Objective To reveal the effects of sulforaphane(SFN)on the ferroptosis pathway and iron homeostasis in rats with diabetic retinopathy(DR).Methods A DR rat model was established by a single intraperitoneal injection of streptozotocin at 65 mg·kg-1.After modeling,the rats were randomly divided into six groups(n=12 per group):Group C(control group),DR group,0.5SFN group,1.0SFN group,2.0SFN group,and 2.0SFN+Erastin group.Group C con-sisted of non-intervention control rats,while the other groups were DR model rats.Groups C and DR were orally adminis-tered 0.5 g·L-1 sodium carboxymethyl cellulose(CMC-Na).The 0.5SFN,1.0SFN,and 2.0SFN groups were orally ad-ministered SFN at 0.5,1.0,and 2.0 mg·kg-1,respectively.The 2.0SFN+Erastin group was orally administered 2.0 mg·kg-1 SFN and simultaneously received a tail intravenous injection of the ferroptosis inducer Erastin at 10.0 mg·kg-1.The intervention lasted for 4 weeks.Fasting blood glucose(FPG)was measured with a glucometer,glycosylated hemoglo-bin(GHb)was detected by visible spectrophotometry,and fasting insulin(FINS)was measured by ELISA.Retinal tissues were subjected to hematoxylin-eosin(HE)staining and periodic acid-Schiff(PAS)staining.The level of reactive oxygen species(ROS)in the retina was detected using the DCFH-DA probe,malondialdehyde(MDA)was measured by the TBA method,and reduced glutathione(GSH)was assessed by spectrophotometry.Retinal Fe2+content was determined by spectrophotometry.The mRNA expression levels of ferritin heavy chain 1(FTH1),ferroportin 1(FPN1),transferrin re-ceptor(TFRC),glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),thioredoxin 1(Trx1),and thioredoxin-interacting protein(TXNIP)in the retina were detected by qRT-PCR.GPX4 protein expression in the retina was detected by Western blot.Results Compared with the DR group,the 0.5SFN,1.0SFN,and 2.0SFN groups showed decreased FPG and GHb,increased FINS,improved retinal morphology with reduced neovascular capillaries,decreased levels of ROS and MDA,increased GSH levels,decreased retinal Fe2+content,increased FTH1 and FPN1 mRNA levels,de-creased TFRC mRNA levels,increased retinal GPX4,SLC7A11,and Trx1 mRNA levels,decreased TXNIP mRNA levels,and increased retinal GPX4 protein levels(all P＜0.05).Compared with the 2.0SFN group,the 2.0SFN+Erastin group showed increased FPG and GHb,decreased FINS,aggravated retinal damage with increased neovascular capillaries,elevat-ed levels of ROS and MDA,decreased GSH levels,increased retinal Fe2+content,decreased FTH1 and FPN1 mRNA levels,increased TFRC mRNA levels,decreased retinal GPX4,SLC7A11,and Trx1 mRNA levels,increased TXNIP mRNA levels,and decreased retinal GPX4 protein levels(all P＜0.05).Conclusion SFN alleviates DR in rats by inhibiting the ferrop-tosis pathway and maintaining iron homeostasis.

