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.

To summarize the nursing experience of a patient with acute injection botulism complicated with respiratory failure.The key nursing points include early standard use of botulinum antitoxin therapy to improve the signs of myasthenia;to strengthen respiratory support and airway management,to carry out respiratory training,and to promote the recovery of respiratory function;swallowing function training and dynamic evaluation were carried out to promote the recovery of swallowing function;narrative nursing was carried out to relieve patient's negative emotions.After 17 days of treatment and nursing care,the patient was removed from the tracheal tube on the 7th day,transferred to the general ward on the 14th day,and discharged successfully on the 17th day with a good prognosis.A telephone follow-up was conducted 4 months after discharge,and the patient recovered well.

Objective To study the efficacy and safety of less invasive surfactant administration(LISA)combined with budesonide and supported by nasal intermittent positive pressure ventilation(NIPPV)in preterm infants with respiratory distress syndrome(RDS).Methods Premature infants with RDS at the gestational age of 26-32 weeks in the neonatal ward of Xuzhou Central Hospital from Feb-ruary 2022 to March 2024 were divided into the observation group and the control group in this prospective randomized controlled trial.The control group suspended nasal continuous positive airway pressure(NCPAP),they were intubated and infused with PS into the lung through endotracheal tube and extubated(INSURE),then continued to receive NCPAP.In the observation group,a LISA tube was insert-ed through the vocal cords under direct vision with direct laryngoscope,then infused pulmonary surfactant(PS)and budesonide into the lung when NIPPV ventilation was applied.The results of blood gas analysis at 1h and 6h after intratracheal instillation of PS,medication administration,clinical efficacy,related complications of budesonide,bronchopulmonary dysplasia(BPD)were compared between the two groups.Results A total of 126 preterm infants with RDS were enrolled in the study,including 65 in the observation group and 61 in the control group.The incidence of regurgitation in the observation group were lower than those in the control group[(10.8％(7/65)vs 24.6％(15/61)],and the differences were statistically significant(P＜0.05).The PaO2/FiO2(P/F)in the observation group at 1h and 6h were higher than those in the control group,while PaCO2were lower than those in the control group,and the differences were statis-tically significant(all P＜0.05).The duration of non-invasive respiratory support(11.4±4.6 days vs 15.9±5.6 days),total oxygen inhaling(14.9±6.9 days vs 21.2±8.5 days),failure rate of machine withdrawal[(10.8％(7/65)vs 24.6％(15/61)],the rate of tracheal intubation within 72h[9.2％(6/65)vs 23.0％(14/61)],and re-administration of PS[18.5％(12/65)vs 34.4％(21/61)],the times of apnea[9.0(3.0-25.0)times vs 17.0(5.0-29.0)times]in the observation group were lower than those in the control group,and the differences were statistically significant(P＜0.05).The occurrence of BPD in the observational group were lower than those in the control group[15.4％(10/65)vs 34.4％(21/61)](P＜0.05).There were no significant differences between two groups in the related complications of budesonide(all P＞0.05).Conclusion LISA combined with budesonide and supported by NIPPV can effectively improve oxygenation,shorten the duration of non-invasive respiratory support,reduce the mechanical ventilation rate,and reduce the incidence of BPD in the treatment of premature infants with RDS at the gestational age of 26-32 weeks.

Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.

Objective:To explore the association between spicy food intake and the risk for cardio/cerebrovascular diseases.Methods:Data were collected from the China Kadoorie Biobank project conducted in Pengzhou, Sichuan Province. Using the Cox proportional hazards regression model, we analyzed the associations of the frequency of spicy food intake, spicy level, types of spicy food, and the age when regular intake of spicy food began (intake in 1 day/week), with the risk for cardio/cerebrovascular disease. Furthermore, the associations with the risks for ischemic heart disease (IHD) and cerebrovascular diseases, as well as the risk of ischemic stroke (IS) and hemorrhagic stroke (HS) were analyzed.Results:A total of 54 859 study participants were included in the study, in whom 49 320 had spicy food intake (89.90%). In these participants, 37 680 (68.69%) had spicy food intake in 6-7 days/week, 5 036 (9.18%) had spicy food intake in 1-5 days/week, and 6 604 (12.03%) had spicy food intake once a week; 5 539 (10.10%) had never/almost never had spicy food intake. After adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of spicy food was associated with reduced risks for IHD (intake in 6-7 days/week: HR=0.86, 95% CI: 0.78-0.95), cerebrovascular diseases (intake in 6-7 days/week: HR=0.88, 95% CI: 0.81-0.96), and IS (intak in 6-7 days/week: HR=0.85, 95% CI: 0.76-0.95). With the increase of spicy food intake frequency, the risk for cardio/cerebrovascular disease decreased (intake in 1-5 days/week: HR=0.91, 95% CI: 0.85-0.98; intake in 6-7 days/week: HR=0.89, 95% CI: 0.84-0.94) (trend test P<0.001). However, no statistical association was found between spicy food intake and the risk for HS. In terms of spicy level, after adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of spicy food was associated with reduced risk for cardio/cerebrovascular disease (moderate: HR=0.86, 95% CI: 0.82-0.90) and cerebrovascular disease (moderate: HR=0.90, 95% CI: 0.84-0.97). With the increase of spicy level, the risk for IHD decreased (moderate: HR=0.86, 95% CI: 0.79-0.93; strong: HR=0.84, 95% CI: 0.74-0.95) (trend test P<0.001). After adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of any type of spicy food was associated with reduced risk for cardio/cerebrovascular disease, IHD, and cerebrovascular disease. Regulat intake of spicy food from age 0-10 years was associated with reduced risk for cardio/cerebrovascular disease, IHD, and cerebrovascular disease. Regular intake of spicy food from age 11-20 years reduced the risk for cardio/cerebrovascular disease and IHD. There was no significant association between the regular intake of spicy food from age 21-79 years and the risks for cardio/cerebrovascular disease, IHD and cerebrovascular disease. Conclusion:The intake of spicy food could reduced the risk for cardio/cerebrovascular diseases, IHD, cerebrovascular diseases and IS in residents aged 30-79 years in Sichuan.

