OBJECTIVE To investigate the mechanism of Xihuang pill （XHP） against diffuse large B-cell lymphoma （DLBCL）. METHODS The active ingredients of XHP and potential therapeutic targets for DLBCL were identified using TCMSP， GeneCards and DisGeNET databases. Protein-protein interaction networks were constructed using the String database and Cytoscape software to screen core components and core targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were then performed. The clinical relevance of core targets was analyzed using the GEPIA and PanCanSurvPlot databases. Molecular docking and molecular dynamics （MD） simulation were conducted to verify the interactions between core components and core targets， and the binding free energy was calculated using the molecular mechanics Poisson-Boltzmann surface area （MM-PBSA） method. The effects of XHP on DLBCL and the related molecular mechanisms were validated using CCK-8 assay， flow cytometry and Western blot. RESULTS Network pharmacology analysis identified 108 active ingredients of XHP and 410 potential therapeutic targets for DLBCL. Six core components （e.g.， 17 beta-estradiol， quercetin） and ten core targets [e.g.， tumor protein 53 （TP53）， proto-oncogene tyrosine-protein kinase Src （SRC）] were obtained. Enrichment analysis indicated that the anti-DLBCL effects of XHP were primarily associated with the apoptotic signaling pathway， the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway and so on. Clinical correlation analysis revealed that TP53 and SRC expression were significantly up-regulated in DLBCL tissues and associated with poor patient prognosis （P＜0.05）. Molecular docking， MD simulations and MM-PBSA calculations confirmed that the SRC-quercetin complex had a mail：stronger and more stable binding affinity. In vitro experiments demonstrated that XHP concentration-dependently inhibited the proliferation of DLBCL cells； compared with control group， XHP medium- and high-dose groups could significantly induce the apoptosis of SU-DHL2 and SU-DHL4 cells， and significantly down- regulated the expressions of SRC protein， phosphorylated （p）-PI3K/PI3K and p-Akt/Akt in SU-DHL4 cells （P＜0.05）. CONCLUSIONS XHP may inhibit the proliferation and induce the apoptosis of DLBCL cells by regulating the SRC/PI3K/Akt signaling pathway.

Objective:The clinical significance of aural fullness in patients with vestibular migraine（VM） remains unclear, and it is yet to be determined whether VM with aural fullness represents a distinct subtype of VM; this study aimed to compare differences in demographic characteristics, clinical manifestations, audiological findings, and vestibular function tests between VM patients with and without aural fullness, and explore whether the former is a subtype of VM and whether it requires differentiated treatment. Methods:A total of 174 VM patients were enrolled, including 75 with aural fullness（aural fullness group） and 99 without aural fullness（non-aural fullness group）; demographic data, vertigo characteristics, medical history, family history, pure-tone audiometry, and vestibular function tests were thoroughly recorded, and independent samples t-test and chi-square test were used for inter-group comparisons. Results:①Regarding demographic characteristics, the age of the aural fullness group was significantly lower than that of the non-aural fullness group[（44.08±13.97） years vs. （49.45±16.05） years, P=0.020）, while the two groups showed consistent gender distribution（more females than males） with no statistically significant difference. ②For aural fullness characteristics, unilateral aural fullness accounted for 65.0% in the aural fullness group, significantly higher than bilateral aural fullness（35.0%, P<0.001）. ③In terms of vertigo characteristics, there were no statistically significant inter-group differences in the nature of attacks（rotational vertigo: 36.0% vs. 41.4%, P=0.463; dizziness: 21.3% vs. 11.1%, P=0.064; rotational vertigo or dizziness: 29.3% vs. 25.3%, P=0.548; dizziness with unsteady gait: 9.3% vs. 11.1%, Fisher P=0.806; visual oscillation with unsteady gait: 4.0% vs. 11.1%, Fisher P=0.086）, duration（several hours: 34.7% vs. 33.3%, P=0.841; several minutes: 22.7% vs. 21.2%, P=0.808; several seconds: 5.3% vs. 8.1%, Fisher P=0.557; several days: 9.3% vs. 9.1%, Fisher P=1.000; multiple combined patterns: 17.3% vs. 15.2%, P=0.686）, or incidence of nausea and vomiting（84.0% vs. 72.7%, P=0.071, no statistical significance）. ④No statistically significant inter-group differences were found in medical history and family history, including motion sickness history（8.0% vs. 4.0%, Fisher P=0.337）, headache history（22.7% vs. 34.3%, P=0.084）, and family history of dizziness（12.0% vs. 14.1%, P=0.666）. ⑤For audiological characteristics, 21.3%（16/75） of patients in the aural fullness group had low-frequency hearing loss, significantly higher