Objective To investigate the mechanism by which 4-week high-intensity interval training(HIIT)regulates the mitochondrial unfolded protein response(UPRmt)in skeletal muscle and improves mitochondrial function in a rat model of chronic unpredictable mild stress(CUMS).Methods Male SPF-grade SD rats(6～8 weeks old)were divided randomly into control(C),model(M),HIIT+control(HC),and HIIT+model(HM)groups.Rats in the M and HM groups were subjected to CUMS for 8 weeks to establish a depression model,while rats in the HC and HM groups received HIIT for 5 d a week for 4 weeks.The exercise regimen consisted of 3 min high-speed(85％～90％Smax)combined with 1 min low-speed(50％～55％Smax)uninterrupted repetitive training(Smax is maximum training speed).Behavioral changes were evaluated at weeks 4 and 8.Tissue samples were taken 24 h after the last behavioral test and skeletal muscle mitochondria were examined by transmission electron microscopy.The ATP and reactive oxygen species(ROS)contents were measured by enzyme-linked immunosorbent assays and protein expression levels of activating transcription factor(ATF)4,ATF5,C/EBP homologous protein(CHOP),and heat shock protein 60(HSP60)were detected by Western blot.Results(1)The body mass,number of crossing grids,number of upright positions,sugar-water preference rate,and ATP content were significantly decreased in group M compared with group C(P＜0.01),while the number of damaged mitochondria,ROS content,ATF4,ATF5,CHOP,and HSP60 protein expression were significantly increased(P＜0.01).(2)After 4-weeks of HIIT intervention,the ATP content and ATF4 and ATF5 protein expression levels were significantly increased in the HC group compared with C group(P＜0.05,P＜0.01).The number of crossing grids,number of upright positions,sugar-water preference rate,ATP content,and ATF4 protein expression were significantly increased in the HM group compared with M group(P＜0.01),while the number of damaged mitochondria,ROS content,and ATF5,CHOP,and HSP60 protein expression levels were significantly decreased(P＜0.01).(3)After 4 weeks of HIIT intervention,the number of crossing grids in CUMS rats was significantly positively correlated with ATF4 protein expression,and ROS content was correlated with CHOP protein expression,number of damaged mitochondria,and ATF5 protein expression(|r|＞0.75,P＜0.01;|r|＞0.75,P＜0.05).Upright frequency was significantly negatively correlated with ATF5 and HSP60 protein expression,the number of crossing grids,the sugar-water preference rate,and the expression of CHOP and HSP60 proteins(|r|＜0.75,P＜0.05).Conclusions 4-week HIIT intervention can improve mitochondrial dysfunction and alleviate depressive-like behavior in CUMS rats by regulating skeletal muscle UPRmt.

Objective To investigate the mechanism by which 4-week high-intensity interval training(HIIT)regulates the mitochondrial unfolded protein response(UPRmt)in skeletal muscle and improves mitochondrial function in a rat model of chronic unpredictable mild stress(CUMS).Methods Male SPF-grade SD rats(6～8 weeks old)were divided randomly into control(C),model(M),HIIT+control(HC),and HIIT+model(HM)groups.Rats in the M and HM groups were subjected to CUMS for 8 weeks to establish a depression model,while rats in the HC and HM groups received HIIT for 5 d a week for 4 weeks.The exercise regimen consisted of 3 min high-speed(85％～90％Smax)combined with 1 min low-speed(50％～55％Smax)uninterrupted repetitive training(Smax is maximum training speed).Behavioral changes were evaluated at weeks 4 and 8.Tissue samples were taken 24 h after the last behavioral test and skeletal muscle mitochondria were examined by transmission electron microscopy.The ATP and reactive oxygen species(ROS)contents were measured by enzyme-linked immunosorbent assays and protein expression levels of activating transcription factor(ATF)4,ATF5,C/EBP homologous protein(CHOP),and heat shock protein 60(HSP60)were detected by Western blot.Results(1)The body mass,number of crossing grids,number of upright positions,sugar-water preference rate,and ATP content were significantly decreased in group M compared with group C(P＜0.01),while the number of damaged mitochondria,ROS content,ATF4,ATF5,CHOP,and HSP60 protein expression were significantly increased(P＜0.01).(2)After 4-weeks of HIIT intervention,the ATP content and ATF4 and ATF5 protein expression levels were significantly increased in the HC group compared with C group(P＜0.05,P＜0.01).The number of crossing grids,number of upright positions,sugar-water preference rate,ATP content,and ATF4 protein expression were significantly increased in the HM group compared with M group(P＜0.01),while the number of damaged mitochondria,ROS content,and ATF5,CHOP,and HSP60 protein expression levels were significantly decreased(P＜0.01).(3)After 4 weeks of HIIT intervention,the number of crossing grids in CUMS rats was significantly positively correlated with ATF4 protein expression,and ROS content was correlated with CHOP protein expression,number of damaged mitochondria,and ATF5 protein expression(|r|＞0.75,P＜0.01;|r|＞0.75,P＜0.05).Upright frequency was significantly negatively correlated with ATF5 and HSP60 protein expression,the number of crossing grids,the sugar-water preference rate,and the expression of CHOP and HSP60 proteins(|r|＜0.75,P＜0.05).Conclusions 4-week HIIT intervention can improve mitochondrial dysfunction and alleviate depressive-like behavior in CUMS rats by regulating skeletal muscle UPRmt.

