Objective To investigate the effect of drug-eluting bead DACE(DEB-TACE)combined with systemic treatment for hepatocellular carcinoma(HCC)in different locations.Methods A total of 204 HCC patients who underwent DEB-TACE combined with systemic therapy(targeted and immunotherapy)were retrospectively collected.According to the anatomical location of HCC,86 cases with lesions located at the main trunk of portal vein(PV)or within 1 cm of the first PV branch were classified into central type group,while 118 cases with lesions located at the other areas were classified as peripheral type group.Follow-up was regularly performed after DEB-TACE until August,2024.The objective response rate(ORR)and disease control rate(DCR)at 1,3,6 and 12 months after DEB-TACE,also patients'progression-free survival(PFS)and overall survival(OS)were compared between groups.Results All patients were followed up for a median of 32.6 months,during which 164 cases died.Significant differences of ORR at 1 and 3 months after DEB-TACE(77.91％[67/86]vs.89.83％[106/118],34.88％[30/86]vs.54.24％[64/118])and DCR at 3 and 6 months after DEB-TACE(51.16％[44/86]vs.66.95％[79/118],34.88％[30/86]vs.50.00％[59/118])were found between groups(all P＜0.05).Patients'PFS(30.18[9.12,48.54]months)and OS(37.36[17.79,56.68])in peripheral type group were better than those in central type group(20.11[11.35,28.87]months and 23.24[3.11,43.47]months,x2=3.971,4.162,P=0.048,0.041).Conclusion The effect of DEB-TACE combined with systemic treatment for peripheral type HCC was better than for central type HCC.

Objective To investigate the effects of sleep deprivation on the firing activity of hippocampal parvalbumin-expressing interneuron(PV-IN)of mice during trace eyeblink conditioning(tEBC)training and during recovery sleep.Methods A total of 15 PV-Cre mice were randomly assigned into a sleep deprivation group(n=8)and a control group(n=7).After daily tEBC training,the sleep deprivation group experienced 1.5 h of sleep deprivation followed by 1.5 h of recovery sleep,and the control group mice were allowed to sleep freely,for 5 consecutive days.Multichannel recording and optogenetic techniques was applied to identify the hippocampal PV-IN in vivo.Results The sleep deprived mice failed to show significant increase in the incidence of conditioned eyeblink response(CR)across 5 training days(P>0.05).On training days 3～5,the CR incidence was significantly lower in the sleep deprived mice than the control mice(P<0.05).The enhancement of conditioned stimulus(CS)-evoked firing activity in hippocampal PV-INs during tEBC training was significantly lower in the sleep deprived mice when compared to the control mice(P<0.05).The sleep deprived mice obtained notably strengthened firing activity of hippocampal PV-INs peri sharp wave ripple events during recovery sleep period when compared with the pre-training sleep period(P<0.05),and the enhancement was remarkably greater than that in the control mice(P<0.05).Sleep deprivation had no obvious effects on the firing activity of hippocampal non PV-IN during either tEBC training or recovery sleep(P>0.05).Conclusion Sleep deprivation produces dual effects on the firing activities of hippocampal PV-INs during tEBC training and recovery sleep.These effects may be the cellular mechanisms of tEBC memory formation and consolidation disorders caused by sleep deprivation.

OBJECTIVE: To assess the safety and topical efficacy of prim-O-glucosylcimifugin (POG) and investigate the molecular mechanisms of its therapeutic effects in atopic dermatitis (AD). METHODS: The effects of POG on human keratinocyte cell viability and its anti-inflammatory properties were evaluated using cell counting kit-8 assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the impact of POG on the differentiation of cluster of differentiation (CD) 4⁺ T cell subsets, including T-helper type (Th) 1, Th2, Th17, and regulatory T (Treg), was examined through in vitro experiments. Network pharmacology analysis was used to elucidate POG's therapeutic mechanisms. Furthermore, the therapeutic potential of topically applied POG was further evaluated in a calcipotriol-induced mouse model of AD. The protein and transcript levels of inflammatory markers, including cytokines, lymphocyte-specific protein tyrosine kinase (Lck) mRNA, and LCK phosphorylation (p-LCK), were quantified using immunohistochemistry, RT-qPCR, and Western blot analysis. RESULTS: POG was able to suppress cell proliferation and downregulate the transcription of interleukin 4 (Il4) and Il13 mRNA. In vitro experiments indicated that POG significantly inhibited the differentiation of Th2 cells, whereas it exerted negligible influence on the differentiation of Th1, Th17 and Treg cells. Network pharmacology identified LCK as a key therapeutic target of POG. Moreover, the topical application of POG effectively alleviated skin lesions in the calcipotriol-induced AD mouse models without causing pathological changes in the liver, kidney or spleen tissues. POG significantly reduced the levels of Il4, Il5, Il13, and thymic stromal lymphopoietin (Tslp) mRNA in the AD mice. Concurrently, POG enhanced the expression of p-LCK protein and Lck mRNA. CONCLUSION Our research revealed that POG inhibits Th2 cell differentiation by promoting p-LCK protein expression and hence effectively alleviates AD-related skin inflammation. Please cite this article as: Zhao H, Ma X, Wang H, Ding XJ, Kuai L, Song JK, Zhang Z, Yang D, Gao CJ, Li B, Zhou M. Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation. J Integr Med. 2025; 23(3): 309-319.
Dermatitis, Atopic/drug therapy* ; Animals ; Humans ; Cell Differentiation/drug effects* ; Phosphorylation/drug effects* ; Mice ; Th2 Cells/drug effects* ; Keratinocytes/drug effects* ; Disease Models, Animal ; Mice, Inbred BALB C ; Calcitriol/analogs & derivatives*

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.

