OBJECTIVE: To investigate the effect of TBL1XR1 mutation on cell biological characteristics of diffuse large B-cell lymphoma (DLBCL). METHODS: The TBL1XR1 overexpression vector was constructed and DNA sequencing was performed to determine the mutation status. The effect of TBL1XR1 mutation on apoptosis of DLBCL cell line was detected by flow cytometry and TUNEL fluorescence assay; CCK-8 assay was used to detect the effect of TBL1XR1 mutation on cell proliferation; Transwell assay was used to detect the effect of TBL1XR1 mutation on cell migration and invasion; Western blot was used to detect the effect of TBL1XR1 mutation on the expression level of epithelial-mesenchymal transition (EMT) related proteins. RESULTS: The TBL1XR1 overexpression plasmid was successfully constructed. The in vitro experimental results showed that TBL1XR1 mutation had no significant effect on apoptosis of DLBCL cells. Compared with the control group, TBL1XR1 mutation enhanced cell proliferation, migration and invasion of DLBCL cells. TBL1XR1 gene mutation significantly increased the expression of N-cadherin protein, while the expression of E-cadherin protein decreased. CONCLUSION TBL1XR1 mutation plays a role in promoting tumor cell proliferation, migration and invasion in DLBCL. TBL1XR1 could be considered as a potential target for DLBCL therapy in future research.
Humans ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Cell Proliferation ; Mutation ; Receptors, Cytoplasmic and Nuclear/genetics* ; Apoptosis ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Cell Movement ; Repressor Proteins/genetics* ; Nuclear Proteins/genetics* ; Cadherins/metabolism*

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*

Objective To investigate the relationship between serum levels of interferon-inducible protein 10(IP-10)and S100 calcium-binding protein A8(S100A8)and the prognosis of patients with severe pneumo-nia(SP).Methods A total of 315 SP patients admitted to the hospital from January 2021 to December 2023 were selected as the SP group,and 315 non-SP patients admitted to the hospital during the same period were selected as the non-SP group.According to the prognosis of SP patients 28 d after admission,they were divided into good prognosis group(199 cases)and poor prognosis group(116 cases).Enzyme-linked immunosorbent assay was used to detect serum IP-10 and S100A8 levels in SP patients.Pearson correlation analysis was used to analyze the correlation between IP-10,S100A8 levels and infection indicators[high-sensitivity C-reactive protein(hs-CRP),procalcitonin(PCT),interleukin-6(IL-6)].Multivariate Logistic regression was used to analyze the influencing factors of poor prognosis in SP patients.Receiver operating characteristic(ROC)curve was used to analyze the value of hs-CRP,PCT,IP-10 and S100A8 levels in predicting the poor prognosis of SP patients.Results The serum levels of IP-10,S100A8,hs-CRP,PCT and IL-6 in SP group were higher than those in non-SP group(P＜0.05).Paerson correlation analysis showed that serum IP-10 level in SP group was positively correlated with hs-CRP,PCT and IL-6(r=0.744,0.757,0.740,P＜0.05).S100A8 level was posi-tively correlated with hs-CRP,PCT and IL-6(r=0.769,0.718,0.744,P＜0.05).There were significant differences in oxygenation index,acute physiology and chronic health evaluation Ⅱ score,clinical pulmonary in-fection score and levels of hs-CRP,PCT,IP-10 and S100A8 between the poor prognosis group and the good prognosis group(P＜0.05).Multivariate Logistic regression analysis showed that hs-CRP,PCT,IP-10 and S100A8 were risk factors for poor prognosis in SP patients,and oxygenation index was a protective factor(P＜0.05).The ROC curve showed that the area under curve(AUC)of the combination of hs-CRP,PCT,IP-10 and S100A8 in predicting poor prognosis of SP patients was 0.965,which was greater than the AUC of the four alone(Zhs-CRP=4.009,ZPCT=4.022,ZIP-10=3.696,ZS100A8=3.309,P＜0.05).Conclusion The serum lev-els of IP-10 and S100A8 are up-regulated in SP patients.The combination of IP-10 and S100A8 has a high pre-dictive value for poor prognosis in SP patients.

