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.

Objective Developing a new type of full-face respiratory protective mask for nuclear facility sites to enhance the sound transmission function and improve the facial adaptability. Methods Combined with feedback from on-site practical needs, this study utilized finite element simulation and ergonomic design methods to investigate the voice transmission units of full-face masks and the facial features of workers at key nuclear facilities. Based on the research results, a new full-face respiratory protection mask structure was designed. Results The optimized structure of passive thin film voice transmission unit significantly enhanced voice transmission efficiency, reducing average voice transmission loss by approximately 70% compared to the control group using thin plate units of equivalent thickness. The existing facial feature test panels insufficiently cover and unevenly classify the facial features of workers at key nuclear facilities. In this study, a specialized test panel based on measurement data achieved a total coverage of 98.5% with high distribution uniformity within each class, providing effective guidance for redesigning full-face mask structural parameters. In comparison to foreign products currently utilized in nuclear facilities, the newly designed full-face mask structure exhibited excellent tightness and structural safety and reliability, and can be cleaned, decontaminated, and reused. Conclusion The results of this study provide significant guidance for improving and optimizing full-face respiratory protection mask used at nuclear facilities, as well as promoting domestic production of high-quality full-face respiratory protection masks.

Objective Some epidemiological studies have shown that pregnant women who develop preeclampsia(PE)have elevated levels of testosterone in their maternal plasma compared to women with normal blood pressure during pregnancy,revealing a potential association between hyperandrogenism in women and PE.To explore the causal relationship between hyperandrogenism and PE,this study selected total testosterone(TT),bioavailable testosterone(BIOT),and sex hormone binding globulin(SHBG)as exposure factors and PE and chronic hypertension with superimposed PE as disease outcomes.Two-sample Mendelian randomization(MR)analyses were used to genetically dissect the causal relationships between the three exposure factors(TT,BIOT,and SHBG)and the outcomes of PE and chronic hypertension with superimposed PE.Methods Two independent genome-wide association study(GWAS)databases were used for the two-sample MR analysis.In the GWAS data of female participants from the UK Biobank cohort,single nucleotide polymorphisms(SNPs)associated with TT,BIOT,and SHBG were analyzed,involving 230 454,188 507,and 188 908 samples,respectively.GWAS data on PE and chronic hypertension with superimposed PE from the Finnish database were used to calculate SNP,involving 3 556 PE cases and 114 735 controls,as well as 38 cases of chronic hypertension with superimposed PE and 114 735 controls.To meet the assumptions of instrumental relevance and independence in MR analysis,SNPs associated with exposure were identified at the genome-wide level(P<5.0×10-8),and those in linkage disequilibrium interference were excluded based on clustering thresholds of R2<0.001 and an allele distance greater than 10 000 kb.Known confounding factors,including previous PE,chronic kidney disease,chronic hypertension,diabetes,systemic lupus erythematosus,or antiphospholipid syndrome,were also identified and the relevant SNPs were removed.Finally,we extracted the outcome data based on the exposure-related SNPs in the outcome GWAS,integrating exposure and outcome data,and removing palindromic sequences.Five genetic causal analysis methods,including inverse variance-weighted method(IVW),MR-Egger regression,weighted median method,simple mode method,and weighted mode method,were used to infer causal relationships.In the IVW,it was assumed that the selected SNPs satisfied the three assumptions and provided the most ideal estimate of the effect.IVW was consequently used as the primary analysis method in this study.Considering the potential heterogeneity among the instrumental variables,random-effects IVW was used for MR analysis.The results were interpreted using odds ratios(OR)and the corresponding 95% confidence interval(CI)to explain the impact of exposure factors on PE and chronic hypertension with superimposed PE.If the CI did not include 1 and had a P value less than 0.05,the difference was considered statistically significant.Sensitivity analysis was conducted to assess heterogeneity and pleiotropy.Heterogeneity was examined using Cochran's Q test,and pleiotropy was assessed using MR-Egger intercept analysis.Additionally,leave-one-out analysis was conducted to examine whether individual SNPs were driving the causal associations.To further validate the findings,MR analyses were performed using the same methods and outcome variables,but with different exposure factors,including waist-to-hip ratio adjusted for BMI(WHRadjBMI)and 25-hydroxyvitamin D levels,with MR results for WHRadjBMI and PE serving as the positive controls and MR results for 25-hydroxyvitamin D levels and PE as the negative controls.Results According to the criteria for selecting genetic instrumental variables,186,127,and 262 SNPs were identified as genetic instrumental variables significantly associated with testosterone indicators TT,BIOT,and SHBG.MR analysis did not find a causal relationship between the TT,BIOT,and SHBG levels and the risk of developing PE and chronic hypertension with superimposed PE.The IVW method predicted that genetically predicted TT(OR[95% CI]=1.018[0.897-1.156],P=0.78),BIOT(OR[95% CI]=1.11[0.874-1.408],P=0.392),and SHBG(OR[95% CI]=0.855[0.659-1.109],P=0.239)were not associated with PE.Similarly,genetically predicted TT(OR[95% CI]=1.222[0.548-2.722],P=0.624),BIOT(OR[95% CI]=1.066[0.242-4.695],P=0.933),and SHBG(OR[95% CI]=0.529[0.119-2.343],P=0.402)were not significantly associated with chronic hypertension with superimposed PE.Additionally,MR analysis using the MR-Egger method,weighted median method,simple mode method,and weighted mode method yielded consistent results,indicating no significant causal relationship between elevated testosterone levels and PE or chronic hypertension with superimposed PE.Heterogeneity was observed for SHBG in the analysis with PE(Cochran's Q test,P=0.01),and pleiotropy was detected for BIOT in the analysis with PE(MR-Egger intercept analysis,P=0.014),suggesting that the instrumental variables did not affect PE through BIOT.Other instrumental variables did not show significant heterogeneity or pleiotropy.Leave-one-out analysis confirmed that the results of the MR analysis were not driven by individual instrumental variables.Consistent with previous MR studies,the results of the control MR analyses using WHRadjBMI and 25-hydroxyvitamin D levels supported the accuracy of the MR analysis approach and the methods used in this study.Conclusion The MR analysis results suggest that current genetic evidence does not support a causal relationship between TT,BIOT,and SHBG levels and the development of PE and chronic hypertension with superimposed PE.This study suggests that elevated testosterone may be a risk factor for PE but not a direct cause.

