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:The biomedical industry in Shenzhen is developing at an accelerating pace; however, bottlenecks exist in its collaboration with medical and health institutions in conducting clinical trials. This has resulted in enterprises and medical institutions being unable to effectively advance the development of trials.Methods:In response to this situation, the Shenzhen Municipal Government has conducted a series of surveys. Employing a mixed qualitative research design to grasp the current development status of the biopharmaceutical industry, it organized experts from relevant fields within pharmaceutical manufacturers and medical institutions across the city. These experts, from diverse perspectives, comprehensively reviewed and analyzed the current status and challenges of clinical trial implementation in Shenzhen, and proposed targeted countermeasures.Results:The outcomes include optimizing the layout of the biomedical industry, enhancing hospitals' capacity and motivation to undertake clinical trials, and refining the existing clinical trial system-all aimed at breaking through the existing challenges and difficulties.Conclusions:The development of biomedicine can drive progress in healthcare, improve patient diagnosis and treatment, and boost urban innovation. By addressing the bottlenecks in clinical trial collaboration and local product application, and breaking down existing barriers through joint efforts, we can promote industrial growth, elevate the professional competence and standards of healthcare institutions, and achieve mutual development and progress.

The use of wastewater analysis, or wastewater-based epidemiology, to assess and monitor the situation of drug abuse is now widely used at home and abroad. However, there is currently a lack of effective evaluation methods and effective ways of comparison, supervision and standardization, which is not conducive to the analysis and comparisons of data in different countries and regions. Quality control techniques can control the laboratory's analytical errors, safeguard the consistency and comparability of identification conclusions, and promote the further improvement of the level and capacity of urban drug governance, thus playing significant roles. This paper provides an overview of sample collection, sample preservation and transportation, laboratory analysis, back-calculation of drug use and external laboratory quality control in the process of wastewater analysis, with a view to exploring more comprehensive scientific and objective methods and approaches suitable for examining and evaluating qualitative and quantitative analysis of drugs in wastewater among laboratories.

Adipose tissue is a critical energy reservoir in animals and humans, with multifaceted roles in endocrine regulation, immune response, and providing mechanical protection. Based on anatomical location and functional characteristics, adipose tissue can be categorized into distinct types, including white adipose tissue (WAT), brown adipose tissue (BAT), beige adipose tissue, and pink adipose tissue. Traditionally, adipose tissue research has centered on its morphological and functional properties as a whole. However, with the advent of single-cell transcriptomics, a new level of complexity in adipose tissue has been unveiled, showing that even under identical conditions, cells of the same type may exhibit significant variation in morphology, structure, function, and gene expression——phenomena collectively referred to as cellular heterogeneity. Single-cell transcriptomics, including techniques like single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq), enables in-depth analysis of the diversity and heterogeneity of adipocytes at the single-cell level. This high-resolution approach has not only deepened our understanding of adipocyte functionality but also facilitated the discovery of previously unidentified cell types and gene expression patterns that may play key roles in adipose tissue function. This review delves into the latest advances in the application of single-cell transcriptomics in elucidating the heterogeneity and diversity within adipose tissue, highlighting how these findings have redefined the understanding of cell subpopulations within different adipose depots. Moreover, the review explores how single-cell transcriptomic technologies have enabled the study of cellular communication pathways and differentiation trajectories among adipose cell subgroups. By mapping these interactions and differentiation processes, researchers gain insights into how distinct cellular subpopulations coordinate within adipose tissues, which is crucial for maintaining tissue homeostasis and function. Understanding these mechanisms is essential, as dysregulation in adipose cell interactions and differentiation underlies a range of metabolic disorders, including obesity and diabetes mellitus type 2. Furthermore, single-cell transcriptomics holds promising implications for identifying therapeutic targets; by pinpointing specific cell types and gene pathways involved in adipose tissue dysfunction, these technologies pave the way for developing targeted interventions aimed at modulating specific adipose subpopulations. In summary, this review provides a comprehensive analysis of the role of single-cell transcriptomic technologies in uncovering the heterogeneity and functional diversity of adipose tissues.