than 5.1% in the non-aural fullness group（χ²=10.66, P=0.001）; among patients with unilateral aural fullness, 28.6%（14/49） had ipsilateral low-frequency hearing loss, significantly higher than 7.7%（2/26） of those with bilateral aural fullness（χ²=4.41, P=0.036）; however, there was no statistically significant difference in the rate of bilateral high-frequency hearing loss between the two groups（54.7%[41/75]vs. 50.5%[50/99], χ²=0.30, P=0.586）. ⑥In vestibular function tests, no statistically significant inter-group differences were observed in smooth pursuit type Ⅲ/Ⅳ（12.5% vs. 13.1%, P=0.913）, caloric test with CP>25%（31.2% vs. 37.4%, P=0.411）, abnormal video head impulse test（vHIT） rate（30.8% vs. 32.6%, P=0.865）, or abnormal vestibular evoked myogenic potential（VEMP） rate（53.8% vs. 38.9%, Fisher P=0.484）. Conclusion:VM patients with aural fullness have an earlier age of onset, with nearly 1/4 accompanied by low-frequency hearing loss; VM patients with and without aural fullness are highly consistent in gender distribution, nature/duration of vertigo, vestibular function impairment, and presence of bilateral high-frequency hearing loss, suggesting that the core clinical phenotypes of the two groups are consistent, while the former has an earlier age of onset and a higher proportion of unilateral hearing loss, which may be related to the pathological mechanism of VM and inner ear microcirculation disorders.
Humans ; Female ; Male ; Middle Aged ; Adult ; Migraine Disorders/classification* ; Young Adult ; Vertigo ; Age of Onset ; Aged ; Hearing Loss

Objective:To investigate the association between abdominal fat-related indicators derived from quantitative computed tomography (QCT) and coronary artery calcification (CAC) in middle-aged and elderly individuals, as well as the diagnostic value of these indicators.Methods:This cross-sectional study enrolled middle-aged and elderly participants who underwent health check-ups at Kaifeng Central Hospital between January and December 2024. Participants were divided into a CAC group and a non-CAC group based on the presence or absence of CAC. The CAC group was then stratified into mild, moderate, and severe subgroups according to CAC severity. General clinical data were collected for all participants. All subjects underwent one-stop QCT scanning of the chest and abdomen. An automated abdominal fat analysis system was used to identify fat distribution regions. If accurate identification was not possible, a semi-automated segmentation algorithm combined with manual correction was applied instead. Two physicians performed the measurements independently, and inter-observer consistency was assessed. The average values were calculated to obtain visceral fat area (VFA) and subcutaneous fat area (SFA). The ratio of visceral fat area to subcutaneous fat area (VFA/SFA) was also computed. Multivariate logistic regression analysis was performed to identify the factors associated with CAC in middle-aged and elderly individuals. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic efficacy of these indicators for CAC. DeLong′s test was used to compare the differences in the area under the curve ( AUC). Results:A total of 252 middle-aged and elderly individuals were included, with a median age of 61 (interquartile rang: 59, 69) years. Of these individuals, 188(74.6%) were males. Among them, 172 were classified into the CAC group and 80 into the non-CAC group. Multivariate logistic regression analysis revealed that VFA, VFA/SFA ratio, age, low-density lipoprotein cholesterol(LDL-C), and hypertension were independently associated with CAC in middle-aged and elderly individuals (all P<0.05). The mild, moderate, and severe CAC subgroups comprised 78, 51, and 43 participants, respectively. Analysis of variance (ANOVA) demonstrated that VFA and VFA/SFA increased with CAC severity, and there were statistically significant differences between the subgroups (all P<0.05). ROC curve analysis showed that the AUCs of VFA and VFA/SFA for diagnosing CAC were 0.841 and 0.810, respectively, with no significant difference between them ( P>0.05). The optimal cutoff values were 177.45 cm2 for VFA (sensitivity: 83.1%, specificity: 72.5%) and 1.592 for VFA/SFA (sensitivity: 65.7%, specificity: 83.7%). For the diagnosis of moderate-to-severe CAC, the AUCs of VFA and VFA/SFA were 0.765 and 0.761, respectively ( P>0.05 for comparison), with cutoff values of 231.75 cm2 (sensitivity: 61.7%, specificity: 83.3%) and 1.962 (sensitivity: 64.9%, specificity: 80.8%). Conclusion:Abdominal VFA and VFA/SFA derived from QCT are independently associated with the presence of CAC in middle-aged and elderly individuals, demonstrating good diagnostic performance for both overall CAC and moderate-to-severe CAC.