ObjectiveTo investigate the effects of modified Xiaoyaosan （JJXYS） on behavioral abnormalities and hippocampal mitochondrial quality control （MQC） in the rat model of post-myocardial infarction depression （PMD） and preliminarily explore its potential mechanism. MethodsA rat model of PMD was established by left anterior descending coronary artery ligation combined with chronic unpredictable mild stress （CUMS）. Rats were randomized into a control group， a model group， a fluoxetine （FLX， 10 mg·kg^-1） group， and low-， medium-， and high-dose JJXYS （JJXYS-L/M/H， 1.12， 2.24， 4.48 g·kg^-1， respectively） groups. Depressive-like behaviors were evaluated by body weight monitoring， sucrose preference test， open field test， and forced swimming test. Hematoxylin-eosin staining and Nissl staining were used to observe hippocampal histomorphology and neuronal changes. Enzyme-linked immunosorbent assay was conducted to determine the serum levels of 5-hydroxytryptamine （5-HT）， dopamine （DA）， interleukin-1 beta （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α）. The mRNA levels of MQC-related genes including peroxisome proliferator-activated receptor-gamma coactivator-1 alpha （PGC-1α）， nuclear respiratory factor 1 （Nrf1）， and transcription factor A， mitochondrial （TFAM） in the hippocampal tissue were measured by real-time PCR. The expression of proteins related to the dynamin-related protein 1 （Drp1）/PTEN-induced putative kinase 1 （PINK1）/Parkin signaling pathway was determined by Western blot. ResultsCompared with the control group， the model group showed restricted body weight gain， aggravated depressive-like behaviors， declined serum 5-HT and DA levels， evident hippocampal neuronal damage and reduced Nissl bodies， as well as downregulated expression of MQC-related genes and proteins （P<0.05）. Compared with the model group， both FLX and JJXYS alleviated the above changes to varying degrees. Moreover， the JJXYS-M and JJXYS-H groups showed more pronounced effects， improving behavioral performance， restoring 5-HT and DA levels， alleviating hippocampal pathological injury， and upregulating the expression of PGC-1α/Nrf1/TFAM mRNA and Drp1/PINK1/Parkin signaling pathway-related proteins （P<0.05）. ConclusionJJXYS can significantly alleviate depressive-like behaviors and neurotransmitter imbalance in the rat model of PMD by regulating hippocampal MQC and upregulating the Drp1/PINK1/Parkin-related pathway. This study provides experimental evidence for the intervention of PMD with JJXYS.

Generalized anxiety disorder (GAD) belongs to the category of emotional diseases in TCM, and its occurrence is closely related to liver depression and qi stagnation, and liver depression and fire syndrome is one of the TCM syndromes of GAD. With the deepening of modern medical research on GAD, microglia have been found to play an important role in the development of liver depression and fire syndrome of GAD. Excessive activation of microglia and transformation to M1 type would cause inflammatory mediator secretion up-regulation and destruction of neurons, etc. When using liver-soothing and heat-clearing medicines such as Bupleuri Radix, Gardeniae Fructus, Dangzhi Xiaoyao San, Yuejiu Pills and other Chinese materia medica or compounds, activation of microglia would be suppressed, and the inflammatory mediators mediated by microglia would also be suppressed, and the neurons could be protected. Therefore, this article discussed the modern biological connotation of the liver depression and fire syndrome of GAD from the perspective of microglia, and summarized the effects of TCM modulation of microglia on the liver depression and fire syndrome of GAD, and concluded that microglia could mediate the development of liver depression and fire syndrome of GAD.

