Objective To investigate the effect of subanesthetic dose of esketamine on emergence agitation(EA)in patients undergoing laparoscopic hernia repair.Methods Seventy-two male patients who treated with lapa-roscopic hernia repair under general anesthesia were randomly divided into AS group(subanesthetic esketamine)and control group.In the AS group,0.2 mg/kg of esketamine was administered intravenously 30 minutes before the surgery ended,while the control group was given an equal volume of normal saline.Upon surgery completion,patients were transferred to PACU with endotracheal tube retained,and the time to extubation was recorded.Hemo-dynamic parameters were measured immediately after extubation and at 10 min,30 min,1 h,and 4 h thereafter.Patients' pain and sedation levels were assessed at the above time points using RASS and VAS,respectively.The incidence of EA was evaluated using the Confusion Assessment Method for the Intensive Care Unit(CAM-ICU).Observation duration in the PACU and recovery outcomes within 24 hours postoperatively were assessed via the QoR-40 and adverse events were recorded.Results Compared to those in the control group,patients in the AS group had higher HR and MAP at 10 min post-extubation,and the changes in HR and MAP over time were more stable(P<0.05).The RASS and VAS scores in the AS group were significantly lower than those in the control group at the time of extubation and all subsequent time points(P<0.05),both groups showed temporal changes in RASS and VAS scores(P<0.05),but the change process in the AS group was more stable(P<0.05).Postoperative extubation time,PACU observation duration,and adverse event rates(delirium,respiratory depression,nausea and vomiting)did not differ significantly between the two groups(P>0.05),while recovery quality was markedly better in the AS group(P<0.05).Conclusion Subanesthetic esketamine effectively alleviates pain and the incidence of EA,supports hemodynamic stability during PACU stay,and enhances recovery quality in patients undergoing laparo-scopic hernia repair,demonstrating clinical value.

Objective To investigate the effect of subanesthetic dose of esketamine on emergence agitation(EA)in patients undergoing laparoscopic hernia repair.Methods Seventy-two male patients who treated with lapa-roscopic hernia repair under general anesthesia were randomly divided into AS group(subanesthetic esketamine)and control group.In the AS group,0.2 mg/kg of esketamine was administered intravenously 30 minutes before the surgery ended,while the control group was given an equal volume of normal saline.Upon surgery completion,patients were transferred to PACU with endotracheal tube retained,and the time to extubation was recorded.Hemo-dynamic parameters were measured immediately after extubation and at 10 min,30 min,1 h,and 4 h thereafter.Patients' pain and sedation levels were assessed at the above time points using RASS and VAS,respectively.The incidence of EA was evaluated using the Confusion Assessment Method for the Intensive Care Unit(CAM-ICU).Observation duration in the PACU and recovery outcomes within 24 hours postoperatively were assessed via the QoR-40 and adverse events were recorded.Results Compared to those in the control group,patients in the AS group had higher HR and MAP at 10 min post-extubation,and the changes in HR and MAP over time were more stable(P<0.05).The RASS and VAS scores in the AS group were significantly lower than those in the control group at the time of extubation and all subsequent time points(P<0.05),both groups showed temporal changes in RASS and VAS scores(P<0.05),but the change process in the AS group was more stable(P<0.05).Postoperative extubation time,PACU observation duration,and adverse event rates(delirium,respiratory depression,nausea and vomiting)did not differ significantly between the two groups(P>0.05),while recovery quality was markedly better in the AS group(P<0.05).Conclusion Subanesthetic esketamine effectively alleviates pain and the incidence of EA,supports hemodynamic stability during PACU stay,and enhances recovery quality in patients undergoing laparo-scopic hernia repair,demonstrating clinical value.

Objective To observe changes in voltage-dependent anion channel 3(VDAC3)in a mouse model of sepsis-induced myocardial injury and to explore its potential mechanism.Methods Twenty male C57BL/6J mice were divided randomly into a Sham group and Sepsis group,respectively(n=10 mice per group).Sepsis was induced by the cecal ligation and puncture(CLP).Serum levels of interleukin(IL)-6,tumor necrosis factor(TNF)-α,creatine kinase MB(CK-MB),and cardiac troponin T(cTnT)were detected by enzyme-linked immunosorbent assay.Pathological changes in heart tissue were observed by hematoxylin and eosin staining.Structural and functional changes in the heart were evaluated by echocardiography.Changes in total glutathione,reduced glutathione(GSH),oxidized glutathione,and malondialdehyde(MDA)in heart tissue were detected by spectrophotometry.The morphological structure of mitochondria in mouse cardiomyocytes was observed by transmission electron microscopy.Expression levels of IL-6,IL-1β,VDAC3,glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),lipocalin-2(LCN2),and prostaglandin-endoperoxide synthase 2(PTGS2)mRNA were detected by real-time quantitative polymerase chain reaction and the localization and expression of VDAC3 and GPX4 proteins in mouse heart tissue were detected by immunofluorescence staining.The correlations between VDAC3 mRNA and GPX4,SLC7A11,PTGS2,LCN2,IL-6,and IL-1β mRNA were analyzed.Expression levels of VDAC3,GPX4,and SLC7A11 proteins were detected by Western blot.Results IL-6,TNF-α,CK-MB,and cTnT levels were significantly higher in the Sepsis group compared with the Sham group(P＜0.05).In the Sepsis group,myocardial fibers were torn,the ventricular wall was thickened and edematous,the mitochondrial membrane was ruptured,and mitochondrial cristae were broken or absent.GSH levels were significantly reduced in the Sepsis group(P＜0.05)and the lipid peroxide MDA was increased in the Sepsis group(P＜0.05)compared with the Sham group.VDAC3,GPX4 and SLC7A11 mRNA and protein levels were all lower in the Sepsis group compared with the Sham group(P＜0.05),while expression levels of IL-6,IL-1β,LCN2,and PTGS2 mRNA were increased(P＜0.05).VDAC3 mRNA was positively correlated with GPX4 and SLC7A11 mRNA levels,and negatively correlated with LCN2,PTGS2,IL-6,and IL-1β.Conclusions VDAC3 expression decreases in myocardial injury,and it may participate in the occurrence of sepsis-induced myocardial injury by regulating ferroptosis.

