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:To evaluate the predictive effect of the loss of signal (LOS) on the recurrent laryngeal nerve (RLN) injury.Methods:The literatures on PubMed, Web of Science, CNKI, and Wanfang Medical Network database were published before 30 April 2023. English search terms included "thyroid gland surgery" "thyroidectomy" "intraoperative neuromonitoring" "intraoperative nerve monitoring" and "recurrent laryngeal nerve". Chinese search terms included "thyroidectomy", "thyroid surgery" "recurrent laryngeal nerve" "intraoperative nerve monitoring". Two evaluators screened the literature, extracted the materials and evaluated the risk of bias of the study independently. If there were different opinions, researchers should resolve which through consultation and ask the third-party researcher when necessary. The Meta-analysis was performed with the Review Manager 5.4 software.Results:A total of thirty-three studies were included and were all analyzed for primary outcome measures while only twenty-six of which were analyzed for secondary outcome measures. Meta-analysis showed that the positive predictive value of LOS in intraoperative nerve monitoring (IONM) was 65% [ OR=1.88, 95% CI: 1.36-2.60]. Then these thirty-three articles included in IONM were divided into I-IONM, C-IONM and mixed groups. Subgroup analysis showed that the positive predictive value of LOS in I-IONM, C-IONM and mixed groups were 62% [ OR=1.63, 95% CI: 1.05-2.52], 75% [ OR=2.93, 95% CI: 1.64-5.22] and 70% [ OR=2.38, 95% CI: 1.77-3.12] respectively. When these thirty-three included articles were divided into Asian, European, North American and Oceania, subgroup analysis showed that the positive predictive value of LOS was 50% [ OR=1.01, 95% CI: 0.44-2.31], 70% [ OR=2.29, 95% CI: 1.60-3.28], 82% [ OR=4.68, 95% CI: 3.79-5.78] and 83% [ OR=4.81, 95% CI: 3.10-7.46] respectively. Meta-analysis of secondary outcome measures in twenty-six articles showed that the negative predictive value of LOS was 99.6% [ RD=1.51, 95% CI: 1.48-1.53], with the sensitivity of 89% [ RD=1.24, 95% CI: 1.11-1.37] and specificity of 98%[ RD=1.43, 95% CI: 1.40-1.47]. Conclusion:The occurrence of LOS during IONM in thyroidectomy has a positive prediction effect and a higher negative prediction effect, sensitivity and specificity on RLN injury.

