ObjectiveTo evaluate the therapeutic effect of Huazhuo SanJie Chubi presciption （HSCD） on chronic gouty arthritis （CGA） rats with low-grade inflammation and to explore the underlying mechanism with a focus on macrophage polarization. MethodsThe 41 male 6-week-old SD rats were randomly allocated， using the random number table， to a normal group （n=8） and a model group （n =33）. CGA with low-grade inflammation was induced in the model group by daily gavage of potassium oxonate （250 mg·kg^-1·d^-1） and hypoxanthine （300 mg·kg^-1·d^-1）， combined with intra-articular injection of a monosodium urate （MSU） crystal suspension （50 μL， 25 g·L^-¹） into the left ankle twice weekly. After 4 weeks of modeling， 3 rats were randomly selected from each group for model validation. The remaining successfully modeled rats were randomly divided into a model group， an HSCD group （10.35 g·kg^-1·d^-1， gavage once daily）， an M1 polarization agonist group （L-methionine sulfoximine， 300 mg·kg^-1， subcutaneous injection every other day）， an M1 polarization agonist + HSCD group， an M2 polarization inhibitor group （PD0325901， 10 mg·kg^-1·d^-1， gavage once daily）， and M2 polarization inhibitor + HSCD group. The corresponding drug or drug combination was administered according to group assignment， whereas rats in the normal and model groups received 0.5% carboxymethyl cellulose sodium （CMC-Na） vehicle （10.35 g·kg^-1·d^-1， gavage once daily）. All interventions were continued for four weeks. During the intervention period， except for the normal group， potassium oxonate （250 mg·kg⁻¹） and hypoxanthine （300 mg·kg^-1） were co-administered by gavage every other day to maintain the model. At the end of treatment， serum uric acid （SUA）， ankle joint diameter and joint swelling index were measured. The levels of high-sensitivity C-reactive protein （hs-CRP）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， chemokine C-C motif ligand 2 （CCL2）， S100 calcium-binding protein A8/A9 （S100A8/A9）， interleukin-10 （IL-10） and arginase-1 （Arg-1） in serum and joint fluid were determined by enzyme-linked immunosorbent assay （ELISA）. High-frequency ultrasound was used to assess MSU deposition in the ankle joint. Hematoxylin-eosin （HE） staining was performed to evaluate synovial histopathological changes. Quantitative Real-time PCR and immunofluorescence were used to detect the mRNA and protein expression of the M1 macrophage polarization markers inducible nitric oxide synthase （iNOS） and the M2 macrophage polarization marker scavenger receptor cysteine-rich type 1 protein M130 （CD163） in synovial tissue. ResultsCompared with the normal group， the model group showed significantly elevated SUA level and joint swelling index， and increased levels of pro-inflammatory cytokines， CCL2， and S100A8/A9 in both serum and joint fluid （P<0.05）， accompanied by MSU deposition and synovial inflammation in the ankle joint. The mRNA and protein expression levels of macrophage polarization M1/M2 markers iNOS and CD163 in synovial tissues were also significantly up-regulated （P<0.05）. Compared with model group， rats in HSCD group had significantly lower SUA levels， attenuated joint swelling， reduced serum levels of pro-inflammatory cytokines， and decreased levels of CCL2 and S100A8/A9 in both serum and joint fluid， accompanied with alleviated MSU deposition and synovial inflammation （P<0.05）. HSCD markedly downregulated the mRNA and protein expression of M1 marker iNOS （P<0.05）， whereas it had no significant effect on the expression of M2 marker CD163. Compared with the M1 polarization agonist group， the M1 polarization agonist + HSCD group showed significantly reduced joint swelling， lower serum levels of pro-inflammatory cytokines， and decreased levels of CCL2 and S100A8/A9 in joint fluid （P<0.05）. In addition， synovial inflammatory cell infiltration and angiogenesis were attenuated， and iNOS mRNA and protein expression levels were significantly reduced （P<0.05）. Compared with the M2 polarization inhibitor group， the M2 polarization inhibitor + HSCD group exhibited reduced joint swelling， decreased levels of CCL2 and S100A8/A9 in joint fluid and ameliorated synovial inflammation （P<0.05）， whereas the levels of anti-inflammatory mediators （IL-10， Arg-1） and CD163 mRNA and protein expression were not significantly increased. ConclusionHSCD alleviates low-grade inflammation in CGA rats， at least in part， by inhibiting macrophage polarization toward the M1 phenotype.

