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.

This study was aimed at exploring the prevalence and drug sensitivity of Gordonia strains isolated from sputum samples in Henan Province,to provide data to aid in the prevention and treatment of Gordonia infection.A combination of 16S rDNA and sec A1 gene sequencing was used to identify the isolated strains,and susceptibility to16 drugs was determined with the broth microdilution method.A total of 21 strains were identified through 16S rDNA gene and sec A1 gene sequencing,including five strains of Gordonia broncians,eight strains of Gordonia paraphernivans,seven strains of Gordonia sputi,and one strain of Gordonia aichiensis.Drug sensi-tivity testing showed high Gordonia sensitivity to drugs such as ceftriaxone,linezolid,doxycycline,amoxicillin/clavulanic acid,mino-cycline,cefotaxime,trimethoprim/sulfamethoxazole,imipenem,tobramycin,and clarithromycin.The sensitivity rates of the isolated strains were 90.48%(19/21),100%(21/21),90.48%(19/21),90.48%(19/21),95.24%(20/21),90.48%(19/21),90.48%(19/21),90.48%(19/21),and 95.24%(20/21),respectively.Gordonia showed high resistance to rifampicin and cefepime,with rates of 28.57%(6/21)and 19.05%(4/21),respectively.Meanwhile,the resistance varied among bacterial strains.The resistance rate of G.sputi to rifampicin reached 71.43%(5/7),whereas that of G.parapffinivoras to cefepime was 37.5%(3/8).The main species of Gordo-nia isolated from sputum samples of patients in Henan Province were G.bronchialis,G.paraffinivoras,G.sputi,and G.aichiensis.Drug sensitivity tests indicated that drugs including amoxicillin/clavulanic acid,ceftriaxone,cefotaxime,tobramycin,clarithromycin,mi-nocycline,trimethoprim/sulfamethoxazole,linezolid,and doxycycline had good antibacterial effects against Gordonia.

Objective To investigate the effects of gut microbiota regulation combined with exercise rehabilitation on non-motor symptoms and neurological function in Parkinson's disease patients.Methods A total of 154 Parkinson's disease patients admitted to our hospital from January 2022 to January 2024 were selected as the subjects of the study.Using a random number table,these 154 patients were evenly divided into a control group and a treatment group,with 77 patients in each group.Both groups received standard treatments,but the control group also underwent exercise rehabilitation therapy,while the treatment group received probiotic supplementation and exercise rehabilitation therapy.The effectiveness of the two groups was then compared.Results Following the 12 weeks,24 weeks therapeutic regimen,The treatment group showed significantly better outcomes(P<0.05).Clinically meaningful reductions were observed in Hoehn-Yahr staging,alongside decreased scores on standardized instruments assessing psychiatric symptoms HAMA,HAMD,SCOPA-AUT,UPDRS Ⅰ-IV and PDSS(P<0.05).Concurrently,the study group exhibited enhanced MMSE(P<0.05).Fecal microbiome analyses revealed a favorable ecological shift characterized by increased colonization of beneficial genera Bifidobacterium and Lactobacillus,with concomitant suppression of pathobionts Enterococcus and Enterobacteriaceae.Gait analysis revealed increased step length,speed,and frequency in the treatment group(P<0.05).Conclusion Patients with Parkinson's disease who received probiotics combined with exercise rehabilitation treatment could effectively improve non-motor symptoms and neurological function,while promoting the balance of intestinal flora,and reduce clinical symptoms.

Objective To explore the risk prediction value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid enhanced magnetic resonance imaging(Gd-EOB-MRI)liver imaging reporting and data system version 2018(LI-RADS v2018)with contrast-enhanced ultrasound(CEUS)LI-RADS version 2017(LI-RADS v2017)in high-risk patients with hepatocellular carcinoma(HCC).Methods The clinical and imaging data of 122 high-risk patients for HCC(with a total of 134 liver lesions)who underwent both Gd-EOB-MRI and CEUS examination at the same time and obtained pathological results within one month were retrospectively col-lected.The nodules were classified according to the CT/MRI LI-RADS v2018 and CEUS LI-RADS v2017 criteria,and the LI-RADS classification results of the two imaging methods were subjected to Cohen's Kappa test.Using pathological results as the gold stand-ard,the diagnostic efficacy of LI-RADS v2018 and LI-RADS v2017 with LR-5 as the standard for HCC was calculated separately.Results The overall consistency between the Gd-EOB-MRI LI-RADS v2018 and CEUS LI-RADS v2017 classification standards was good(Kappa=0.691,P＜0.001).Using LR-5 as the standard for diagnosing HCC,the sensitivity of Gd-EOB-MRI and CEUS was 84.7％and 81.2％,the specificity was 79.6％and 73.5％,the positive predictive value was 87.8％and 84.1％,the negative predictive value was 75.0％and 69.2％,and the accuracy was 82.8％and 78.4％,respectively.There was no statistically significant difference in the diagnostic efficacy of the diagnosis of HCC by LR-5 between the two imaging methods(P＞0.05).Conclusion The Gd-EOB-MRI LI-RADS v2018 and CEUS LI-RADS v2017 classifica-tion standards show good overall agreement.The diagnostic efficacy of Gd-EOB-MRI for HCC using LR-5 classification is better than that of CEUS.

