Cardiomyopathy is a group of heterogeneous myocardial diseases with a variety of specific phenotypes that can lead to cardiovascular death or progressive heart failure in severe cases.Because of the severity and complexity of these diseases,the search for new regulatory mechanisms to prevent and treat cardiomyopathy is particularly urgent.Iron death is a form of programmed cell death that differs from other forms of iron dependence and is characterized by the accumulation of iron-dependent lipid peroxides.Studies have shown that iron death can be involved in the occurrence and progression of cardiomyopathy through different signaling pathways.Therefore,targeted regulation of iron death is a new strategy to prevent cardiomyopathy.In this paper,the mechanism of iron death and its important role in cardiomyopathy were reviewed to find the potential relationship between iron death and cardiomyopathy and provide more ideas for the treatment of various cardiomyopathies in the future.

Objective:To investigate the changes of thyroid hormones and the flow velocity of superior thyroid artery in patients with Graves' disease and Hashimoto's thyrotoxicosis before and after treatment with methimazole.Methods:A case-control study was conducted to select 45 cases of Graves' disease and 45 cases of Hashimoto's thyroiditis from October 2021 to December 2022 in the Department of Endocrinology, North China University of Science and Technology Affiliated Hospital. The changes of thyroid hormone and blood flow velocity of superior thyroid artery in patients with Graves' disease and Hashimoto's thyroiditis before and after treatment with methimazole were analyzed. Measurement data satisfying normal distribution were expressed by xˉ±s, and the mean between two groups was compared by t test. Measurement data not satisfying normal distribution were expressed by M( Q1, Q3), and the median between two groups was compared by Wilcoxon rank sum test. χ 2 test was used to compare the constituent ratio of enumeration data among groups. Results:There was no significant difference in thyroid stimulating hormone (TSH) between the two groups before treatment, and there was no significant difference in TSH between the two groups after 1 month and 3 months of treatment (all P>0.05). The levels of free triiodothyronine (FT3) were (24.09±9.29) pmol/L and (17.41±9.36) pmol/L in Graves' disease group and Hashimoto's thyroiditis group respectively before treatment. FT4 were (60.23±20.82) and (43.47±21.71) pmol/L, respectively, and the peak stolie vloiy (PSV) were (69.53±5.70) and (52.65±4.64) cm/s, respectively in Graves' disease group and Hashimoto's thyroiditis group respectively before treatment. There were significant differences between the two groups ( t values wrere 3.39 and 3.74, Z=13.83, all P<0.001). The difference of FT3 between one month after treatment and before treatment was (-6.36±5.32) and (-12.64±9.08) pmol/L ( t=4.02, P<0.001) and the difference in FT3 between 3 months of treatment and before treatment was (-10.14±9.50) and (-17.80±11.17) pmol/L, respectively ( t=3.51, P<0.001) between the Graves disease group and the Hashimoto's thyroiditis group. The difference in FT4 between the Graves disease group and the Hashimoto's thyroiditis group after 1 month of treatment and before treatment was (-28.47±10.09) and (-20.57±14.48) pmol/L ( t=7.01, P<0.001), and the difference of FT4 was (-47.06±20.57) and (-30.17±20.54) pmol/L ( t=3.91, P<0.001) between the Graves disease group and the Hashimoto toxin group. The difference between one month after treatment and before treatment was (-13.10(-34.10,-2.60)) and (-10.50(-27.5,-0.20)) cm/s ( Z=2.63, P=0.009), respectively. The difference between 3 months and before treatment was (-31.40(-53.20,-12.70)) and (-19.90(-46.00,-4.70)cm/s ( Z=4.40, P<0.001)) between the Graves disease group and the Hashimoto's thyroiditis group, and the difference was statistically significant. Conclusion:Thyroid hormone levels were decreased after treatment with methimazole in patients with diffuse toxic goiter and Hashimoto toxemia, but the difference was not statistically significant. The PSV level of superior thyroid artery in patients with diffuse toxic goiter was significantly lower than that in patients with Hashimoto's thyrotoxicosis.