Objective: To investigate the regulatory relationship between long non-coding RNA LINC01578 and c-Myc, and to explore the effect of LINC01578 on the metabolic process of oral squamous cell carcinoma(OSCC). Methods: After c-Myc was knocked down in OSCC cell line CAL27, LINC01578, a long non-coding RNA that is positively regulated by c-Myc, was identified by high-throughput sequencing technology. qRT-PCR was employed to measure the expression levels of c-Myc and LINC01578 in OSCC tissues and adjacent normal tissues. Following overexpression or knockdown of c-Myc in CAL27 and HN6 cells, qRT-PCR was conducted to validate the consistency with sequencing results. The binding of c-Myc to the LINC01578 promoter was confirmed using a dual luciferase reporter assay. Seahorse, ATP production and lactate production assays were utilized to examine the impact of c-Myc on glucose metabolism in OSCC via LINC01578. Colony formation assays assessed the proliferative capacity of OSCC cell lines. Results: qRT-PCR analysis revealed significantly higher expression levels of c-Myc LINC01578 in OSCC tissues compared to adjacent tissues( P < 0. 05 ) , confirming that c⁃Myc positively regulates LINC01578 expression. Consistent with sequencing data , c⁃Myc overexpression markedly upregulated LINC01578 (P < 0. 001) , while c⁃Myc knockdown led to a significant decrease in LINC01578 levels(P < 0. 000 1) . Dual lu ciferase reporter gene assays demonstrated that c⁃Myc directly targets and transcriptionally enhanced LINC01578 ex⁃ pression(P < 0. 001) . Seahorse experiments indicated that c⁃Myc promoted glucose metabolism in OSCC through LINC01578 regulation(P < 0. 05) . Colony formation assays showed that LINC01578 overexpression enhanced OS⁃ CC cell proliferation , whereas LINC01578 knockdown inhibited it. Conclusion c⁃Myc upregulates LINC01578 expression in OSCC cells , thereby modulating glycolysis and promoting cell proliferation.

Objective: To explore the role of leukemia inhibitory factor (LIF) in dental pulp inflammation . Methods: Human dental pulp stem cells (hDPSCs) were cultured in vitro as the target cells , the inflammatory response was induced by lipopolysaccharide (LPS) , and high-throughput sequencing was used to detect relevant highly ex- pressed genes in the inflammatory state . The expression of LIF under graded concentrations of LPS stimulation was detected by real-time fluorescence quantitative PCR (qPCR) . The expression levels of interleukin-6 (IL-6) , inter- leukin-1β(IL-1β) , and tumor necrosis factor-α(TNF-α) were detected after LIF knockdown and overexpression in hDPSCs by qPCR . Normal and inflammatory pulp tissues were collected , and the expression of LIF in both tis- sues was detected by qPCR and immunofluorescence (IF) . Results: The expression level of LIF increased in hu- man dental pulp cells after LPS stimulation . The expression level of LIF was subsequently elevated in inflammatory pulp induced by graded concentrations of LPS . The expression of IL-6 , IL-1β, and TNF-αwas significantly down- regulated in hDPSCs after LIF knockdown in response to LPS stimulation , while LIF overexpression upregulated the expression of these cytokines . qPCR and IF assays showed high expression of LIF in inflamed pulp tissue . Conclusion LIF is involved in dental pulp inflammation and promotes the development of pulpitis .

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

In order to meet the demand of the high-end medical market,some public hospitals have explored the establishment of specialized diagnosis and treatment centers,providing high-end customized medical services at special registration prices.The establishment of the International Medical Center is an effective supplement to public welfare healthcare and an important measure for public hospitals to innovate and enhance themselves under the concept of value based healthcare.It conducts pioneering research and exploration on the cost-benefit accounting of international medical centers in public hospitals,and compares it with the accounting situation of conventional departments.By analyzing and calculating cost-effectiveness,medical indicators,and DRG data,the key points and difficulties of lean operation in international medical centers are explored.Innovative methods and ideas for platform fine accounting are proposed,which have guiding significance for its development direction.

In order to meet the demand of the high-end medical market,some public hospitals have explored the establishment of specialized diagnosis and treatment centers,providing high-end customized medical services at special registration prices.The establishment of the International Medical Center is an effective supplement to public welfare healthcare and an important measure for public hospitals to innovate and enhance themselves under the concept of value based healthcare.It conducts pioneering research and exploration on the cost-benefit accounting of international medical centers in public hospitals,and compares it with the accounting situation of conventional departments.By analyzing and calculating cost-effectiveness,medical indicators,and DRG data,the key points and difficulties of lean operation in international medical centers are explored.Innovative methods and ideas for platform fine accounting are proposed,which have guiding significance for its development direction.

