BACKGROUND: Doxorubicin hydrochloride (DOX) is extensively used in the treatment of various tumors. However, its clinical application is limited due to dose-dependent cardiotoxicity. Currently, few effective strategies exist to mitigate or eliminate DOX-induced cardiomyopathy (DIC). Although ferroptosis is implicated in DIC and its inhibition partially alleviates the condition, the direct targets of DOX in the progression of cardiotoxicity remain unclear. This study aimed to discover the direct targets of DOX in ferroptosis-mediated DIC. METHODS: A DOX pulldown assay was performed to identify proteins specifically binding to DOX in murine hearts, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify candidate proteins. A cardiac injury mouse model was established by DOX treatment. Based on this, multiple ferroptosis biomarkers were detected by flow cytometry, quantitative real-time polymerase chain reaction, western blotting, immunochemistry, etc. Besides, specific activator and inhibitor of signaling pathways were applied to illuminate molecular mechanisms. RESULTS: Glutathione S-transferase P1 (GSTP1) was identified as a DOX target. GSTP1 activity was inhibited in DOX-treated cardiomyocytes, while its overexpression significantly alleviated DIC. Moreover, GSTP1 overexpression inhibited acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. Mechanistically, GSTP1 overexpression suppressed c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing reactive oxygen species (ROS) production and inhibiting ferroptosis in DIC. CONCLUSIONS This study identifies the DOX/GSTP1/JNK axis as a critical pathway mediating ACSL4-dependent ferroptosis in DIC. GSTP1 is highlighted as a potential key mediator of ferroptosis and a promising therapeutic target for DIC.

This article introduces Professor LIU Xing's clinical experience in treatment of peripheral facial paralysis at the recovery and sequelae stages with the combination of acupotomy, cupping and herbal medication. Based on the analysis of etiology and pathogenesis of peripheral facial paralysis, Professor LIU believes that "invasion of pathogenic wind to collaterals and obstruction of qi and blood" is crucial. Therefore, the treatment focuses on "dispelling wind and harmonizing blood". The compound therapeutic mode is proposed, with acupotomy, cupping and herbal decoction involved, in which, "three-step sequential method of acupotomy" is predominated. Firstly, in the prone position, five "feng" (wind) points are stimulated in patient, Fengfu (GV16), Fengchi (GB20), Yifeng (TE17), Bingfeng (SI12) and Fengmen (BL12). Secondly, in the lateral position, three-facial points are stimulated (FaceⅠneedle: Yangbai [GB14]-Yuyao [EX-HN4]; Face Ⅱ needle: Sibai [ST2]-Quanliao [SI18]; Face Ⅲ needle: Jiache [ST6]-Dicang [ST4]) to restore the deviated facial muscles. Finally, in the supine, two Dantian points are stimulated on the forehead and chest, respectively (upper Dantian: Yintang [GV24⁺], middle Dantian: Danzhong [CV17]), to regulate qi and blood. As the adjunctive therapies, cupping is used to remove stasis, and herbal decoction is to harmonize the body interior. In view of holistic regulation, the treatment is administered in accordance with the affected meridians, so as to expel wind, remove obstruction in collaterals and regulate qi and blood.
Humans ; Facial Paralysis/drug therapy* ; Drugs, Chinese Herbal/administration & dosage* ; Acupuncture Therapy ; Male ; Female ; Middle Aged ; Adult ; Combined Modality Therapy ; Acupuncture Points ; Cupping Therapy ; Aged ; Young Adult