Objective To reveal the effects of sulforaphane(SFN)on the ferroptosis pathway and iron homeostasis in rats with diabetic retinopathy(DR).Methods A DR rat model was established by a single intraperitoneal injection of streptozotocin at 65 mg·kg-1.After modeling,the rats were randomly divided into six groups(n=12 per group):Group C(control group),DR group,0.5SFN group,1.0SFN group,2.0SFN group,and 2.0SFN+Erastin group.Group C con-sisted of non-intervention control rats,while the other groups were DR model rats.Groups C and DR were orally adminis-tered 0.5 g·L-1 sodium carboxymethyl cellulose(CMC-Na).The 0.5SFN,1.0SFN,and 2.0SFN groups were orally ad-ministered SFN at 0.5,1.0,and 2.0 mg·kg-1,respectively.The 2.0SFN+Erastin group was orally administered 2.0 mg·kg-1 SFN and simultaneously received a tail intravenous injection of the ferroptosis inducer Erastin at 10.0 mg·kg-1.The intervention lasted for 4 weeks.Fasting blood glucose(FPG)was measured with a glucometer,glycosylated hemoglo-bin(GHb)was detected by visible spectrophotometry,and fasting insulin(FINS)was measured by ELISA.Retinal tissues were subjected to hematoxylin-eosin(HE)staining and periodic acid-Schiff(PAS)staining.The level of reactive oxygen species(ROS)in the retina was detected using the DCFH-DA probe,malondialdehyde(MDA)was measured by the TBA method,and reduced glutathione(GSH)was assessed by spectrophotometry.Retinal Fe2+content was determined by spectrophotometry.The mRNA expression levels of ferritin heavy chain 1(FTH1),ferroportin 1(FPN1),transferrin re-ceptor(TFRC),glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),thioredoxin 1(Trx1),and thioredoxin-interacting protein(TXNIP)in the retina were detected by qRT-PCR.GPX4 protein expression in the retina was detected by Western blot.Results Compared with the DR group,the 0.5SFN,1.0SFN,and 2.0SFN groups showed decreased FPG and GHb,increased FINS,improved retinal morphology with reduced neovascular capillaries,decreased levels of ROS and MDA,increased GSH levels,decreased retinal Fe2+content,increased FTH1 and FPN1 mRNA levels,de-creased TFRC mRNA levels,increased retinal GPX4,SLC7A11,and Trx1 mRNA levels,decreased TXNIP mRNA levels,and increased retinal GPX4 protein levels(all P＜0.05).Compared with the 2.0SFN group,the 2.0SFN+Erastin group showed increased FPG and GHb,decreased FINS,aggravated retinal damage with increased neovascular capillaries,elevat-ed levels of ROS and MDA,decreased GSH levels,increased retinal Fe2+content,decreased FTH1 and FPN1 mRNA levels,increased TFRC mRNA levels,decreased retinal GPX4,SLC7A11,and Trx1 mRNA levels,increased TXNIP mRNA levels,and decreased retinal GPX4 protein levels(all P＜0.05).Conclusion SFN alleviates DR in rats by inhibiting the ferrop-tosis pathway and maintaining iron homeostasis.

