The study aims to examine the effects and potential mechanisms of disulfiram (DSF) on cardiac hypertrophic injury, focusing on the role of transforming growth factor-β-activated kinase 1 (TAK1)-mediated pan-apoptosis (PANoptosis). H9C2 cardiomyocytes were treated with angiotensin II (Ang II, 1 µmol/L) to establish an in vitro model of myocardial hypertrophy. DSF (40 µmol/L) was used to treat cardiomyocyte hypertrophic injury models, either along or in combination with the TAK1 inhibitor, 5z-7-oxozeaenol (5z-7, 0.1 µmol/L). We assessed cell damage using propidium iodide (PI) staining, measured cell viability with CCK8 assay, quantified inflammatory factor levels in cell culture media via ELISA, detected TAK1 and RIPK1 binding rates using immunoprecipitation, and analyzed the protein expression levels of key proteins in the TAK1-mediated PANoptosis pathway using Western blot. In addition, the surface area of cardiomyocytes was measured with Phalloidin staining. The results showed that Ang II significantly reduced the cellular viability of H9C2 cardiomyocytes and the binding rate of TAK1 and RIPK1, significantly increased the surface area of H9C2 cardiomyocytes, PI staining positive rate, levels of inflammatory factors [interleukin-1β (IL-1β), IL-18, and tumor necrosis factor α (TNF-α)] in cell culture media and p-TAK1/TAK1 ratio, and significantly up-regulated key proteins in the PANoptosis pathway [pyroptosis-related proteins NLRP3, Caspase-1 (p20), and GSDMD-N (p30), apoptosis-related proteins Caspase-3 (p17), Caspase-7 (p20), and Caspase-8 (p18), as well as necroptosis-related proteins p-MLKL, RIPK1, and RIPK3]. DSF significantly reversed the above changes induced by Ang II. Both 5z-7 and exogenous IL-1β weakened these cardioprotective effects of DSF. These results suggest that DSF may alleviate cardiac hypertrophic injury by inhibiting TAK1-mediated PANoptosis.
Animals ; MAP Kinase Kinase Kinases/physiology* ; Rats ; Myocytes, Cardiac/pathology* ; Disulfiram/pharmacology* ; Cardiomegaly ; Apoptosis/drug effects* ; Cell Line ; Angiotensin II ; Necroptosis/drug effects* ; Interleukin-1beta/metabolism* ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Lactones ; Resorcinols ; Zearalenone/administration & dosage*

Objective To explore the differences in neck and lumbar spine injuries among different types of aircraft pilots and the correlation between body surface temperature and the severity of injury.Methods Data were collected by questionnaire surveys and medical examinations.Forty male pilots were selected as research objects,including 14 fighter pilots and 26 helicopter pilots,aged between 28 and 39 years,with a height range of 168 to 178 cm,and a total flight time of 600 to 2 000 h.Infrared thermal imaging was employed for skin temperature.A questionnaire survey was conducted for the assessment of the common site and degree of pain.The relationship between body surface temperature and pain was investigated.Results Fighter pilots mainly complained of discomfort in the neck and scapular region,while helicopter pilots were more likely to experience lower back pain.The skin temperature in the affected regions was significantly higher than that in the surrounding normal regions in both fighter pilots and helicopter pilots(P<0.05).The pain score was positively related with elevated temperature in the affected areas(P<0.05).Conclusion It is found that fighter pilots are more prone to neck and scapular pain,while helicopter pilots are more likely to experience lower back pain.The severity of pain is positively related with increased temperature in the affected areas.Infrared thermal imaging can be used to assess temperature variation at injured sites and the location of training injuries among pilots.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Objective To analyze the differences of brain activity between first-episode untreated depressive patients with and without suicidal ideation(SI),and its correlations with clinical characteristics.Methods A total of 40 major depressive disorder(MDD)patients with SI(MDD+SI group),40 patients without SI MDD(MDD+NSI group),and 40 healthy controls(HC)(HC group)were enrolled.The 17-item Hamilton depression scale(HAMD-17)and Beck scale for suicide ideation(BSI)were used to assess the severity of depression and SI,respectively.MRI data were collected.The values of fractional amplitude of low-frequency fluctuation(fALFF)were calculated.Results(1)Compared with the HC group,the MDD+NSI group showed decreases in the fALFF val-ues of the default network and attention network.The fALFF values of the attention network in the MDD+SI group showed decreases.Compared with the MDD+NSI group,the MDD+SI group showed decreases in the fALFF values of the attention network.(2)The fALFF values in the left middle frontal gyrus were negatively correlated with the total score of HAMD-17(r=-0.55;P<0.001)in the MDD+NSI group,while the fALFF values in the left middle frontal gyrus were negatively correlated with the total score of HAMD-17(r=-0.53;P<0.001)and the total score of BSI(r=-0.51;P<0.001)in the MDD+SI group.(3)The optimal critical value of fALFF value in left middle frontal gyrus for predicting SI occurrence in MDD patients was-0.039,area under the curve(AUC)was 0.76,sensitivity was 0.63,and specificity was 0.80.Conclusion The decreased local activity intensity in the left middle frontal gyrus of the brain might be the central mechanism for the occurrence of SI in MDD patients.In addition,the left middle frontal gyrus might have certain value in identifying SI and predicting the severity of SI.