Objective: To explore the assocation of the family environment and depressive symptoms among primary and middle school students, so as to provide suggestions for further maximizing the utility of family environment in the growth of primary and secondary school students, as well as prevention and intervention of depressive symptoms among children and adolescents. Methods: From June to July 2024, through a multistage cluster random sampling method, 8 800 primary and middle school students aged 10 to 18 from 36 schools in 3 cities (Datong, Lvliang, Linfen) in Shanxi Province. A self designed questionnaire was used to conduct a family environment survey, including family socioeconomic conditions, family structure, family parenting behavior, family member health behavior, etc; and the depression symptoms of primary and secondary school students were investigated by Patient Health Questionnaire-9. The χ 2 test and binary Logistic regression to method were used to analyze the association of the family environment with depressive symptoms among primary and secondary school students, and to analyze gender and urban-rural heterogeneity in this association. Results: The detection rate of depressive symptoms among primary and middle school students was 46.7% ( n = 4 111 ). Among them, the detection rates of depressive symptoms for male and female students were 45.7% and 47.7% respectively, and the detection rates for rural and urban students were 48.0% and 44.9% respectively. The results of binary Logistic regression model showed that in the family environment, factors such as the father s education level (junior high school: OR =0.84), self assessed family socio economic status (average: OR =0.78, good: OR =0.80), parental support and understanding (yes: OR = 0.55 ), family atmosphere (harmonious: OR =0.66), living arrangement (living only with father or mother: OR =1.31, living with parents and grandparents: OR =1.19), and family rearing style (combining punishment and reward: OR =1.42, punishment only: OR =1.25) were related to depressive symptoms in primary and middle school students in Shanxi Province ( P <0.05). From the perspective of gender heterogeneity, the living arrangement (living only with father or mother: OR =1.67, others: OR =1.67) had a statistically significant association with depressive symptoms in male students ( P <0.05). From the perspective of urban rural heterogeneity, the living arrangement (living only with father or mother: OR =1.38) had a statistically significant association with depressive symptoms in rural primary and middle school students ( P <0.05). Conclusions The family environment has an important impact on depressive symptoms in primary and middle school students. Family functioning should be fully exerted to prevent depressive symptoms in primary and middle school students.

[Purpose]To analyze the incidence and mortality of female breast cancer in Zhejiang cancer registration areas in 2021 and the trends from 2000 to 2021.[Methods]The data of cancer inci-dence,mortality and population data reported by cancer registration areas in Zhejiang Province from 2000 to 2021 were collected.The crude incidence/mortality rates,age-standardized rates ad-justed by Chinese standard population(ASIRC,ASMRC)and world standard population(ASIRW,ASMRW),cumulative rates(0～74 years old),truncated rates(35～64 years old),proportion of fe-male breast cancer and age-specific rate were calculated.The average annual percentage change(AAPC)of female breast cancer incidence and mortality rates in Zhejiang from 2000 to 2021 was calculated using Joinpoint software.[Results]In 2021,there were 7 262 new cases of female breast cancer in Zhejiang cancer registration areas,accounting for 12.70％of all new female can-cer cases.The crude incidence rate,ASIRC and ASIRW were 65.71/105,42.03/105 and 39.22/105,respectively.The cumulative incidence rate(0～74 years old)was 4.26％,and the truncated rate(35～64 years old)was 98.34/105.The ASIRC in urban and rural areas were 43.15/105 and 40.15/105,respectively.There were 992 deaths of female breast cancer,accounting for 6.97％of all female cancer deaths.The crude mortality rate,ASMRC and ASMRW were 8.98/105,4.62/105 and 4.47/105,respectively.The cumulative mortality rate(0～74 years old)was 0.48％,and the truncated rate(35～64 years old)was 8.89/105.The ASMRC in urban and rural areas were 4.79/105 and 4.34/105,respectively.The incidence rate of female breast cancer reached the peak at the age group of 60～64 years old,and the mortality rate reached the peak at the age group of 85 years old and above.From 2000 to 2021,the crude incidence rate,ASIRC and ASIRW of female breast cancer in Zhejiang cancer registration areas showed significant increasing trends(all P＜0.05).The crude mortality rate and ASMRW of female breast cancer also showed significant increasing trends(all P＜0.05).[Conclusion]The incidence rate of female breast cancer in Zhejiang Province was higher than the national average,while the mortality rate was lower than the national average in 2021.Both the incidence and mortality rates showed increasing trends from 2000 to 2021.Fur-thermore,distinct urban-rural disparities existed in both incidence and mortality characteristics.

