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

Background::Pathological scars are a disorder that can lead to various cosmetic, psychological, and functional problems, and no effective assessment methods are currently available. Assessment and treatment of pathological scars are based on cutaneous manifestations. A two-photon microscope (TPM) with the potential for real-time non-invasive assessment may help determine the under-surface pathophysiological conditions in vivo. This study used a portable handheld TPM to image epidermal cells and dermal collagen structures in pathological scars and normal skin in vivo to evaluate the effectiveness of treatment in scar patients. Methods::Fifteen patients with pathological scars and three healthy controls were recruited. Imaging was performed using a portable handheld TPM. Five indexes were extracted from two dimensional (2D) and three dimensional (3D) perspectives, including collagen depth, dermo-epidermal junction (DEJ) contour ratio, thickness, orientation, and occupation (proportion of collagen fibers in the field of view) of collagen. Two depth-dependent indexes were computed through the 3D second harmonic generation image and three morphology-related indexes from the 2D images. We assessed index differences between scar and normal skin and changes before and after treatment.Results::Pathological scars and normal skin differed markedly regarding the epidermal morphological structure and the spectral characteristics of collagen fibers. Five indexes were employed to distinguish between normal skin and scar tissue. Statistically significant differences were found in average depth ( t = 9.917, P <0.001), thickness ( t = 4.037, P <0.001), occupation ( t= 2.169, P <0.050), orientation of collagen ( t = 3.669, P <0.001), and the DEJ contour ratio ( t = 5.105, P <0.001). Conclusions::Use of portable handheld TPM can distinguish collagen from skin tissues; thus, it is more suitable for scar imaging than reflectance confocal microscopy. Thus, a TPM may be an auxiliary tool for scar treatment selection and assessing treatment efficacy.

Objectives:To investigate the relationship between total ischemic time(TIT)and the risk of major adverse cardiovascular events(MACE,including all-cause death,non-fatal myocardial infarction,non-fatal ischemic stroke)within 1 year after primary percutaneous coronary intervention(PPCI)in patients with ST segment elevation myocardial infarction(STEMI)with TIT≤720 minutes. Methods:A total of 1 812 STEMI patients who underwent PPCI and had a TIT≤720 minutes in the Chest Pain Center of the General Hospital of the Southern Theatre Command of PLA from January 1,2011 to December 31,2021 were selected as the research subjects.Logistic regression and Cox regression models were used to analyze the association between TIT and the risk of MACE in the hospital and within 1 year after discharge.The restricted cubic spline(RCS)analysis was used to analyze the dose-response relationship between TIT and the risk of MACE. Results:Among 1 812 patients,the incidence of MACE during hospitalization was 3.26%,and the incidence of MACE within 1 year after discharge was 6.84%in 1 651 patients who survived.RCS analysis showed that TIT had an approximate logarithmic linear relationship with the risk of MACE during hospitalization and within 1 year after discharge,and the risk of MACE increased with longer TIT.Multivariate logistic regression analysis showed that compared with the group with a TIT of≤480 minutes,the risk of MACE during hospitalization increased by 77.7%(OR=1.777,95%CI:1.020-2.929,P=0.038)in the group with a TIT of more than 480 minutes.Multivariate Cox proportional hazards regression analysis showed that compared with the group with a TIT of≤280 minutes,the risk of MACE within 1 year after discharge increased by 106.7%(HR=2.067,95%CI:1.384-3.089,P<0.001)in the group with a TIT of more than 280 minutes. Conclusions:In STEMI patients after PPCI,the risk of MACE during hospitalization significantly increases when TIT exceeds 480 minutes,and the risk of MACE within 1 year after discharge significantly increases when TIT exceeds 280 minutes.