Objective To explore the action mechanism of long non-coding RNA(lncRNAs)lncRNA KCTD13-DT in oral squamous cell carcinoma(OSCC)and its potential interaction with transcription factor c-Myc,providing a potential diagnostic and therapeutic target for patients with OSCC.Methods The expression of lncRNA KCTD13-DT in OSCC and paracancerous tissues was detected by qRT-PCR.The effects of c-Myc overexpression and knock-down on human tongue squamous carcinoma cells HN6 and CAL27 were detected by qRT-PCR.Fluorescence in si-tu hybridization(FISH)assessed the localization of lncRNA KCTD13-DT in cells.A dual luciferase reporter gene was used to analyze the role of c-Myc in target binding to the promoter region of lncRNA KCTD13-DT.Stable cell lines with knockdown or overexpression of lncRNA KCTD13-DT were constructed in human OSCC cell lines HN6 and CAL27 by lentiviral infection,and the knockdown and overexpression efficiencies of lncRNA KCTD13-DT were detected by qRT-PCR.Cell proliferation changes were detected by growth curve assay,CCK-8 assay,colony forma-tion assay,and cell migration was detected by scratch assay and Transwell.Results lncRNA KCTD13-DT expres-sion level was reduced in OSCC tissues and OSCC cells(HN6,CAL27),and Western blot verified that after knoc-king down and overexpression of c-Myc in HN6 and CAL27,the qRT-PCR experiments showed that c-Myc nega-tively regulated lncRNA KCTD13-DT,and overexpression of c-Myc significantly down-regulated lncRNA KCTD13-DT;knockdown of c-Myc significantly up-regulated lncRNA KCTD13-DT levels.Dual luciferase reporter gene showed that c-Myc could target lncRNA KCTD13-DT,and c-Myc could be involved in regulating and repressing the transcriptional activity of lncRNA KCTD13-DT.FISH showed that lncRNA KCTD13-DT mainly existed in the nu-cleus.Growth curve assay,CCK-8 assay,cell scratch assay,Transwell,and colony formation assay showed that knockdown of lncRNA KCTD13-DT promoted the growth and proliferation of OSCC cells,and overexpression of ln-cRNA KCTD13-DT significantly inhibited the proliferation and migration of OSCC cells.Conclusion lncRNA KCTD13-DT is negatively regulated by c-Myc.Knockdown of lncRNA KCTD13-DT promotes cell proliferation,while overexpression of it inhibits cell growth.

Post-stroke depression (PSD) is a serious and common complication of stroke, which seriously affects the rehabilitation of stroke patients. To date, the pathogenesis of PSD is unclear and effective treatments remain unavailable. Here, we established a mouse model of PSD through photothrombosis-induced focal ischemia. By using a combination of brain imaging, transcriptome sequencing, and bioinformatics analysis, we found that the hippocampus of PSD mice had a significantly lower metabolic level than other brain regions. RNA sequencing revealed a significant reduction of miR34b-3p, which was expressed in hippocampal neurons and inhibited the translation of eukaryotic translation initiation factor 4E (eIF4E). Furthermore, silencing eIF4E inactivated microglia, inhibited neuroinflammation, and abolished the depression-like behaviors in PSD mice. Together, our data demonstrated that insufficient miR34b-3p after stroke cannot inhibit eIF4E translation, which causes PSD by the activation of microglia in the hippocampus. Therefore, miR34b-3p and eIF4E may serve as potential therapeutic targets for the treatment of PSD.
Animals ; Mice ; Depression ; Eukaryotic Initiation Factor-4E/metabolism* ; MicroRNAs/metabolism* ; Neurons/metabolism* ; Stroke/metabolism*