Occupational silicosis (hereinafter referred to as "silicosis") exhibited individual differences in disease susceptibility, with genetic factors playing a crucial role in its onset and progression. Cytokines, such as interleukin (IL)-1RA +2018T>C locus, tumor necrosis factor-α -308G>A and -238G>A locus, transforming growth factor (TGF)-β1 +915G>C locus, were related to the development of silicosis. However, relationship between IL-17F +7488A>G and TGF-β1 -509T>C locus with silicosis had shown inconsistent results across different studies. Regulatory proteins such as matrix metalloproteinase (MMP)-2 -735C>T locus, MMP-9 rs3918242 locus, heat shock protein (HSP) 70-1+190G>C locus, carboxypeptidase M rs12812500 locus, family sequence similarity gene 13A (FAM13A) rs2609255 locus, and desmoplakin rs2076304 locus were also related to the development of silicosis. The A allele of the non-coding RNA miRNA-4508 rs6576457 increased the risk of developing silicosis-related pulmonary fibrosis in dust-exposed workers. The polymorphism in the long non-coding RNA ADGRG3 rs1814521 was related to silicosis susceptibility. Additionally, six circular RNAs of small nucleolar RNA host gene 14 rs17115143 sequence might be potential biomarkers of silicosis. Human leukocyte antigen-DR (HLA-DR) genes demonstrated a dual role in both risk and protection against silicosis, while angiotensin I-converting enzyme (ACE) gene polymorphisms likely affected silicosis development by modulating serum ACE activity. However, the mechanisms by which certain genetic variations affected susceptibility to silicosis remain unclear. Prospective studies with large-scale samples combining genetics, epidemiology, bioinformatics, and biofunctional studies are needed to promote the development of biomarkers for silicosis susceptibility and disease course, and clinical therapies.

Objective To observe the relationship between functional connectivity(FC)of frontoparietal network(FPN)and cognitive function in patients with cerebral small vessel disease(CSVD)using resting-state functional MRI(rs-fMRI).Methods rs-fMRI of 50 CSVD patients with cognitive impairment(CI group),65 CSVD patients with normal cognition(NC group)and 60 healthy controls(HC group),as well as outcomes of neuropsychological tests were retrospectively analyzed.Brain regions with different FC of FPN were compared among 3 groups and between each 2 groups.Partial correlation analysis was used to evaluate the correlations of FC of brain regions value being statistically different between CI and NC groups and cognitive scores.Results Significant differences of FC in bilateral cingulate gyrus,left middle frontal gyrus,right supramarginal gyrus,right inferior parietal lobule and right medial superior frontal gyrus were found among groups(FWE correction,all P＜0.05).Compared with NC group,FC of left cingulate gyrus decreased,of right inferior frontal gyrus and right medial superior frontal gyrus increased in CI group(FWE correction,all P＜0.05).The decreased FC value of left cingulate gyrus was negatively correlated with clock drawing test score in CSVD patients(r=-0.159,P=0.049).Conclusion CSVD patients with or without CI had extensive abnormal FC of FPN,and the left cingulate gyrus was associated with patient's cognitive function.

Objective:To summarize the best evidence for external auditory canal irrigation in patients with cerumen embolism.Methods:The clinical decisions, guidelines, systematic reviews, expert consensus, group standards, evidence summaries, and randomized controlled trials regarding external auditory canal irrigation in patients with cerumen embolism were retrieved from databases and websites such as BMJ Best Practice, UpToDate, Guidelines International Network, National Institute for Health and Clinical Excellence, Joanna Briggs Institute Evidence-Based Health Care Center Database, PubMed, Embase, China National Knowledge Infrastructure, WanFang data, and China Biology Medicine disc. The search period was from database establishment to February 15, 2023. Six researchers screened the literature, evaluated the methodological quality, and extracted and summarized the best evidence for external auditory canal irrigation in patients with cerumen embolism.Results:A total of nine articles were included, including one clinical decision, two guidelines, two systematic reviews, one group standard, and three randomized controlled trials. Sixteen pieces of evidence were summarized from six aspects of operators: pre-operation evaluation and preparation, operation process, post-operation handling, health education, and adverse reactions during operation.Conclusions:This paper summarizes the best evidence for external auditory canal irrigation in patients with cerumen embolism. Medical and nursing staff should carefully select and apply evidence based on clinical scenarios and patient's wishes.

