Atherosclerosis is a chronic vascular disease caused by lipid deposition in the inner wall of blood vessels.Ferroptosis is a non-apoptotic form of cell death characterized by iron dependence and lipid reactive oxygen accumulation.Recent studies have shown that ferroptosis is closely related to the occurrence and development of atherosclerosis.This article explained the correlation between ferroptosis and atherosclerosis from the aspects of foam cell formation,endothelial cell death,vascular smooth muscle proliferation and calcification,and believed that ferroptosis runs through its pathological process.By combing the current research status of the mechanism of Chinese materia medica regulating ferroptosis to treat atherosclerosis,it can be seen that TCM monomers and compounds can reduce endothelial cell dysfunction and inflammatory response,slow down oxidative stress levels,and reduce the accumulation of oxidized lipids under the intima of arterial blood vessels by regulating ferroptosis p53,Nrf2 signaling pathway,amino acid metabolism,lipid metabolism,etc.,so that the blood vessels reach homeostasis,which can provide a reference for the exploration of clinical treatment strategies for atherosclerosis.

Aim To examine the pathogenesis of disul-fide death gene in vascular dementia(VD)by bioin-formatics analysis of disulfide death differentially ex-pressed genes(DEGs)combined with experimental verification.Methods The death DEGs of disulfide were screened and their correlation was analyzed.The VD patients data in the data set were analyzed by clus-tering and typing and gene set variation.The clustering risk of DEGs was tested with a nomogram model,and the optimal learning model was predicted.After the es-tablishment of VD rat model,water maze test,HE stai-ning and RT-qPCR detection were performed to verify the results of health information.Results Four DEGs including SLC7A11 were obtained,which had antago-nistic or synergistic interaction with each other.The genetic data could be divided into two subtypes with significant differences.After typing,VD disulfide DEGs were mainly concentrated in GnRH signaling pathways.The accuracy of the nomogram prediction model was high.Generalized linear was the best ma-chine learning model.Compared with the sham opera-tion group,the escape latency of rats in the model group was prolonged,the number of crossing platforms decreased,the relative mRNA expression levels of Slc3a2 and Slc7a11 decreased,and LRPPRC in-creased.Conclusions SLC7A11 and other disulfide death DEGs and its related GnRH signaling pathway may be an important part of the pathogenesis of VD di-sulfide death.SLC3A2,LRPPRC and SLC7A11 can be used as characteristic genes in the regulation of VD by disulfide death,which may affect VD progression through the regulation of disulfide death.

Objective:To analyze the association of apolipoprotein E(ApoE),soluble semaphoring 4D(sSema4D),and cyclophilin A(CypA)levels with unfavorable outcome in patients with chronic heart failure(CHF).Methods:We retrospectively enrolled 108 patients with CHF admitted in the Fifth Affiliated Hospital of Zhengzhou Universi-ty between March 2019 and March 2022.According to the outcome during 6-month follow-up,patients were di-vided into favorable outcome group(n=71)and unfavorable outcome group(n=37).ApoE,sSema4D and CypA levels were compared between the two groups,and multivariate Logistic regression was employed to identify the risk factors of unfavorable outcome within 6-month follow-up in CHF patients.Results:Compared to patients in the favorable outcome group,those in the unfavorable outcome group had significant higher proportion of NYHA classⅣ(59.46％vs.25.35％),serum creatinine[(80.74±3.89)μmol/L vs.(71.36±3.63)μmol/L],ApoE[(69.87±4.25)mg/L vs.(47.36±3.17)mg/L],sSema4D[(916.62±7.32)ng/L vs.(426.42±6.25)ng/L]and CypA[(6.74±1.32)ng/L vs.(4.38±0.72)ng/L](P＜0.001 all).Multivariate Logistic regression indicated that NY-HA class Ⅳ(OR=2.782,95％CI 1.166～6.636),serum creatinine(OR=29.893,95％CI 6.782～131.768),ApoE(OR=12.046,95％CI 4.694～30.913),sSema4D(OR=8.390,95％CI 2.260～31.146)and CypA(OR=6.486,95％CI 1.780～23.635)were independent risk factors for unfavorable outcome within 6-month follow-up in CHF patients(P＜0.05 or＜0.01).Conclusion:The levels of ApoE,sSema4D and CypA were closely associated with short-term unfavorable outcome in patients with chronic heart failure.

