A chemical investigation of secondary metabolites (SMs) from Aspergillus nidulans resulted in the identification of five novel dioxopiperazine (DKP)-diphenyl ether hybrids, designated as diphenylemestrins A-E (1-5). These compounds 1-5 represent the first known dimers combining DKP and diphenyl ether structures, with compound 4 featuring an uncommon dibenzofuran as the diphenyl ether component. The structural elucidation and determination of absolute stereochemistry were accomplished through spectroscopic analysis and electronic circular dichroism (ECD) calculations. Notably, diphenylemestrin C (3) exhibited moderate cytostatic activity against NB4 cells, with a half maximal inhibitory concentration (IC₅₀) value of 21.99 μmol·L^-1, and induced apoptosis at higher concentrations.
Aspergillus nidulans/metabolism* ; Diketopiperazines/pharmacology* ; Molecular Structure ; Phenyl Ethers/pharmacology* ; Humans ; Apoptosis/drug effects* ; Cell Line, Tumor

Objective:To investigate the protective effect of quercetin against 5-fluorouracil(5-FU)-induced damage in the human immortalized keratinocytes(HACAT),and to elucidate its possible mechanism.Methods:The HACAT cells were divided into control group(normal cultured cells),5-FU group(treated with 7.5 mg·L-1 5-FU for 24 h),and low,medium,and high doses of quercetin groups(HACAT cells treated with 25,50,and 75 μmol·L-1 quercetin combined with 7.5 mg·L-15-FU for 24 h).Cell counting kit-8(CCK-8)assay was used to detect the survival rates of HACAT cells treated with different doses(0,10,25,50,75 and 100 μmol·L-1)of quercetin in various groups.The fluorescent probe of reactive oxygen species(ROS)was used to detect ROS levels in the HACAT cells in various groups.Annexin Ⅴ-FITC/PI double staining was used to detect the apoptosis of HACAT cells in various groups.Western blotting method was used to detect the expression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),Cleaved Caspase-3,cyclooxygenase-2(COX-2),interleukin-1 β(IL-1β),and interleukin-6(IL-6)in the HACAT cells in various groups.Results:The CCK-8 assay results showed that compared with 0 μmol·L-1 quercetin group,the survival rates of HACAT cells in 10,25,50 and 75 μmol·L-1quercetin groups showed no significant differences(P＞0.05),while the survival rates of HACAT cells in 100 μmol·L-1 quercetin group was significantly decreased(P＜0.05).Compared with 5-FU group,the survival rates of the HACAT cells in low,medium and high doses of quercetin group were significantly increased(P＜0.05).Compared with 5-FU group,the ROS levels in low,medium,and high doses of quercetin groups were significantly decreased(P＜0.05).Annexin Ⅴ-FITC/PI double staining assay showed that compared with 5-FU group,the apoptotic rates in low,medium and high doses of quercetin groups were significantly decreased(P＜0.05).The Western blotting results showed that compared with 5-FU group,the expression levels of Bcl-2 protein in medium and high doses of quercetin groups were significantly increased(P＜0.05),the expression levels of Bax and Cleaved Caspase-3 proteins in low,medium and high doses of quercetin groups were significantly decreased(P＜0.05),the expression levels of COX-2 protein in medium and high doses of quercetin groups were significantly decreased(P＜0.05),and the expression levels of IL-1β and IL-6 proteins in medium dose of quercetin group were significantly decreasd(P＜0.05).Conclusion:Quercetin has protective effect on 5-FU-induced damage in the HACAT cells,and its mechanism may be related to the reduction of the expression of ROS and inflammatory factor COX-2 which attenuate the apoptosis.