Objective:To investigate the clinicopathological and molecular characteristics of neurocutaneous melanosis in children caused by NRAS gene variants.Methods:Three cases of neurocutaneous melanosis from Children's Hospital of Fudan University (case 1 and case 2) and Shanghai Children′s Hospital, School of Medicine Shanghai Jiaotong University (case 3) from July 2022 to February 2023 were collected. The clinical, histopathological, immunohistochemical and genetic results of three patients were retrospectively analyzed. The literatures were reviewed.Results:The patients were all female, aged 5, 4 and 3 years, respectively. The patients presented with severe headache with other symptoms of increased intracranial pressure. Physical examination showed multiple congenital melanocytic nevi throughout the body. Imaging examination showed intracranial masses, which were located in the right cerebellum, pineal gland and left temporal lobe, respectively. The maximum diameters were 39.1 mm, 72.8 mm and 52.2 mm, respectively. Histologically, the tumor showed diffuse sheets of round or oval-shaped cells arranged in nests, with marked nuclear atypia, eosinophilic cytoplasm, dark nuclei, and prominent nucleoli. Giant tumor cells were seen and mitotic figures were easily observed. There were hemorrhage and necrosis. Pigment granules were found in the cytoplasm and stroma in case 1 and case 2. Immunohistochemically, the tumor cells showed diffuse and strong staining of SOX10, S-100, HMB45 and Melan A, but did not express GFAP and CKpan. The Ki-67 proliferation index ranged from 30% to 80%. Genetic testing showed that case 1 and case 2 had NRAS Q61K matation, and case 3 had NRAS Q61R mutation. Case 1 and case 3 underwent complete resection of the tumor combined with chemotherapy. Case 2 was diagnosed by biopsy and underwent resection after chemotherapy and radiotherapy. All patients were followed up for 18, 21 and 25 months, respectively. All patients died due to complications such as increased intracranial pressure and hydrocephalus.Conclusions:Neurocutaneous melanosis is a congenital neurocutaneous syndrome caused by abnormal development of embryonic neuroectodermal melanoblasts. Most cases are associated with somatic mutations of NRAS gene. Clinicians should pay attention to the skin manifestations and neuroimaging examination in patients with unexplained intracranial hypertension or epilepsy. The diagnosis of neurocutaneous melanosis depends on histopathology and genetic testing.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease lacking effective therapy. Metformin, an antidiabetic medication, has shown promising therapeutic properties in preclinical fibrosis models; however, its precise cellular targets and associated mechanisms in fibrosis resolution remain incompletely defined. Most research on metformin's effects has focused on mesenchymal and inflammatory responses with limited attention to epithelial cells. In this study, we utilized Sftpc lineage-traced and Fgfr2b conditional knockout mice, along with BMP2/PPARγ and AMPK inhibitors, to explore metformin's impact on alveolar epithelial cells in a bleomycin-induced pulmonary fibrosis model and cell culture. We found that metformin increased the proliferation and differentiation of alveolar type 2 (AT2) cells, particularly the recently identified injury-activated alveolar progenitors (IAAPs)-a subpopulation characterized by low SFTPC expression but enriched for PD-L1. Single-cell RNA sequencing revealed a reduction in apoptosis among mature AT2 cells. Interestingly, metformin's therapeutic effects were not significantly affected by BMP2 or PPARγ inhibition, which blocked the lipogenic differentiation of myofibroblasts. However, Fgfr2b deletion in Sftpc lineage cells significantly impaired metformin's ability to promote fibrosis resolution, a process linked to AMPK signaling. In conclusion, metformin alleviates fibrosis by directly activating AT2 cells, especially the IAAPs, through a mechanism that involves AMPK and FGFR2b signaling, but is largely independent of BMP2/PPARγ pathways.