Objective:To investigate the relationship between carotid atherosclerosis(CAS)and subclinical left ventricular(LV)dysfunction in type 2 diabetes mellitus patients with preserved LV ejection fraction(LVEF).Methods:A total of 120 patients with type 2 diabetes mellitus who had LVEF≥50% were selected in the Department of Endocrinology, the First Affiliated Hospital of Air Force Medical University from June 2021 to October 2021. The global longitudinal strain(GLS)was obtained by two-dimensional speckle tracking echocardiography(STE)to assess subclinical LV systolic function. The mitral ratio of peak early to late diastolic filling velocity(E/A), and mitral velocity to early diastolic velocity of the mitral annulus(E/E′)ratio were obtained by pulsed tissue Doppler echocardiography to assess LV diastolic function. Acrroding to bilateral carotid ultrasound examination, the subjects were divided into normal carotid arteries group( n=46) and CAS group( n=74). Demographics and biochemical parameters were compared between two groups. Binary logistic regression and Pearson correlation analysis were used to evaluate the relationship between CAS and subclinical LV dysfunction. Results:The CAS group had a higher proportion of men, older age, and a longer duration of diabetes than the normal carotid arteries group(all P<0.05). There was no difference in LVEF and GLS between the two groups [normal carotid arteries group vs CAS group, LVEF: (60.72±4.73)% vs(60.07±4.28)%; GLS: (18.24±3.72)% vs(17.81±3.47)%, respectively; both P>0.05]. However, compared with normal carotid arteries group, E/A ratio was decreased and E/E′ ratio was significantly increased in CAS group(both P<0.01). Pearson correlation analysis showed that GLS was not correlated with carotid plaque thickness and carotid intima-media thickness(CIMT; both P>0.05). By contrast, E/E′ ratio was positively correlated with carotid plaque thickness and CIMT(both P<0.05). Binary logistic regression analysis showed that GLS and E/E′ ratio were not associated with CAS( both P>0.05). However, decreased E/A ratio was significantly associated with the existence of CAS( OR=0.09, 95% CI 0.01-0.67, P=0.018). Conclusions:In type 2 diabetes mellitus patients without overt heart failure and with preserved LVEF, the occurrence of CAS is not associated with subclinical LV systolic impairment assessed by GLS, but is significantly associated with LV diastolic dysfunction, and is independent of traditional cardiovascular risk factors.