The " liver disease affecting to the spleen" theory first appeared in Nanjing and was further elaborated in Jingui Yaolue. This theory encapsulates the traditional Chinese medicine principles of the " unity of the five viscera" and the " preventive treatment of disease" . The theory emphasizes that the spleen is the pivotal point where depression may progress from a functional disorder to an organic disease. The liver governs the emotions and qi flow, whereas the spleen is responsible for qi, blood, and body. In the early stages of the disease, emotional disorders and qi flow disorders primarily affect the liver, manifesting as depression or low mood. As the condition progresses, the liver (Wood) overacts on the spleen (Earth), disrupting liver and spleen functions and causing qi and blood disharmony. This stage is marked by fatigue and psychomotor retardation. Prolonged illness depletes qi and blood, eventually involving all five viscera, disrupting the harmony of the five spirits, and affecting both body and spirit. At this advanced phase, intense emotional distress or agitation often arises, accompanied by a heightened risk of suicide. The disease progression follows a dynamic " qi-blood-spirit" pattern, in which depression begins in the liver, characterized by qi stagnation, then affects the spleen, involving blood disharmony. In later stages, the disease eventually affects all viscera, with profound effects on both physical and mental health. Treatment strategies should align with the disease stage. Early intervention should focus on regulating the flow of qi, treating the liver, and strengthening the spleen. In the middle stages, qi and blood should be harmonized while promoting the harmonized functions of the liver and spleen. In the later stages, treatment should harmonize the five viscera to restore balance between body and spirit. Guided by this theory, integrating modern medical understanding of the progression of depression from emotional to somatic symptoms and adopting a stage-based approach to treatment in clinical practice can yield effective therapeutic outcomes for managing depression and related disorders.

Objective To explore the impact of ten-eleven translocation 2(TET2)mutations on imiquimod(IMQ)-induced psoriatic skin inflammation using a TET2-knockout(TET2-/-)mouse model.Methods Mice were divided randomly into a wild-type(WT)vaseline group,WT imiquimod group,TET2-/-vaseline group,and TET2-/-imiquimod group.IMQ was used to establish a psoriasis-like dermatitis model,and the degree of skin lesions and pathological changes in mice in the WT imiquimod and TET2-/-imiquimod groups were observed and compared daily during the modeling period.The mice were sacrificed when the phenotype had reached the peak and the spleen index was recorded in each group.Gene expression levels of the inflammatory factors tumor necrosis factor(TNF)-α,interleukin(IL)-6,IL-17A,and IL-23 in mouse back lesions were detected by quantitative reverse transcription polymerase chain reaction.Skin histopathology was compared in hematoxylin/eosin-stained sections.IL-17,interferon(INF)-γ,and TNF-α protein expression levels in the back skin of mice in the four groups were detected by immunohistochemistry.The ultrastructure of the dermis and epidermis was observed using transmission electron microscopy.Results TET2 expression was down-regulated in skin lesions in WT imiquimod group.Dermatitis lesions were more severe and progressed faster in TET2-/-imiquimod group compared with WT imiquimod group,and the psoriasis area and severity index score and spleen index were both higher.mRNA expression levels of TNF-α,IL-6,IL-17A,and IL-23 in skin lesions were higher and epidermal thickening and inflammatory cell infiltration were increased,and protein expression levels of IL-17,INF-γ,and TNF-α were significantly higher in skin lesions in TET2-/-imiquimod group compared with WT imiquimod group.In addition,cell junctions were absent in skin lesions in TET2-/-imiquimod group and mitochondrial ridges were broken and dissolved,mitochondrial vacuoles were present,and the texture of the mitochondrial membrane was darker.Conclusions Loss of TET2 promotes the inflammatory response and exacerbates IMQ-induced psoriasis-like dermatitis injury in mice.