Objective To provide a reference for medication therapy management(MTM)of diabetic patients complicated with abnormal blood pressure fluctuation.Methods A 71-year-old female diabetic patient with combined hypertension and abnormal blood pressure fluctuations was referred by the doctor to the pharmacy clinic.The pharmacists provided MTM services through pharmacy inquiry,medication evaluation,medication reconciliation,drug use education,and pharmacy follow-up.They reconciliated the medication regimen based on plasma glucose levels and dynamic blood pressure rhythms.Results Through twelve times MTM services for fourteen weeks,the atherosclerotic cardiovascular disease(ASCVD)risk factors,including morning peak blood pressure,fasting plasma glucose(FPG),plasma glucose two hours post breakfast(P2h PG)and glycosylated hemoglobin(HbA1c),reduced from 163/115 mmHg,7.54 mmol·L-1,12.87 mmol·L-1 and 7.2%before MTM to 137/84 mmHg,6.42 mmol·L-1,8.79 mmol·L-1 and 6.4%after MTM services,and the trough blood pressure post breakfast raised from 86/64mmHg to 115/76 mmHg.The patient's plasma glucose and blood pressure were effectively managed and controlled,and the abnormal non-spoon-shaped hypertension rhythm changed to the normal spoon-shaped diurnal blood pressure rhythm,and the patient's dizziness symptoms disappeared after breakfast.Conclusion The hospital develops pharmacy clinics,where pharmacists provide MTM services for patients with chronic diseases such as hypertension and diabetes,promote clinical rational drug use,and improve the level of patient health management.

Objective:To investigate the relationship among seminal oxidation-reduction potential(nORP),sperm DNA frag-mentation(DFI)and semen parameters in patients with varicocele.Methods:Clinical data of 522 patients treated in the reproduc-tive andrology clinic of the Northern Theater General Hospital from November 2023 to December 2023 were retrospectively analyzed,in-cluding 435 men of childbearing age and 87 men of infertile age.The patients were divided into the varicocele group(n=116)and non-varicocele group(n=406)according to clinical diagnosis.The differences of seminal plasma nORP,DFI,sperm high DNA stain ability(HDS)and semen parameters were analyzed between the two groups.The relationship among general clinical data,seminal plasma nORP,semen parameters,DFI and HDS in patients with varicocele were further analyzed.According to the severity of varico-cele,the patients were divided into three groups,including mild,moderate and severe.And the differences of seminal plasma nORP and semen parameters,DFI and HDS among all groups were analyzed.The differences of seminal plasma nORP,semen parameters,DFI and HDS were compared between the varicocele and non-varicocele groups.Results:The total sperm count,sperm concentra-tion,progressive motility sperm percentage(PR％)and normal sperm morphology rate(NSMR)in patients with varicocele were sig-nificantly lower than those in control group(P＜0.05).And seminal plasma nORP,DFI and HDS in patients with varicocele were sig-nificantly higher than those in control group(P＜0.05).Seminal plasma nORP in patients with varicocele was significantly negatively correlated with total sperm,sperm concentration and NSMR(P＜0.05),and significantly positively correlated with DFI and HDS(P＜0.05).There were significant differences in nORP,total sperm count,sperm concentration,PR％,DFI and HDS among mild,moderate and severe varicocele groups(P＜0.05).Seminal plasma nORP,sperm concentration,PR％and DFI in severe group were significantly lower than those in mild and moderate groups(P＜0.05).Sperm count and HDS in severe group were significantly lower than those in mild group(P＜0.05).In infertile patients,seminal plasma nORP,DFI and HDS in varicocele group were significantly higher than those in control group(P＜0.05).And PR％in varicocele group was significantly lower than that in control group(P＜0.05).Conclusions:Seminal plasma nORP in patients with varicocele may be an important marker of oxidative stress affecting DFI and semen parameters.