[Objective]To evaluate the terminal hair growth of different body positions among in pregnant women ,analyze the contribution of each area to the diagnosis to hirsutism ,to improve the mFG scoring system.[Method]Pregnant women aged 20~41 years,with normal range of total testosterone levels and non-hirsute were recruited at their prenatal care in Sun Yat-sen Memorial Hospital,Sun Yat-sen University. They were followed up before pregnancy,at the 5th and the 9th week,the 10th and the 14th week, the 15th and the 20th week,the 21th and the 24th week of gestation. Then 72 more cases of pregnant women were recruited and followed up at 15~24th week. At each time of followed up,their total testosterone(TT)levels was examined by liquid chromatography tandem mass spectrometry(LC/MS-MS)and terminal hair growth were assessed by mFG score. Significant difference procedure least(LSD) analysis of variance was used to compare the levels of testosterone and mFG score in different gestational weeks. Receiver operating characteristics(ROC)analysis and logistics analysis were conducted to evaluate the contributory strength of hair growth in each body position for the diagnosis of hirsutism. The scores in the body area which made a significant contribution to the total were summed up and termed the simplified mFG score(sFG score). Following,the sFG scores were subjected to ROC analysis to determine the thresh-old that would maximize both the sensitivity and specificity of the measure to accurately distinguish hirsute from non-hirsute patients.[Results]Among the forty three pregnant women who were followed-up from before pregnancy to 24th week,the mean±SD for TT was (1.09 ± 0.59)nmol/L before pregnancy,and(1.13 ± 0.40),(1.28 ± 0.38),(1.83 ± 0.63),(1.82 ± 0.52)nmol/L for 5~ 9th,10~14th,15~20th week,and the mFG score was 1.65 ± 0.60,2.30 ± 0.45,3.60 ± 0.68,4.20 ± 0.41 and 4.40 ± 0.77,respectively. The order of the facial and body sites presented with new terminal hair growth was upper abdomen,lower abdomen,lower back,up-per lip,thighs,upper back,chest,upper arm,and chin,in sequence. After analyzing 115 cases(including the 72 cases recruited later),ROC analysis showed that the diagnostic value of different sites for hirsutism(mFG≥5):upper lip>lower back>thighs>lower abdomen>upper arm>upper back>chest/upper abdomen. Four sites among them ,namely upper lip ,lower back ,thighs and lower abdomen had the best diagnostic value,and the AUC for ROC were 0.779,0.728,0.675,and 0.626,respectively. Both ROC and logistic analysis indicated that he most significant body areas in defining hirsutism(defined as an mFG score≥5)were the upper lip, lower back,thighs,and lower abdomen. Using a cut-off value of 3,the combination of the four areas has the best sensitivity and specificity in distinguishing hirsute from non-hirsute women. [Conclusion]The study suggested that the mFG score increased as pregnancy progressed before the 24 weeks of gestation. The subset of upper lip,lower back,thighs and lower abdomen may be a reli-able simplification of mFG system for the evaluation of excess hair growth. The cut-off value was of≥3.