Bronchial asthma is a kind of heterogeneous respiratory disease, and its emergency diagnosis and treatment face multiple challenges. This article, based on the evolution of domestic and international guidelines and consensus, explores the current confusions and shortcomings in the emergency treatment of asthma, considering the clinical specifics of emergency medicine. Due to the limited applicability of classifications such as "refractory asthma" and "severe asthma" in emergency settings, as well as the complex diagnostic process that makes clinical operations difficult, it is proposed to unify the diagnostic terminology as "acute exacerbation of bronchial asthma" (mild, moderate, severe, critical severe) in emergency work. Assessment indicators, such as arterial oxygen partial pressure (PaO₂), partial pressure of arterial carbon dioxide (PaCO₂), arterial oxygen saturation (SaO₂), peak expiratory flow (PEF). Simplified were simplified. The clinical diagnosis and emergency management should prioritize the approach outlined in the Chinese guidelines for the prevention and treatment of bronchial asthma (basic version). For mild-to-moderate and severe exacerbations, a tiered treatment strategy is recommended, focusing on rapid symptom relief, standardized glucocorticoid use, and dynamic efficacy assessment. Additionally, the urgent need for formulating a Chinese expert consensus on emergency diagnosis and treatment of bronchial asthma is highlighted, along with promoting multicenter prospective studies to optimize emergency protocols and improve patient prognosis.
Humans ; Asthma/therapy* ; Practice Guidelines as Topic

OBJECTIVE: To analyze the clinical and genetic characteristics of a Chinese pedigree affected with congenital Isolated growth hormone deficiency (IGHD). METHODS: A pedigree presenting with Pituitary stalk interruption syndrome (PSIS) (including the proband, his two younger sisters and both parents) who had visited the Capital Institute of Pediatrics Affiliated to Capital Medical University in September 2020 was selected as the study subject. Clinical data were collected. Peripheral blood samples were collected from the proband and his family members. Following the extraction of genomic DNA, whole-exome sequencing (WES) was carried out, and candidate variants were validated by Sanger sequencing. The pathogenicity of the candidate variants was classified based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the Institute Pediatrics of Capital Medical University (Ethics No.: SHERLL2025033). RESULTS: The proband and one younger sister (Ⅱ3) presented with growth retardation, short stature, and a doll-like facies. Another younger sister (Ⅱ2) and both parents had normal heights and appearance. Sanger sequencing confirmed that the proband and his younger sister (Ⅱ3) both harbored compound heterozygous variants of the GHRHR gene, namely c.776C>A (p.T259K) and c.1166G>A (p.R389Q). The other younger sister (Ⅱ2) and the parents were heterozygous carriers. The c.1166G>A (p.R389Q) variant was unreported previously. Based on the guidelines from the ACMG, it was classified as variant of uncertain significance (PM2_Supporting+BP4). Bioinformatics analysis indicated a deleterious effect on the protein function. CONCLUSION Variants of the GHRHR gene probably underlay the pathogenesis of IGHD in this pedigree. Above finding has provided a basis for the clinical diagnosis and genetic counseling for this family.
Child ; Female ; Humans ; Male ; China ; Dwarfism, Pituitary/genetics* ; Exome Sequencing ; Human Growth Hormone/deficiency* ; Mutation ; Pedigree ; Receptors, Neuropeptide/genetics* ; Receptors, Pituitary Hormone-Regulating Hormone/genetics* ; East Asian People/genetics*