This study was aimed at exploring the prevalence and drug sensitivity of Gordonia strains isolated from sputum samples in Henan Province,to provide data to aid in the prevention and treatment of Gordonia infection.A combination of 16S rDNA and sec A1 gene sequencing was used to identify the isolated strains,and susceptibility to16 drugs was determined with the broth microdilution method.A total of 21 strains were identified through 16S rDNA gene and sec A1 gene sequencing,including five strains of Gordonia broncians,eight strains of Gordonia paraphernivans,seven strains of Gordonia sputi,and one strain of Gordonia aichiensis.Drug sensi-tivity testing showed high Gordonia sensitivity to drugs such as ceftriaxone,linezolid,doxycycline,amoxicillin/clavulanic acid,mino-cycline,cefotaxime,trimethoprim/sulfamethoxazole,imipenem,tobramycin,and clarithromycin.The sensitivity rates of the isolated strains were 90.48%(19/21),100%(21/21),90.48%(19/21),90.48%(19/21),95.24%(20/21),90.48%(19/21),90.48%(19/21),90.48%(19/21),and 95.24%(20/21),respectively.Gordonia showed high resistance to rifampicin and cefepime,with rates of 28.57%(6/21)and 19.05%(4/21),respectively.Meanwhile,the resistance varied among bacterial strains.The resistance rate of G.sputi to rifampicin reached 71.43%(5/7),whereas that of G.parapffinivoras to cefepime was 37.5%(3/8).The main species of Gordo-nia isolated from sputum samples of patients in Henan Province were G.bronchialis,G.paraffinivoras,G.sputi,and G.aichiensis.Drug sensitivity tests indicated that drugs including amoxicillin/clavulanic acid,ceftriaxone,cefotaxime,tobramycin,clarithromycin,mi-nocycline,trimethoprim/sulfamethoxazole,linezolid,and doxycycline had good antibacterial effects against Gordonia.

Objective To investigate the effects of gut microbiota regulation combined with exercise rehabilitation on non-motor symptoms and neurological function in Parkinson's disease patients.Methods A total of 154 Parkinson's disease patients admitted to our hospital from January 2022 to January 2024 were selected as the subjects of the study.Using a random number table,these 154 patients were evenly divided into a control group and a treatment group,with 77 patients in each group.Both groups received standard treatments,but the control group also underwent exercise rehabilitation therapy,while the treatment group received probiotic supplementation and exercise rehabilitation therapy.The effectiveness of the two groups was then compared.Results Following the 12 weeks,24 weeks therapeutic regimen,The treatment group showed significantly better outcomes(P<0.05).Clinically meaningful reductions were observed in Hoehn-Yahr staging,alongside decreased scores on standardized instruments assessing psychiatric symptoms HAMA,HAMD,SCOPA-AUT,UPDRS Ⅰ-IV and PDSS(P<0.05).Concurrently,the study group exhibited enhanced MMSE(P<0.05).Fecal microbiome analyses revealed a favorable ecological shift characterized by increased colonization of beneficial genera Bifidobacterium and Lactobacillus,with concomitant suppression of pathobionts Enterococcus and Enterobacteriaceae.Gait analysis revealed increased step length,speed,and frequency in the treatment group(P<0.05).Conclusion Patients with Parkinson's disease who received probiotics combined with exercise rehabilitation treatment could effectively improve non-motor symptoms and neurological function,while promoting the balance of intestinal flora,and reduce clinical symptoms.