When senescence induction is based on DNA damage, senescent cells display a unique phenotype, which has been termed “senescence-associated secretory phenotype”( SASP ) . SASP, including proinflammatory cytokines, growth factors, chemokines, matrix remodeling enzymes and other cytokines, may be an important driver of chronic inflammation and therefore may be part of a vicious cycle of inflammation, DNA damage and senescence. Senescence-associated secretory products released by such cells can affect the neighboring cells and further exacer-bate their regenerative capacity. SASP is associated with many chronic age-related diseases.

Objective To compare the difference of serum adiponectin levels between polycystic ovary syndrome (PCOS) patients and age, boby mass index (BMI) and insulin-resistance index matched controls, and explore its influence factors.Methods Case-control study, involving 97 women with PCOS and 116 age, BMI, fasting plasma glucose and insulin levels, homeostasis model assessment-insulin resistance index (HOMA-IR) matched controls.Hormone profiles, and serum adiponectin levels were measured and compared.Hormone profiles and serum adiponectin levels were compared among the four PCOS phenotypes.Multiple regression analysis was used to evaluate the factors affecting serum adiponectin levels.Results (1) Serum adiponectin level was significantly lower in PCOS group [(21 ± 16) mg/L] than controls [(25± 13) mg/L, P=0.038], and the same result in stratified analysis on weight height ratio (WHR, ≥0.8 and ＜0.8).(2) There was statistical differences in testosterone among different four PCOS phenotypes (P=0.001), there were no statistical differences in FSH, LH, WHR and serum adiponectin levels among four PCOS phenotypes (P＞0.05).(3) WHR and PCOS status were independent determinants of serum adiponectin levels (P＜0.05).Conclusions Low serum adiponectin levels in the women with PCOS is correlated with PCOS per se, independent of insulin resistance and obese.This fact supports the further study of the effect of adiponection in the pathophysiology of PCOS and its log-term impact.

Objective To explore the effect of oris(oral)muscles training on speech language rehabilitation for autism spectrum disorders children.Methods 40 cases were divided into 2 groups,20 cases in each group.The control group was treated with language cognitive training.The observation group was treated with language cognitive combined with oris(oral)muscles training.The treatment was given for 6 months.S -S(sign -significate relationgs) was used to evaluate the language development quotient of the two groups.Results After treatment,the language development quotient was significantly improved compared with before treatment(P <0.05),and the language expres-sion quotient of the observation group was more effective than the control group(t =2.434,P <0.05).The language comprehension quotient and operation quotient of the two groups had no significant differences.Conclusion Oris muscles training combined with language cognitive is more effective on language expression capability of autism spec-trum disorders children.

Objective To observe the effect of sensory integration training on motor function of cerebral palsy children.Methods 42 children with cerebral palsy were divided into two groups,with 22 cases in observation group,20 cases in control group.All children were treated with mainly Bobath technique based rehabilitation therapy,while those of observation group were added sensory integration training for 3 months.We used GMFM-88 to estimate the gross motor function of the two groups.Results After treatment,the scores of GMFM-88 significantly improved in both groups,GMFM scores of the observation group were more effective than thoes of the control group(t =2.481,P =0.018).Conclusion Sensory integration training based on tradition neural movement therapy can improve gross motor function in children with cerebral palsy,can significantly improve the curative effect of rehabilitation.

Objective To observe the effects of body weight support training on walking ability of children with cerebral palsy. Methods 40 cases were divided into observation group (n=20) and control group (n=20). All the children accepted rehabilitation therapy based on Bobath approach and biofeedback, while those of observation group accepted body weight support training in addition, for 2 months. They were assessed with Gross Motor Function Measure (GMFM) D and E dimension before and after treatment. Results Both the scores of D and E dimension significantly improved in both groups after treatment (P<0.05), and improved more in the observation group than in the control group (P<0.05). Conclusion Body weight support training can further improve the walking ability in children with cerebral palsy.