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Phospholipid pharmaceutical excipients are primarily composed of a glycerol backbone,fatty acid chains,and phosphate groups.Due to their amphiphilic structure and unique physicochemical properties,they are commonly used as emulsifiers and carrier materials in pharmaceutical formulations.The pharmacopoeias of various countries have included phospholipid based pharmaceutical excipients and specified the testing methods and limits for their critical quality attributes.This article focuses on the current inclusion status,characteristic indicators,component content determination indicators,and functionality-related indicators determination methods and limits of phospholipid pharmaceutical excipients of various countries,in order to provide references and a basis for the rational applicatione of phospholipid pharmaceutical excipients.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Phospholipid pharmaceutical excipients are primarily composed of a glycerol backbone,fatty acid chains,and phosphate groups.Due to their amphiphilic structure and unique physicochemical properties,they are commonly used as emulsifiers and carrier materials in pharmaceutical formulations.The pharmacopoeias of various countries have included phospholipid based pharmaceutical excipients and specified the testing methods and limits for their critical quality attributes.This article focuses on the current inclusion status,characteristic indicators,component content determination indicators,and functionality-related indicators determination methods and limits of phospholipid pharmaceutical excipients of various countries,in order to provide references and a basis for the rational applicatione of phospholipid pharmaceutical excipients.

Objective:To investigate the association between abdominal fat-related indicators derived from quantitative computed tomography (QCT) and coronary artery calcification (CAC) in middle-aged and elderly individuals, as well as the diagnostic value of these indicators.Methods:This cross-sectional study enrolled middle-aged and elderly participants who underwent health check-ups at Kaifeng Central Hospital between January and December 2024. Participants were divided into a CAC group and a non-CAC group based on the presence or absence of CAC. The CAC group was then stratified into mild, moderate, and severe subgroups according to CAC severity. General clinical data were collected for all participants. All subjects underwent one-stop QCT scanning of the chest and abdomen. An automated abdominal fat analysis system was used to identify fat distribution regions. If accurate identification was not possible, a semi-automated segmentation algorithm combined with manual correction was applied instead. Two physicians performed the measurements independently, and inter-observer consistency was assessed. The average values were calculated to obtain visceral fat area (VFA) and subcutaneous fat area (SFA). The ratio of visceral fat area to subcutaneous fat area (VFA/SFA) was also computed. Multivariate logistic regression analysis was performed to identify the factors associated with CAC in middle-aged and elderly individuals. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic efficacy of these indicators for CAC. DeLong′s test was used to compare the differences in the area under the curve ( AUC). Results:A total of 252 middle-aged and elderly individuals were included, with a median age of 61 (interquartile rang: 59, 69) years. Of these individuals, 188(74.6%) were males. Among them, 172 were classified into the CAC group and 80 into the non-CAC group. Multivariate logistic regression analysis revealed that VFA, VFA/SFA ratio, age, low-density lipoprotein cholesterol(LDL-C), and hypertension were independently associated with CAC in middle-aged and elderly individuals (all P<0.05). The mild, moderate, and severe CAC subgroups comprised 78, 51, and 43 participants, respectively. Analysis of variance (ANOVA) demonstrated that VFA and VFA/SFA increased with CAC severity, and there were statistically significant differences between the subgroups (all P<0.05). ROC curve analysis showed that the AUCs of VFA and VFA/SFA for diagnosing CAC were 0.841 and 0.810, respectively, with no significant difference between them ( P>0.05). The optimal cutoff values were 177.45 cm2 for VFA (sensitivity: 83.1%, specificity: 72.5%) and 1.592 for VFA/SFA (sensitivity: 65.7%, specificity: 83.7%). For the diagnosis of moderate-to-severe CAC, the AUCs of VFA and VFA/SFA were 0.765 and 0.761, respectively ( P>0.05 for comparison), with cutoff values of 231.75 cm2 (sensitivity: 61.7%, specificity: 83.3%) and 1.962 (sensitivity: 64.9%, specificity: 80.8%). Conclusion:Abdominal VFA and VFA/SFA derived from QCT are independently associated with the presence of CAC in middle-aged and elderly individuals, demonstrating good diagnostic performance for both overall CAC and moderate-to-severe CAC.

