ObjectiveTo explore the mechanism by which Sini San （SNS） inhibits ferroptosis， alleviates inflammation and myocardial injury， and improves myocardial infarction （MI）. MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， its target sites were predicted using the SwissTargetPrediction Database， and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards， Online Mendelian Inheritance in Man （OMIM） database， DrugBank， Therapeutic Target Database （TTD）， FerrDb database and literature review， respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction （PPI） network was constructed using the STRING database， and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in， and the biological functions were clustered by the MCODE plug-in. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group， the model group， the SNS group， and the trimetazidine （TMZ） group. The mice were subcutaneously injected with isoprenaline （ISO， 5 mg·kg^-1·d^-1） to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram （ECG）， and the tissue morphology changes were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， reduced glutathione （GSH）， and malondialdehyde （MDA） levels were detected by biochemical assay. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of interleukin （IL）-6 and 4-hydroxynonenal （4-HNE）. Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 （p-STAT3） in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6， IL-18， solute carrier family 7 member 11 （SLC7A11）， arachidonic acid 15-lipoxygenase （ALOX15）， and glutathione peroxidase 4 （GPx4） in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained， and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation， and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 （P0.01）， down-regulated the expression of ALOX15 mRNA （P0.01）， up-regulated the level of serum GSH， and the expressions of SLC7A11 and GPx4 mRNA， reduced MDA and 4-HNE levels （P0.05， P0.01）. Additionally， SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis， reduced the area of MI， alleviated inflammation and myocardial injury， lowered the levels of serum CK， CK-MB， LDH， IL-6， and the mRNA expression levels of IL-16 and IL-18 （P0.05）， and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels， inhibit ferroptosis in cardiomyocytes， alleviate inflammation and myocardial injury， thereby improving MI.

ObjectiveTo explore the mechanism by which Sini San （SNS） inhibits ferroptosis， alleviates inflammation and myocardial injury， and improves myocardial infarction （MI）. MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， its target sites were predicted using the SwissTargetPrediction Database， and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards， Online Mendelian Inheritance in Man （OMIM） database， DrugBank， Therapeutic Target Database （TTD）， FerrDb database and literature review， respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction （PPI） network was constructed using the STRING database， and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in， and the biological functions were clustered by the MCODE plug-in. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group， the model group， the SNS group， and the trimetazidine （TMZ） group. The mice were subcutaneously injected with isoprenaline （ISO， 5 mg·kg^-1·d^-1） to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram （ECG）， and the tissue morphology changes were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， reduced glutathione （GSH）， and malondialdehyde （MDA） levels were detected by biochemical assay. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of interleukin （IL）-6 and 4-hydroxynonenal （4-HNE）. Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 （p-STAT3） in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6， IL-18， solute carrier family 7 member 11 （SLC7A11）， arachidonic acid 15-lipoxygenase （ALOX15）， and glutathione peroxidase 4 （GPx4） in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained， and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation， and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 （P0.01）， down-regulated the expression of ALOX15 mRNA （P0.01）， up-regulated the level of serum GSH， and the expressions of SLC7A11 and GPx4 mRNA， reduced MDA and 4-HNE levels （P0.05， P0.01）. Additionally， SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis， reduced the area of MI， alleviated inflammation and myocardial injury， lowered the levels of serum CK， CK-MB， LDH， IL-6， and the mRNA expression levels of IL-16 and IL-18 （P0.05）， and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels， inhibit ferroptosis in cardiomyocytes， alleviate inflammation and myocardial injury， thereby improving MI.

ObjectiveTo systematically investigate the discrepancies between employment preferences and actual job placements among postgraduate students in rehabilitation medicine, explore the influencing factors, and elucidate the underlying mechanisms of their employment decisions. MethodsA cross-sectional questionnaire survey was conducted among 100 full-time postgraduate students who had graduated from Capital Medical University School of Rehabilitation in the past six years. A self-designed questionnaire was used to collect information on personal background, self-assessed competencies, employment preferences, and actual job placements. Logistic regression models were employed to analyze the factors influencing employment preferences and actual job placements, respectively. ResultsEmployment preferences among rehabilitation medicine postgraduates were highly concentrated on large tertiary hospitals (79.0%), yet the actual placement rate (61.0%) showed a significant gap. Preference for tertiary hospitals showed no significant association with individual factors such as gender, degree type or self-assessed competencies (P > 0.05). Univariate analysis revealed that those who entered tertiary hospitals scored significantly higher in self-assessed clinical skills, research ability, communication and coordination, and resource integration (|t| > 3.661, P < 0.001), and demonstrated clearer career planning (P = 0.012). Multivariate logistic regression analysis did not identify any independent predictors of actual employment within the context of this study sample (P > 0.05). ConclusionEmployment among rehabilitation medicine postgraduates is characterized by highly homogeneous preferences coexisting with complexity of factors influencing actual employment. It is recommended to optimize the training system, deepen personalized career education, and establish diversified employment guidance mechanisms to promote rational talent flow and facilitate the balanced development of the rehabilitation medical service system.

