Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective:To analyze the clinical features of children with infection-related eosinophilic lung diseases (ELD) caused by common respiratory pathogens.Methods:A retrospective cohort study was conducted. The clinical features, auxiliary examinations, treatments, and prognoses of 134 children with infection-related ELD caused by common respiratory pathogens at Yuying Children′s Hospital from January 2014 to June 2024 were collected. Participants were divided into the mild and severe groups based on whether the proportion of eosinophils in bronchoalveolar lavage fluid (BALF) exceeded 0.25. Chi-square test or Fisher exact test was used to analyze the differences between the two groups, and Logistic regression was performed to examine the correlation between BALF eosinophilia and the clinical outcomes.Results:Among the 134 children, 73 were males and 61 were females, with an age of 6.9 (4.6, 8.8) years on admission. A total of 154 pathogen detections were recorded, including 116 cases (75.3%) of Mycoplasma pneumoniae, 8 cases (5.2%) of influenza A virus, 6 cases (3.9%) of Streptococcus pneumoniae, and 6 cases (3.9%) of Chlamydia pneumoniae, among others. The percentage of eosinophils in the BALF of all children was 0.10 (0.07, 0.15). There were 117 cases in the mild group and 17 cases in the severe group. Compared with the mild group, significantly greater proportion of children in the severe group presented dyspnea (10/17 vs. 17.1% (20/117)), wheezing (7/17 vs. 8.5% (10/117)), respiratory failure (8/17 vs. 7.7% (9/117)), single lobe ≥2/3 consolidation (7/17 vs. 12.8% (15/117)), atelectasis (7/17 vs. 12.0% (14/117)), pleural effusion (7/17 vs. 16.2% (19/117)), plastic bronchiolitis (4/17 vs. 4.3% (5/117)), and systemic corticosteroid prescription (14/17 vs. 51.3% (60/117)) (all P<0.05). Univariate Logistic regression analysis revealed that severe eosinophilia in BALF was significantly associated with an elevated risk of respiratory failure ( OR=10.67, 95% CI 3.31-34.38, P<0.001), single lobe ≥2/3 consolidation ( OR=4.76, 95% CI 1.57-14.41, P=0.006), atelectasis ( OR=5.15, 95% CI 1.69-15.72, P=0.004), pleural effusion ( OR=3.61, 95% CI 1.22-10.67, P=0.020), and plastic bronchitis ( OR=6.89, 95% CI 1.64-28.94, P=0.008). Among the 126 children who were followed up, 106 cases (84.1%) were cured, 20 cases (15.9%) improved, and no relapses or deaths occurred. Conclusions:Mycoplasma pneumoniae and influenza A virus are common pathogens in children with infection-related ELD and the percentage of eosinophils in BALF is mildly increased, and the severe cases exhibit more severe clinical features and more significant pulmonary abnormalities, such as lobar consolidation and lung atelectasis. The prognosis is generally favorable.

Listeria brainstem encephalitis with myelitis is extremely rare in clinical practice.Since the clinical manifestations are non-specific,MRI is helpful for diagnosis.Positive cerebrospinal fluid culture is considered the gold standard for diagnosis.This article reports a case of an immunocompetent individual with listeria brainstem encephalitis with myelitis,aiming to enhance the awareness of this condition.
Humans ; Brain Stem/pathology* ; Diagnostic Errors ; Encephalitis/complications* ; Encephalomyelitis, Acute Disseminated/diagnosis* ; Listeriosis/complications* ; Myelitis/complications*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective:To analyze the clinical features of children with infection-related eosinophilic lung diseases (ELD) caused by common respiratory pathogens.Methods:A retrospective cohort study was conducted. The clinical features, auxiliary examinations, treatments, and prognoses of 134 children with infection-related ELD caused by common respiratory pathogens at Yuying Children′s Hospital from January 2014 to June 2024 were collected. Participants were divided into the mild and severe groups based on whether the proportion of eosinophils in bronchoalveolar lavage fluid (BALF) exceeded 0.25. Chi-square test or Fisher exact test was used to analyze the differences between the two groups, and Logistic regression was performed to examine the correlation between BALF eosinophilia and the clinical outcomes.Results:Among the 134 children, 73 were males and 61 were females, with an age of 6.9 (4.6, 8.8) years on admission. A total of 154 pathogen detections were recorded, including 116 cases (75.3%) of Mycoplasma pneumoniae, 8 cases (5.2%) of influenza A virus, 6 cases (3.9%) of Streptococcus pneumoniae, and 6 cases (3.9%) of Chlamydia pneumoniae, among others. The percentage of eosinophils in the BALF of all children was 0.10 (0.07, 0.15). There were 117 cases in the mild group and 17 cases in the severe group. Compared with the mild group, significantly greater proportion of children in the severe group presented dyspnea (10/17 vs. 17.1% (20/117)), wheezing (7/17 vs. 8.5% (10/117)), respiratory failure (8/17 vs. 7.7% (9/117)), single lobe ≥2/3 consolidation (7/17 vs. 12.8% (15/117)), atelectasis (7/17 vs. 12.0% (14/117)), pleural effusion (7/17 vs. 16.2% (19/117)), plastic bronchiolitis (4/17 vs. 4.3% (5/117)), and systemic corticosteroid prescription (14/17 vs. 51.3% (60/117)) (all P<0.05). Univariate Logistic regression analysis revealed that severe eosinophilia in BALF was significantly associated with an elevated risk of respiratory failure ( OR=10.67, 95% CI 3.31-34.38, P<0.001), single lobe ≥2/3 consolidation ( OR=4.76, 95% CI 1.57-14.41, P=0.006), atelectasis ( OR=5.15, 95% CI 1.69-15.72, P=0.004), pleural effusion ( OR=3.61, 95% CI 1.22-10.67, P=0.020), and plastic bronchitis ( OR=6.89, 95% CI 1.64-28.94, P=0.008). Among the 126 children who were followed up, 106 cases (84.1%) were cured, 20 cases (15.9%) improved, and no relapses or deaths occurred. Conclusions:Mycoplasma pneumoniae and influenza A virus are common pathogens in children with infection-related ELD and the percentage of eosinophils in BALF is mildly increased, and the severe cases exhibit more severe clinical features and more significant pulmonary abnormalities, such as lobar consolidation and lung atelectasis. The prognosis is generally favorable.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

OBJECTIVE: To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN). METHODS: A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014. RESULTS: A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer. CONCLUSIONS No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.
Humans ; Retrospective Studies ; Incidence ; Carcinoma, Hepatocellular ; Liver Neoplasms/epidemiology* ; Kidney Diseases/chemically induced* ; Aristolochic Acids/adverse effects*

Mutations in myosin heavy chain 7(MYH7)and myosin binding protein C3(MYBPC3)genes encoding thick filaments are the main cause of hypertrophic cardiomyopathy(HCM),while a small part of HCM is caused by mutations of troponin C1,slow skeletal and cardiac type(TNNC1),troponin T2,cardiac type(TNNT2),troponin I3,cardiac type(TNNI3),actin alpha cardiac muscle 1(ACTC1),and tropomyosin 1(TPM1)genes encoding thin filaments.In this review,we mainly introduce the detailed mechanism and research status of HCM caused by mutations of the gene encoding cardiomyocyte sarcomere in the past few years,in order to provide reference for further study of the pathogenesis and treatment of HCM.