induce ferroptosis in BMECs， and ferroptosis levels could reach a peak as the intervention continued. In terms of cellular antioxidant capacity， compared with those in the blank group， the cell vitality， GSH in the hormone group decreased significantly， and the levels of ROS， SOD， MDA， and ferrous ions were significantly increased （P<0.01）. Compared with those in the hormone group， the cell viability， GSH were significantly increased， and the levels of ROS， SOD， MDA， and ferrous ions were decreased in the ICA group （P<0.01）. Compared with those in the ICA group， the cell vitality， GSH in the ferroptosis agonist group decreased significantly， and the levels of ROS， SOD， MDA， and ferrous ions increased significantly （P<0.01）. In terms of the relationship between ferroptosis and autophagy， compared with the blank group， the hormone group had significantly increased expression levels of LC3B， sTfR， Beclin1， and FTL and significantly decreased expression levels of GPX4 （P<0.01）. Compared with the hormone group， The ICA group had significantly decreased expression levels of LC3B， sTfR， and FTL and significantly increased expression levels of Beclin 1 and GPX4 （P<0.01）. Compared with those in the ICA group， the expression levels of LC3B， sTfR， and FTL increased in the rapamycin group， and those of Beclin 1 and GPX4 decreased （P<0.01）. In terms of cell ferroptosis and apoptosis，compared with the blank group， the hormone group had significantly increased expression levels of FTL， sTfR and Caspase-3 and significantly decreased expression levels of GPX4， and Bcl-2 （P<0.01）. Compared with the hormone group， the ICA group had significantly decreased expression levels of FTL， sTfR and Caspase-3 and significantly increased expression levels of GPX4， and Bcl-2 （P<0.01）. Compared with those in the ICA group， the expression levels of FTL， sTfR and Caspase-3 in the ferroptosis agonist group were increased， and the expression levels of GPX4， and Bcl-2 were decreased （P<0.01）. In terms of cell function，compared with that in the blank group， the ability of cell migration and tube formation was significantly decreased in the hormone group （P<0.01）. Compared with that in the hormone group， the cell migration and tube formation ability in the ICA group were significantly increased （P<0.01）. ConclusionFerroptosis is involved in steroid-induced damage in BMECs. ICA can inhibit steroid-induced ferroptosis in BMECs， and the mechanism may be associated with the inhibition of ferroptosis by regulating autophagy.

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:Zinc-based alloy medical implant materials have excellent mechanical properties,complete degradability and good biocompatibility,and are mainly used in orthopedic implants,cardiovascular stents,bile duct stents,tracheal stents,nerve catheters,etc. OBJECTIVE:To review the research progress of biodegradable zinc-based alloys in bone defect repair and prospect the promising research direction and achievements of zinc-based materials. METHODS:After searching PubMed,Web of Science,WanFang Data,and CNKI databases from the establishment of the database to June 2023,various relevant articles on biodegradable zinc-based alloys for bone implant material research were collected.The basic characteristics of biodegradable zinc based alloys were summarized,and the role of zinc-based alloys in promoting bone tissue repair was sorted and summarized.The current research hotspots and shortcomings were discussed. RESULTS AND CONCLUSION:(1)Zinc-based alloys have good biocompatibility.Using zinc-based alloys as the matrix material,with the help of scaffold structure construction technology and coating optimization process,the bone conductivity of zinc-based alloys will be effectively improved,and their degradation products will have efficient bone induction to regulate the gene expression of osteoblasts and osteoclasts,thereby promoting the repair and reconstruction of bone defects.(2)However,in the research on optimizing zinc-based alloys,the coating process is relatively insufficient,and additive loading technology is still lacking.(3)Zinc-based alloys have excellent mechanical and biological properties.Through special processes,their bone conductivity and osteoinductivity can be increased to effectively improve their ability to promote bone repair and reconstruction,and it is expected to further achieve the development of personalized transplant materials.Further research and development are needed to optimize the integration of coating and additive loading technologies into zinc-based alloys.