With the continuous deepening of the concept of precision diagnosis and treatment for lung cancer, how to achieve higher efficiency and accuracy in the screening, diagnosis, and treatment pathways in clinical practice has become an important issue that urgently needs to be overcome. The current clinical difficulty lies in the fact that despite continuous advancements in imaging and molecular diagnostic technologies, there are still limitations in manual efficiency and subjective experience when it comes to massive data analysis and multi-scale feature extraction. Artificial intelligence (AI), especially algorithm systems based on deep learning, is an innovative technology capable of deeply empowering medical big data. This method utilizes algorithms such as convolutional neural networks, combined with radiomics, pathomics, and multi-modal data fusion analysis, demonstrating immense potential in early precise detection and benign-malignant differentiation of pulmonary nodules, digital pathological subtype recognition and non-invasive prediction of driver genes, precise 3D surgical planning and automatic delineation of radiotherapy target volumes, as well as dynamic risk warning during follow-up. This innovative technology provides a brand-new solution for realizing intelligent and individualized lung cancer diagnosis and treatment models. This consensus, based on the latest evidence from evidence-based medicine and combined with the development trends in the AI field and real-world clinical needs, was ultimately formed by gathering the consensus opinions of multidisciplinary experts in radiology, pathology, thoracic surgery, and other fields. The main content covers the application specifications of AI in the three core scenarios of lung cancer screening, diagnosis, and treatment, the technical standards for data collection and algorithm validation, as well as the ethical and regulatory challenges faced at the current stage. It aims to clarify the applicable boundaries of AI as a clinical auxiliary decision support tool, providing scientific guidance and standardized exploration directions for peers currently engaged in or planning to carry out AI-assisted clinical diagnosis, treatment, and translation of lung cancer.

OBJECTIVES: To explore the therapeutic mechanism of Arctium lappa extract for treatment of Post-Viral Pneumonia Pulmonary Fibrosis (PPF). METHODS: The chemical constituents of Arctium lappa extracts were identified using UHPLC-Q-TOF-MS/MS. Mouse models of pulmonary fibrosis established by tracheal instillation of bleomycin were treated with Arctium lappa extract, and body weight changes were recorded and lung tissue pathology was examined using HE and Masson staining. Metabolomics analysis was used to identify the differential metabolites and the associated metabolic pathways in the treated mice. The common targets of viral pneumonia and pulmonary fibrosis were acquired from the publicly available databases, and the core targets and active constituents were screened using the protein-protein interaction (PPI) network, GO and KEGG enrichment analyses, and molecular docking, and a "gene-metabolite" regulatory network was constructed. The expressions of the core targets were detected in the lung tissues of the treated mice using Western blotting. RESULTS: Fifty-three chemical constituents were identified from Arctium lappa extract. In the mouse models of pulmonary fibrosis, treatment with Arctium lappa extract significantly improved weight loss and ameliorated lung inflammation and fibrosis. The differential metabolites in the treated mice were enriched in energy metabolism pathways involving citrate cycle, pentose phosphate pathway, glycolysis, tryptophan metabolism, glutamate metabolism and glutathione metabolism, which regulated the production of energy metabolism intermediates. Twenty-three key active compounds (mostly lignans and phenolic acids) and 82 core targets were screened, which were associated with the non-canonical Smad signaling pathways (including PI3K/AKT, HIF-1, MAPK, and Foxo) that participated in the regulation of energy metabolism. Arctium lappa extract also regulated the expressions of epithelial-mesenchymal transition (EMT)‑related proteins (fibronectin, vimentim, and Snail, etc.) and inhibited MAPK signaling pathway activation. CONCLUSIONS Preliminary findings suggest that Arctium lappa treats fibrosis by regulating metabolism to inhibit EMT and involves the modulation of non-canonical Smad signaling pathways, such as MAPK providing theoretical support for its clinical application and further research in treating PPF.