Objective:To screen the main characteristic variables affecting the incidence of cardiovascular and cerebrovascular diseases,and to construct the Bayesian network model of cardiovascular and cerebrovascular disease incidence risk based on the top 10 characteristic variables,and to provide the reference for predicting the risk of cardiovascular and cerebrovascular disease incidence.Methods:From the UK Biobank Database,315 896 participants and related variables were included.The feature selection was performed by categorical boosting(CatBoost)algorithm,and the participants were randomly divided into training set and test set in the ratio of 7∶3.A Bayesian network model was constructed based on the max-min hill-climbing(MMHC)algorithm.Results:The prevalence of cardiovascular and cerebrovascular diseases in this study was 28.8％.The top 10 variables selected by the CatBoost algorithm were age,body mass index(BMI),low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),the triglyceride-glucose(TyG)index,family history,apolipoprotein A/B ratio,high-density lipoprotein cholesterol(HDL-C),smoking status,and gender.The area under the receiver operating characteristic(ROC)curve(AUC)for the CatBoost training set model was 0.770,and the model accuracy was 0.764;the AUC of validation set model was 0.759 and the model accuracy was 0.763.The clinical efficacy analysis results showed that the threshold range for the training set was 0.06-0.85 and the threshold range for the validation set was 0.09-0.81.The Bayesian network model analysis results indicated that age,gender,smoking status,family history,BMI,and apolipoprotein A/B ratio were directly related to the incidence of cardiovascular and cerebrovascular diseases and they were the significant risk factors.TyG index,HDL-C,LDL-C,and TC indirectly affect the risk of cardiovascular and cerebrovascular diseases through their impact on BMI and apolipoprotein A/B ratio.Conclusion:Controlling BMI,apolipoprotein A/B ratio,and smoking behavior can reduce the incidence risk of cardiovascular and cerebrovascular diseases.The Bayesian network model can be used to predict the risk of cardiovascular and cerebrovascular disease incidence.

Objective To explore the mechanism of curcumin in enhancing gemcitabine sensitivity by regulating pancreatic cancer cells.Methods In order to verify the effect of curcumin on p53 and NF-κB p65 nuclear translocation in pancreatic cancer cell PANC1,the pancreatic cancer PANC1 cells were treated with 0,10,20,30 μmol/L curcumin to obtain the blank group,10 μmol/L curcumin group,20 μmol/L curcumin group and 30 μmol/L curcumin group.The intracellular distribution of NF-κB p65 was determined by immunofluo-rescence staining under fluorescence microscope.The expression level of p53 protein in cells was determined by Western blot.The expression level of p53 mRNA was determined by reverse transcription-real-time fluo-rescence quantitative PCR.The combined use of miRstar and JASPAR softwares predicted to seek microRNA (miRNA) potentially regulated by NF-κB p65 nuclear translocation.The double luciferase reporting assay was used to respectively verify the relationship between miRNA and p53.In order to verify whether curcumin in-fect the sensitivity of PANC1 cell through NF-κB p65/miR-266-5p/p53 axis,the gemcitabine group was ob-tained by 10 μmol/L gemcitabine treating cells,and the curcumin combined gemcitabine group was obtained by 20 μmol/L curcumin and 10 μmol/L gemcitabine treating cells.After the cells were treated with curcumin (20 μmol/L) and gemcitabine (10 μmol/L),oligonucleotides mimic NC and miR-26b-5p mimic were trans-fected into cells,and the mimic NC group and miR-26b-5p group were obtained.pcDNA3.1 no-load plasmid and pcDNA3.1-p53 overexpression plasmid were transfected into cells,respectively,and the pcDNA3.1 group and p53 group were obtained.The cell activity was detected by MTT assay.The cellular apoptosis level was determined by Annexin V/PI double staining.Results Compared with the blank group,the intracellular p53 mRNA and protein expression levels in the various curcumin treated groups (10,20,30 μmol/L curcumin groups) all were increased.Compared with the blank group,the expression level of NF-κB p65 in the nucleus of 20μmol/L curcumin group was decreased.The miRstar and JASPAR prediction software found 8 miRNA that may be regulated by NF-κB p65 nuclear translocation,in which 3 miRNA had potential to target p53 genes,especially miR-26b-5p effect was most significant.The double luciferase report experiment confirmed that miR-26b-5p did interact with p53.Compared with the mimic NC group,the expression levels of p53 mR-NA and protein in the mimic miR-26b-5p group were decreased.Compared with the gemcitabine group,the cell viability in the curcumin combined gemcitabine group was decreased and the apoptosis rate was increased.Compared with the mimic NC group,the cell activity in the mimic miR-26b-5p group was increased and the apoptosis level was decreased.Moreover compared with the pcDNA3.1 group,the cell activity in the pcDNA3.1-p53 group was decreased and the apoptosis level was increased.Conclusion Curcumin reduces the expression of miR-26b-5p gene by inhibiting the nuclear translocation of NF-κB p65 protein,and then increase the p53 gene and protein expression,and enhance the sensitivity of pancreatic cancer cells to gemcitabine by the NF-κB p65/miR-26b-5p/p53 axis.