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 Recurrent pregnancy loss(RPL)presents a formidable challenge for individuals undergoing in vitro fertilization-embryo transfer(IVF-ET),forming both a clinical dilemma and a focal point for scientific inquiry.This study endeavors to investigate the intricate interplay between clinical features,such as age,body mass index(BMI),and waist-to-hip ratio(WHR),and routine laboratory parameters,including sex hormones,blood composition,liver and thyroid functions,thyroid antibodies,and coagulation indicators,in RPL patients undergoing IVF-ET.By meticulously analyzing these variables,we aim to uncover the latent risk factors predisposing individuals to RPL.Identifying potential factors such as advanced maternal age,obesity,and insulin resistance will provide clinicians with vital insights and empirical evidence to strengthen preventive strategies aimed at reducing miscarriage recurrence.Methods This retrospective case-controlled study included RPL patients who underwent IVF-ET treatment at Sun Yat-sen Memorial Hospital,Sun Yat-sen University,between January 2012 and March 2021 as the case cohort,compared with women receiving assisted reproductive treatment due to male infertility as the control cohort.The fasting peripheral blood was collected 5 days before the first menstrual cycle at least 12 weeks after the last abortion.The clinical characteristics and relevant laboratory indexes of the two groups were compared.Employing both univariate and multivariate logistic regression analyses,we sought to unearth potential high-risk factors underlying RPL.Additionally,a linear trend analysis was conducted to assess the linear relationship between total testosterone(TT)levels and the number of miscarriages.Results In contrast to the control cohort,the RPL cohort exhibited significant increases in age,BMI,and WHR(P<0.05).Notably,TT levels were markedly lower in the RPL cohort(P=0.022),while no significant differences were observed between the two groups concerning basal follicle-stimulating hormone,luteinizing hormone,estradiol,progesterone,prolactin levels,and anti-Müllerian hormone levels(P>0.05).Moreover,fasting insulin(FINS)levels and HOMA-IR index were notably elevated in the RPL cohort relative to the control cohort(P<0.001),although no significant differences were observed in fasting blood glucose levels(P>0.05).Furthermore,the neutrophil(NEU)count and NEU-to-lymphocyte ratio were notably higher in the RPL cohort(P<0.01).Univariate logistic regression analysis identified several factors,including age≥35 years old,BMI≥25 kg/m2,WHR>0.8,FINS>10 mU/L,HOMA-IR>2.14,NEU count>6.3×109 L-1,and an elevated NEU/lymphocyte ratio(NLR),as significantly increasing the risk of RPL(P<0.05).Although TT levels were within the normal range for both cohorts,higher TT levels were associated with a diminished RPL risk(odds ratio[OR]=0.67,95% confidence interval[CI]:0.510-0.890,P=0.005).After adjustments for confounding factors,age≥35 years old(OR=1.91,95% CI:1.06-3.43),WHR>0.8(OR=2.30,95% CI:1.26-4.19),and FINS>10 mU/L(OR=4.50,95% CI:1.30-15.56)emerged as potent risk factors for RPL(P<0.05).Conversely,higher TT levels were associated with a reduced RPL risk(OR=0.59,95% CI:0.38-0.93,P=0.023).Furthermore,the linear trend analysis unveiled a discernible linear association between TT levels and the number of miscarriages(Ptrend=0.003),indicating a declining trend in TT levels with escalating miscarriage occurrences.Conclusion In patients undergoing IVF-ET,advanced maternal age,lower TT levels,increased WHR,and elevated FINS levels emerged as potent risk factors for RPL.These findings provide clinicians with valuable insights and facilitate the identification of patients who are at high risks and the formulation of preventive strategies to reduce the recurrence of miscarriages.

[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.

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 observe the clinical effect of TCM diet therapy on type-2 diabetes.[Method] Select the said patients 76 cases,randomly divide them into treatment group and control group with 38 cases in each group,which were administered with routine western medicine,while the treatment one was added with TCM diet medication.[Result] Compare the fasting glucose before medication,showing marked difference(P

BACKGROUND: Cytridinie triphosphate(CTP) is predominantly used for cerebrovascualr accident and its sequelae, brain concussion, cerebral arteriosclerosis, senile dementia. What about its effect on diabetic peripheral neuropathies?OBJECTIVE: To observe the efficacy of cytridine triphosphate in improving nerve function and nerve conduction velocity in diabetic peripheral neuropathy.DESIGN: A prospective and randomized and controlled trial based on the patients.SETTING: Endocrine department of a military medical university.SUBJECTS: Totally 50 patients with diabetic peripheral neuropathy, hospitalized in Endocrine Department of Xijing Hospital of Fourth Military Medical University, were enrolled in this study from September 1999 to February 2000. All the patients were according to the including criteria, including 28 male and 22 female patients. They were randomly divided into treatment and control group averagely. Informed consent was obtained from all patients.METHODS: The 25 patients in treatment group received daily intravenous injection of 60 mg CTP. The other 25 in the control group received 100 mg vitamin B1 and 500 μg vitamin B12 and 20 mg scopolamine(654-2) and 100 mL saline as well every day. The treatment lasted for 14 days. The nerve conduction velocity was orthodromicly measured by surface electrode.MAIN OUTCOME MEASURES: Nerve conduction velocity in both groups.RESULTS: After treatment, the nerve conduction velocities of median nerve,ulnar nerve, fibular nerve, tibial nerve in the treatment group were higher than those in the control group (P < 0.05- 0. 01 ) . The neurological symptom and sign score in the treatment group(1. 4 ± 0.5, 3.0 ± 0.5) was less than that in the control group(2.6±0.3, 4.0±0.3) (t=3.255,2.005, P <0.05).CONCLUSION: CTP is effective in improving nerve conduction velocity in diabetic peripheral neuropathy.