AIM To establish the near-infrared spectroscopy quantitative models for moisture,23-acetylalismol B and 23-acetylalismol C in Alismatis Rhizoma decoction pieces.METHODS The near-infrared spectroscopy(NIRS)data were collected in 95 batches of decoction pieces,after which drying method was adopted in the content determination of moisture,HPLC was applied to determining the contents of 23-acetylalismol B and 23-acetylalismol C,the quantitative models were established by partial least squares method combined with feature extraction algorithms.RESULTS The model training determination coefficients were 0.952 6,0.958 1 and 0.920 8,along with the prediction determination coefficients of 0.930 0,0.905 2 and 0.906 4,the residual prediction deviations(PRD)of 4.00,3.58 and 3.46,and the root mean square error ratios of prediction values to calibration values(RMSEP/RMSEC)of 1.15,1.11 and 1.06,respectively.CONCLUSION The quantitative models based on NIRS exhibit good prediction effects,which can be used for the rapid quality detection of Alismatis Rhizoma decoction pieces.

Objective To investigate the correlation between cognitive impairment and depression in elderly patients with type 2 diabetes mellitus(T2DM).Methods Based on China Health and Retirement Longitudinal Study in 2011,totally 521 elderly T2DM patients were enrolled,and according to the results of minimum mental state examination(MMSE)and their education lev-els,they were divided into a cognitively impaired group(437 cases)and a cognitively normal group(84 cases).Center for ED Epidemiological Survey Depression Scale was used to assess the depression symptoms.The correlation between cognitive impairment and depression was analyzed.Results Compared with the cognitively normal group,the cognitively impaired group had signifi-cantly advanced age(71.98±5.29 year vs 69.42±3.98 year,P=0.000),larger proportion of de-pression(60.6％vs 35.7％,P=0.000),and higher C-reactive protein level(5.09±12.80 mg/L vs 2.25±2.43 mg/L,P=0.000),and obviously lower ratios of being married(72.1％vs 86.9％,P=0.001)and having cardiovascular disease(20.1％vs 32.1％,P=0.010),and decreased estimated glomerular filtration rate[77.15±15.88 ml/(min·1.73 m2)vs 81.91±13.55 ml/(min·1.73 m2),P=0.001].Multivariate logistic regression analysis showed that cognitive impairment was an independent risk factor for the development of depression in elderly T2DM patients(OR=3.44,95％CI:1.89-6.27,P＜0.01).ROC curve analysis indicated that the AUC value of MMSE score in predicting depression in elderly T2DM patients was 0.669(95％CI:0.626-0.709,P＜0.01).The direct effect of cognitive impairment and the mediating effect of loneliness on depression in elderly T2DM patients accounted for 72.22％and 27.78％of the total effect,respectively.Conclu-sion Cognitive impairment is associated with the presence of depression in elderly T2DM pa-tients,and loneliness plays a mediating role.

Objective: To explore the potential category patterns of risk prevention and control behaviors of HIV infection among young students who have sex with men (MSM) and their impact on HIV infection and late detection, aiming to optimize intervention strategies. Methods: From September 2017 to December 2024, a total of 1 637 MSM young students in Tianjin were recruited through both online and offline channels. Latent class analysis was applied to classify 11 HIV risk prevention and control behaviors [condom use during the most recent anal sex in the past 6 months, consistent condom use, use of water based lubricants, abstinence from recreational drugs, regular on site professional testing, fixed sexual partners, partner testing, awareness of partner s HIV testing results, testing before sexual activity, nucleic acid testing, and use of pre exposure prophylaxis (PrEP) or post exposure prophylaxis (PEP)]. Multivariate Logistic regression analyzed associations between demographic characteristics/intervention services factors and latent classes. Differences in HIV infection and late detection across behavior patterns were compared. Results: HIV risk prevention and control behaviors among MSM students were classified into three latent classes:condom dependent group (38.42%), low prevention group (27.73%), and comprehensive prevention group (33.85%). Students who received condom promotion/testing services were more likely to belong to the comprehensive prevention group ( OR =5.58), while those who received peer education were less likely to the comprehensive prevention group ( OR =0.43) (both P <0.01). Among the MSM student population, the HIV infection rate was 4.83%, with 2.26% of cases detected late. The HIV infection rate (1.45%) and late detection proportion (0.82%) in the comprehensive prevention group were lower than those in the low prevention group (7.89% and 3.83%, respectively) ( χ 2=16.20, 7.31, both P <0.01). Conclusions HIV risk prevention and control behaviors among MSM young students exhibit significant heterogeneity. Comprehensive prevention strategies can effectively reduce HIV infection and late detection risks. It is necessary to optimize peer education content and improve the accessibility of diversified prevention measures such as PrEP/PEP to enhance HIV prevention and control.