Background and Aims:Microsatellite-stable(MSS)colorectal cancer(CRC)generally exhibits poor responsiveness to immune checkpoint inhibitors(ICIs),and effective immunotherapy strategies remain lacking.Anti-angiogenic agents such as bevacizumab(BEV)can improve the tumor immune microenvironment and act synergistically with ICIs.This multicenter real-world study compared the efficacy of different immunotherapy-based combination regimens in patients with MSS/MSI-L/pMMR advanced CRC,aiming to identify the optimal treatment strategy.Methods:A total of 100 patients with MSS/MSI-L/pMMR advanced CRC who received systemic treatment between November 2019 and February 2025 at four tertiary hospitals in Hunan,China,were retrospectively enrolled.Patients were classified into six treatment groups:chemotherapy alone,chemotherapy+targeted therapy,immunotherapy alone,immunotherapy+chemotherapy,immunotherapy+targeted therapy,and immunotherapy+chemotherapy+targeted therapy.The primary endpoints were overall survival(OS)and progression-free survival(PFS),while secondary endpoints were objective response rate(ORR)and disease control rate(DCR).Additionally,among patients receiving immunotherapy,subgroup analysis was performed according to BEV administration.Results:Among all 100 patients,the immunotherapy+chemotherapy+targeted therapy group achieved the highest ORR(32.0%)and DCR(76.0%)and was the only regimen yielding a complete response(CR).Compared with chemotherapy or immunotherapy alone,the triplet regimen significantly improved OS(P<0.05);although PFS improvement did not reach statistical significance,a clear late-stage separation of survival curves was observed.In the immunotherapy subgroup,BEV-containing regimens achieved markedly better outcomes than non-BEV regimens,with DCR of 75.0%vs.48.8%,median OS of 18.9 vs.11.5 months,and median PFS of 13.8 vs.7.2 months(all P<0.001).Cox regression analysis showed that compared with chemotherapy alone,the triplet regimen significantly reduced the risk of death(HR=0.11)and disease progression(HR=0.25)(both P=0.002).Vascular invasion was identified as an adverse prognostic factor for PFS(HR=3.0,P=0.007).Conclusion:This multicenter real-world study demonstrated that combining immunotherapy with chemotherapy and targeted therapy significantly improves DCR and survival outcomes in patients with MSS/MSI-L/pMMR advanced CRC,with BEV-containing triplet regimens providing the most pronounced benefit.BEV may enhance immune responsiveness by modulating the tumor microenvironment and promoting effector T-cell infiltration,offering a promising therapeutic direction for"immune-cold"CRC.Prospective randomized studies are warranted to further validate its clinical value and define appropriate patient populations.