Objective : To pathological changes and inducible nitric oxide synthase(iNOS), phosphorylated insulin receptor substrate 1 serine 307(p-IRS1ser 307), phosphorylated protein kinase B serine 473(p-AKTser 473), glycogen synthase kinase-3β(GSK-3β), and gluconeogenic synthase(GS) proteins were observed in the liver of rats under the condition of chronic intermittent hypoxia-replicated oxygen in control. And to explore the role of iNOS/IRS1/AKT/GSK-3β signaling pathway in chronic intermittent hypoxia-induced insulin resistance. Methods : Forty SD rats were randomly divided into a control group(NC group) and an experimental group(CIH group), with 20 rats in each group. The NC group was placed in a normoxic environment for 12 weeks, while the CIH group was first subjected to intermittent hypoxia for 8 weeks, and then resumed normoxic rearing until the 12th week. Fasting blood glucose(FBG) and fasting insulin(FINS) were measured at baseline, week 8 and week 12, and liver tissues were taken for pathology and measurement of iNOS, p-IRS1ser 307, p-AKTser 473, GSK3β and GS levels, to compare the differences between groups. Results: t baseline, there was no significant difference in liver pathology between the two groups, and the observed indexes were not statistically significant(P>0.05); at 8 weeks, compared with the NC group, liver pathology in the CIH group showed significant disorganization of hepatic blood sinusoids and hepatocyte cords, obvious hepatocyte edema, smaller nuclei, increased lymphocyte infiltration, and a small number of fat vacuoles, significantly higher levels of FBG, FINS, insulin resistance index(HOMA-IR), iNOS mRNA, p-IRS1ser 307 protein, GSK-3β protein levels, and decreased p-AKTser 473 protein and GS protein levels, all of which were statistically significant(allP<0.05). IRS1ser 307 protein, GSK-3β protein levels were increased, p-AKTser 473 protein and GS protein levels were decreased, and the differences were statistically significant(allP<0.05); at 12 weeks, no lymphocyte infiltration was seen in the CIH group compared with that of the NC group and fat vacuoles significantly increased, and there was no improvement in the other pathological damage that had already occurred, and the levels of p-AKTser 473 protein significantly increased. AKTser 473 protein level significantly increased, p-IRS1ser 307 protein and GS protein levels were significantly reduced, all of which were statistically significant(allP<0.05), and the rest of the observational indexes were not statistically significant. Pearson′s correlation analysis showed that HOMA-IR of CIH group was significantly positively correlated with the levels of iNOS mRNA, p-IRS1ser 307 protein, and GSK-3β protein at 8 weeks(r=0.874, 0.817,0.872;allP<0.05), and significantly negatively correlated with the levels of p-AKTser 473 protein and GS protein(r=-0.886,-0.879;allP<0.05). Conclusion Chronic intermittent hypoxia can lead to hepatic pathological damage that cannot be reversed even by reoxygenation interventions and may mediate the development of insulin resistance by upregulating the IRS1/AKT/GSK-3β signaling pathway through the upregulation of iNOS mRNA expression.

The brain-gut axis is an important channel to realize the functional integration of the central nervous system and the enteric nervous system between the brain and the intestine. It is the medium for the occurrence and development of depression and plays an important role in the pathogenesis of depression. From the perspective of modern medicine and TCM, based on the theory of "brain-gut axis", this article discussed the operation method and mechanism of acupuncture at abdominal ring acupoint in the treatment of depression in Zhuang medicine, in order to provide new ideas for acupuncture treatment of depression.

Objective To comprehensively understand the map of transcripts during mitosis and their regulatory mechanisms of HAP 1 cells by conducting transcriptome sequencing analysis after being released by mitotic synchro-nization arrest.Methods HAP1 cells were subjected to mitotic synchronous arrest with nocodazole and samples were collected after 0,20,80 min release,and RNA sequencing(RNA-seq)were performed.The transcriptome data was cleaned and the differentially expressed genes,expression trend clustering and functional enrichment com-bined with the protein interaction network were analyzed to explore the changes of signaling pathways in HAP 1 cells during mitosis.Results The transcriptome of HAP1 cells after synchronous release from mitosis underwent significant changes in time series,and differential gene cluster analysis revealed four gene clusters were enriched in important biological processes such as p53 signaling and cytoplasmic translation.Conclusions The transcriptome time-dependent dynamic changes during mitosis in HAP1 cells are coordinated regulation of key signaling pathways including cellular stress response,translational control and chromatin remodeling,ensuring a balance between growth and stress response upon mitotic exit.