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.

BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

Brain-computer interface (BCI) technology is an innovative and cutting-edge medical advancement that enables direct interaction between the brain and external devices, facilitating the reconstruction of daily functions for patients or serving as a method for neuro-regulation therapy. Although this technology offers a broad range of clinical applications, there are problems as potential risks, individual variations, and the need for long-term monitoring of its effects during utilization. Consequently, the comprehensive evaluation of its safety and effectiveness poses a considerable challenge for regulatory agencies. This study provides a concise introduction to the development history and various types of BCI technology, followed by a summary of the regulatory situation for different types of BCI medical devices in the United States. Furthermore, the regulatory requirements imposed by the US FDA on this product category are analyzed. Finally, the article concludes by presenting a summary and future perspective on the current development of BCI technology, with the aim of offering beneficial insights and guidance for the regulation of BCI medical devices.
Brain-Computer Interfaces ; United States ; United States Food and Drug Administration ; Humans ; Electroencephalography

Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

This article introduces a high-magnification electronic endoscope system that utilizes a continuous zoom optical design,enabling high-magnification imaging at the cellular level.By selecting an appropriate initial retrofocus structure,the optimized modulation transfer function(MTF)curve of the zoom objective lens approaches the diffraction limit.Additionally,the tip and operation parts of the system incorporate modular gas-tight sealing and multiple layers of protective structure.The design employs efficient sealing materials and precise packaging techniques to ensure the system's sealing performance.The experimental results indicate that,under conventional imaging,the resolution is equivalent to 39.37 μm in object space,and the field of view angle is larger than 140 degrees.At magnified imaging,the resolution is equivalent to 2.78 μm in object space,and the observed actual field of view is greater than 800 μm×700 μm.When used with a 26-inch display monitor,the high-magnification electronic endoscope can achieve 500×optical magnification,allowing for the observation of features at the cellular level.Currently,this product has successfully achieved mass production and has undergone multiple animal trials,demonstrating its wide range of potential applications and significant clinical value.

To improve the evaluation indicators of medical quality in TCM hospitals; To realize objective, fair, and accurate evaluation of the quality of TCM. Based on relevant literature on medical quality in traditional Chinese medicine hospitals research and thematic group discussions, 21 evaluation indicators for TCM characteristics were formed. A questionnaire survey was conducted among 40 experts, and 37 were effectively collected, with a positive coefficient of 92.50%. After two rounds of expert consultation, the evaluation indicators were determined to be: the intensity of outpatient use of TCM decoction pieces (utilization rate of TCM decoction pieces, prescription number of TCM decoction pieces, dosage of TCM decoction pieces, and service price of TCM decoction pieces), the intensity of the use of TCM technology (proportion of TCM technology, number of TCM projects, cost of TCM technology, and course of treatment). Case studies were conducted on relevant data from 10 departments using the operational decision support system (BI) platform of Yueyang Integrated Traditional Chinese and Western Medicine Hospital affiliated with Shanghai University of Traditional Chinese Medicine to verify the rationality of indicators. The 10 departments were analyzed and evaluated, and the results obtained were basically consistent with the actual medical quality situation of the hospital. The indicators used in this study can reflect the actual medical quality situation, and have a certain degree of scientificity, feasibility, and applicability, providing reference for improving the medical quality evaluation indicators of TCM hospitals.

ObjectiveTo investigate the menstrual conditions of women infected with COVID-19 in Shanghai and analyze the influencing factors. MethodsFrom December 2022 to March 2023， menstrual data from 281 women infected with COVID-19 in Shanghai were collected with a questionnaire survey， including usual menstrual characteristics， the most recent menstrual period post-infection， symptoms of infection， and medication usage. According to the crossover period between the menstrual period and the infection period of the respondents， the samples were divided into two groups for comparative analysis： those whose menstrual and infection periods overlapped （positive group） and those whose menstruation started after conversion to virus-negative （negative conversion group）. ResultsAmong the 281 respondents， 196 （65.8%） experienced menstrual changes. Among them， 145 （51.6%） had changes in menstrual volume， color and texture， and 109 （38.8%） had changes in menstrual duration or cycle. Decreased menstrual volume （22.1%）， darker color （23.49%）， thicker texture （21.0%）， increased blood clots （16.7%）， and prolonged duration （21.8%） were observed in both groups. The rate of changes in menstrual volume， color， and texture was higher in the positive group （56.8%， 69/110） than that in negative group （37.3%， 76/171） （P<0.05）. Regarding the menstrual cycle changes， the rate of early onset was higher in the positive group （14.5%） compared to the negative conversion group （3.5%）（P<0.05）， while the rate of delayed menstruation was higher in the negative conversion group （25.1%） than that in the positive group （5.5%） （P<0.05）. Correlation analysis showed a weak association between sore throat and menstrual changes （r=0.154， P<0.05）. ConclusionSome women infected with COVID-19 experience short-term changes in their menstrual conditions， characterized by reduced volume， darker color， thick texture， increased clots， and prolonged menstrual duration， reflecting a pathogenesis of blood stasis. Menstruation during the infection period tends to occur earlier， while delayed menstruation is more prevalent at post-conversion.