Arctium/chemistry* ; Animals ; Pulmonary Fibrosis/metabolism* ; Mice ; Metabolomics ; Network Pharmacology ; Plant Extracts/pharmacology* ; Signal Transduction ; Drugs, Chinese Herbal/pharmacology* ; Molecular Docking Simulation

OBJECTIVE: To explore the effects of different endotracheal tube cuff pressure management modes on cuff sealing and the pressure exerted on the tracheal wall. METHODS: A prospective self-controlled study was conducted. Eleven patients undergoing endotracheal intubation and mechanical ventilation with an automatic airway management system (AGs) admitted to the Second Medical Centre of the Chinese People's Liberation Army General Hospital from October 1, 2020, to April 1, 2022, were enrolled as the study subjects. Within 24 hours after the establishment of artificial airway and mechanical ventilation, four cuff pressure management modes were randomly applied to each patient for 24 hours in sequence: automatic cuff pressure management mode [modeI: the safe range of cuff pressure was set at 20-35 cmH₂O (1 cmH₂O≈0.098 kPa), and the CO₂ pressure above the endotracheal tube cuff was automatically detected by AGs every 5 minutes to determine the cuff sealing status, and the cuff pressure was automatically adjusted], constant cuff pressure (25 cmH₂O) management mode (mode II: the cuff pressure was monitored by AGs through a pressure sensor, and the cuff pressure was maintained at 25 cmH₂O via a pressure pump), constant cuff pressure (30 cmH₂O) management mode (mode III: the cuff pressure was monitored by AGs through a pressure sensor, and the cuff pressure was maintained at 30 cmH₂O via a pressure pump), and manual cuff pressure management mode (mode IV: the cuff pressure was manually measured by nurses every 6-8 hours using a cuff pressure gauge to keep the cuff pressure at 25-30 cmH₂O after inflation). The CO₂ pressure above the endotracheal tube cuff (at 60-minute intervals) and the cuff pressure changes (at 50-ms intervals) were recorded to compare the differences in number of cuff leaks [no leak was defined as CO₂ pressure = 0, small leak as 0 < CO₂ pressure < 2 mmHg (1 mmHg≈0.133 kPa), and large leak as CO₂ pressure ≥ 2 mmHg] and cuff pressure among modesI-IV. RESULTS: A total of 24 CO₂ pressure measurements were taken per patient across the four modes, resulting in a total of 264 detections for each mode. Regarding the cuff leak, the total number of leak and large leak in modeIwas significantly lower than that in modes II-IV [total leak: 30 cases (11.36%) vs. 81 cases (30.68%), 70 cases (26.52%), 103 cases (39.02%); large leak: 15 cases (5.68%) vs. 50 cases (18.94%), 48 cases (18.18%), 66 cases (25.00%), all P < 0.05]. There was no significant difference in the number of cuff leak between modes II and III, and mode IV had the most severe cuff leak. In terms of cuff pressure, since mode IV required blocking the cuff tube from the AGs tube and the AGs cuff pressure management module did not actually work, real-time monitoring of cuff pressure was not possible. Therefore, cuff pressure changes were only analyzed in modes I-III. Each of the 11 patients underwent 24-hour cuff pressure monitoring under modes I-III, with 19 008 000 monitoring times for each mode. The cuff pressure in mode I was between that in modes II and III [cmH₂O: 27.09 (26.10, 28.14) vs. 26.60 (25.92, 27.47), 31.01 (30.33, 31.88), both P < 0.01]. Moreover, the number of extreme values of cuff pressure > 50 cmH₂O in mode I was significantly lower than that in modes II and III [19 900 cases (0.105%) vs. 22 297 cases (0.117%), 27 618 cases (0.145%), both P < 0.05]. CONCLUSION Dynamically monitoring the CO₂ pressure above the cuff to guide the adjustment of endotracheal tube cuff pressure can achieve better cuff sealing with a relatively lower cuff pressure load.