Objective To study the correlation between the serum ferritin level and the pathological classification,tumor stage,PD-L1 expression,disease control rate(DCR),and survival period of patients with lung cancer.Methods A total of 85 patients with lung cancer admitted to our hospital from February 2020 to February 2021 were selected as the research subjects.All patients received immunotherapy,and the serum ferritin levels of patients before and after immunotherapy were detected.Meanwhile,according to the difference in serum ferritin levels before and after immunotherapy,the patients were divided into the increased group(31 cases)and the decreased group(54 cases).The correlation between the serum ferritin level and the pathological classification,tumor stage and PD-L1 expression level of patients was analyzed,and the DCRs and survival periods of patients with serum ferritin level≥300 ng/mL and<300 ng/mL before treatment were compared,as well as the increased group and the decreased group.The survival curve of patients in each group was analyzed by the Kaplan-Meier.Results Patients with tumor stage Ⅰ to Ⅲ showed significantly lower serum ferritin levels than patients with tumor stage Ⅳ(P<0.05).The DCR,3-year survival rate and progression-free survival(PFS)of patients with serum ferritin level≥300 ng/mL were significantly lower/shorter than those of patients with serum ferritin level<300 ng/mL(P<0.05).The DCR,3-year survival rate and PFS of patients in the increased group were significantly lower/shorter than those in the decreased group(P<0.05).Conclusion The increased serum ferritin level in lung cancer patients before treatment and the further increase after treatment are significantly associated with the reduced efficacy of immunotherapy and the shortened survival period.The combination of baseline serum ferritin levels before treatment and dynamic changes after treatment may serve as a clinical biomarker panel for predicting immunotherapy outcomes.

Objective To investigate the correlation of the characteristics of symptomatic middle cerebral artery plaques with the risk of stroke recurrence based on high-resolution vessel wall imaging(HR-VWI).Methods Totally 83 patients hospitalized for acute ischemic stroke(AIS)and transient ischemic attack(TIA)at Jingmen People's Hospital and Yichang Central People's Hospital from January 2019 to August 2022 were selected prospectively,who all underwent the treatment with antiplatelet aggregation and intensive lipid lowering by statins.During the follow-up,AIS or TIA recurrences were determined in case of newly found symptoms of neurological impairment in the same supply area of the responsible vessel or new infarct foci confirmed by cranial diffusion weighted imaging(DWI).The patients with AIS or TIA recurrences were enrolled into a recurrence group,and the remained ones were divided into a non-recurrence group.The recurrence group went through HR-VWI scanning within two weeks of recurrence and statin treatment,and the non-recurrence group was examined with HR-VWI half a year after receiving statin treatment.All the patients had their clinical indexes compared before and after statin treatment,the baseline data of the two groups underwent univariate analysis,and Logistic regression analysis was performed for the high-risk factors related to recurrence.SPSS 22.0 software was used for statistical analysis.Results After six months of statin treatment,all the patients were improved in TC,TG,luminal stenosis rate,high T1WI signal,plaque burden,plaque enhancement rate and NIHSS score,with the differences being significant(all P＜0.05).Univariate analysis showed the recurrence group had higher plaque enhancement rates(P=0.012)and higher plaque burden(P=0.047)when compared with the non-recurrence group,with the differences being significant;the two groups were not statistically different in luminal stenosis rate,high T1WI signal,plaque thickness and remodeling index(all P＞0.05).Multivariate logistic regression analysis indicated the plaque enhancement rate was independently correlated with stroke recurrence within 6 months(P=0.027).Conclusion HR-VWI can effectively assess MCA plaque characteristics in recurrent stroke patients,and high plaque enhancement rate faciliates the evaluation of stroke recurrence.[Chinese Medical Equipment Journal,2025,46(2):63-67]