Objectives:This study aims to explore the relationship between the pericoronary fat attenuation index(FAI)and triglyceride-glucose(TyG)index and atrial fibrillation recurrence after radiofrequency catheter ablation(RFCA)in patients with atrial fibrillation(AF).Methods:This retrospective study enrolled consecutive AF patients who underwent their first successful RFCA at the Affiliated Hospital of Xuzhou Medical University from 2019 to 2023.Pericoronary FAI was quantitatively measured,and the TyG index was calculated.Patients were divided into three groups according to the TyG index quartile:T1 group(TyG index<8.45,n=114);T2 group(8.45≤TyG index≤8.93,n=114);T3 group(TyG index>8.93,n=120).Linear regression was used to analyze the correlation between the TyG index and proximal FAI of three coronary arteries.Logistic regression was employed to explore the correlation between pericoronary FAI,TyG index,and AF recurrence post-RFCA,restrictive cubic splines(RCS)were plotted.Additive interaction and mediation analyses were used to explore the role of pericoronary FAI in the relationship between the TyG index and post-RFCA AF recurrence.Subgroup analysis was performed to explore the predictive value of the TyG index for postoperative recurrence in different patient subgroups.Results:A total of 348 patients were included.After adjusting for confounding factors using linear regression analysis,each unit increase in the TyG index was associated with a 5.389 HU increase in left circumfleex artery(LCX-FAI)(95%CI:3.874-6.904,P<0.001).During one-year follow-up,90 cases(25.86%)experienced AF recurrence.RCS analysis indicated that there was no significant nonlinear relationship between LCX-FAI,TyG index,and AF recurrence after RFCA(Pnon-linear=0.378,Pnon-linear=0.469).The recurrence rate of AF in patients with TyG index>9.08 and LCX-FAI>-83.65 HU was about 57.737 times higher than those with TyG index≤9.08 and LCX-FAI≤-83.65 HU(OR=57.737,95%CI:23.755-155.656,P<0.001).There was an additive interaction between the TyG index and LCX-FAI:relative excess risk due to interaction(RERI)was 50.901(95%CI:0.215-101.587),attributable proportion due to interaction(AP)was 0.882(95%CI:0.769-0.994),and the synergy index(S)was 9.713(95%CI:3.380-27.910).Mediation analysis indicated that LCX-FAI mediated 22%of the relationship between the TyG index and AF recurrence.Subgroup analysis revealed no multiplicative interaction between the type of atrial fibrillation and the TyG index in terms of AF recurrence risk(Pinteraction=0.562).Conclusions:In patients with atrial fibrillation,the TyG index is positively correlated with LCX-FAI,patients with TyG index>9.08 and LCX-FAI>-83.65 HU have significantly increased risk of AF recurrence after RFCA.LCX-FAI partially mediates the relationship between the TyG index and post-RFCA recurrence.Furthermore,the TyG index can effectively predict AF recurrence in both persistent and paroxysmal atrial fibrillation patients.

Objectives:This study aims to explore the relationship between the pericoronary fat attenuation index(FAI)and triglyceride-glucose(TyG)index and atrial fibrillation recurrence after radiofrequency catheter ablation(RFCA)in patients with atrial fibrillation(AF).Methods:This retrospective study enrolled consecutive AF patients who underwent their first successful RFCA at the Affiliated Hospital of Xuzhou Medical University from 2019 to 2023.Pericoronary FAI was quantitatively measured,and the TyG index was calculated.Patients were divided into three groups according to the TyG index quartile:T1 group(TyG index<8.45,n=114);T2 group(8.45≤TyG index≤8.93,n=114);T3 group(TyG index>8.93,n=120).Linear regression was used to analyze the correlation between the TyG index and proximal FAI of three coronary arteries.Logistic regression was employed to explore the correlation between pericoronary FAI,TyG index,and AF recurrence post-RFCA,restrictive cubic splines(RCS)were plotted.Additive interaction and mediation analyses were used to explore the role of pericoronary FAI in the relationship between the TyG index and post-RFCA AF recurrence.Subgroup analysis was performed to explore the predictive value of the TyG index for postoperative recurrence in different patient subgroups.Results:A total of 348 patients were included.After adjusting for confounding factors using linear regression analysis,each unit increase in the TyG index was associated with a 5.389 HU increase in left circumfleex artery(LCX-FAI)(95%CI:3.874-6.904,P<0.001).During one-year follow-up,90 cases(25.86%)experienced AF recurrence.RCS analysis indicated that there was no significant nonlinear relationship between LCX-FAI,TyG index,and AF recurrence after RFCA(Pnon-linear=0.378,Pnon-linear=0.469).The recurrence rate of AF in patients with TyG index>9.08 and LCX-FAI>-83.65 HU was about 57.737 times higher than those with TyG index≤9.08 and LCX-FAI≤-83.65 HU(OR=57.737,95%CI:23.755-155.656,P<0.001).There was an additive interaction between the TyG index and LCX-FAI:relative excess risk due to interaction(RERI)was 50.901(95%CI:0.215-101.587),attributable proportion due to interaction(AP)was 0.882(95%CI:0.769-0.994),and the synergy index(S)was 9.713(95%CI:3.380-27.910).Mediation analysis indicated that LCX-FAI mediated 22%of the relationship between the TyG index and AF recurrence.Subgroup analysis revealed no multiplicative interaction between the type of atrial fibrillation and the TyG index in terms of AF recurrence risk(Pinteraction=0.562).Conclusions:In patients with atrial fibrillation,the TyG index is positively correlated with LCX-FAI,patients with TyG index>9.08 and LCX-FAI>-83.65 HU have significantly increased risk of AF recurrence after RFCA.LCX-FAI partially mediates the relationship between the TyG index and post-RFCA recurrence.Furthermore,the TyG index can effectively predict AF recurrence in both persistent and paroxysmal atrial fibrillation patients.

