OBJECTIVES: To study genotype-phenotype correlations in children with FGFR3 variants and to improve clinical recognition of related disorders. METHODS: Clinical data of 95 patients aged 0-18 years harboring FGFR3 variants, confirmed by whole‑exome sequencing at Shanghai Children's Medical Center from January 2012 to December 2023, were retrospectively reviewed. Detailed phenotypic characterization was performed for 22 patients with achondroplasia (ACH) and 10 with hypochondroplasia (HCH). RESULTS: Among the 95 patients, 52 (55%) had ACH, 24 (25%) had HCH, 9 (9%) had thanatophoric dysplasia, 3 (3%) had syndromic skeletal dysplasia, 2 (2%) had severe achondroplasia with developmental delay and acanthosis nigricans, and 5 (5%) remained unclassified. A previously unreported FGFR3 variant, c.1663G>T, was identified. All 22 ACH patients presented with disproportionate short stature accompanied by limb dysplasia, commonly with macrocephaly, a depressed nasal bridge, bowed legs, and frontal bossing; complications were present in 17 (77%). The 10 HCH patients predominantly exhibited disproportionate short stature with limb dysplasia and depressed nasal bridge. CONCLUSIONS ACH is the most frequent phenotype associated with FGFR3 variants, and missense variants constitute the predominant variant type. The degree of FGFR3 activation appears to correlate with the clinical severity of skeletal dysplasia.
Humans ; Receptor, Fibroblast Growth Factor, Type 3/genetics* ; Child ; Male ; Child, Preschool ; Female ; Infant ; Adolescent ; Dwarfism/genetics* ; Achondroplasia/genetics* ; Lordosis/genetics* ; Infant, Newborn ; Retrospective Studies ; Genetic Association Studies ; Bone and Bones/abnormalities* ; Phenotype ; Limb Deformities, Congenital

Microplastics pose a serious threat to the environment and human health,but the circulating distribution and transport processes of microplastics in organisms have not been fully assessed.Therefore,it is of great significance to construct a probe that can image trace microplastics and visually monitor their circulation and transport in vivo.Afterglow semiconducting polymers are attractive for applications in biological imaging as they do not contain heavy metal ions,are easy to biodegrade and allow high signal-to-noise ratio afterglow imaging without continuous excitation.In this study,with styrene as reaction monomer,polyvinylpyrrolidone as surfactant,and sodium persulfate as initiator,afterglow polystyrene microspheres for in vivo imaging of microplastics were prepared.During the polymerization process,poly[(9,9-di(2-ethylhexyl)-9H-fluo-rene-2,7-vinylene)-co-(1-methoxy-4-(2-ethylhexyloxy)-2,5-phenylenevinylene)](PF-MEHPPV)and photosensitizer silicon 2,3-naphthalocyanine bis(trihexylsilyloxide)(NCBS)were co-doped into polystyrene microspheres.The prepared afterglow polystyrene microspheres exhibited an afterglow duration of 96 h and a tissue penetration depth of 1.8 cm.It was found that co-doping of PF-MEHPPV and NCBS had little effect on the particle size and Zeta potential of the microspheres,and allowed to monitor the afterglow luminescence signal in vivo for 24 h.Imaging of mouse organs after anatomy showed that the afterglow signal was still observed in the stomach of mice 48 h after gavage.This study provided a new method for imaging and tracing microplastics in vivo.

Diabetic peripheral neuropathy(DPN)is a group of neurodegenerative diseases involving the peripheral nervous system.Long chain non-coding RNA(lncRNA)is an important regulatory factor in normal life activities and disease development,widely involved in gene expression regulation,epigenetic regulation,transcription and control and other biological processes.In recent years,a large number of studies have found that lncRNAs can affect the development of DPN by participating in the pathogenesis of DPN such as metabolic disorders,oxidative stress,neuroinflammation,vascular damage,cell autophagy,apoptosis and so on.This paper elaborates on the regulatory role of lncRNAs in the pathogenesis of DPN,with a view to providing scientific references and new ideas for clinical research.

Aim To explore the protective effect of Zishen Huoxue Prescription on OGD/R-induced primary hippocampal neuron damage in rats and the possible mechanism. Methods After the isolated primary hippocampal neurons were identified by immunofluorescence, OGD/R induced neuronal damage, and the changes of autophagic flux at different re-oxygenation time were observed by confocal laser scanning microscopy. After OGD/R-induced primary hippocampal neurons were intervened with serum containing Zishen Huoxue Prescription, cell viability was detected by CCK-8, cell apoptosis was detected by flow cytometry, autophagosomes were detected by transmission electron microscopy, and autophagy-related protein expressions were detected by Western blot. Results 10% Zishen Huoxue Prescription-containing serum could significantly improve cell viability and reduce the proportion of cell apoptosis, increase the number of autophagosomes in neurons, and up-regulate the expression of autophagy-related protein PINK1, Parkin, and pATG16L1. Conclusions Zishen Huoxue Prescription can effectively resist OGD/R-induced apoptosis of primary hippocampal neurons in rats, and its effect may be related to the regulation of PINK1-Parkin pathway to promote mitophagy.