Objective:To discuss the effect of cell division cycle protein 20(CDC20)on the proliferation and cell cycle of endometrial carcinoma(EC)cells,and to clarify its mechanism.Methods:Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods were used to detect the expression levels of CDC20 mRNA and protein in human endometrial stromal T-HESC cell and EC cells(KLE,RL95-2,ZJB-ENC1,and ECC-1 cells).The RL95-2 cells were selected for the subsequent experiments.CDC20 shRNA interference lentivirus was transfected into the RL95-2 cells and the cells were divided into control group,sh-NC group(infected with negative control lentivirus),sh-CDC20 group(infected with CDC20 shRNA interference lentivirus),sh-NC+SM04690 group(infected with negative control lentivirus followed by treatment with 64 nmol·L-1 Wnt/β-catenin signaling pathway inhibitor SM04690 for 48 h),and sh-CDC20+SM04690 group(infected with CDC20 shRNA interference lentivirus followed by treatment with 64 nmol·L-1 SM04690 for 48 h).RT-qPCR and Western blotting methods were used to detect the expression levels of CDC20 mRNA and proteins in the cells in various groups;CCK-8 method was used to detect the proliferation activities of the RL95-2 cells in various groups;BrdU assay was used to detect the percentages of BrdU positive cells in various groups;flow cytometry was used to detect the percentages of the cells at G2/M stage in various groups;Western blotting method was used to detect the expression levels of β-catenin,oncogene c-Myc,and cyclin D1 proteins in the cells in various groups.Results:Compared with T-HESC cells,the expression levels of CDC20 mRNA and protein in the KLE,RL95-2,ZJB-ENC1,and ECC-1 cells were significantly increased(P＜0.05),and the highest expression levels of CDC20 mRNA and protein were observed in RL95-2 cells.Compared with sh-NC group,the proliferation activities and percentages of the BrdU positive cells in sh-CDC20 group and sh-NC+SM04690 group were significantly decreased(P＜0.05),the percentages of the cells at G2/M phase were significantly increased(P＜0.05),and the expression levels of β-catenin,c-Myc,and cyclin D1 proteins were significantly decreased(P＜0.05).Compared with sh-CDC20 group,the proliferation activity and percentage of BrdU positive cells in sh-CDC20+SM04690 group were significantly decreased(P＜0.05),the percentage of the cells at G2/M phase was significantly increased(P＜0.05),and the expression levels of β-catenin,c-Myc,and cyclin D1 proteins in the cells were significantly decreased(P＜0.05).Conclusion:CDC20 is highly expressed in the EC cells.Silencing CDC20 may inhibit the cell proliferation by inducing G2/M phase arrest in the RL95-2 cells through the regulation of Wnt/β-catenin signal transduction.