Humans ; Intubation, Intratracheal/instrumentation* ; Pressure ; Prospective Studies ; Respiration, Artificial ; Male ; Airway Management/methods* ; Female ; Middle Aged

Liver diseases have become a major challenge threating the global health, posing a heavy burden on both social and personal well-being. In recent years, the development of the gut-liver axis theory has provided new research perspectives and intervention strategies for the prevention and treatment of liver diseases. Natural products, recognized as biological molecules with diverse sources, rich activities, and minimal side effects, demonstrate great potential in regulating intestinal flora and improving liver health. Studies have shown that natural products such as saponins, polyphenols, polysaccharides, and alkaloids can regulate the composition and metabolites of intestinal flora, thereby intervening in liver diseases. In this paper, we systematically review the role of natural products in the regulation of the intestinal flora-gut-liver axis and summarize recent research progress in the prevention and treatment of liver diseases. Furthermore, we outline the challenges and limitations currently facing the study in this field. Finally, this paper makes an outlook on the clinical application of natural products in treating liver diseases and discusses future research directions, aiming to give new insights into the mechanisms by which natural products regulate the intestinal flora-gut-liver axis and the applications of these products in the prevention and treatment of liver diseases.
Humans ; Gastrointestinal Microbiome/drug effects* ; Liver Diseases/prevention & control* ; Biological Products/pharmacology* ; Polyphenols/pharmacology* ; Saponins/pharmacology* ; Intestines/microbiology* ; Alkaloids/pharmacology* ; Polysaccharides/pharmacology* ; Liver

Objective:To investigate the mechanism of microRNA-597-3p ( miR-579-3p) in improving hypoxic-ischemic encephalopathy (HIE) by regulating the interleukin-1 receptor-associated kinase 1 (IRAK1)/tumor necrosis factor receptor-associated factor 6 (TRAF6)/transforming growth factor-β-activated kinase 1 (TAK1)/nuclear factor-κB (NF-κB) signaling pathway. Methods:Peripheral blood of healthy neonates ( n=5) and HIE newborns ( n=5) from June 2023 to June 2024 in the No.215 Hospital of Shaanxi Nuclear Industry were collected. The differential expression of miRNA in peripheral blood of neonates with HIE was analyzed by next-generation sequencing. The oxygen-glucose deprivation (OGD) method was used to establish the HIE cell model, which was designated as the OGD group, while cells without OGD treatment served as the control group. Rat adrenal pheochromocytoma PC12 cells were transfected with miR-579-3p mimic (mimic), mimic negative control (mimic-NC), miR-579-3p inhibitor (inhibitor), inhibitor negative control (inhibitor-NC), respectively, and divided into the mimic group, mimic-NC group, inhibitor group, inhibitor-NC group. On the basis of mimic group and inhibitor group, IRAK1 overexpression plasmid ( oeIRAK1) and IRAK1 small interfering RNA plasmid ( siIRAK1) were transfected respectively, which were divided into oeIRAK1 group and siIRAK1 group. The relative expression level of mRNA was detected by real-time reverse transcription-PCR. The absorbance ( A) value was detected by cell counting kit-8 assay. The apoptosis rate was detected by Annexin Ⅴ-fluorescein isothiocyanate/propidium iodide double staining. The relative expression of protein was detected by Western blotting. The levels of pro-inflammatory factors and anti-oxidative stress factors were detected by enzyme-linked immunosorbent assay. Bioinformatics analysis was used to predict the binding site between miR-579-3p and IRAK1, and the dual-luciferase reporter assay was performed to validate their targeting relationship. A total of 12 7-day-old SD rats were selected and randomly divided into the HIE group and the sham group by the random number table method. In the HIE group, the right common carotid artery of rats was permanently occluded, followed by hypoxia exposure, whereas rats in the sham group only underwent common carotid artery exposure without ligation or hypoxia treatment. Immunohistochemical staining was used