Objective:To compare the clinical efficacy and adverse events of chemoradiotherapy (CRT) combined with immunotherapy versus CRT alone in patients with locally recurrent esophageal squamous cell carcinoma (ESCC) after surgery.Methods:A total of 221 patients with postoperative locally recurrent ESCC who underwent CRT at the Affiliated Huai′an No. 1 People′s Hospital of Nanjing Medical University from January 2020 to December 2022 were retrospectively analyzed. Patients were divided into two groups according to treatment modality: the CRT group ( n=118) and the CRT plus immunotherapy group (combined group, n=103). Among the combined group, 39 patients received camrelizumab, 33 received sintilimab, and 31 received tislelizumab. Short-term efficacy, survival outcomes, and treatment-related adverse events were compared between the two groups. The Cox proportional hazards model was used to analyze prognostic factors for overall survival (OS). Results:No statistically significant differences were observed in baseline clinicopathological characteristics between the two groups. The objective response rate (ORR) in the combined group was 72.8%, significantly higher than 55.9% in the CRT group ( P=0.009). The 1- and 2-year OS rates in the CRT group were 68.6% and 41.5%, respectively, while the 1- and 2-year progression-free survival (PFS) rates were 56.8% and 30.5%, respectively. In the combined group, the 1- and 2-year OS rates were 84.5% and 55.3%, and the 1- and 2-year PFS rates were 67.0% and 42.7%, respectively. The differences in both OS and PFS between the two groups were statistically significant ( P=0.001 and 0.023, respectively). Multivariate analysis showed that Karnofsky performance status score of 70, TNM stage III, and CRT alone were independent risk factors for OS ( P=0.035, 0.031, and 0.002, respectively). The incidence of grade ≥3 adverse events did not differ significantly between the two groups ( P=0.550). A total of 85 grade 1-2 immune-related adverse events (irAEs) and 7 grade ≥3 irAEs occurred in 65 patients in the combined group. Subgroup analysis suggested that tislelizumab combined with CRT showed the most favorable efficacy and safety profile. Conclusion:For patients with locally recurrent ESCC after surgery, concurrent chemoradiotherapy combined with immunotherapy demonstrates promising efficacy with tolerable safety, and may offer a potential therapeutic advantage.

Objective To compare the stress magnitude and distribution of the restorations,remaining tooth tissues,and bonding interfaces of endodontically mandibular first molar with different buccolingual residual tooth tissue thicknesses in two different restorations.Methods The finite element method was used to model the restorations of mandibular first molars with different buccolingual residual tissue thicknesses after root canal treatment.The vertical and oblique loads were applied to record the stress magnitude and distribution of restorations,residual tissues,and bonding interfaces of the different restorations.Results Three different models of mandibular first molar were designed based on the amount of buccal and glossal side dental tissue.Based on this simulation of the dental preparation of FO and EC and the preparation of the prosthesis,generating 6 different groups:FO repair in A1 group,thickness of the buccal tooth tissue is 2mm;A2 group was repaired by FO,thickness of the buccal tooth tissue is 3mm;A3 Group was performed with FO repair,thickness of the buccal and lingual remaining tooth tissue is 4mm;In B1 group,with EC repair,thickness of buccal tooth tissue is 2mm;In B2 group with EC repair,thickness of buccal tooth tissue is 3mm;In B3 group,using EC repair,thickness of remaining dental tissue on buccal and lingual side was 4mm.Results Two loading modes,the restoration such as effect force distribution are concentrated around the loading point,dentin effect force are concentrated in the tooth neck,the full coverage of high embedded group restoration-dental resin interface maximum main stress(MPS)is concentrated in the hole wall and shaft wall Angle,the pulp cavity setting crown group restoration-dental resin interface MPS focus in the bottom wall angle of the pulp cavity setting hole type.In the model of tooth tissue thickness in the same buccal-lingual side,except that the peak effect force of the restoration was greater than the peak of the full coverage crown,the peak of the observed index of the full coverage crown was greater than that of the whole cavity.Conclusion Endocrown can better protect the tooth tissue after root canal treatment,and it is recommended to choose endocrown for restoration after root canal treatment.