Objective To observe the role of tumor necrosis factor-α (TNF-α) and platelet-derived growth factor-B (PDGF-B) in kiwi fruit essence-mediated protection of radiation-induced lung injury (RILI) in rats. Methods 96 male healthy Sprague-Dawley rats were divided into normal control group, model group, and kiwi fruit essence treatment group(60 and 240 mg/kg) by the random number table method, with 24 animals in each group. The whole lungs underwent 6 MV X-ray irradiation (18 Gy) to induce RILI animal models in rats of the latter three groups. On the next day after irradiation, rats in the latter two groups were intragastrically administrated with 60 or 240 mg/kg kiwi fruit essence, once a day. The rats in the normal control and model groups were treated with 9 g/L sodium chloride solution. Eight rats in the latter three groups were randomly sacrificed on days 14, 28, and 56, while normal control rats were sacrificed on day 56 as the overall control. Blood samples were collected and separated. Serum concentrations of TNF-α and PDGF-B were detected using ELISA. The lung tissues were isolated for HE and Masson staining to evaluate alveolitis and pulmonary fibrosis (PF). The hydroxyproline (HYP) content in lung tissues was detected. The mRNA and protein expression of pulmonary TNF-α and PDGF-B were determined by quantitative real-time PCR and immunohistochemistry. Results Compared with the model group, treatment with 60 and 240 mg/kg kiwi fruit essence group significantly reduced alveolitis on days 14 and 28 as well as PF lesions on days 28 and 56. Compared with the normal control group, HYP content in the lung tissue of the model group increased on day 28 and day 56, while TNF-α and PDGF-B levels in the serum and lung tissues increased at each time point. Compared with the model group during the same period, 60 and 240 mg/kg kiwi fruit essence element treatment group reported the diminished levels of serum and pulmonary TNF-α on day 14 and day 28. Consistently, the lung tissue HYP content and serum and pulmonary PDGF-B levels on day 28 and day 56 were reduced. In addition, the above indicators in the 240 mg/kg kiwi fruit essence treatment group were lower than those for the 60 mg/kg kiwi fruit essence treatment group. Conclusion Kiwi fruit essence can alleviate RILI in rats, which is related to the down-regulation of TNF-α expression at the early stage and decreased PDGF-B level at the middle and late stages.
Animals ; Male ; Rats ; Fruit/metabolism* ; Lung/radiation effects* ; Lung Injury/prevention & control* ; Oils, Volatile ; Proto-Oncogene Proteins c-sis/metabolism* ; Pulmonary Fibrosis ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha/metabolism* ; Actinidia/chemistry*

Objective To explore the impact of sinomenine on bleomycin A5-induced pulmonary fibrosis (PF) in rats and the underlying mechanism. Methods MRC-5 cells were cultured and treated with sinomenine to determine its optimal concentration and time through the MTT assay. Subsequently, MRC-5 cells were incubated with 80 μmol/L sinomenine for 48 hours or transfected with miR-21 mimic/a disintegrin-like and metalloproteinase with thrombospondin type 1 motif (ADAMTS-1) siRNA prior to sinomenine treatment. The expression of miR-21, ADAMTS-1, collagen type 1 (Col1) and collagen type 3 (Col3) was detected by quantitative real-time PCR (qRT-PCR) and/or Western blot analysis. Thirty SD rats were randomly divided into control group, sinomenine group and sinomenine combined with miR-21 agomir group, with 10 animals in each group. Bleomycin A5 were intratracheally administered to establish the PF model. Then, rats in control group, sinomenine group and sinomenine +miR-21 agomir group were treated with 9 g/L sodium chloride solution, sinomenine and sinomenine+miR-21 agomir, respectively. On day 28, all rats were sacrificed. HE and Masson staining was performed in pulmonary tissue. The expression of ADAMTS-1, Col1 and Col3 in pulmonary tissue were detected by qRT-PCR and/or Western blot analysis. ELISA was used to measure serum procollagen type 1 carboxyterminal propeptide (P1CP) and procollagen type 3 aminoterminal propeptide (P3NP) levels. Results Administration of sinomenine decreased miR-21 levels, up-regulated ADAMTS-1 expression, and promoted Col1 and Col3 degradation in MRC-5 cells. Importantly, interfering with the miR-21/ADAMTS-1 signaling pathway partially reversed the promotive effect of sinomenine on Col1 and Col3 degradation. Treatment of SD rats with sinomenine reduced alveolitis and PF scores, decreased serum P1CP and P3NP levels, up-regulated pulmonary ADAMTS-1 expression, and down-regulated Col1 and Col3 expression. However, these effects were reversed by miR-21 agomir. Conclusion Sinomenine promotes Col1 and Col3 degradation and inhibits PF in rats by miR-21/ADAMTS-1 pathway.
Rats ; Animals ; Pulmonary Fibrosis/genetics* ; Procollagen/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction ; Bleomycin/adverse effects* ; Collagen Type III/metabolism* ; MicroRNAs/metabolism*