Objective To evaluate the value of a nomogram model based on ultrasonographic features and inflammatory indicators in the preoperative noninvasive prediction of pathological grading of urothelial carcinoma of bladder(UCB).Methods A retrospective analysis was conducted on 471 patients with pathologically confirmed UCB,and the patients were assigned to high-grade group(401 cases)or low-grade group(70 cases).Basic clinical data(gender,age,macroscopic hematuria),ultrasonographic features(lesion location,blood flow signal,etc.),and blood inflammatory indicators(e.g.neutrophil-to-lymphocyte ratio[NLR])were collected.Independent predictors were screened using univariate and multivariate logistic regression,and a nomogram model was constructed.Model performance was evaluated using the receiver operating characteristic(ROC)curve,calibration curve,and decision curve analysis(DCA).Results Multivariate logistic analysis identified gender(odds ratio[OR]=2.68),age(OR=1.08),macroscopic hematuria(OR=3.19),lesion located in the trigone(OR=4.59),positive blood flow signal(OR=2.87),and NLR(OR=1.03)were independent predictors of high-grade UCB(all P＜0.05).The combined model(clinical features+ultrasonographic characteristics+inflammatory indicators)achieved an area under curve(AUC)of 0.892,which was significantly higher than the clinical feature-only model(AUC=0.799)and the clinical+ultrasonographic model(AUC=0.856).The calibration curve demonstrated good consistency between predicted and actual outcomes,and DCA confirmed its optimal clinical net benefit.Conclusion The nomogram model integrating clinical features,ultrasonographic characteristics,and inflammatory indicators can effectively discriminate UCB pathological grading,providing a reliable preoperative noninvasive assessment tool for personalized treatment decisions.

[Purpose]To analyze the incidence and mortality of female breast cancer in Zhejiang cancer registration areas in 2021 and the trends from 2000 to 2021.[Methods]The data of cancer inci-dence,mortality and population data reported by cancer registration areas in Zhejiang Province from 2000 to 2021 were collected.The crude incidence/mortality rates,age-standardized rates ad-justed by Chinese standard population(ASIRC,ASMRC)and world standard population(ASIRW,ASMRW),cumulative rates(0～74 years old),truncated rates(35～64 years old),proportion of fe-male breast cancer and age-specific rate were calculated.The average annual percentage change(AAPC)of female breast cancer incidence and mortality rates in Zhejiang from 2000 to 2021 was calculated using Joinpoint software.[Results]In 2021,there were 7 262 new cases of female breast cancer in Zhejiang cancer registration areas,accounting for 12.70％of all new female can-cer cases.The crude incidence rate,ASIRC and ASIRW were 65.71/105,42.03/105 and 39.22/105,respectively.The cumulative incidence rate(0～74 years old)was 4.26％,and the truncated rate(35～64 years old)was 98.34/105.The ASIRC in urban and rural areas were 43.15/105 and 40.15/105,respectively.There were 992 deaths of female breast cancer,accounting for 6.97％of all female cancer deaths.The crude mortality rate,ASMRC and ASMRW were 8.98/105,4.62/105 and 4.47/105,respectively.The cumulative mortality rate(0～74 years old)was 0.48％,and the truncated rate(35～64 years old)was 8.89/105.The ASMRC in urban and rural areas were 4.79/105 and 4.34/105,respectively.The incidence rate of female breast cancer reached the peak at the age group of 60～64 years old,and the mortality rate reached the peak at the age group of 85 years old and above.From 2000 to 2021,the crude incidence rate,ASIRC and ASIRW of female breast cancer in Zhejiang cancer registration areas showed significant increasing trends(all P＜0.05).The crude mortality rate and ASMRW of female breast cancer also showed significant increasing trends(all P＜0.05).[Conclusion]The incidence rate of female breast cancer in Zhejiang Province was higher than the national average,while the mortality rate was lower than the national average in 2021.Both the incidence and mortality rates showed increasing trends from 2000 to 2021.Fur-thermore,distinct urban-rural disparities existed in both incidence and mortality characteristics.