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans ; Consensus ; Critical Care/methods* ; Intensive Care Units ; Pain/drug therapy* ; Analgesics/therapeutic use* ; Delirium/therapy* ; Critical Illness

Objective: To analyse the efficacy of recombinant human growth hormone (rhGH) treatment in children born small for gestational age (SGA) with syndormic and non-syndormic short stature. Methods: The clinical data of 59 children born SGA who were diagnosed as short stature and admitted to the Center of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital from July 2012 to June 2021 were collected and analyzed. According to the 2019 consensus on short stature, they were divided into syndromic group and non-syndromic group. Before treatment and 6, 12, 18 and 24 months after treatment, height standard deviation score (Ht-SDS), difference of height standard deviation (∆Ht-SDS) and homeostasis model assessment-insulin resistance index (HOMA-IR) were compared between groups, while Ht-SDS and HOMA-IR were compared before and after treatment. Independent t test or Kruskal-Wallis test were used for comparison between the 2 groups, and paired t test or Mann-Whitney U test were used for the intra-group comparison. Results: Among the 59 cases, 37 were males and 22 females, aged (5.5±2.3) years. There was no significant difference in Ht-SDS after 12 months of treatment between 2 groups (0.9±0.4 vs. 1.2±0.4, t=1.68, P=0.104) or in height SDS after 24 months of treatment (1.4±0.7 vs. 1.9±0.5, t=1.52, P=0.151). After 12 months of treatment, the insulin resistance index of the non-syndromic group was significantly higher than that of the syndromic group (2.29 (1.43, 2.99) vs. 0.90 (0.55, 1.40), Z=-2.95, P=0.003). There were significant differences in Ht-SDS between 6 months and before treatment, 12 months and 6 months in syndromic type (Z=7.65, 2.83 P<0.001, P=0.020), but all were significant differences in non-syndromic type between 6 months and before treatment, 12 months and 6 months, 18 months and 12 months, 24 months and 18 months (Z=11.95, 7.54, 4.26, 3.83, all P<0.001). Conclusion: The efficacy of rhGH treatment in children born SGA is comparable between syndromic and non-syndromic short stature cases, but non-syndromic children treated with rhGH need more frequent follow-up due to the risk of insulin resistance.
Child ; Female ; Humans ; Male ; Body Height ; Gestational Age ; Human Growth Hormone/therapeutic use* ; Infant, Small for Gestational Age ; Insulin ; Insulin Resistance ; Recombinant Proteins ; Child, Preschool

Objective:To investigate the quality of rehabilitation medical service in tertiary general hospitals in Gansu Province. Methods:Stratified sampling was used to sample tertiary general hospitals in Gansu Province for on-site surveys in 2017. A quality evaluation index system was established in the view of medical service providers, including 17 indicators, based on Donabedian model and experts' opinions. Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) and Rank-sum Ratio were applied to make a comprehensive evaluation on the overall service quality of the hospital rehabilitation medical service. Results:A total of 27 tertiary general hospitals were sampled, in 13 cities/prefectures of Gansu Province. For the structure quality, the compliance rate of the business operation area and the number of beds in the rehabilitation medicine department were 77.78% and 51.85% respectively; while the compliance rates of the physicians, therapists and nurses were all less than 50%. For the process and results quality, the compliance rates were all more than 85%. For the overall quality of rehabilitation medical service, five hospitals were classified as Good, located in Lanzhou, Tianshui and Jiayuguan; 18 hospitals were classified as Medium, located in Longnan, Longdong, Lanzhou and surround, Linxia and Hexi regions; four hospitals classified as Poor, located in Lanzhou and Tianshui. Conclusion:The overall quality of rehabilitation services in the tertiary general hospitals of Gansu Province needs to be improved, and the development of rehabilitation services is uneven in various regions. Comprehensive evaluation provides an important reference to promote the rational distribution of rehabilitation medical resources and improve the quality of rehabilitation medical services.