[摘 要] 目的：评估细胞分裂周期蛋白20（CDC20）在子宫内膜癌（EC）中的表达，探讨其对EC细胞RL95-2周期和凋亡的影响及可能的机制。方法：从癌症基因组图谱（TCGA）数据库获取EC的mRNA表达矩阵以及患者的临床信息，通过R语言分析CDC20 mRNA的差异表达情况及其与肿瘤分期的相关性，qPCR及WB法检测CDC20在RL95-2细胞中的表达；向RL95-2细胞转染sh-CDC20以敲减CDC20的表达，采用CCK-8法和流式细胞术检测敲减CDC20对RL95-2细胞增殖活力、细胞周期分布和凋亡的影响，WB法分析对Mcl-1/p-Chk1信号活性的影响；建立RL95-2细胞裸鼠移植瘤模型，评估敲减CDC20对肿瘤生长的抑制作用及对移植瘤组织中Mcl-1/p-Chk1信号轴和细胞凋亡的影响。结果：CDC20在EC组织及RL95-2细胞中呈高表达（均P<0.01），且CDC20的高表达与EC的分期有关联。敲减CDC20可显著降低RL95-2细胞增殖活力（P<0.01），阻滞细胞周期于G1期（P<0.01），促进细胞凋亡（P<0.01），抑制细胞中Mcl-1和p-Chk1的表达（P<0.05或P<0.01）。敲减CDC20可显著抑制RL95-2细胞裸鼠移植瘤的生长（P<0.01），降低移植瘤组织内Mcl-1和p-Chk1的表达（P<0.01），促进移植瘤细胞凋亡（P<0.01）。结论：CDC20在EC组织中呈高表达且与肿瘤分期有关联，敲减CDC20能够抑制RL95-2细胞及其裸鼠移植瘤的生长而促进凋亡，这可能与Mcl-1/p-Chk1信号轴有关。

AIM: To explore the protective effects of sinomenine (SIN) on oxidative stress and pulmonary fibrosis and its relationship with the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. METHODS: MRC-5 cells were treated with hydrogen peroxide (H2O2) to establish the oxidative stress injury model, followed by administration with SIN. Cell viability was detected using the CCK-8 method. The biochemical kits were employed to measure malondialdehyde (MDA) content and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities. The protein expression of Keap1 and Nrf2 was examined by western blot. Thirty SD rats were randomly divided into control group, bleomycin A5 (BLM) group and BLM + SIN group, with 10 animals in each group. Bleomycin A5 were intratracheally administered to the rats in BLM group and BLM+SIN group to establish the pulmonary fibrosis model. The rats in control group received the same volume of 9 g/L sodium chloride solution. The second day after model construction, the rats in BLM+SIN group were gavaged with SIN, while the rats in the other two groups were treated with 9 g/L sodium chloride solution. On day 28, all rats were sacrificed. Pulmonary tissue was isolated, and HE and Masson staining was performed to observe the pathological changes. The MDA content and SOD, GSH-Px and CAT activities in pulmonary tissue were evaluated. Western blot was used to assay pulmonary tissues Keap1 and Nrf2 protein expression. RESULTS: When compared with H2O2 group, SIN treatment increased cell viability, decreased MDA content, elevated SOD, GSH-Px and CAT activities, down-regulated Keap1 expression, and promoted nuclear translocation of Nrf2 in MRC-5 cells. In comparison with BLM group, administration of SIN decreased alveolitis and pulmonary fibrosis pathological changes and scores as well as pulmonary tissue MDA content, enhanced pulmonary tissues SOD, GSH-Px and CAT activities, down-regulated pulmonary tissues Keap1 expression, and raised Nrf2 levels in the nucleus. CONCLUSION: SIN alleviates oxidative stress and pulmonary fibrosis possibly by activating the Keap1/Nrf2 signaling pathway.