Objective:To analyze the clinical efficacy and prognostic factors of comprehensive treatment for atypical teratoid / rhabdomyoma tumor (AT/RT).Methods:Clinical data of children diagnosed with AT/RT who underwent radiotherapy in Department of Oncology of Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine from November 2012 to September 2022 were retrospectively analyzed. Pearson Chi-square test or continuous-corrected Chi-square test or Fisher's exact probability method were used for inter-group comparison of categorical variables. Independent sample t-test or Wilcoxon rank-sum test were used for inter-group comparison of continuous variables. Kaplan-Meier method was used to calculate the 1-year and 2-year overall survival (OS) rate and progression free survival (PFS) rate. Univariate and multivariate Cox regression analyses were employed to determine relevant prognostic factors. Results:A total of 45 patients were included, with a male/female ratio of 1.65:1, including 27 children aged ≥3 years old. All patients received surgery and radiotherapy in which 39 patients received chemotherapy, 41 craniospinal irradiation (CSI), and 4 whole brain or focal radiation therapy. The median follow-up was 28 (13.5, 49) months. A total of 14 patients died after comprehensive treatment. The 1-year OS rate was 80.0% and the PFS rate was 71.1%. The 2-year OS rate was 75.5% and the PFS rate was 65.7%. Survival prognostic analysis showed negative imaging assessment after radiotherapy ( HR=0.087, 95% CI: 0.011-0.697, P=0.022) was a favorable factor for PFS. The primary tumor<4.8 cm ( HR=0.221, 95% CI: 0.052-0.935, P=0.040) and CSI ( HR=0.085, 95% CI: 0.011-0.651, P=0.018) were favorable factors for OS. In subgroup analysis, CSI also improved OS in children aged ≥3 years ( HR=0.014, 95% CI: 0-0.470, P=0.017), but there was no significant difference in PFS. In children without cerebrospinal fluid dissemination, negative radiographic results after radiotherapy ( HR=0.066, 95% CI: 0.009-0.481, P=0.007; HR=0.076, 95% CI: 0.008-0.695, P=0.024, respectively) and CSI (HR=0.105, 95% CI: 0.012-0.937, P=0.044; HR=0.054, 95% CI: 0.005-0.629, P=0.020, respectively) were favorable factors for PFS and OS in children, and the primary tumor<4.8 cm also suggested a longer OS ( HR=0.094, 95% CI: 0.013-0.690, P=0.020). Conclusions:Comprehensive treatment including radiotherapy improves clinical prognosis of children with AT/RT. Our study shows that negative imaging results after radiotherapy are associated with PFS improvement. The primary tumor<4.8 cm and CSI are favorable factors for OS. CSI is also a significantly positive prognostic factor in children aged ≥3 years and those without cerebrospinal fluid dissemination.

Breast cancer remains a leading cause of mortality in women worldwide.Triple-negative breast cancer(TNBC)is a particularly aggressive subtype characterized by rapid progression,poor prognosis,and lack of clear therapeutic targets.In the clinic,delineation of tumor heterogeneity and development of effective drugs continue to pose considerable challenges.Within the scope of our study,high hetero-geneity inherent to breast cancer was uncovered based on the landscape constructed from both tumor and healthy breast tissue samples.Notably,TNBC exhibited significant specificity regarding cell prolif-eration,differentiation,and disease progression.Significant associations between tumor grade,prog-nosis,and TNBC oncogenes were established via pseudotime trajectory analysis.Consequently,we further performed comprehensive characterization of the TNBC microenvironment.A crucial epithelial subcluster,E8,was identified as highly malignant and strongly associated with tumor cell proliferation in TNBC.Additionally,epithelial-mesenchymal transition(EMT)-associated fibroblast and M2 macrophage subclusters exerted an influence on E8 through cellular interactions,contributing to tumor growth.Characteristic genes in these three cluster cells could therefore serve as potential therapeutic targets for TNBC.The collective findings provided valuable insights that assisted in the screening of a series of therapeutic drugs,such as pelitinib.We further confirmed the anti-cancer effect of pelitinib in an orthotopic 4T1 tumor-bearing mouse model.Overall,our study sheds light on the unique characteristics of TNBC at single-cell resolution and the crucial cell types associated with tumor cell proliferation that may serve as potent tools in the development of effective anti-cancer drugs.