Objectives: To evaluate the immunogenicity of Methods: Protein extracts from Results: Immunization with Conclusion This is the advanced study to investigate the immunogenicity of
Animals ; Antibodies, Bacterial/immunology* ; Antigens, Bacterial/immunology* ; Bacterial Proteins/immunology* ; Cross Reactions ; Cytokines/immunology* ; Female ; Genome, Bacterial ; Immunoglobulin G/immunology* ; Immunoglobulin M/immunology* ; Macrophages/immunology* ; Mice, Inbred BALB C ; Mycobacterium avium Complex/immunology* ; Mycobacterium tuberculosis/immunology* ; Tuberculosis Vaccines/administration & dosage* ; Whole Genome Sequencing

Qishen Yiqi Dripping Pills(QSYQ) are used clinically to treat various myocardial ischemic diseases, such as angina pectoris, myocardial infarction, and heart failure; however, the molecular mechanism of QSYQ remains unclear, and the scientific connotation of traditional Chinese medicine(TCM) compatibility has not been systematically explained. The present study attempted to screen the critical pathway of QSYQ in the treatment of myocardial ischemia by network pharmacology and verify the therapeutic efficacy with the oxygen-glucose deprivation(OGD) model, in order to reveal the molecular mechanism of QSYQ based on the critical pathway. The key targets of QSYQ were determined by active ingredient identification and target prediction, and underwent pathway enrichment analysis and functional annotation with David database to reveal the biological role and the critical pathway of QSYQ. Cell counting Kit-8(CCK-8), lactate dehydrogenase(LDH), and Western blot tests were launched on high-content active ingredients with OGD cell model to reveal the molecular mechanism of QSYQ based on the critical pathway. The results of network pharmacology indicated that QSYQ, containing 18 active ingredients and 82 key targets, could protect cardiomyocytes by regulating biological functions, such as nitric oxide biosynthesis, apoptosis, inflammation, and angiogenesis, through TNF signaling pathway, HIF-1 signaling pathway, PI3 K-Akt signaling pathway, etc. HIF-1 signaling pathway was the critical pathway. As revealed by CCK-8 and LDH tests, astragaloside Ⅳ, salvianic acid A, and ginsenoside Rg_1 in QSYQ could enhance cell viability and reduce LDH in the cell supernatant in a concentration-dependent manner(P<0.05). As demonstrated by the Western blot test, astragaloside Ⅳ significantly down-regulated the protein expression of serine/threonine-protein kinase(Akt1) and hypoxia-inducible factor 1α(HIF-1α) in the HIF-1 signaling pathway, and up-regulated the protein expression of vascular endothelial growth factor A(VEGFA). Salvianic acid A significantly down-regulated the protein expression of upstream phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3 CA) and downstream HIF-1α of Akt1. Ginsenoside Rg_1 significantly down-regulated the expression of HIF-1α protein and up-regulated the expression of VEGFA. The therapeutic efficacy of QSYQ on myocardial ischemia was achieved by multiple targets and multiple pathways, with the HIF-1 signaling pathway serving as the critical one. The active ingredients of QSYQ could protect cardiomyocytes synergistically by regulating the targets in the HIF-1 signaling pathway to inhibit its expression.
Drugs, Chinese Herbal/pharmacology* ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Myocardial Ischemia/genetics* ; Signal Transduction ; Vascular Endothelial Growth Factor A

The balance of glucose and lipid metabolism is a coordinated result of multiple factors and organs, and is one of the fundamental requirements for the maintenance of human health. As the most important organ for human metabolism, liver plays a key role in regulating glucose and lipid metabolism. With the advances of researches, the number of publications related to hepatic glucose and lipid metabolism has increased rapidly, which posed a challenge for grasping the hot research topics and developmental trends of hepatic glucose and lipid metabolism in a short time. To solve such problem, we developed an information analysis method, which systematically analyzes the research status, research techniques, and hot research topics of the hepatic glucose and lipid metabolism research field through Medical Subject Headings (MeSH) of related papers and high-throughput experimental data. The results showed that the number of publications related to hepatic glucose and lipid metabolism, especially publications by Chinese scholars, has increased dramatically in this century, along with the remarkable increment of the numbers of authors and affiliations per paper. Such increment is in part positively correlated with the impact of publications. Nowadays, various types of high-throughput experimental techniques have become the main research methods for genetic studies of hepatic glucose and lipid metabolism. Transcription factors, such as peroxisome proliferator-activated receptors (PPARs), sterol regulatory element binding proteins (SREBPs), and NF-E2-related factor 2 (Nrf2), have become the new research hotspots. These results systematically showed the current focuses and developmental trends of hepatic glucose and lipid metabolism research, and the data analysis method developed in this work can also be applied to other research fields.
Glucose/metabolism* ; Humans ; Lipid Metabolism ; Liver