AIM To establish the near-infrared spectroscopy quantitative models for moisture,23-acetylalismol B and 23-acetylalismol C in Alismatis Rhizoma decoction pieces.METHODS The near-infrared spectroscopy(NIRS)data were collected in 95 batches of decoction pieces,after which drying method was adopted in the content determination of moisture,HPLC was applied to determining the contents of 23-acetylalismol B and 23-acetylalismol C,the quantitative models were established by partial least squares method combined with feature extraction algorithms.RESULTS The model training determination coefficients were 0.952 6,0.958 1 and 0.920 8,along with the prediction determination coefficients of 0.930 0,0.905 2 and 0.906 4,the residual prediction deviations(PRD)of 4.00,3.58 and 3.46,and the root mean square error ratios of prediction values to calibration values(RMSEP/RMSEC)of 1.15,1.11 and 1.06,respectively.CONCLUSION The quantitative models based on NIRS exhibit good prediction effects,which can be used for the rapid quality detection of Alismatis Rhizoma decoction pieces.

Objective To investigate the effect of drug-eluting bead DACE(DEB-TACE)combined with systemic treatment for hepatocellular carcinoma(HCC)in different locations.Methods A total of 204 HCC patients who underwent DEB-TACE combined with systemic therapy(targeted and immunotherapy)were retrospectively collected.According to the anatomical location of HCC,86 cases with lesions located at the main trunk of portal vein(PV)or within 1 cm of the first PV branch were classified into central type group,while 118 cases with lesions located at the other areas were classified as peripheral type group.Follow-up was regularly performed after DEB-TACE until August,2024.The objective response rate(ORR)and disease control rate(DCR)at 1,3,6 and 12 months after DEB-TACE,also patients'progression-free survival(PFS)and overall survival(OS)were compared between groups.Results All patients were followed up for a median of 32.6 months,during which 164 cases died.Significant differences of ORR at 1 and 3 months after DEB-TACE(77.91％[67/86]vs.89.83％[106/118],34.88％[30/86]vs.54.24％[64/118])and DCR at 3 and 6 months after DEB-TACE(51.16％[44/86]vs.66.95％[79/118],34.88％[30/86]vs.50.00％[59/118])were found between groups(all P＜0.05).Patients'PFS(30.18[9.12,48.54]months)and OS(37.36[17.79,56.68])in peripheral type group were better than those in central type group(20.11[11.35,28.87]months and 23.24[3.11,43.47]months,x2=3.971,4.162,P=0.048,0.041).Conclusion The effect of DEB-TACE combined with systemic treatment for peripheral type HCC was better than for central type HCC.

Objective To investigate the correlation between cognitive impairment and depression in elderly patients with type 2 diabetes mellitus(T2DM).Methods Based on China Health and Retirement Longitudinal Study in 2011,totally 521 elderly T2DM patients were enrolled,and according to the results of minimum mental state examination(MMSE)and their education lev-els,they were divided into a cognitively impaired group(437 cases)and a cognitively normal group(84 cases).Center for ED Epidemiological Survey Depression Scale was used to assess the depression symptoms.The correlation between cognitive impairment and depression was analyzed.Results Compared with the cognitively normal group,the cognitively impaired group had signifi-cantly advanced age(71.98±5.29 year vs 69.42±3.98 year,P=0.000),larger proportion of de-pression(60.6％vs 35.7％,P=0.000),and higher C-reactive protein level(5.09±12.80 mg/L vs 2.25±2.43 mg/L,P=0.000),and obviously lower ratios of being married(72.1％vs 86.9％,P=0.001)and having cardiovascular disease(20.1％vs 32.1％,P=0.010),and decreased estimated glomerular filtration rate[77.15±15.88 ml/(min·1.73 m2)vs 81.91±13.55 ml/(min·1.73 m2),P=0.001].Multivariate logistic regression analysis showed that cognitive impairment was an independent risk factor for the development of depression in elderly T2DM patients(OR=3.44,95％CI:1.89-6.27,P＜0.01).ROC curve analysis indicated that the AUC value of MMSE score in predicting depression in elderly T2DM patients was 0.669(95％CI:0.626-0.709,P＜0.01).The direct effect of cognitive impairment and the mediating effect of loneliness on depression in elderly T2DM patients accounted for 72.22％and 27.78％of the total effect,respectively.Conclu-sion Cognitive impairment is associated with the presence of depression in elderly T2DM pa-tients,and loneliness plays a mediating role.