The anatomical structure of the bifurcation of the internal carotid artery and its surrounding skull base space is complex and has certain variations. There are many branches and perforating arteries in this department that supply important intracranial structures. In some intracranial aneurysm clipping surgeries, attention should be paid to protection to prevent intraoperative damage and reduce the occurrence of postoperative complications. This article proposes the concept of the bifurcation complex of the internal carotid artery for the first time, and reviews the anatomical characteristics and variations of the bifurcation complex of the internal carotid artery and its branch arterial blood vessels, as well as the surgical treatment of aneurysms in this area, in order to provide reference for further clinical research.

Objective:To explore the effectiveness of the comprehensive healthcare management model for children with bacterial meningitis after discharge.Methods:This study was a retrospective cohort study that included 268 children with bacterial meningitis who were discharged from the infectious medicine ward of Beijing Children′s Hospital from September 2018 to September 2023. The children were managed with a multidisciplinary collaborative comprehensive healthcare management model after discharge. Outpatient data at 1 month and 6, 12 and 24 months after discharge were collected, including (height, weight, body mass index, nutritional feeding status, hearing and vision screening results, Gesell developmental assessment results and intervention guidance services. The follow-up interval or frequency was dynamically adjusted or increased according to the child′s situation. The paired sample t-test and chi square test were applied to compare the differences in Gesell developmental quotient (DQ) and developmental delay rate between the first and last assessments to preliminarily explore the effectiveness of the comprehensive healthcare management model for children with bacterial meningitis after discharge. Results:All the 268 children completed their first assessment one month after discharge, and 37 children were found to have abnormal physical growth, mainly obesity (28 children), and another 9 children were malnutrition. Nutritional intervention and feeding guidance services were provided to all the 37 children, and as of the last follow-up, 20 children′s physical growth evaluations had turned normal. A total of 188 children completed at least 2 developmental assessments, with an interval of (14.2±9.4) months between the first and last assessments (range: 3.1-49.5 months). The DQ values of in the energy region of adaptability, gross motor skills, fine motor skills, language, and personal social skills at the last assessment were significantly higher than those at the first assessment [(91.93±13.28) vs (80.73±15.96) points, (91.69±12.96) vs (78.31±16.58) points, (89.32±16.11) vs (80.68±15.63) points, (90.10±16.65) vs (82.04±18.43) points, (92.01±14.05) vs (77.82±17.42) points]; moreover, the rates of developmental delay in each energy region were significantly lower than those at the initial assessment (9.6% vs 35.1%, 9.6% vs 42.0%, 18.1% vs 33.0%, 13.3% vs 31.9%, 9.6% vs 42.0%) (all P<0.05). Among the 200 children who completed the hearing screening, 18 were found with hearing abnormalities, and 2 were diagnosed with hearing loss in the Otolaryngology Department. Among 217 children who completed vision screening, 23 had abnormalities, and 5 were diagnosed with ophthalmic abnormalities in Ophthalmology Department (2 with strabismus, 2 with refractive errors, and 1 with optic nerve injury). Two children were found to have autism-like behavior during monitoring, and were referred to a developmental behavior clinic to be diagnosed with autism spectrum disorder and were given early diagnosis and intervention guidance. Conclusion:The comprehensive healthcare management model for children with bacterial meningitis after discharge can integrate clinical and healthcare resources, which is beneficial for improving the prognosis and enhancing the quality of life for children with special health status.

Objective:To evaluate the effect of obesity on the displacement of a left-sided double-lumen tube (DLT) during positional changes.Methods:This was a prospective cohort study. Six hundred and two patients who underwent elective chest surgery and required insertion of a left-sided DLT from February 2020 to November 2023 in our hospital were selected and divided into 2 groups based on the body mass index (BMI): obesity group (BMI≥28 kg/m 2,n=208) and non-obesity group (18.5 kg/m 2≤BMI<28 kg/m 2,n=394). General characteristics of patients, history of chest surgery, DLT model, depth of DLT placement in supine position, height/depth of placement (H/D) ratio, and distance of DLT displacement were recorded. DLT displacement was defined as a displacement distance of ≥15 mm. The logistic regression was used for analysis of the relationship between BMI and left DLT shift during positional changes. The receiver operating characteristic curve was used to evaluate the accuracy of BMI in predicting the left-sided DLT displacement during positional changes. Results:Compared with non-obese group, the depth of DLT placement was significantly reduced, the H/D ratio was increased, the distance of DLT displacement was increased, and the incidence of DLT displacement was increased in obese group ( P<0.05). The results of binary logistic regression analysis showed that a BMI≥28 kg/m 2 was an independent risk factor for DLT displacement ( OR value [95% confidence interval]=4.18 (2.36-7.38), P<0.001). The sensitivity of BMI in predicting the left-sided DLT displacement during positional changes was 77.4%, and the specificity was 69.6%, with an optimal cutoff value of 27.48 kg/m 2 and an area under the receiver operating characteristic curve of 0.757. Conclusions:Obesity can increase the probability of the left-sided DLT displacement during positional changes.