Objective To observe the effect of emodin on lung injury in rats with stroke associated pneumonia(SAP)through regulating Janus kinase 2(JAK2)/signal transducer and activators of transcription 3(STAT3)signaling pathway.Methods The SAP rat model was established by modified thread embolization method combined with intratracheal injection of Pseudomonas aeruginosa method.The successfully modeled rats were randomly divided into model group,emodin low-and high-dose groups and emodin high-dose+coumermycin(JAK2 activator)group,with 12 rats in each group,and another 12 SD rats were selected as the sham-operated group.After the intervention,the partial pressure of arterial blood gas indexes such as carbon dioxide(PaCO2)and partial pressure of oxygen(PaO2)were measured,the ratio of lung wet/dry mass(W/D)was determined,the inflammatory cell count in the bronchoalveolar lavage fluid(BALF)was detected,the histopathological feature in the lung tissues was observed by hematoxylin-eosin(HE)staining and the pathological injury was scored,enzyme-linked immunosorbent assay(ELISA)was used to detect myeloperoxidase(MPO)activity in the lung tissues and interleukin 6(IL-6)and cyclooxygenase 2(COX-2)levels in BALF and serum,and Western Blot was used to detect the expression of JAK2/STAT3 pathway key proteins in lung tissues.Results Compared with the sham-operated group,the model group rats showed that more obvious pathological injury in lung tissues was seen,and PaCO2 value,ratio of lung W/D,white blood cell count and eosinophils count in BALF,pathological injury score,MPO activity in lung tissues,IL-6 and COX-2 levels in BALF and serum,and ratios of p-JAK2/JAK2 and p-STAT3/STAT3 in lung tissues were significantly increased,and PaO2 value was significantly decreased,the differences being statistically significant(P<0.05);compared with the model group,the emodin low-and high-dose groups rats showed that the pathological injury in lung tissues was reduced,PaCO2 value,ratio of lung W/D,white blood cell count and eosinophils count in BALF,pathological injury score,MPO activity in lung tissues,IL-6 and COX-2 levels in BALF and serum,and ratios of p-JAK2/JAK2 and p-STAT3/STAT3 in lung tissues were all decreased,and PaO2 value was increased,the differences being statistically significant(P<0.05),and the improvement effect was more stronger in high-dose emodin group;coumermycin attenuated the improvement effect of emodin on the above various indexes in the model rats.Conclusion Emodin can reduce the inflammation levels in SAP rats through inhibiting the activation of JAK2/STAT3 signaling pathway,thus reducing the lung tissue damage and improving the lung function of rats.

Atherosclerosis is a chronic vascular disease caused by lipid deposition in the inner wall of blood vessels.Ferroptosis is a non-apoptotic form of cell death characterized by iron dependence and lipid reactive oxygen accumulation.Recent studies have shown that ferroptosis is closely related to the occurrence and development of atherosclerosis.This article explained the correlation between ferroptosis and atherosclerosis from the aspects of foam cell formation,endothelial cell death,vascular smooth muscle proliferation and calcification,and believed that ferroptosis runs through its pathological process.By combing the current research status of the mechanism of Chinese materia medica regulating ferroptosis to treat atherosclerosis,it can be seen that TCM monomers and compounds can reduce endothelial cell dysfunction and inflammatory response,slow down oxidative stress levels,and reduce the accumulation of oxidized lipids under the intima of arterial blood vessels by regulating ferroptosis p53,Nrf2 signaling pathway,amino acid metabolism,lipid metabolism,etc.,so that the blood vessels reach homeostasis,which can provide a reference for the exploration of clinical treatment strategies for atherosclerosis.