Objective:To investigate the clinical manifestations, treatment, and outcomes of Barth syndrome (BTHS).Methods:A retrospective analysis was conducted on 21 pediatric patients diagnosed with BTHS between January 2010 and December 2023 at Beijing Children′s Hospital, Beijing Anzhen Hospital, and Beijing JingDu Children′s Hospital. Clinical data including gender, age at onset, initial symptoms, clinical manifestations, personal history, family genetic history, and laboratory tests (neutrophil count, echocardiography, electrocardiogram and genetic testing) were reviewed.Results:All the 21 patients were male, with the age of onset at 4.1 (1.1, 9.3) months. Main clinical manifestations included heart failure (18 cases), neutropenia (16 cases), respiratory symptoms (15 cases), 3-methylpentenediuria (7 cases),develop retardation (8 cases), gastrointestinal symptoms (7 cases), fatigue and anorexia (6 cases), and recurrent infection (2 cases). Electrocardiogram abnormalities included ST changes (18 cases), flattened T wave and low voltage of limb leads (2 cases), and abnormal Q waves in lead Ⅰ and avL (1 case). Echocardiographic features showed increased trabeculation, interventricular septum and left ventricular wall thickening, and left ventricular enlargement with reduced ejection fraction. Genetic testing identified TAZ gene variations in all 21 patients: 11 missense mutations, 2 nonsense mutations, 2 frameshift mutations, 2 whole code mutations, 2 exon deletions, 1 splicing mutation, and 1 synonymous mutation. Fifteen mutations were maternally inherited, 2 were de novo, and 4 lacked verified variant origin.In terms of treatment, all 18 patients with heart failure received routine heart failure treatment, of whom 11 patients also received intravenous immunoglobulin and corticosteroids. After the follow-up of 91.0 (75.5, 109.5) months, 15 of the 18 patients showed restoration of cardiac function after 4.5 (3.0, 9.8) months of treatment, with one case of significant improvement, while 2 cases suddenly died.Conclusions:BTHS predominantly affects males with early onset, mainly characterized by abnormal cardiac structure and function, along with clinical features including fatigue, delayed growth and development, and neutropenia. Early diagnosis and intervention, including heart failure treatment, intravenous immunoglobulin, and corticosteroids, can lead to significant improvement in cardiac function, though sudden death remains a risk.

The 20th National Congress of the Communist Party of China emphasized the expansion of international scientific and technological exchanges and cooperation. Against this backdrop, the radiological health research institutions bear important responsibilities in the field of international radiological health. As a key institution in the industry, the National Institute for Radiological Protection (NIRP), Chinese Center for Disease Control and Prevention shoulders the important mission of promoting international exchanges in radiation health in China. A case study was conducted on the NIRP using data of official overseas visits from 2010 to 2024. The SWOT analysis was used to comprehensively and systematically examine the strengths, weaknesses, opportunities, and challenges of NIRP in international cooperation and exchanges. To effectively enhance the depth and scope of international exchanges, this article proposes a series of innovative optimization strategies such as establishing dedicated personnel positions to ensure efficient handling of affairs, implementing stringent approval procedures to guarantee the rationality and compliance of overseas visits, strengthening pre-departure training to improve the professionalism of outbound personnel, conducting follow-up evaluations to continuously refine management practices, and centralizing the management of official passports to ensure their secure use. This article aims to provide practical optimization strategies for the management of official overseas visits for NIRP and other similar institutions, promote international exchanges and cooperation in the field of radiation health, and help China play a more important role in the global radiation health field.

BACKGROUND: Despite some studies identifying a potential association between obesity and chronic obstructive pulmonary disease (COPD) risk, previous research had overlooked the dynamic nature of body weight over time, leading to inconsistent findings. The purpose of this study is to elucidate the relationship between adult weight change and COPD risk by adjusting for potential confounding factors. METHODS: We conducted a retrospective analysis using data from ten NHANES cycles (1999-2018), including adults aged 40-74 years. Weight change patterns were assessed using BMI at three time points and classified into five categories per period. Absolute weight change was also grouped into five levels. Multivariate logistic regression models, incorporating sampling weights, were used to examine associations between weight change and COPD, adjusting for demographic and lifestyle covariates. RESULTS: Compared with participants who maintained normal weight, stable obesity participants had increased risk of COPD from age 25 years to 10 years before the survey (OR = 1.45, 95% CI = 1.15 to 1.83), in the 10 years period before the survey (OR = 1.75, 95% CI = 1.47 to 2.08), and from age 25 years to survey (OR = 1.84, 95% CI = 1.46 to 2.31). Three periods indicate that weight gain in adulthood was associated with risk of COPD. In addition, substantial weight gain of more than 20 kg was associated with a higher risk of COPD. In stratified analyses, we also observed a more significant association between weight change and the risk of COPD in never smokers compared to former smokers. CONCLUSIONS Our study suggested that stable obesity and weight gain in adulthood were associated with an increased risk of COPD compared to those who maintain a normal weight, and that the association between weight gain and the incidence of COPD appears closer in patients who have never smoked.