Objective:To compare the effects of left paratracheal pressure (LPP) and cricoid pressure (CP) during mask ventilation in obese patients.Methods:Sixty patients of either sex, aged 18-60 yr, with 28 kg/m 2≤body mass index<35 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, scheduled for general anesthesia, were divided into 2 groups ( n=30 each) using a random number table method: LPP group and CP group. In LPP group, pressure was applied beside the trachea, above the clavicle towards the vertebral direction, while in CP group, pressure was applied downwards to the cricoid cartilage, with a force of pressure between 25-35 N. The spatial relationship between the esophagus, trachea, and cricoid cartilage, the presence of air shadows in the gastric antrum during mask ventilation, and the cross-sectional area (CSA) of the gastric antrum before and after mask ventilation as well as the airway pressure during mask ventilation were observed. Results:In both groups, the esophagus was located in the left of the trachea in the supraclavicular region. There were no statistically significant differences in the airway pressure during mask ventilation and the CSA of the gastric antrum prior to mask ventilation between the two groups ( P>0.05). Compared to LPP group, the proportion of patients with air shadows in the gastric antrum during mask ventilation was significantly increased, and the CSA of the gastric antrum was increased after mask ventilation in CP group ( P<0.05). Conclusions:Compared to CP, LPP can decrease the development of air entering the stomach during mask ventilation and reduce the CSA of the gastric antrum after mask ventilation in obese patients.

Objective:To investigate the effect and associated mechanism of tumor tissue-infiltrating NK cells after receiving radiotherapy for hepatocellular carcinoma (HCC).Methods:A HCC tumor-bearing mouse model was constructed using human hepatocellular carcinoma cell line (SK-Hep-1) and divided into four groups: control, radiotherapy, NK cell clearance, and NK clearance combined with radiotherapy. Tumor growth condition was simultaneously recorded. The NK cell ratio in peripheral blood and the NK cell intratumoral infiltration condition were detected by flow cytometry and immunohistochemistry. Lentiviral-constructed SK-Hep-1 cells was used to detect the effect of radiotherapy on the regulation of CXCL10 and NK cell chemotaxis following EZH2 overexpression. SK-Hep-1 cells were irradiated in vitro and in vivo. The expression levels of EZH2 and CXCL10 mRNA and protein in the two groups of cell lines and mouse tumor tissues were detected by reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), western blotting (WB), and immunohistochemistry. The chemotaxis and blocking experiments were used to validate the chemotaxis effect of CXCL10 on NK cells. The independent sample t-test was used to compare the groups. P<0.05 was considered statistically significant. Results:The HCC tumor-bearing mouse model experiment showed that HCC tumor growth was most remarkable in the NK clearance combined with the radiotherapy group compared to the radiotherapy group ( P<0.05). Compared with the control group, the number of NK cells in the peripheral blood of nude mice in the radiotherapy group was significantly reduced, while the NK cell intratumoral infiltration was significantly increased ( P<0.05). Flow cytometry and immunohistochemistry showed invitro and invivo expressional alterations. The average expression levels of EZH2 mRNA and protein in hepatocellular carcinoma cell lines and tumor tissues were decreased in the radiotherapy group than the control group and mouse tumor tissues ( P<0.05), while the mRNA and protein expression levels of CXCL10 increased ( P<0.05). The cell supernatant following radiotherapy enhanced NK cell chemotaxis but inhibited CXCL10 neutralization. EZH2 overexpression validated that radiotherapy up-regulated CXCL10 mRNA and down-regulated protein expression levels in in vitro and in vivo experiments ( P<0.05). The chemotactic effect on NK cells was significantly weakened with EZH2 overexpression following radiotherapy. Conclusion:NK cells, as immune effector cells, are directly involved in radiotherapy- activated anti-HCC immunity. Importantly, radiotherapy inhibits EZH2 expression in hepatocellular carcinoma, thereby upregulating CXCL10 expression and enhancing intratumoral NK cell invasion.