Objective:To identify the risk factors of venous thromboembolism (VTE) in postoperative renal transplantation recipients by Meta-analysis, and to provide evidence-based reference for clinical staff to develop early VTE prevention strategies.Methods:PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, VIP database, Wanfang database and Chinese Biomedical Literature Database were searched to collect the studies on the risk factors of postoperative VTE in kidney transplant recipients. The search period was from the establishment of the database to March 10, 2024. After literature screening, data extraction and quality evaluation were conducted independently by two researchers, Meta-analysis was performed using RevMan 5.3 software.Results:A total of 15 literatures with 20 influencing factors were included. Meta-analysis showed that age ( MD = 6.36, 95% CI 2.56-10.17, P<0.05), body mass index ( MD = 1.83, 95% CI 0.15-3.50, P<0.05), VTE history ( OR = 2.04, 95% CI 1.08-3.86, P<0.05), blood transfusion history ( OR = 3.77, 95% CI 2.43-5.83, P<0.05), glomerular filtration rate ( MD = -5.54, 95% CI -9.93 - -0.91, P<0.05), donor age ( MD = 3.18, 95% CI 1.10-5.25, P<0.05), combination of malignant tumor ( OR = 2.87, 95% CI 1.45-5.68, P<0.05), end-stage renal disease as polycystic kidney disease ( OR = 1.76, 95% CI 1.39-2.22, P<0.05), and interstitial nephritis ( OR = 1.60, 95% CI 1.06-2.40, P<0.05) were the influencing factors for postoperative VTE in renal transplant recipients. Conclusions:Clinical medical staff should actively identify high-risk groups for VTE after kidney transplantation by considering the 8 influencing factors determined by this study, and take targeted measures early to reduce the risk of postoperative VTE.

Objective To observe the effects of growth differentiation factor-15(GDF-15)on collateral circulation and cardiac function in rats with acute myocardial infarction(AMI)in relation to the nitric oxide(NO)/cyclic guanosine monophosphate(cGMP)/protein kinase G(PKG)signaling pathway.Methods An AMI rat model was constructed by ligating the left anterior descending coronary artery.After modeling,the rats were divided randomly into Sham,Model,and GDF-15 groups(n=12 rats per group).Rats in the GDF-15 group were injected intraperitoneally with recombinant GDF-15 protein,and the other two groups were injected with the same amount of normal saline twice a week for 8 consecutive weeks.Cardiac function was detected by echocardiography.Pathological damage to rat myocardial tissue was detected by hematoxylin and eosin staining and the collateral circulation was observed by CD31 immunohistochemical staining.Vascular endothelial growth factor(VEGF)mRNA expression was detected by quantitative polymerase chain reaction.Transcriptomic sequencing of heart tissues in the model and GDF-15 groups was performed and differentially expressed genes(DEGs)were screened.Pathway enrichment analysis of the DEGS was carried out according to the Kyoto Encyclopedia of Genes and Genomes(KEGG).Nitric oxide(NO),reactive oxygen species(ROS),and cGMP were detected using kits,and VEGF,endothelial nitric oxide synthase(eNOS)monomer,p-eNOSser1177monomer,eNOS dimer,and PKG protein were detected by Western blot.Results Left ventricular end-systolic diameter(LVEDs)and left ventricular end-diastolic diameter(LVEDd)were increased(P＜0.001),and left ventricular ejection fraction(LVEF)and the short-axis shortening rate(FS)were decreased in the Model group compared with the Sham group(P＜0.001).Myocardial cell necrosis was more severe,vascular density in the infarcted area was decreased(P＜0.05),but VEGF mRNA and protein levels were no change(P＞0.05),and levels of NO,eNOS dimer,cGMP,and PKG protein were decreased(P＜0.05),and expression levels of ROS,eNOS monomer,and p-eNOSser1177 monomer were increased(P＜0.05).LVEDs and LVEDd decreased(P＜0.05),LVEF and FS increased(P＜0.01),myocardial cell necrosis was relieved,vascular density in the infarcted area increased significantly(P＜0.0001),and VEGF mRNA levels increased(P＜0.0001),compared with the Model group.Transcriptomic sequencing identified 324 DEGs,including 230 up-regulated and 94 down-regulated genes.According to KEGG enrichment analysis,the cGMP-PKG signaling pathway showed the most significant difference in the T20 pathway.VEGF,NO,eNOS dimer,cGMP,and PKG protein levels were all increased(P＜0.05),while ROS,eNOS monomer,and p-eNOSser1177 monomer were decreased in the GDF-15 group(P＜0.05).Conclusions GDF-15 can promote collateral circulation in ischemic myocardium and improve cardiac function by inhibiting eNOS decoupling and activating the NO/cGMP/PKG pathway.

