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*

With the deepening of molecular biology and cell biology research,the regulatory mechanism of autophagy has been gradually revealed,providing new ideas for the treatment of numerous diseases.Autophagy may be closely related to pathological changes such as apoptosis resistance of fibroblast-like synoviocytes,disturbances in bone metabolic homeostasis,and antigen presentation,the regulation of autophagy homeostasis may be an important approach for the treatment of rheumatoid arthritis(RA).In this paper,we provide a review on the pathological mechanism of autophagy in RA,with a view to providing a theoretical basis for later studies.

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.

In recent decades,the incidence of human papillomavirus(HPV)-associated oropharyngeal squamous cell carcinoma(OPSCC)has shown a marked increase.Significant changes have also occurred in the OPSCC diagnosis and treatment paradigm.Deter-mining HPV status prior to treatment is now essential,and radiotherapy/chemotherapy,immunotherapy,and minimally invasive surgical techniques have progressively emerged as key modalities for managing OPSCC.However,alongside these paradigm shifts,a comprehen-sive technical consensus guiding the entire diagnostic and therapeutic process for OPSCC patients is currently lacking.Given China's large population base and the rising incidence of OPSCC,an expert panel convened to develop a clinical technical consensus on OPSCC diagno-sis and management tailored to China's specific context.This consensus aims to further enhance and standardize understanding of OPSCC management techniques among relevant healthcare professionals.

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.

Aim To investigate the neuroprotective effect of Takeda G protein-coupled receptor-5(TGR5)activated by INT-777 on hypoxic-ischemic encephalop-athy(HIE)in neonatal rats.Methods Seven-day-old SD rats were randomly divided into the sham opera-tion group(Sham,S),model group(HIE,G),INT-777 low-dose(L),medium-dose(M),and high-dose(H)groups.The modified Rice-Vanucci method was used to construct the HIE model and Intranasal admin-istration 1 h after modeling.Short-term neurobehavioral tests were performed 48 h after modeling to evaluate the neurological function of neonatal rats,TTC staining was used to determine the volume of cerebral infarction,dry and wet specific gravity was used to determine the brain water content,ferrous ion kit was used to deter-mine the brain ferrous ion content,HE staining was used to observe the pathological damage of brain tis-sue,Nissl staining was used to observe the loss of Nissl substance,Transmission electron microscopy(TEM)was used to observe the mitochondrial morphological changes of cortical neurons,and Western blot was em-ployed to detect the expression of ferroptosis-related proteins TFR1 and GPX4.Results Compared with group S,group G had increased short-term neurobehav-ioral test consumption time,higher scores,increased cerebral infarct volume,brain water content,and brain ferrous iron content,significant brain tissue damage on the affected side,severe loss of Nissl substance,smaller neuronal mitochondria,decreased mitochondrial cris-tae,and increased expression of TFR1 and reduced ex-pression of GPX4.Compared with group G,the INT-777 administration group had a shorter consumption time for short-term neurobehavioral tests,lower scores,the cerebral infarction volume,brain water content,and brain ferrous ion content decreased,the brain tissue damage on the affected side was reduced,and there was insignificant loss of Nissl substance,larger neuronal mi-tochondrial volume,increased mitochondrial cristae,re-duced expression of TFR1,and increased expression of GPX4.Conclusions INT-777 agonist TGR5 has a protective effect against hypoxic-ischemic encephalopa-thy in neonatal rats,and its mechanism of action may be related to the inhibition of neuronal ferroptosis.

Oropharyngeal squamous cell carcinoma(OPSCC)is a malignant tumor originating from the squamous epithelium of the oro-pharyngeal mucosa,accounting for more than 90％of oropharyngeal malignancies.In recent years,human papillomavirus(HPV)infec-tion has become one of the primary etiological factors of oropharyngeal squamous carcinoma.The incidence of HPV-associated oropharyn-geal squamous carcinoma has been rising annually,with a noticeable trend toward younger populations,posing a significant threat to hu-man health.Due to the distinct biological behavior and clinical characteristics of HPV-associated oropharyngeal squamous carcinoma com-pared to its non-HPV-related counterpart,the diagnostic and treatment strategies for oropharyngeal squamous carcinoma have undergone substantial changes.Prevention and screening for oropharyngeal squamous carcinoma are of critical importance.The diagnostic and treat-ment process involves multi-disciplinary collaboration,including oral and maxillofacial surgery,otolaryngology,head and neck surgery,oncology,radiology and pathology.Based on evidence from clinical practice,a comprehensive,integrated diagnostic and therapeutic ap-proach has been established,centered around the concept of"prevention,screening,diagnosis,treatment,and rehabilitation",covering the entire patient lifecycle and providing a valuable reference for clinical practice.

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.