Objective:To explore the possibility of using a inferior gluteal artery perforator flap (IGAPF) for breast reconstruction in the patient who did not have suitable donor site in back and abdomen.Methods:In November 2024, a 25-year-old unmarried and childless woman with right breast cancer received immediate right breast reconstruction by a right free IGAPF after modified right mastectomy in the Department of Breast and Thyroid Surgery, Second Affiliated Hospital of Hainan Medical University. The locations of perforators were confirmed by both Multi-detector computed tomography angiography (MDCTA) and portable Doppler blood flow detector before surgery. The IGAPF was designed to take the inferior gluteal wrinkle as the lower edge, the axis of the flap was parallel to the inferior gluteal wrinkle, and the width of the flap was estimated where the incision could be directly closed. The size of right IGAPF was 6.0 cm×19.0 cm. Sharp dissection was performed between the sarcolemma and muscle fibres of gluteus, then the perforators were dissected along the direction of muscle fibres of gluteus. The vascular pedicle was kept at about 8.0 cm in length. The diameter of artery was about 2.0 mm and that for the veins was about 1.5 mm. End-to-end anastomoses with the right thoracodorsal artery and vein were successfully carried out. The donor site was directly closed, and it was hidden in the inferior gluteal wrinkle. Postoperative outpatient clinical review was made.Results:Pathological examination reported: an invasive carcinoma of right breast, axillary lymph node metastasis (2/10). The patient recovered well and the flap survived without any complication, i.e. ischemic necrosis, infection and haematoma. The patient was off-bed at 3 days and discharged at 13 days after surgery. At the 40 days of postoperative follow-up, the patient achieved a good recovery and the lower limb activity was not affected by the surgery. The patient was satisfied with the reconstructed breast and donor site recovery. The patient followed with scheduled chemotherapy and subsequent radiotherapy. The volume of reconstructed breast was smaller than the other breast, of which the patient was fully informed before the surgery.Conclusion:A free IGAPF provides an alternative donor sites for achieving a breast reconstruction due to the reliable pedicle vessels and invisible donor scars.

Objective:To explore the associations of temperature, relative humidity, and their interaction effect with fall risk.Methods:Data on fall cases were collected using the national injury surveillance system from May to September, in 2006-2022 in Hubei Province. Combined with the meteorological and air pollution data, we conducted a time-stratified case-crossover design and used conditional logistic regression models and distributed lag nonlinear models to examine the exposure-response relationships between temperature, humidity, and fall risk. We further divided the low and the high temperature groups and the low and the high relative humidity groups and analyzed the excess risk ( ER) of falls attributed to dry-hot or wet-hot events. Finally, we calculated the additive interactions of temperature and humidity on fall risk. Results:A total of 55 401 fall cases were included. With the increase in temperature and relative humidity decrease, the exposure-response curves of fall showed nonlinear upward trends among all populations. Gender and age differences were found in temperature-fall and relative humidity-fall risk relationships. Compared with wet-non-hot (normal temperature and high relative humidity) events, the ER of fall in dry-hot (high temperature and low relative humidity) events was 14.80% (95% CI: 9.69%- 20.15%), and the ER of wet-hot (high temperature and high relative humidity) events was 9.59% (95% CI: 2.52%-17.13%). However, there was no statistically significant difference between dry-hot and wet-hot events in the fall, and no statistically significant difference between different genders, ages, occupations, and fall occurred place (all P>0.05). No significant synergistic additive interaction was found between temperature and relative humidity on fall risk (relative excess risk due to interaction=-0.08, 95% CI: -0.19-0.02). Conclusions:Higher temperatures and lower relative humidity were associated with increased fall risk. Both dry-hot and wet-hot events had a higher risk of fall, while high temperature and low humidity have no synergistic effect on fall risk.

Objective:To explore the associations of temperature, relative humidity, and their interaction effect with fall risk.Methods:Data on fall cases were collected using the national injury surveillance system from May to September, in 2006-2022 in Hubei Province. Combined with the meteorological and air pollution data, we conducted a time-stratified case-crossover design and used conditional logistic regression models and distributed lag nonlinear models to examine the exposure-response relationships between temperature, humidity, and fall risk. We further divided the low and the high temperature groups and the low and the high relative humidity groups and analyzed the excess risk ( ER) of falls attributed to dry-hot or wet-hot events. Finally, we calculated the additive interactions of temperature and humidity on fall risk. Results:A total of 55 401 fall cases were included. With the increase in temperature and relative humidity decrease, the exposure-response curves of fall showed nonlinear upward trends among all populations. Gender and age differences were found in temperature-fall and relative humidity-fall risk relationships. Compared with wet-non-hot (normal temperature and high relative humidity) events, the ER of fall in dry-hot (high temperature and low relative humidity) events was 14.80% (95% CI: 9.69%- 20.15%), and the ER of wet-hot (high temperature and high relative humidity) events was 9.59% (95% CI: 2.52%-17.13%). However, there was no statistically significant difference between dry-hot and wet-hot events in the fall, and no statistically significant difference between different genders, ages, occupations, and fall occurred place (all P>0.05). No significant synergistic additive interaction was found between temperature and relative humidity on fall risk (relative excess risk due to interaction=-0.08, 95% CI: -0.19-0.02). Conclusions:Higher temperatures and lower relative humidity were associated with increased fall risk. Both dry-hot and wet-hot events had a higher risk of fall, while high temperature and low humidity have no synergistic effect on fall risk.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