Objective To explore the impact of ten-eleven translocation 2(TET2)mutations on imiquimod(IMQ)-induced psoriatic skin inflammation using a TET2-knockout(TET2-/-)mouse model.Methods Mice were divided randomly into a wild-type(WT)vaseline group,WT imiquimod group,TET2-/-vaseline group,and TET2-/-imiquimod group.IMQ was used to establish a psoriasis-like dermatitis model,and the degree of skin lesions and pathological changes in mice in the WT imiquimod and TET2-/-imiquimod groups were observed and compared daily during the modeling period.The mice were sacrificed when the phenotype had reached the peak and the spleen index was recorded in each group.Gene expression levels of the inflammatory factors tumor necrosis factor(TNF)-α,interleukin(IL)-6,IL-17A,and IL-23 in mouse back lesions were detected by quantitative reverse transcription polymerase chain reaction.Skin histopathology was compared in hematoxylin/eosin-stained sections.IL-17,interferon(INF)-γ,and TNF-α protein expression levels in the back skin of mice in the four groups were detected by immunohistochemistry.The ultrastructure of the dermis and epidermis was observed using transmission electron microscopy.Results TET2 expression was down-regulated in skin lesions in WT imiquimod group.Dermatitis lesions were more severe and progressed faster in TET2-/-imiquimod group compared with WT imiquimod group,and the psoriasis area and severity index score and spleen index were both higher.mRNA expression levels of TNF-α,IL-6,IL-17A,and IL-23 in skin lesions were higher and epidermal thickening and inflammatory cell infiltration were increased,and protein expression levels of IL-17,INF-γ,and TNF-α were significantly higher in skin lesions in TET2-/-imiquimod group compared with WT imiquimod group.In addition,cell junctions were absent in skin lesions in TET2-/-imiquimod group and mitochondrial ridges were broken and dissolved,mitochondrial vacuoles were present,and the texture of the mitochondrial membrane was darker.Conclusions Loss of TET2 promotes the inflammatory response and exacerbates IMQ-induced psoriasis-like dermatitis injury in mice.

BackgroundThe occurrence rate of dangerous behaviors in patients with severe mental disorders is higher than that of the general population. In China， there is limited research on the prediction of dangerous behaviors in community-dwelling patients with severe mental disorders， particularly in terms of predicting models using data mining techniques other than traditional methods. ObjectiveTo explore the influencing factors of dangerous behaviors in community-dwelling patients with severe mental disorders and testing whether the classification decision tree model is superior to the Logistic regression model. MethodsA total of 11 484 community-dwelling patients with severe mental disorders who had complete follow-up records from 2013 to 2022 were selected on December 2023. The data were divided into a training set （n=9 186） and a testing set （n=2 298） in an 8∶2 ratio. Logistic regression and classification decision trees were separately used to establish predictive models in the training set. Model discrimination and calibration were evaluated in the testing set. ResultsDuring the follow-up period， 1 115 cases （9.71%） exhibited dangerous behaviors. Logistic regression results showed that urban residence， poverty， guardianship， intellectual disability， history of dangerous behaviors， impaired insight and positive symptoms were risk factors for dangerous behaviors （OR=1.778， 1.459， 2.719， 1.483， 3.890， 1.423， 2.528， 2.124， P<0.01）. Being aged ≥60 years， educated， not requiring prescribed medication and having normal social functioning were protective factors for dangerous behaviors （OR=0.594， 0.824， 0.422， 0.719， P<0.05 or 0.01）. The predictive effect in the testing set showed an area under curve （AUC） of 0.729 （95% CI： 0.692~0.766）， accuracy of 70.97%， sensitivity of 59.71%， and specificity of 72.05%. The classification decision tree results showed that past dangerous situations， positive symptoms， overall social functioning score， economic status， insight， household registration， disability status and age were the influencing factors for dangerous behaviors. The predictive effect in the testing set showed an AUC of 0.721 （95% CI： 0.705~0.737）， accuracy of 68.28%， sensitivity of 64.46%， and specificity of 68.60%. ConclusionThe classification decision tree does not have a greater advantage over the logistic regression model in predicting the risk of dangerous behaviors in patients with severe mental disorders in the community. ［Funded by Chengdu Medical Research Project （number， 2020052）］