Objective: To investigate the objective characteristics of tongue manifestation in different stages of damp-heat syndrome in diabetic kidney disease (DKD). Methods: A cross-sectional study enrolled 134 patients with DKD G3-5 stages who met the diagnostic criteria for damp-heat syndrome in DKD. The patients were treated at Dongzhimen Hospital, Beijing University of Chinese Medicine, from May 2023 to January 2024. The patients were divided into three groups: DKD G3, DKD G4, and DKD G5 stage, with 53, 33, and 48 patients in each group, respectively. Clinical general data (gender, age, and body mass index) and damp-heat syndrome scores were collected from the patients. The YZAI-02 traditional Chinese medicine (TCM) AI Tongue Image Acquisition Device was used to capture tongue images from these patients. The accompanying AI Open Platform for TCM Tongue Diagnosis of the device was used to analyze and extract tongue manifestation features, including objective data on tongue color, tongue quality, coating color, and coating texture. Clinical data and objective tongue manifestation characteristics were compared among patients with DKD G3-5 based on their DKD damp-heat syndrome status. Results: No statistically significant difference in gender or body mass index was observed among the three patient groups. The DKD G3 stage group had the highest age (P<0.05). The DKD G3 stage group had a lower score for symptoms of poor appetite and anorexia(P<0.05) than the DKD G5 group. No statistically significant difference was observed in damp-heat syndrome scores among the three groups. Compared with the DKD G5 stage group, the DKD G3 stage group showed a decreased proportion of pale color at the tip and edges of the tongue (P<0.05). The DKD G4 stage group exhibited an increased proportion of crimson at the root of the tongue, a decreased proportion of thick white tongue coating at the root, a decreased proportion of pale color at the tip and edges of the tongue, an increased hue value (indicating color tone) of the tongue color in the middle, an increased brightness value (indicating color lightness) of the tongue coating color in the middle, and an increased thickness of the tongue coating (P<0.05). No statistically significant difference was observed in other tongue color proportions, color chroma values, body characteristics, coating color proportions, coating color chroma values, and coating texture characteristics among the three groups. Conclusion Tongue features differ in different stages of DKD damp-heat syndrome in multiple dimensions, enabling the inference that during the DKD G5 stage, the degree of qi and blood deficiency in the kidneys, heart, lungs, liver, gallbladder, spleen, and stomach is prominent. Dampness is more likely to accumulate in the lower jiao, particularly in the kidneys, whereas heat evil in the spleen and stomach is the most severe. These insights provide novel ideas for the clinical treatment of DKD.

This study aims to explore the effects and action mechanisms of the active ingredients in Buyang Huanwu Decoction(BYHWD), namely tetramethylpyrazine(TMP) and hydroxy-safflor yellow A(HSYA), on oxygen-glucose deprivation/reglucose-reoxygenation(OGD/R)-induced inflammation and oxidative stress of microglia(MG). Network pharmacology was used to screen the effective monomer ingredients of BYHWD and determine the safe concentration range for each component. Inflammation and oxidative stress models were established to further screen the best ingredient combination and optimal concentration ratio with the most effective anti-inflammatory and antioxidant effects. OGD/R BV2 cell models were constructed, and BV2 cells in the logarithmic growth phase were divided into a normal group, a model group, an HSYA group, a TMP group, and an HSYA + TMP group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory cytokines such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6). Oxidative stress markers, including superoxide dismutase(SOD), nitric oxide(NO), and malondialdehyde(MDA), were also measured. Western blot was used to analyze the protein expression of both inflammation-related pathway [Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)] and oxidative stress-related pathway [nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)]. Immunofluorescence was used to assess the expression of proteins such as inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1). The most effective ingredients for anti-inflammatory and antioxidant effects in BYHWD were TMP and HSYA. Compared to the normal group, the model group showed significantly increased levels of IL-1β, TNF-α, IL-6, NO, and MDA, along with significantly higher protein expression of NF-κB, TLR4, Nrf2, and HO-1 and significantly lower SOD levels. The differences between the two groups were statistically significant. Compared to the model group, both the HSYA group and the TMP group showed significantly reduced levels of IL-1β, TNF-α, IL-6, NO, and MDA, lower expression of NF-κB and TLR4 proteins, higher levels of SOD, and significantly increased protein expression of Nrf2 and HO-1. Additionally, the expression of the M1-type MG marker iNOS was significantly reduced, while the expression of the M2-type MG marker Arg-1 was significantly increased. The results of the HSYA group and the TMP group had statistically significant differences from those of the model group. Compared to the HSYA group and the TMP group, the HSYA + TMP group showed further significant reductions in IL-1β, TNF-α, IL-6, NO, and MDA levels, along with significant reductions in NF-κB and TLR4 protein expression, an increase in SOD levels, and elevated Nrf2 and HO-1 protein expression. Additionally, the expression of the M1-type MG marker iNOS was reduced, while the M2-type MG marker Arg-1 expression increased significantly in the HSYA + TMP group compared to the TMP or HSYA group. The differences in the results were statistically significant between the HSYA + TMP group and the TMP or HSYA group. The findings indicated that the combined use of HSYA and TMP, the active ingredients of BYHWD, can effectively inhibit OGD/R-induced inflammation and oxidative stress of MG, showing superior effects compared to the individual use of either component.
Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Glucose/metabolism* ; Cell Line ; Inflammation/genetics* ; Oxygen/metabolism* ; Pyrazines/pharmacology* ; Microglia/metabolism* ; NF-E2-Related Factor 2/immunology* ; NF-kappa B/immunology* ; Toll-Like Receptor 4/immunology* ; Anti-Inflammatory Agents/pharmacology* ; Humans