Humans ; Pulmonary Disease, Chronic Obstructive/etiology* ; Middle Aged ; Male ; Female ; Adult ; Aged ; Retrospective Studies ; Weight Gain ; Obesity/complications* ; Risk Factors ; United States/epidemiology* ; Nutrition Surveys ; Body Mass Index

OBJECTIVE: To investigate whether the G protein-coupled estrogen receptor (GPER) can attenuates acute lung injury in mice with exertional heat stroke (EHS) by inhibiting ferroptosis. METHODS: Sixty SPF-grade male C57BL/6 mice were randomly divided into four groups: normal control group (control group), EHS model group (EHS group), dimethyl sulfoxide (DMSO) solvent group (EHS+DMSO group), and GPER-specific agonist G1 group (EHS+G1 group), with 15 mice in each group. All mice underwent 14 days of adaptive training at 24-26 centigrade before modeling, and the EHS model was established using a high-temperature treadmill device. After successful modeling, the mice were allowed to cool naturally at room temperature. In the EHS+G1 group, 40 μg/kg of the GPER-specific agonist G1 was slowly injected intraperitoneally immediately after modeling. In the EHS+DMSO group, 40 μg/kg of DMSO was slowly injected intraperitoneally immediately after modeling. The control group received no treatment. Five hours after modeling, abdominal aortic blood was collected, and lung tissues were harvested after euthanasia. The lung coefficient was calculated to evaluate lung injury. Lung histopathological changes were observed under a light microscope after hematoxylin-eosin (HE) staining, and a lung histopathological score was assigned. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), malondialdehyde (MDA), and Fe²⁺ in lung tissue. Immunofluorescence was used to detect the expression of glutathione peroxidase 4 (GPX4). Real-time polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of GPX4, ferroportin 1 (FPN1), and ferritin heavy chain 1 (FTH1). Western blotting was performed to detect the protein expression of GPX4, FPN1, and FTH1. RESULTS: Compared with the control group, the lung coefficient and lung histopathological score were significantly increased in the EHS group. HE staining showed significant thickening and unevenness of the alveolar septa and alveolar walls, partial alveolar collapse, and extensive erythrocyte, inflammatory cell, and plasma-like material extravasation in the alveolar spaces. Serum levels of TNF-α, IL-1β, MDA, and Fe²⁺ were significantly elevated. Immunofluorescence staining showed a significant decrease in GPX4-positive expression in lung tissue. Western blotting and RT-PCR showed significantly reduced protein and mRNA expression of GPX4, FPN1, and FTH1 in lung tissue. Compared with the EHS group, the EHS+G1 group showed a significant reduction in lung coefficient and lung histopathological score [lung coefficient (mg/g): 3.9±0.1 vs. 4.6±0.3, lung histopathological score: 4.2±0.2 vs. 6.9±0.2, both P < 0.05]. HE staining revealed reduced severity of lung tissue fluid extravasation, inflammatory infiltration, decreased hemorrhage, and less severe alveolar structural damage. Serum levels of TNF-α, IL-1β, MDA, and Fe²⁺ were significantly reduced [TNF-α (ng/L): 44.3±0.2 vs. 64.6±0.3, IL-1β (ng/L): 69.3±0.4 vs. 97.8±0.2, MDA (nmol/L): 2.8±0.3 vs. 3.6±0.5, Fe²⁺ (nmol/L): 0.021±0.004 vs. 0.028±0.004, all P < 0.05]. Immunofluorescence staining showed a significant decrease in GPX4-positive expression in lung tissue (fluorescence intensity: 35.53±2.41 vs. 16.45±0.31, P < 0.05). RT-PCR and Western blotting showed significantly increased mRNA and protein expression of GPX4, FPN1, and FTH1 in lung tissue [mRNA expression: GPX4 mRNA (2^-ΔΔCt): 0.44±0.05 vs. 0.09±0.01, FPN1 mRNA (2^-ΔΔCt): 0.77±0.17 vs. 0.42±0.14, FTH1 mRNA (2^-ΔΔCt): 0.75±0.04 vs. 0.58±0.01; protein expression: GPX4/β-actin: 0.96±0.11 vs. 0.24±0.04, FPN1/β-actin: 1.26±0.21 vs. 0.44±0.14, FTH1/β-actin: 0.27±0.12 vs. 0.15±0.07; all P < 0.05]. However, there were no statistically significant differences in any of the above indicators between the EHS+DMSO group and the EHS group. CONCLUSION Activation of GPER can attenuate EHS-related lung injury in mice, and its mechanism may be related to the activation of the GPX4 signaling pathway and inhibition of ferroptosis.