to detect the expression of protein in brain tissue of HIE rats. The least significant difference t-test was used for comparison between the two groups, and one-way analysis of variance was used for comparison between multiple groups. Results:Compared with the healthy neonates, a total of 278 differentially expressed miRNAs were detected in the peripheral blood of neonates with HIE, among which miR-579-3p showed the most significant downregulation. The relative expression level of miR-579-3p in the mimic group (15.78±1.93) was significantly higher than that in the mimic-NC group (1.00±0.14) ( P<0.01), and in the inhibitor group (0.29±0.14) was significantly lower than that in inhibitor-NC group (1.00±0.14) ( P<0.01). The A value in the mimic group (0.89±0.09) was significantly higher than that in the mimic-NC group (0.52±0.08) ( P<0.01), and in the inhibitor group (0.30±0.05 ) was significantly lower than that in the inhibitor-NC group (0.56±0.07) ( P<0.05). The apoptosis rate of mimic group [(7.47±1.53)%] was significantly lower than that in the mimic-NC group [(30.97±3.47)%] ( P<0.05), and in the inhibitor group [(49.05±4.21)%] was significantly lower than that in the inhibitor-NC group [(35.51±3.64)%] ( P<0.01). The relative expression level of cysteine aspartic acid specific protease-3 ( Caspase-3) and B-cell lymphoma-2 (Bcl-2) associated X protein ( Bax) (1.21±0.10, 1.40±0.13), the relative expression of cleaved Caspase-3 and Bax (1.00±0.13, 1.13±0.09), the levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α [(45.15±5.14, 38.34±5.69) pg/mg] in the mimic group were significantly lower than those in the mimic-NC group [2.10±0.14, 2.37±0.16, 2.29±0.09, 2.27±0.12, (95.67±9.05, 63.99±5.24) pg/mg] (all P<0.01). The relative expression level of Bcl-2 and Claspin (1.03±0.09, 1.00±0.04), the relative expression of Bcl-2 and Claspin (1.21±0.06, 0.94±0.09), the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) [(67.65±6.86, 58.07±5.20) U/mg] in the mimic group were significantly higher than those in the mimic-NC group [(0.51±0.05, 0.52±0.02, 0.58±0.05, 0.46±0.07, 42.08±5.86, 29.80±4.85) U/mg] ( P<0.05, 0.01). The relative expression level of Caspase-3 and Bax (2.72±0.16, 2.97±0.10), the relative expression of cleaved Caspase-3 and Bax (3.25±0.17, 2.76±0.16), the levels of IL-6 and TNF-α [(122.80±11.59, 92.58±7.56) pg/mg] in the inhibitor group were significantly higher than those in the inhibitor-NC group [(1.86±0.14, 2.12±0.10, 2.35±0.15, 1.82±0.15, (88.13±8.59, 68.61±6.17) pg/mg] ( P<0.05, 0.01). The relative expression levels of Bcl-2 and Claspin mRNA (0.17±0.04, 0.20±0.06), the relative expression of Bcl-2 and Claspin proteins (0.11±0.03, 0.13±0.05), the levels of SOD and GSH-Px [(16.62±3.19, 12.01±1.92) U/mg] in the inhibitor group were significantly lower than those in the inhibitor-NC group [0.54±0.05, 0.54±0.05, 0.53±0.10, 0.45±0.07, (38.09±5.47, 30.90±3.87) U/mg] ( P<0.05, 0.01). IRAK1 was identified as a putative target of miR-579-3p. The relative luciferase activity of wild-type IRAK1 in the mimic group (0.45±0.05) was significantly lower than that in the mimic-NC group (1.00±0.08) ( P<0.01). The relative expression levels of IRAK1, TRAF6, TAK1 and NF-κB mRNA in the mimic group (0.96±0.09, 0.96±0.11, 1.34±0.16, 1.74±0.20), the relative expression of IRAK1, TRAF6, TAK1, and phosphorylated NF-κB (p-NF-κB) proteins (0.96±0.20, 1.27±0.19, 1.34±0.18, 1.16±0.19) were all lower than those in the mimic-NC group (1.96±0.17, 1.88±0.24, 2.39±0.23, 2.44±0.20, 2.33±0.22, 2.17±0.24, 2.25±0.28, 2.06±0.28) (all P<0.01). The relative expression levels of IRAK1, TRAF6, TAK1 and NF-κB mRNA in the inhibitor group (2.54±0.15, 2.61±0.13, 2.97±0.15, 2.99±0.20), the relative expression of IRAK1, TRAF6, TAK1 and p-NF-κB proteins (3.73±0.34, 3.17±0.25, 3.68±0.22, 3.29±0.20) were all higher than those in the inhibitor-NC group (1.87±0.18, 1.84±0.19, 2.15±0.24, 2.24±0.26, 2.35±0.23, 1.94±0.25, 2.05±0.27, 2.17±0.29) (all P<0.01). The A value in the oeIRAK1 group (0.66±0.07) was significantly lower than that in the mimic group (0.94±0.10) ( P<0.05), and in the siIRAK1 group (0.51±0.08) was significantly higher than that in the inhibitor group (0.23±0.05) ( P<0.05). The apoptosis rate in the oeIRAK1 