OBJECTIVE: To explore the efficacy and apoptosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute myeloid leukemia (AML) with ASXL1 mutation. METHODS: The clinical data of 80 AML patients with ASXL1 mutation treated in our hospital from January 2019 to December 2021 were retrospectively analyzed. The clinical characteristics of the patients were summarized, and the therapeutic effect and prognostic factors of allo-HSCT for the patients were analyzed. RESULTS: Among the 80 patients, 38 were males and 42 were females, and the median age was 39(14-65) years. There were 17 patients in low-risk group, 25 patients in medium-risk group and 38 patients in high-risk group. ASXL1 mutation co-occurred with many other gene mutations, and the frequent mutated genes were TET2 (71.25%), NRAS (18.75%), DNMT3A (16.25%), NPM1 (15.00%), CEBPA (13.75%). Among medium and high-risk patients, 29 underwent allo-HSCT, while 34 received chemotherapy. The 2-year overall survival (OS) rate and disease-free survival (DFS) rate of the allo-HSCT group were 72.4% and 70.2%, while those of the chemotherapy group were 44.1% and 34.0%, respectively. The statistical analysis showed significant differences between the two groups (both P < 0.01). Multivariate analysis showed that age at transplantation >50- years and occurrence of acute graft-versus-host disease after transplantation were poor prognostic factors for OS and DFS in transplantation patients. CONCLUSION Allo-HSCT can improve the prognosis of AML patients with ASXL1 mutation.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Middle Aged ; Mutation ; Adult ; Repressor Proteins/genetics* ; Adolescent ; Retrospective Studies ; Aged ; Nucleophosmin ; Young Adult ; Transplantation, Homologous ; Prognosis ; Survival Rate

Objective: To understand the incidence risk and risk factors of tuberculosis (TB) among middle school students in Chongqing, so as to provide a basis for formulating TB prevention and control strategies. Methods: From September to December 2022, 32 181 middle school students were selected as the study cohort from 15 administrative districts in Chongqing by using the stratified cluster random sampling method. All cohort members were screened with the tuberculin skin test (TST), and relevant information was collected from January 1, 2023 to December 31, 2024. On the basis of active screening, the follow up data of the participants were compared with the National Tuberculosis Management Information System to obtain the incidence status of the study subjects. The Log rank test was used to compare the TB incidence rates among students with different characteristics, and a Cox proportional hazards model was established to analyze the incidence risk and risk factors of TB. Results: The TST screening rate of the cohort members was 93.0%. During the 2 year follow up period, a total of 36 TB cases occurred, with a cumulative incidence rate of 111.87/100 000 and an incidence density of 55.95/100 000. Among them, the cumulative incidence rate of students from public schools (170.44/ 100 000 ) was higher than that of students from private schools (41.16/100 000), the cumulative incidence rate of students in schools located in high epidemic areas (153.95/100 000) was higher than that in medium epidemic areas (69.00/100 000), and the difference was statistically significant ( χ 2=11.49, 4.73, both P <0.05). The Log-rank test for different TST results showed that the difference in TB comulative incidence rate between students with strongly positive TST results (216.55/ 100 000 ) and those with negative TST results (81.40/100 000) was statistically significant ( χ 2=5.85, P <0.05). Univariate analysis using the Cox proportional hazards model revealed that the risk of TB was lower in students from private schools ( HR=0.25, 95% CI = 0.10-0.59) and students in medium epidemic areas ( HR=0.46, 95%CI =0.23-0.94); whereas the risk of TB was increased in students with strongly positive TST results ( HR=1.39, 95%CI =1.05-1.84) (all P <0.05). Multivariate Cox regression analysis showed that the risk of TB in students from private schools was lower than that of students from public schools ( HR=0.23, 95%CI=0.08-0.62, P <0.05). Conclusions The annual average incidence rate of TB among middle school students in Chongqing is at a relatively high level. It is necessary to strengthen the management and intervention for student groups, including those in public schools, those in schools located in high epidemic areas, and those with strongly positive TST results, so as to reduce the incidence rate of TB.