From the perspective of competitive endogenous RNA(ceRNA) constructed by metastasy-associated lung adenocarcinoma transcript 1(Malat1) and microRNA 16-5p(miR-16-5p), the improvement mechanism of Tonggu Xiaotong Capsules(TGXTC) on the imbalance and disorder of "cholesterol-iron" metabolism in chondrocytes of osteoarthritis(OA) was explored. In vivo experiments, 60 8-week-old C57BL/6 mice were acclimatized and fed for 1 week and then randomly divided into two groups: blank group(12 mice) and modeling group(48 mice). The animals in modeling group were anesthetized by 5% isoflurane inhalation, which was followed by the construction of OA model. They were then randomly divided into model group, TGXTC group, Malat1 overexpression group, and TGXTC+Malat1 overexpression(TGXTC+Malat1-OE) group, with 12 mice in each group. The structural changes of mouse cartilage tissues were observed by Masson staining after the intervention in each group. RT-PCR was employed to detect the mRNA levels of Malat1 and miR-16-5p in cartilage tissues. Western blot was used to analyze the protein expression of ATP-binding cassette transporter A1(ABCA1), sterol regulatory element-binding protein(SREBP), cytochrome P450 family 7 subfamily B member 1(CYP7B1), CCAAT/enhancer-binding protein homologous protein(CHOP), acyl-CoA synthetase long-chain family member 4(ACSL4), and glutathione peroxidase 4(GPX4) in cartilage tissues. In vitro experiments, mouse chondrocytes were induced by thapsigargin(TG), and the combination of Malat1 and miR-16-5p was detected by double luciferase assay. The fluorescence intensity of Malat1 in chondrocytes was determined by fluorescence in situ hybridization. The miR-16-5p inhibitory chondrocyte model was constructed. RT-PCR was used to analyze the levels of Malat1 and miR-16-5p in chondrocytes under the inhibition of miR-16-5p. Western blot was adopted to analyze the regulation of TG-induced chondrocyte proteins ABCA1, SREBP, CYP7B1, CHOP, ACSL4, and GPX4 by TGXTC under the inhibition of miR-16-5p. The results of in vivo experiments showed that,(1) compared with model group, TGXTC group exhibited a relatively complete cartilage layer structure. Compared with Malat1-OE group, TGXTC+Malat1-OE group showed alleviated cartilage surface damage.(2) Compared with model group, TGXTC group had a significantly decreased Malat1 mRNA level and an increased miR-16-5p mRNA level in mouse cartilage tissues(P<0.01).(3) Compared with the model group, the protein levels of ABCA1 and GPX4 in the cartilage tissue of mice in the TGXTC group increased, while the protein levels of SREBP, CYP7B1, CHOP and ACSL4 decreased(P<0.01). The results of in vitro experiments show that,(1) dual-luciferase was used to evaluate that miR-16-5p has a targeting effect on the Malat1 gene.(2)Compared with TG+miR-16-5p inhibition group, TG+miR-16-5p inhibition+TGXTC group had an increased mRNA level of miR-16-5p and an decreased mRNA level of Malat1(P<0.01).(3) Compared with TG+miR-16-5p inhibition group, TG+miR-16-5p inhibition+TGXTC group exhibited increased expression of ABCA1 and GPX4 proteins and decreased expression of SREBP, CYP7B1, CHOP, and ACSL4 proteins(P<0.01). The reasults showed that TGXTC can regulate the ceRNA of Malat1 and miR-16-5p to alleviate the "cholesterol-iron" metabolism disorder of osteoarthritis chondrocytes.
Animals ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Chondrocytes/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice, Inbred C57BL ; Mice ; Osteoarthritis/drug therapy* ; Iron/metabolism* ; Male ; Cholesterol/metabolism* ; Humans ; Capsules ; RNA, Competitive Endogenous