Objective To observe the effects of growth differentiation factor-15(GDF-15)on collateral circulation and cardiac function in rats with acute myocardial infarction(AMI)in relation to the nitric oxide(NO)/cyclic guanosine monophosphate(cGMP)/protein kinase G(PKG)signaling pathway.Methods An AMI rat model was constructed by ligating the left anterior descending coronary artery.After modeling,the rats were divided randomly into Sham,Model,and GDF-15 groups(n=12 rats per group).Rats in the GDF-15 group were injected intraperitoneally with recombinant GDF-15 protein,and the other two groups were injected with the same amount of normal saline twice a week for 8 consecutive weeks.Cardiac function was detected by echocardiography.Pathological damage to rat myocardial tissue was detected by hematoxylin and eosin staining and the collateral circulation was observed by CD31 immunohistochemical staining.Vascular endothelial growth factor(VEGF)mRNA expression was detected by quantitative polymerase chain reaction.Transcriptomic sequencing of heart tissues in the model and GDF-15 groups was performed and differentially expressed genes(DEGs)were screened.Pathway enrichment analysis of the DEGS was carried out according to the Kyoto Encyclopedia of Genes and Genomes(KEGG).Nitric oxide(NO),reactive oxygen species(ROS),and cGMP were detected using kits,and VEGF,endothelial nitric oxide synthase(eNOS)monomer,p-eNOSser1177monomer,eNOS dimer,and PKG protein were detected by Western blot.Results Left ventricular end-systolic diameter(LVEDs)and left ventricular end-diastolic diameter(LVEDd)were increased(P＜0.001),and left ventricular ejection fraction(LVEF)and the short-axis shortening rate(FS)were decreased in the Model group compared with the Sham group(P＜0.001).Myocardial cell necrosis was more severe,vascular density in the infarcted area was decreased(P＜0.05),but VEGF mRNA and protein levels were no change(P＞0.05),and levels of NO,eNOS dimer,cGMP,and PKG protein were decreased(P＜0.05),and expression levels of ROS,eNOS monomer,and p-eNOSser1177 monomer were increased(P＜0.05).LVEDs and LVEDd decreased(P＜0.05),LVEF and FS increased(P＜0.01),myocardial cell necrosis was relieved,vascular density in the infarcted area increased significantly(P＜0.0001),and VEGF mRNA levels increased(P＜0.0001),compared with the Model group.Transcriptomic sequencing identified 324 DEGs,including 230 up-regulated and 94 down-regulated genes.According to KEGG enrichment analysis,the cGMP-PKG signaling pathway showed the most significant difference in the T20 pathway.VEGF,NO,eNOS dimer,cGMP,and PKG protein levels were all increased(P＜0.05),while ROS,eNOS monomer,and p-eNOSser1177 monomer were decreased in the GDF-15 group(P＜0.05).Conclusions GDF-15 can promote collateral circulation in ischemic myocardium and improve cardiac function by inhibiting eNOS decoupling and activating the NO/cGMP/PKG pathway.