ObjectiveThe traditional Chinese medicine Strychnos nux-vomica L. (SN) has the clinical effect of reducing swelling and relieving pain; however, SN is toxic due to its alkaloid components. Little is known about the endogenous metabolic changes induced by SN toxicity in rats and their potential effects on the metabolic dysregulation of intestinal microbiota. Therefore, toxicological investigation of SN is of great significance to its safety assessment. In this study, the toxic mechanisms of SN were explored using a combination of metabonomics and 16S rRNA gene sequencing. MethodsThe toxic dose, intensity, and target organ of SN were determined in rats using acute, cumulative, and subacute toxicity tests. UHPLC-MS was used to analyze the serum, liver, and renal samples of rats after intragastric SN administration. The decision tree and K Nearest Neighbor (KNN) model were established based on the bootstrap aggregation (bagging) algorithm to classify the omics data. After samples were extracted from rat feces, the high-throughput sequencing platform was used to analyze the 16S rRNA V3-V4 region of bacteria. ResultsThe bagging algorithm improved the accuracy of sample classification. Twelve biomarkers were identified, where their metabolic dysregulation may be responsible for SN toxicity in vivo. Several types of bacteria such as Bacteroidetes, Anaerostipes, Oscillospira and Bilophila, were demonstrated to be closely related to physiological indices of renal and liver function, indicating that SN-induced liver and kidney damage may be related to the disturbance of these intestinal bacteria. ConclusionThe toxicity mechanism of SN was revealed in vivo, which provides a scientific basis for the safe and rational clinical use of SN.

Sulforaphane is a naturally occurring active substance derived from cruciferous vegetables with potent antioxidant and anticancer properties. Researches have shown that sulforaphane has good bioavailability and can be absorbed by the small intestine through passive transport, followed by excretion in the form of urine via the hydrophobic acid pathway. In addition, since sulforaphane is easy to be absorbed and metabolized, wrapping sulforaphane with nanomaterials can improve its bioavailability and stability, prolong its action time in human body, and better utilize its therapeutic effect. In terms of mechanism of action, sulforaphane can activate Nrf2 and HSF1 signaling pathways, induce the expression of phase II detoxification enzymes HO-1, NADPH, GST and HSP, thus regulating the concentration of oxidative stress ROS in vivo; inhibit NF-κB signaling pathway, thus suppressing the expression of inflammatory factors TNF-α, IL-1 and IL-6; regulate epigenetic modifications, thus inhibiting HDAC and DNMT, and increasing the concentration of histone H3 and H4. By regulating the expression levels of the above factors, sulforaphane can affect the occurrence and development of cancer, neurodegenerative diseases and other diseases. In recent years, several phase I/II clinical trials have shown that sulforaphane has good drug-generating properties. For example, researchers have found that patients with skin cancer have not shown any health problems and their corresponding functional problems have improved greatly after long-term use of sulforaphane. This suggests that in the future sulforaphane has a very high medicinal potential for the treatment of cancer and neurodegenerative diseases. In this paper, we review the pharmacokinetics, target of action and safety of sulforaphane and its research progress in tumor and neurodegenerative diseases to provide a reference for the future application of sulforaphane in the treatment of tumor and neurodegenerative diseases.

Veno-arterial extracorporeal membrane oxygenation is an effective method to reduce perioperative adverse events such as cardiogenic shock in patients undergoing complex high-risk indicated percutaneous coronary intervention.Femoral artery and femoral vein are the main routes for conventional veno-arterial extracorporeal membrane oxygenation in China,while the cases of extracorporeal membrane oxygenation insertion via axillary artery are relatively rare.However,the axillary artery intubation veno-arterial extracorporeal membrane oxygenation assisted mode has been regarded as one of the routine clinical paths for the treatment of critically ill patients in foreign countries.This paper reports a case of an elderly male patient who underwent high risk and complex percutaneous coronary interventional therapy by right axillary artery implantation with extracorporeal membrane oxygenation assisted circulation due to the difficulty of femoral artery approach.In order to provide reference for the selection of clinical extracorporeal membrane oxygenation technique route.