Objective: To investigate the prevalence of hyperactivity behavior in children aged 3-6 in Yunnan Province, to explore its relationship with neuropsychological development, so as to provide clues for early prevention and intervention of attention deficit hyperactivity disorder (ADHD) in children. Methods: A total of 1 321 children aged 3 to 6 from 10 kindergartens in 5 prefectures (cities) of Yunnan Province were selected by stratified random sampling method from October 2022 to May 2023. Teacher Rating Scale (TRS) was used to investigate childrens hyperactive behavior and coexistent behavior. A qualified evaluator applied the Developmental Scale for Children Aged 0-6 Years to assess the development of 5 ability areas of gross motor movement，fine movement，adaptive ability，language and social behavior. Statistical analysis was performed using Wilcoxon rank sum test and χ2 test. Binary Logistic regression was applied to analyze the score of their hyperactivity behavior and its relationship with other behavior problems and neuropsychological development. Results: The detection rate of hyperactivity behavior was 8.6% in children aged 3 to 6 years, 12.8% in boys and 4.1% in girls (χ2=31.53, P<0.01). The detection rate of hyperactivity in 3yearold children was 13.9%, which was higher than that in 4yearold (9.2%) and 5yearold children (7.0%) (χ2=8.73, P<0.05). The detection rate of inattentionpassivity of rural children (14.6%) was higher than that of urban children (5.9%) (χ2=22.23, P<0.01). Binary Logistic regression analysis showed that the higher the level of adaptive development, the lower the risk of hyperactivity (OR=0.58, 95%CI=0.39-0.86), the higher the risk of hyperactivity (OR=0.57, 95%CI=0.35-0.91), the higher the risk of conduct problems (OR=0.57, 95%CI=0.37-0.87), inattentionpassivity (OR=0.49, 95%CI=0.33-0.74) were also at lower risk (P<0.05). Children with higher levels of fine motor development had a lower risk of inattentionpassivity (OR=0.59, 95%CI=0.37-0.93, P<0.05). Conclusions Hyperactivity in boys and inattentionpassivity in rural children requires more attention. It is necessary to strengthen childrens early adaptive ability and fine motor training to prevent hyperactive behavior and inattention.

Background::Previous studies have reported associations of specific maternal and paternal lifestyle factors with offspring’s cognitive development during early childhood. This study aimed to investigate the prospective associations between overall parental lifestyle and offspring’s cognitive performance during adolescence and young adulthood in China.Methods::We included 2531 adolescents aged 10-15 years at baseline in 2010 from the China Family Panel Studies. A healthy parental lifestyle score (ranged 0-5) was constructed based on the following five modifiable lifestyle factors: Smoking, drinking, exercise, sleep, and diet. Generalized estimating equation models were used to examine the association between baseline parental healthy lifestyle scores and offspring’s fluid and crystallized intelligence in subsequent years (2012, 2014, 2016, and 2018).Results::Offspring in the top tertile of parental healthy lifestyle scores performed better in overall fluid intelligence (multivariable-adjusted β = 0.53, 95% confidence interval [CI]: 0.29-0.77) and overall crystallized intelligence (multivariable-adjusted β = 0.35, 95% CI: 0.16-0.54) than those in the bottom tertile of parental healthy lifestyle scores. The results were similar after further adjustment for the offspring’s healthy lifestyle scores and persisted across the subgroups of parental socioeconomic status. Additionally, maternal and paternal healthy lifestyle scores were independently associated with better offspring’s cognitive performance, with significant contribution observed for paternal never-smoking, weekly exercise, and diversified diet. When both parents and offspring adhered to a healthier lifestyle, we observed the highest level of the offspring’s overall crystallized intelligence. Conclusions::Our study indicates that parental adherence to a healthier lifestyle is associated with significantly better offspring’s cognitive performance during adolescence and early adulthood, regardless of socioeconomic status. These findings highlight the potential cognitive benefits of promoting healthy lifestyles among parents of adolescents.