Objective:To identify the risk factors of venous thromboembolism (VTE) in postoperative renal transplantation recipients by Meta-analysis, and to provide evidence-based reference for clinical staff to develop early VTE prevention strategies.Methods:PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, VIP database, Wanfang database and Chinese Biomedical Literature Database were searched to collect the studies on the risk factors of postoperative VTE in kidney transplant recipients. The search period was from the establishment of the database to March 10, 2024. After literature screening, data extraction and quality evaluation were conducted independently by two researchers, Meta-analysis was performed using RevMan 5.3 software.Results:A total of 15 literatures with 20 influencing factors were included. Meta-analysis showed that age ( MD = 6.36, 95% CI 2.56-10.17, P<0.05), body mass index ( MD = 1.83, 95% CI 0.15-3.50, P<0.05), VTE history ( OR = 2.04, 95% CI 1.08-3.86, P<0.05), blood transfusion history ( OR = 3.77, 95% CI 2.43-5.83, P<0.05), glomerular filtration rate ( MD = -5.54, 95% CI -9.93 - -0.91, P<0.05), donor age ( MD = 3.18, 95% CI 1.10-5.25, P<0.05), combination of malignant tumor ( OR = 2.87, 95% CI 1.45-5.68, P<0.05), end-stage renal disease as polycystic kidney disease ( OR = 1.76, 95% CI 1.39-2.22, P<0.05), and interstitial nephritis ( OR = 1.60, 95% CI 1.06-2.40, P<0.05) were the influencing factors for postoperative VTE in renal transplant recipients. Conclusions:Clinical medical staff should actively identify high-risk groups for VTE after kidney transplantation by considering the 8 influencing factors determined by this study, and take targeted measures early to reduce the risk of postoperative VTE.

Objective To explore the effect and mechanism of Baicalein in the treatment of hyperuricemia.Methods The mouse model of hyperuricemia was established by yeast extract combined with potassium oxazinate.The effect and potential mechanism of Baicalein in the treatment of hyperuricemia were studied by biochemical indexes,pathological changes,non-target metabonomics and network pharmacology.Results Baicalein could reduce the contents of serum uric acid,creatinine and blood urea nitrogen,reduce the inflammatory injury of renal tissue,up-regulate the expression level of uric acid excretion protein and down-regulate the expression level of uric acid reabsorption protein.Nine disease-related targets such as BCL2,SIRT1 and XDH were screened by network pharmacology.Six key metabolic pathways including nicotinic acid and nicotinamide metabolism,caffeine metabolism and purine metabolism were screened by metabonomics analysis.Conclusions Baicalein can treat hyperuricemia and reduce renal injury,and its mechanism may be related to the metabolic pathways of nicotinic acid and nicotinamide regulated by SIRT1 and quinolinate.

Objective To determine the blood physiological and biochemical indexes in the inbred SHANXI MU strain of spontaneous type 2 diabetes(T2DM)Chinese hamsters.Methods Chinese hamsters with spontaneously developed T2DM and normal hamsters(n=10 hamsters per group),aged 12 months,were selected for the study.Fasting blood samples were collected and 15 physiological parameters and 16 biochemical indicators were analyzed using a Sysmex XT automated hematology analyzer and Hitachi fully automatic biochemical analyzer.Results The white cell count,red cell count,platelet count,hemoglobin level,alanine transaminase,aspartate transaminase,glutamate,total cholesterol,triglycerides,and uric acid all differed significantly between the diabetic and control groups(P＜0.05).Conclusions The change of blood physiological and biochemical indexes in the Chinese hamster spontaneous T2DM model were in line with the trend in human T2DM incidence,thus providing basic data for the application of this model.

The clinical data of a patient with Klinefelter syndrome (KS) complicated by partial androgen insensitivity syndrome (PAIS) was retrospectively analyzed.The patient, a 2-month-and-22-day-old baby, was admitted to Children′s Hospital Affiliated to Zhengzhou University due to abnormal external genitalia in October 2021.Upon birth, the patient exhibited abnormal external genitalia, manifested as clitoral hypertrophy.Hormonal examinations were consistent with those of peers, while chromosomal analysis revealed 47, XXY.Due to the severe undermasculinization, whole exome sequencing was conducted, indicating a heterozygous variant of the AR gene (c.1847G>A, p.Arg616His). The patient was diagnosed with PAIS, and her elder sister was diagnosed with complete androgen insensitivity syndrome.For further treatment, a multidisciplinary comprehensive evaluation is needed.This is a rare case of KS combined with PAIS, suggesting the possibility of AR gene mutations in KS children with severe undermasculinization.