Objective To investigate the improvement of interleukin-1 receptor associated kinase(IRAK1)/nuclear factor κB(NF-κB)signaling pathway regulated by"srperficiality-origin matching acupoints"electroacupuncture on intestinal damage in diabetic rats and lipid metabolism.Methods SD rats were randomly separated into control group,diabetes group,diabetes+electroacupuncture group,diabetes+pcDNA group,diabetes+pcDNA-IRAK1 group,diabetes+electroacupuncture+pcDNA group,and diabetes+electroacupuncture+pcDNA-IRAK1 group,18 rats in each group.Except for the control group,rats in other groups were fed with high glucose and high fat diet and intraperitoneal injection of streptozotocin(STZ)to construct the model of diabetes rats.After successful modeling,rats in each group were treated every other day for 8 consecutive weeks.The weight,fasting blood glucose,serum triglycerides and total cholesterol levels of rats were detected.16S rRNA amplicon sequencing was applied to detect the relative abundance of rat gut microbiota;the intestinal permeability and water content of rats were tested.Immunohistochemistry was applied to detect the average optical densities of zonula occludens-1(ZO-1)proteins in small intestine tissue.Western blot was applied to detect the expression of IRAK1,phosphorylated nuclear factor inhibitory protein(p-IκBα),and phosphorylated nuclear factor B p65(p-NF-κB p65)proteins in rat small intestine tissue.Results Compared with the control group,the levels of fasting blood glucose,triglyceride,total cholesterol,relative abundances of Firmicutes,Proteobacteria,Actinomycetes,Allobaculum,fluorescein isothiocyanate(FITC)-glucan concentration,intestinal water content and the expression of IRAK1,p-IκBα,p-NF-κB p65 proteins in the diabetes group increased significantly(P<0.05).Weight,the relative abundance of Bacteroidetes,Lactobacillus,Romboutsia,Lachnospiraceae,Ruminocoaceae,the average optical densities of occludin and ZO-1 proteins decreased significantly(P<0.05).Compared with the diabetes group,the levels of fasting blood glucose,triglyceride,total cholesterol,relative abundances of Firmicutes,Proteobacteria,Actinomycetes,Allobaculum,FITC-glucan concentration,intestinal water content and the expression of IRAK1,p-IκBα,p-NF-κB p65 proteins in the diabetes+electroacupuncture group decreased significantly(P<0.05).Weight,the relative abundance of Bacteroidetes,Lactobacillus,Romboutsia,Lachnospiraceae,Ruminocoaceae,the average optical densities of occludin and ZO-1 proteins increased significantly(P<0.05),the change trend of corresponding indicators in the diabetes+pcDNA-IRAK1 group was opposite to the above(P<0.05).Compared with the diabetes+electroacupuncture group and the diabetes+electroacupuncture+pcDNA group,the levels of fasting blood glucose,triglyceride,total cholesterol,relative abundances of Firmicutes,Proteobacteria,Actinomycetes,Allobaculum,FITC-glucan concentration,intestinal water content and the expression of IRAK1,p-IκBα,p-NF-κB p65 proteins in the diabetes+electroacupuncture+pcDNA-IRAK1 group increased significantly(P<0.05).Weight,the relative abundance of Bacteroidetes,Lactobacillus,Romboutsia,Lachnospiraceae,Ruminocoaceae,the average optical densities of occludin and ZO-1 proteins decreased significantly(P<0.05).Conclusion"Srperficiality-origin matching acupoints"electroacupuncture may improve intestinal flora imbalance and intestinal barrier damage in diabetes rats by inhibiting IRAK1/NF-κB signaling pathway,and improve diabetic glucose and lipid metabolism.

Children with autism spectrum disorder(ASD)frequently have comorbid gastrointestinal problems,with constipation being the most prevalent.The onset and severity of constipation are closely related to the core symptoms of ASD,and improving constipation can alleviate these core symptoms.However,the mechanisms underlying comorbid constipation in ASD remain unclear.Multidisciplinary assessment is the foundation of clinical management for comorbid constipation in ASD.Targeted pharmacological therapy,dietary interventions,gut microbiota modulation,and complementary and alternative medicine interventions can be chosen for personalized treatment.This review summarizes the mechanisms,assessment,and clinical management of comorbid constipation in ASD and aims to provide a reference for comprehensive interventions in ASD.

Objective:To comprehensively analyze the current situation of the policy tools for primary healthcare medication continuity and security in China,and to provide advice for improving the policy system of primary healthcare medication continuity and security.Methods:Based on the theory of policy tools,a two-dimensional analysis framework of"policy tools-policy goals"was constructed.Results:A total of 407 policy text codes were generated from 58 policy texts included in the analysis.Among them,the supply-based policy tools were the most(41.03%),followed by environmental(37.59%)and demand-based(21.38%);the policy goals mainly focused on promoting the equipment and linkage of medication(21.84%),optimizing the types of medication(18.88%),and improving the centralized supply and distribution of medication(18.25%).Conclusions:Significant regional disparities exist in the design and implementation of China's primary healthcare medication continuity and security policies.Certain policy tools are absent,policy objectives lack comprehensive coverage,and coordination remains inadequate.It is suggested to optimize regional policy layouts through differentiated configuration and cross-regional coordination,enhance policy adaptability by refining policy tool combinations,strengthen weak segments and vertical coordination,promote the articulation of primary healthcare medication based on tight medical consortium,and finally build a systematic and dynamically adaptive primary healthcare medication continuity and security policy system.