BACKGROUND:Rheumatoid arthritis is a chronic autoimmune disease characterized by joint pain,swelling,and dysfunction.Acupuncture,as a traditional medical treatment,has proved its effectiveness and safety in many diseases.However,the efficacy of acupuncture in the treatment of rheumatoid arthritis remains controversial.Therefore,the purpose of this study is to evaluate and explore the effect of Tiaodu Tongmai acupuncture in the treatment of preclinical rheumatoid arthritis of different ages through the generalized estimating equation,and to provide a basis for the application of acupuncture in rheumatoid arthritis. OBJECTIVE:To investigate the effect of Tiaodu Tongmai acupuncture therapy on preclinical rheumatoid arthritis(pre-RA)patients at different ages based on generalized estimating equation. METHODS:A total of 123 patients with preclinical rheumatoid arthritis treated from January to September 2023 were selected as the study objects and divided into study group(n=64)and control group(n=59)according to different treatment methods.The study group was given Tiaodu Tongmai acupuncture treatment,and the control group was given acetaminophen tablets.The baseline balance was adjusted by propensity score matching method.The clinical efficacy and cytokine levels before and after treatment between the two groups were compared.The generalized estimating equation model was established to evaluate the efficacy of Tiaodu Tongmai acupuncture therapy on preclinical rheumatoid arthritis patients at different ages. RESULTS AND CONCLUSION:(1)After 0 days of treatment,there were significant differences in joint pain and C-reactive protein expression between study and control groups(P＜0.05).After 4 weeks of treatment,there were significant differences in visual analogue scale scores,joint pain,C-reactive protein and erythrocyte sedimentation rate between the two groups(P＜0.05).After 8 weeks of treatment,there were significant differences in visual analogue scale scores,C-reactive protein and erythrocyte sedimentation rate between the two groups(P＜0.05).After 12 weeks of treatment,there were significant differences in visual analogue scale scores,C-reactive protein and erythrocyte sedimentation rate between the two groups(P＜0.05).(2)The total effective rate of the study group was 93.75%,while that of the control group was 79.17%.The clinical efficacy of the study group was significantly better than that of the control group(P＜0.05).(3)There were significant differences in interleukin-6,interferon-γ,macrophage migration inhibitory factor,rheumatoid factor IgA,rheumatoid factor IgM,metallomatrix proteinase 3,metallomatrix proteinase 9,and anti-cyclic citrulline antibody in the study group before and after treatment(P＜0.05).The levels of interleukin-6,interferon-γ,rheumatoid factor IgA,rheumatoid factor IgM,metallomatrix proteinase 3,metallomatrix proteinase 9,and anti-cyclic citrulline antibody in the control group after treatment were significantly different from those before treatment(P＜0.05).There were significant differences in interleukin-6,interferon-γ,macrophage migration inhibitory factor,rheumatoid factor IgA,rheumatoid factor IgM,metallomatrix proteinase 3,and anti-cyclic citrulline antibody between the two groups after treatment(P＜0.05).(4)After 12 weeks of treatment,the comprehensive efficacy of patients of all ages in the study group was better than that of the control group(P＜0.05).After 8 weeks of treatment,the comprehensive efficacy of patients aged 23-35,36-50,and 51-60 years old in the study group was better than that of the control group(P＜0.05),and the comprehensive efficacy of patients aged 18-22 years old was comparable between the two groups.After 4 weeks of treatment,the comprehensive efficacy of patients aged 36-50 and 51-60 years old in the study group was better than that of the control group(P＜0.05),and the comprehensive efficacy was comparable between the two groups of patients aged 18-22 and 23-35 years.Overall,Tiaodu Tongmai acupuncture therapy has advantages in treating preclinical rheumatoid arthritis patients aged 36-50 and 51-60 years.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

To investigate the role of the nucleotide-binding domain and leucine-rich-repeat-contai-ning family member X1(NLRX1)in the replication of Newcastle disease virus(NDV),the ex-pression level of NLRX1 was examined following infection of 10-day-old specific pathogen-free(SPF)chicks and HD11 cells with the NDV NA-1 strain.Additionally,the proliferation of NDV,the expression of pro-inflammatory cytokines in HD11 cells,and the oxidative stress status were e-valuated in the presence of either overexpressed or underexpressed NLRX1.The results demonstra-ted that NA-1 infection led to an increase in NLRX1 expression both in vivo and in vitro.Further-more,overexpression of NLRX1 inhibited viral proliferation,enhanced the expression of cellularIL-1β,IL-6,and IFN-β,without affecting levels of autophagy or apoptotic cells.However,NLRX1 elevation resulted in elevated mRNA levels of iNOS,Keap1,Nrf2,NQO1,and HO-1 within 24 h.In conclusion,NLRX1 suppresses NDV proliferation by promoting early ROS production.

Objective:To discuss the postoperative survival of the gastric cancer patients with different expression levels of myeloid ecotropic viral integration site 1(MEIS1),and to analyze the predictive value of MEIS1 expression in the prognosis evaluation of gastric cancer.Methods:In a gastric cancer survival cohort,215 patients who underwent radical gastrectomy were selected.Immunohistochemical staining was used to detect the expression levels of MEIS1 in both gastric cancer and adjacent normal tissues.The relationship between expression level of MEIS1 and the clinicopathological characteristics of the patients were analyzed by x2 test or Fisher's exact probability method;survival curves were plotted by Kaplan-Meier method;the differences in survival of the patients between MEIS1 high expression group and MEIS1 low expression group were compared by Log-rank test;multivariate Cox proportional hazards regression model was used to calculate the hazard ratios(HR)and 95％confidence intervals(CI)to assess the relationship between MEIS1 expression level and the survival of the gastric cancer patients.Results:The immunohistochemical staining result showed that the expression level of MEIS1 in gastric cancer tissue was decreased.The univariate analysis results showed that the patients with high MEIS1 expression had a longer overall survival than those with low expression(P=0.049),and had a better prognosis.The multivariate Cox proprotional hazards regression analysis results showed that the low MEIS1 expression and high TNM stage were the independent risk factors for poor prognosis of the patients with gastric cancer(HR=1.577,95％CI:1.011-2.460,P=0.045;HR=2.709,95％CI:1.708-4.297,P＜0.001).Conclusion:The gastric cancer patients with low expression of ME1S1 have a shorter postoperative overall survival;MEIS1 is a promising biomarker for prognosis assessment of the patients after radical gastrectomy.

