OBJECTIVES: To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). METHODS: Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. RESULTS: In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). CONCLUSIONS Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans ; Methotrexate/toxicity* ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood* ; Male ; Female ; Child ; Child, Preschool ; gamma-Glutamyl Hydrolase/genetics* ; Antimetabolites, Antineoplastic/adverse effects* ; Infant ; Polymorphism, Genetic ; Adolescent ; Genotype ; Polymorphism, Single Nucleotide

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective:To elucidate the etiological and epidemiological characteristics and epidemiological patterns of viral acute respiratory infections (ARI) in Shanghai during 2023, with the aim of providing robust laboratory evidence for effective prevention and control strategies against related respiratory diseases and facilitating risk assessment.Methods:Respiratory pathogens were detected in the clinical surveillance specimens submitted by sentinel hospitals through multiplex PCR, as part of the multi-pathogen surveillance of acute respiratory infections in Shanghai during 2023. The obtained detection result were statistically analyzed in conjunction with sample information.Results:The positive detection rate of viral pathogens in 2023 was 21.17% (984/4 648), with rates of 33.53% (504/1 503) observed in ILI cases and 15.62% (480/3 145) in SARI cases. Influenza A virus (FluA) was the predominant virus detected, accounting for 13.7% (637/4 648). Other viruses identified in the surveillance samples included influenza B virus (Flu B), human rhinovirus/enterovirus (HRV/HEV), respiratory syncytial virus (RSV), human metapneumovirus (HMPV), parainfluenza virus (PIV), adenovirus (ADV) and human bocavirus (HBoV). Regarding temporal distribution, HRV/HEV and RSV exhibited the highest detection rates during the second quarter at 2.27% each (28/1 236). PIV had its peak during the third quarter at a rate of 2.49% (35/1 405), and HMPV showed prevalence mainly during the third and fourth quarters, with detection rates of 2.63% (37/1 405) and 2.35% (32/1 360), respectively.Conclusions:In acute respiratory infection surveillance cases in Shanghai in 2023, Flu A emerged as the predominant respiratory pathogen. The detection rate of HMPV ranked second only to Flu A, while other respiratory viruses such as HRV/HEV, RSV, and PIV were detected during different seasons and co-circulated. The prevalence of various respiratory viruses varied among different infected populations and over times.

Objective To investigate the clinical application value of colorectal double contrast-enhanced ultrasonography in diagnosing colorectal lesions and TN staging of colorectal cancer.Methods The clinical data of 479 patients with positive colorectal doulble contrast-enhanced ultrasonography results admitted to some hospital from November 2019 to December 2022 were selected retrospectively.The distributions of colorectal lesions and TN stages of colorectal cancer diagnosed by colorectal double contrast-enhanced ultrasonography were counted using the pathological results as the gold standard.The clinical diagnostic efficacy of colorectal double contrast-enhanced ultrasonography for TN staging of colorectal cancer was analyzed,and the ROC curves of the T and N staging models for diagnosing colorectal cancer were plotted by applying the 1VSRest strategy.SAS 9.4 statistical software was used to analyze the data.Results Among the 479 patients included,there were 462 cases in which the pathological diagnosis and ultrasound diagnosis were consistent with each other,with a compliance rate of 96.5％;there were 427 cases of colorectal cancer,accounting for 89.1％.Colorectal double contrast-enhanced ultrasonography had the accuracies being 96％,82％,63％,79％and 97％respectively for T1,T2,T3,T4a and T4b stages of colorectal cancer,with the micro-mean value of the accuracy being 83％.The accuracies were 62％,68％and 80％for NO,N1 and N2 stages of colorectal cancer,with the micro-mean value of the accuracy being 70％.The micro-mean value for T staing model to diagnose colorectal cancer was 0.92,and the macro-mean value was 0.84;the micro-mean value for N staing model to diagnose colorectal cancer was 0.88,and the macro-mean value was 0.85.Conclusion Colorectal doube contrast-enhanced ultrasonography is effective for diagnosing colorectal lesions,and provides references for TN staging of colorectal cancer.[Chinese Medical Equipment Journal,2024,45(7):62-66]