group [(23.32±2.40)%] was significantly higher than that in the mimic group [(9.02±1.23)%] ( P<0.05), and in the siIRAK1 group [(28.27±2.57)%] was significantly lower than that in the inhibitor group [(48.96±4.60)%] ( P<0.01). The levels of IL-6 and TNF-α in the oeIRAK1 group [(85.10±6.98, 59.49±5.78) pg/mg] were significantly higher than those in the mimic group [(47.51±8.87, 23.65±3.75) pg/mg], and the levels of SOD and GSH-Px [(49.58±5.63, 41.31±6.21) U/mg] were significantly lower than those in the mimic group [(81.22±6.94, 62.26±5.44) U/mg] ( P<0.05, 0.01). The levels of IL-6 and TNF-α in the siIRAK1 group [(108.25±9.47, 74.87±8.71) pg/mg] were significantly lower than those in the inhibitor group [(142.65±13.88, 104.49±9.18) pg/mg], and the levels of SOD and GSH-Px [(35.87±3.69, 34.89±4.96) U/mg] were significantly higher than those in the inhibitor group [(15.55±3.70, 15.62±3.30) U/mg] ( P<0.05, 0.01). The relative expression level of miR-579-3p in the HIE group (0.47±0.11) was significantly lower than that in the sham group (1.00±0.09) ( P<0.01). The levels of IL-6 and TNF-α in the HIE group [(62.18±6.42, 68.42±4.91) pg/mg] were significantly higher than those in the sham group [(20.77±4.68, 31.16±4.95) pg/mg], and the levels of SOD and GSH-Px [(22.63±3.33, 19.07±2.86) U/mg] were significantly lower than those in the sham group [(47.89±4.58, 56.55±4.45) U/mg] (all P<0.01). The relative levels of TLR4, IRAK1, TRAF6, TAK1, NF-κB, and Caspase-3 mRNA, TLR4, IRAK1, TRAF6, TAK1, p-NF-κB, and cleaved Caspase-3 proteins in the HIE group (1.87±0.24, 2.03±0.21, 2.23±0.20, 1.85±0.18, 1.91±0.20, 2.36±0.20, 2.36±0.28, 2.16±0.28, 1.95±0.27, 2.05±0.26, 2.34±0.24, and 2.72±0.23) were all higher than those in the sham group (1.00±0.15, 1.00±0.11, 1.00±0.09, 1.00±0.05, 1.00±0.12, 1.00±0.15, 1.00±0.15, 1.00±0.21, 1.00±0.10, 1.00±0.14, 1.00±0.19, 1.00±0.16) (all P<0.01), which were consistent with the immunohistochemical staining results. Conclusions:miR-579-3p might alleviate HIE-induced neuronal damage by regulating the IRAK1/TRAF6/TAK1/NF-κB signaling pathway.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Objective:To analyze the genetic characteristics of the prevalent strains of Varicella-Zoster virus (VZV) in the population of Dali, Yunnan, and to understand its evolutionary status in the population of Dali.Methods:Herpes fluid and 163 sera were collected from 249 patients clinically suspected to have varicella or herpes zoster in the Department of Dermatology of the Second People′s Hospital of Dali city, Yunnan province, China, from 2023 to 2024. The levels of VZV-specific IgG and IgM antibodies in serum were detected using enzyme-linked immunoassay. Viral DNA was extracted from the herpes fluid, and the cycle threshold ( Ct) of the samples was detected using quantitative real-time polymerase chain reaction (qPCR), and some samples with Ct ≦ 22 were selected for sequencing by next-generation sequencing technology (next-generation sequencing). Next-generation sequencing (NGS) was used to obtain 90 whole genome sequences of VZV, and the sequencing result were compared with the sequences of reference strains for multiple sequence comparison and evolutionary analysis. Snapgene was used to translate the nucleotides into amino acids, and the result were compared with the amino acid sequences of the reference strain. Results:Of the 90 VZV whole-genome sequences, one whole-genome sequence was from an adult varicella patient, and the remaining 89 whole-genome sequences were from herpes zoster patients. The serum-specific IgG antibody positivity rate was 99.4%, and the IgM antibody positivity rate was 52.8%. The result of both single nucleotide polymorphism (SNPs) site typing and genome-wide phylogenetic tree analysis showed that 83 of the 90 VZV whole-genome sequences in this study were on the same branch as Clade 2, and 7 VZV whole-genome sequences were on the branch of Clade 9.Conclusions:The main endemic branch in Dali region in 2023-2024 was Clade 2, with the emergence of Clade 9 branch; there were amino acid mutations in the proteins encoded by ORF22 and ORF68 in 83 VZV whole genome sequences of Clade 2 branch, and the mutations did not cause significant changes to the protein structure.