Objective:To explore the effect of continuous nursing based on Siebens domain management model in patients with Parkinson's disease after deep brain stimulation.Methods:From January 2021 to June 2022, convenience sampling was used to select 169 Parkinson's disease patients who underwent deep brain electrical stimulation in the Functional Neurosurgery of Beijing Tiantan Hospital as the study subject. The patients were divided into a control group of 84 cases and an observation group of 85 cases using the random number table method. The control group received routine continuous nursing, while the observation group received the continuous nursing based on Siebens domain management model on the basis of the control group. This study compared the Activity of Daily Living (ADL) Scale, Morisky Medication Adherence Scale (MMAS), 39-item Parkinson Disease Questionnaire (PDQ-39), Parkinson's Disease Sleep Scale (PDSS) scores, and unexpected program control rate between two groups of patients after six months of discharge.Results:After six months of discharge, the ability of daily living score, quality of life score, and sleep quality score of both groups of patients improved compared to before intervention ( P<0.05), and the medication adherence of the observation group patients improved compared to before intervention ( P<0.05), and the differences were statistically significant. The ability of daily living score, medication adherence, quality of life score, and sleep quality score of the observation group patients after six months were higher than those of the control group, and the differences were statistically significant ( P<0.05). Within six months after discharge, the unexpected program control rate of the observation group was statistically lower than that of the control group ( P<0.05) . Conclusions:In the treatment and discharge rehabilitation process of Parkinson's patients treated with deep brain electrical stimulation, adopting continuous nursing based on the Siebens domain management model can help ensure patient medication compliance, improve postoperative sleep quality and quality of life, reduce unexpected program control frequency, and have certain clinical practice value.

Cervical cancer, the most common gynecological malignancy, significantly and adversely affects women's physical health and well-being. Traditional surgical interventions and chemotherapy, while potentially effective, often entail serious side effects that have led to an urgent need for novel therapeutic methods. Photothermal therapy (PTT) has emerged as a promising approach due to its ability to minimize damage to healthy tissue. Connecting a biothiol detection group to PTT-sensitive molecules can improve tumor targeting and further minimize potential side effects. In this study, we developed a near-infrared fluorescence (NIRF)/photoacoustic (PA) dual-mode probe, S-NBD, which demonstrated robust PTT performance. This innovative probe is capable of activating NIRF/PA signals to enable the detection of biothiols with high emission wavelength (838 nm) and large Stokes shift (178 nm), allowing for in vivo monitoring of cancer cells. Additionally, the probe achieved an outstanding photothermal conversion efficiency of 67.1%. The application of laser irradiation (660 nm, 1.0 W/cm², 5 min) was able to achieve complete tumor ablation without recurrence. In summary, this seminal study presents a pioneering NIRF/PA dual-mode dicyanoisophorone-based probe for biothiol imaging, incorporating features from PTT for the first time. This pioneering approach achieves the dual objectives of improving tumor diagnosis and treatment.

Objective:To observe the effect of Ba Duan Jin(Eight-brocade Exercise)plus Tuina(Chinese therapeutic massage)in treating primary dysmenorrhea due to cold-induced blood stasis in female college students and on the score of fatigue scale-14(FS-14). Methods:Seventy-two female college students with primary dysmenorrhea due to cold-induced blood stasis were randomized into a Tuina group and a joint group,with 36 cases in each group.The Tuina group only received Tuina manipulations.In the joint group,besides the same Tuina manipulations,patients practiced Ba Duan Jin.For both groups,the once-daily intervention was conducted from 6 d before the menstrual period until menstrual day 1 for 3 menstrual cycles.Changes in the scores of COX menstrual symptom scale(CMSS),visual analog scale(VAS),and FS-14 after the intervention were observed.Clinical efficacy was also estimated. Results:During the process,1 case dropped out in the Tuina group,and 35 cases completed the intervention;2 cases dropped out in the joint group,and 34 cases completed the intervention.The total effective rate was 94.1%in the joint group,higher than 88.6%in the Tuina group(P<0.05).After treatment,the symptom duration and intensity scores in the scores of CMSS,VAS,and FS-14 declined in both groups(P<0.05 or P<0.01);the CMSS symptom duration score and FS-14 score were lower in the joint group than in the Tuina group(P<0.05). Conclusion:Tuina manipulations alone or combined with Ba Duan Jin practice can effectively treat primary dysmenorrhea due to cold-induced blood stasis in female college students;when combined with Ba Duan Jin practice,Tuina manipulations can more significantly improve pain duration and fatigue,suggesting the advantages of combining Tuina Gongfa and manipulations.