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective To investigate the clinical characteristics of preoperative intestinal symptoms in patients with bowel endometriosis and to compare the effects of shaving versus segmental bowel resection on postoperative intestinal function.Methods A total of 105 patients diagnosed with bowel endometriosis and treated by the same surgical team at the Obstetrics and Gynecology Hospital,Fudan University between Aug 1,2013 and Dec 30,2017 were prospectively enrolled in this study.Clinical data were collected via outpatient visits and telephone follow-ups at four time points:preoperative(T0)and postoperative(T1:Nov 2018;T2:Nov 2020;T3:Apr 2024).The primary outcome was bowel symptoms and gastrointestinal function scores;secondary outcome was pain scores.A generalized estimating equation(GEE)model was used to analyze the interaction effect of surgical approach and follow-up time on outcomes.Results Ultimately,a total of 89 patients were included(15.24%loss to follow-up),among whom 79 patients(88.76%)underwent shaving excision.Preoperatively,46 patients(51.68%)presented with bowel symptoms,primarily anus bulge(21 cases,46.65%)and diarrhea(15 cases,32.61%)during menstruation.Postoperatively,there was a significant increase in constipation rates(T1:71.43%;T2:50.00%;T3:72.00%).Both surgical groups exhibited significant improvements in dysmenorrhea,gastrointestinal discomfort scores as well as gastrointestinal quality of life index(P<0.000 5).However,the segmental resection group had significantly higher scores for low anterior resection syndrome,constipation compared with the shaving excision group(P=0.02 and P=0.05).Conclusion Approximately half of the patients with bowel endometriosis exhibit typical bowel symptoms preoperatively,such as anus bulge and diarrhea.Both shaving excision and segmental resection effectively alleviate pain;however,shaving excision demonstrates an advantage regarding preservation of bowel function,whereas segmental resection may elevate risks associated with postoperative constipation or altered defecation patterns due to structural changes.The selection of surgical approach should carefully balance lesion removal and functional preservation,moreover,be sure that potential risks are thoroughly informed to patients prior to surgery.

Aim To investigate the effect of cordycepin(COR)on gentamicin(GEN)-induced nephrotoxicity and the molecular mechanism of inhibiting oxidative stress and ferroptosis induced by GEN.Methods The oral SD rats were divided into a control group,GEN group,and GEN+COR group.Following the success-ful setting up of the animal model,the serum creatinine(CR)and urea nitrogen(BUN)levels of rats were measured,and renal tissue injury was assessed using HE staining.In addition,the contents of malondialde-hyde and glutathione in kidney tissues of SD rats in each group were detected,and the expressions of fer-roptosis markers GPX4 and SLC7A11 were analyzed by Western blot.Results Compared with the control group,CR and BUN in GEN-stimulated group signifi-cantly increased(P＜0.01),and the level of CR and BUN was effectively reduced after 50 mg·kg-1 COR oral administration.HE results also showed that COR could alleviate the kidney tissue damage caused by GEN.COR could reverse the increase of malondialde-hyde level and the decrease of glutathione level caused by GEN in rat kidney tissue,and COR could restore the decrease of GPX4 and SLC7A11 protein levels induced by GEN.Conclusion COR can reduce GEN-induced kidney injury by inhibiting oxidative stress and ferrop-tosis.