Animals ; Mice, Inbred C57BL ; Male ; Mice ; Heat Stroke/metabolism* ; Receptors, G-Protein-Coupled ; Ferroptosis ; Receptors, Estrogen ; Acute Lung Injury/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-1beta/metabolism* ; Lung Injury ; Lung/metabolism*

Objective:To investigate the clinical manifestations, treatment, and outcomes of Barth syndrome (BTHS).Methods:A retrospective analysis was conducted on 21 pediatric patients diagnosed with BTHS between January 2010 and December 2023 at Beijing Children′s Hospital, Beijing Anzhen Hospital, and Beijing JingDu Children′s Hospital. Clinical data including gender, age at onset, initial symptoms, clinical manifestations, personal history, family genetic history, and laboratory tests (neutrophil count, echocardiography, electrocardiogram and genetic testing) were reviewed.Results:All the 21 patients were male, with the age of onset at 4.1 (1.1, 9.3) months. Main clinical manifestations included heart failure (18 cases), neutropenia (16 cases), respiratory symptoms (15 cases), 3-methylpentenediuria (7 cases),develop retardation (8 cases), gastrointestinal symptoms (7 cases), fatigue and anorexia (6 cases), and recurrent infection (2 cases). Electrocardiogram abnormalities included ST changes (18 cases), flattened T wave and low voltage of limb leads (2 cases), and abnormal Q waves in lead Ⅰ and avL (1 case). Echocardiographic features showed increased trabeculation, interventricular septum and left ventricular wall thickening, and left ventricular enlargement with reduced ejection fraction. Genetic testing identified TAZ gene variations in all 21 patients: 11 missense mutations, 2 nonsense mutations, 2 frameshift mutations, 2 whole code mutations, 2 exon deletions, 1 splicing mutation, and 1 synonymous mutation. Fifteen mutations were maternally inherited, 2 were de novo, and 4 lacked verified variant origin.In terms of treatment, all 18 patients with heart failure received routine heart failure treatment, of whom 11 patients also received intravenous immunoglobulin and corticosteroids. After the follow-up of 91.0 (75.5, 109.5) months, 15 of the 18 patients showed restoration of cardiac function after 4.5 (3.0, 9.8) months of treatment, with one case of significant improvement, while 2 cases suddenly died.Conclusions:BTHS predominantly affects males with early onset, mainly characterized by abnormal cardiac structure and function, along with clinical features including fatigue, delayed growth and development, and neutropenia. Early diagnosis and intervention, including heart failure treatment, intravenous immunoglobulin, and corticosteroids, can lead to significant improvement in cardiac function, though sudden death remains a risk.

This report describes the case of a 43-year-old male presenting with severe anemia (hemoglobin, HGB 35 g/L). A comprehensive evaluation encompassing bone marrow morphology (24% ring sideroblasts), genetic testing (SF3B1-negative), iron metabolism studies (ferritin 1 179 μg/L), and imaging (liver MRI T2* value 1.1 ms) was performed for diagnosis, treatment planning, and assessment of outcomes. Initially diagnosed as having myelodysplastic syndrome with ring sideroblasts (MDS-RS), the patient experienced relapse after 10 months of luspatercept treatment. Following the identification of a significant retrospective history of heavy alcohol consumption (250 g/day for 20 years), vitamin B 6 therapy resulted in a rapid increase in HGB to 85 g/L within 10 days, reaching 134 g/L after one month, confirming a diagnosis of alcohol-induced sideroblastic anemia (SA). This case highlights that in SA lacking clonal evidence, the exclusion of reversible causes such as alcoholism should be prioritized. While luspatercept demonstrated short-term efficacy in this patient with non-clonal SA, caution is warranted regarding potential masking of the underlying etiology. Concurrent monitoring of iron overload and early initiation of iron chelation therapy are crucial in alcoholic SA to prevent hepatic damage.