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

This study aimed to investigate the mechanism by which Shegan Mahuang Decoction(SGMH) and its bitter Chinese herbs(BCHs) regulated the lung-gut axis through the bitter taste receptor 14(TAS2R14)/secretory immunoglobulin A(SIgA)/thymic stromal lymphopoietin(TSLP) to intervene in the epithelial cell barrier of cold asthma rats. Fifty SD rats were randomly divided into the following five groups: normal group, model group, dexamethasone group, SGMH group, and BCHs group. A 10% ovalbumin(OVA) solution was used to sensitize the rats via subcutaneous injection on both sides of the abdomen and groin, combined with 2% OVA atomization and cold(2-4 ℃) stimulation to induce a cold asthma model in rats. The SGMH, BCHs, and dexamethasone groups were given corresponding treatments by gavage and nebulization, while the normal and model groups received normal saline by gavage and nebulization. After the final stimulation, pathological changes in the lung and intestine tissues were observed using hematoxylin-eosin(HE) and periodic acid-Schiff(PAS) staining. Lung function was assessed by measuring the ratio of forced expiratory volume in the first second to forced vital capacity(FEV1/FVC), the ratio of the average flow rate at 25%-75% of forced vital capacity to foned vital capacity(FEV25%-75%/FVC), the peak expiratory flow(PEF), and pulmonary resistance(RL). The levels of IL-4, IL-5, IL-13, and TNF-α in serum, and sIgA in serum, intestinal, and bronchial mucosa were detected by enzyme-linked immunosorbent assay(ELISA). The expression of TAS2R14 protein in lung tissue was detected by Western blot(WB). The content of short-chain fatty acids(SCFAs) in rat feces was determined by gas chromatography-mass spectrometry(GC-MS). The effect of TAS2R14/TSLP on lipopolysaccharide(LPS)-induced inflammation in epithelial cells in the BCHs group was observed, and the expression of TAS2R14 and TSLP in cells was detected by WB. Compared with the normal group, the model group showed reduced water intake, diet, and body weight, increased infiltration of inflammatory cells in the lung and intestinal tissues, goblet cell hyperplasia, significantly decreased FEV1/FVC, FEV25%-75%/FVC, and PEF, and significantly increased RL. Moreover, serum levels of IL-4, IL-5, IL-13, and TNF-α were elevated, and sIgA levels in serum, intestine, and bronchial mucosa were significantly decreased. TAS2R14 expression in lung tissues was inhibited, and the content of acetic acid, propionic acid, and butyric acid in feces was significantly reduced. In the LPS group, TSLP expression increased, and TAS2R14 expression decreased. Compared with the model group, the general condition of rats in the SGMH and BCHs groups improved, with reduced infiltration of inflammatory cells and goblet cell hyperplasia in the lung and intestinal tissues. FEV1/FVC, FEV25%-75%/FVC, and PEF significantly increased, and RL significantly decreased. Serum levels of IL-4, IL-5, IL-13, and TNF-α decreased, while sIgA levels in serum, intestine, and bronchial mucosa significantly increased, and TAS2R14 expression was activated in lung and intestinal tissues. The content of acetic acid, propionic acid, and butyric acid in feces significantly increased. Compared with the model group, the BCHs group and the agonist group showed inhibited TSLP expression and increased TAS2R14 expression. The results showed that both SGMH and BCHs could reduce lung and intestinal inflammatory reactions, improve lung function, and regulate the content of intestinal SCFAs in asthmatic rats. There was no significant difference in TAS2R14 protein expression between the SGMH and BCHs groups, indicating that the clinical efficacy of BCHs may be related to the activation of the bitter receptor TAS2R14 and the regulation of immune inflammatory mediators in lung and intestinal epithelial cells.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Rats, Sprague-Dawley ; Lung/metabolism* ; Asthma/metabolism* ; Cytokines/immunology* ; Male ; Receptors, G-Protein-Coupled/immunology* ; Epithelial Cells/metabolism* ; Thymic Stromal Lymphopoietin ; Immunoglobulin A, Secretory/genetics* ; Humans ; Cold Temperature

Aim To determine the effect of histamine H

Shegan Mahuang Decoction has been used in clinical practice for thousands of years, and is a classical formula for treating asthma and other respiratory diseases, with the effects of ventilating lung, dispersing cold, and relieving cough and asthma. This paper summarized the history, clinical application and mechanism of Shegan Mahuang Decoction, and predicted its quality markers(Q-markers) based on the "five principles" of Q-markers. The results suggested that irisflorentin, tectoridin, tectorigenin, irigenin, ephedrine, pseudoephedrine, asarinin, methyleugenol, shionone, epifriedelanol, tussilagone, 6-gingerol, trigonelline, cavidine, schizandrin, and schizandrin B could be used as Q-markers of Shegan Mahuang Decoction, which provided a basis for the quality control and subsequent research and development of Shegan Mahuang Decoction.
Humans ; Ephedra sinica ; Drugs, Chinese Herbal/pharmacology* ; Asthma/drug therapy* ; Lung ; Cough/drug therapy*

Objective: To compare the predictive efficacy of the two thrombosis risk assessment scores (Padua and IMPEDE scores) in venous thromboembolism (VTE) within 6 months in patients with newly diagnosed multiple myeloma (NDMM) in China. Methods: This study reviewed the clinical data of 421 patients with NDMM hospitalized in Beijing Jishuitan Hospital from April 2014 to February 2022. The sensitivity, specificity, accuracy, and Youden index of the two scores were calculated to quantify the thrombus risk assessment of VTE by the Padua and IMPEDE scores. The receiver operating characteristics curves of the two evaluation scores were drawn. Results: The incidence of VTE was 14.73%. The sensitivity, specificity, accuracy, and Youden index of the Padua score were 100%, 0%, 14.7%, and 0% and that of the IMPEDE score was 79%, 44%, 49.2%, and 23%, respectively. The areas under the curve of Padua and IMPEDE risk assessment scores were 0.591 and 0.722, respectively. Conclusion: IMPEDE score is suitable for predicting VTE within 6 months in patients with NDMM.
Humans ; Venous Thromboembolism/etiology* ; Multiple Myeloma/diagnosis* ; Risk Assessment ; Risk Factors ; ROC Curve ; Retrospective Studies