OBJECTIVE To investigate the effect of Jiawei Tianwang Buxin Dan(JWBXD)on insomnia in rats exposed to simulated high-altitude conditions.METHODS ① Thirty SD rats were randomly divided into the normal control,model,model+Jiawei Tianwang Buxin Dan(JWBXD,9.6 mg·kg-1),model+Tianwang Buxin Dan(TWBXD,9.6 mg·kg-1),and model+diazepam(DZP,3 mg·kg-1)groups.Rats,except for the normal control group,were subjected to a low-pressure,low-oxygen animal experimental chamber simulating a 5000 m altitude.Respective drugs were ig administrated once daily at 9:00 for seven days,and signal acquisition and sleep analysis were conducted by a wireless physiological sig-nal telemetry system.②Forty rats were randomly divided into five groups as described in ①.Through-out the experiment,the general condition and body mass of the rats were observed daily.Drug adminis-tration lasted for seven days,and grip strength was tested one hour after the final administration.ELISA was used to measure the levels of corticotropin-releasing hormone(CRH),adrenocorticotropic hor-mone(ACTH),corticosterone(CORT),and melatonin(MLT)in serum.Western blotting was performed to measure the expression levels of core clock proteins period circadian regulator 2(Per2),circadian locomotor output cycles(Clock),cryptochrome 2(Cry2),brain-muscle arnt-like protein 1(Bmal1),nuclear receptor subfamily 1,group D member 1(NR1D1),glycogen synthase kinase-3β(GSK-3β),as well as acetylserotonin O-methyltransferase(ASMT)in the hypothalamus and pineal gland,respectively.RESULTS ① Compared with the normal control group,the model group exhibited a decrease in total sleep time(P<0.01),an increase in wakefulness(P<0.01),a significant reduction in slow wave sleep(SWS)(P<0.05)and the mean bouts duration(P<0.05).Compared with the model group,both DZP and JWBXD(P<0.01)prolonged sleep time and suppressed wakefulness(P<0.01)in the hypoxic envi-ronment.DZP and JWBXD prolonged SWS(P<0.05,P<0.01),while TWBXD had no significant effect.JWBXD improved the mean bouts duration of SWS in the model rats(P<0.01),whereas no such improvement was observed in model+DZP and model+TWBXD groups.② Compared with the normal control group,the model group showed a significant decrease in forelimb grip strength(P<0.01),increased levels of serum ACTH(P<0.05),CRH,and CORT(P<0.01),and decreased MLT levels(P<0.05).The expression levels of Per2,Cry2,GSK-3β,and NR1D1 in the hypothalamus were downregu-lated(P<0.05,P<0.01),while Bmal1 and Clock were upregulated(P<0.05,P<0.01).ASMT expression in the pineal gland was decreased(P<0.05).Compared with the model group,JWBXD and TWBXD enhanced forelimb grip strength(P<0.01),reduced serum CORT and ACTH levels(P<0.05),decreased CRH levels(P<0.01),and restored MLT levels(P<0.01).JWBXD upregulated the expression levels of Per2,Cry2,GSK-3β and NR1D1 in the hypothalamus(P<0.05,P<0.01),but downregulated Bmal1 and Clock expression(P<0.05,P<0.01).TWBXD downregulated Bmal1 expression in the hypothalamus(P<0.01)and increased NR1D1 expression(P<0.05).DZP significantly enhanced the expression levels of Per2,Cry2 and NR1D1 in the hypothalamus(P<0.01).JWBXD,TWBXD and DZP improved ASMT expression in the pineal gland(P<0.05).CONCLUSION JWBXD can improve sleep structure and prolong the duration of SWS in rats exposed to simulated high-altitude conditions.The mechanisms may involve the regulation of core clock protein expressions in the hypothalamus,promotion of mela-tonin secretion,and inhibition of HPA axis hyperactivity.