Ischemic stroke is the most common type of stroke,characterized by a complex pathophysiology in which inflammato-ry responses play a pivotal role,significantly affecting patient outcomes.Following a stroke,the disruption of the blood-brain barrier facilitates interactions between the central nervous system(CNS)and the peripheral immune system,triggering a cascade of inflammatory responses that exacerbate ischemic brain injury.Microglia(MG),as the primary immune cells of the CNS,are highly sensitive to cerebral ischemia and interact with various peripheral immune cells to regulate the inflammatory response.For instance,neutrophils participate in early MG-mediated in-flammatory responses through the release of neutrophil extracel-lular traps;T cells interact with MG,exerting bidirectional effects on the spread of brain inflammation and tissue repair.Additionally,other immune cells such as B cells,monocytes/macrophages,and dendritic cells contribute to these processes through complex immune regulatory networks,influencing MG's inflammatory functions and its capacity for tissue repair.This re-view delves into the interaction mechanisms between MG and pe-ripheral immune cells,providing novel insights into the dynamic changes of post-stroke inflammation and potential directions for precision therapies aimed at modulating immune balance.

Breast cancer is a kind of malignant tumor with a complex mechanism， and its morbidity and mortality are increasing year by year， which seriously threatens women's health. At present， the main clinical treatments are surgical resection， radiotherapy， chemotherapy， and drug therapy， but they are often accompanied by side effects and adverse reactions， which affect the therapeutic effect. Traditional Chinese medicine （TCM） has the advantages of multi-component and multi-target treatment in the fight against breast cancer. The wnt/β-catenin signaling pathway is one of the classic pathways in cancer research. Abnormally activated Wnt/β-catenin signaling pathway inhibits β-catenin degradation by blocking the formation of Axin/glycogen synthase kinase 3β/adenomatous polyposis coli complex， thus promoting β-catenin nuclear metastasis， and it binds to T cell transcription factor/lymphoenhancer factor-1 to initiate downstream target genes and further interfere with the proliferation， migration， and invasion of tumor cells to affect the tumor process. Previous studies have shown that TCM monomers and compounds can mediate the Wnt/β-catenin signaling pathway to inhibit the malignant phenotype of breast cancer cells， thus playing an anti-breast cancer role， and the biochemical process involved in the regulation of therapeutic drugs has not been systematically combed. By analyzing and collating Chinese and foreign literature at the present stage， this paper discussed the association mechanism between Wnt/β-catenin signaling pathway and breast cancer and analyzed the internal mechanism of TCM monomers and compounds in mediating Wnt/β-catenin signaling pathway to exert anti-breast cancer effect. The statistical results showed that the flavonoids， alkaloids， and terpenoids in TCM monomers could target the Wnt/β-catenin signaling pathway and block the further development of malignant phenotype of breast cancer cells. TCM compounds with functions of clearing heat and detoxifying， promoting blood circulation and removing blood stasis， and tonifying kidney and liver were commonly used to intervene in the Wnt/β-catenin signaling pathway to prevent breast cancer. Compared with the current inhibitors of Wnt/β-catenin signaling pathway， the application of TCM monomers and compounds is expected to bring low-toxicity and high-efficiency breast cancer treatment drugs to the clinical practice， and the existing results provide a reference for the subsequent screening， research， and development of TCM small-molecule compounds and TCM compounds against breast cancer.

ObjectiveFor prepubertal and urgently treated malignant tumor patients, ovarian tissue cryopreservation and transplantation represent more appropriate fertility preservation methods. Current clinical practices often involve freezing ovarian tissue with high concentrations of cryoprotectants (CPAs) and thawing with water baths. These processes lead to varying degrees of toxicity and devitrification damage to ovarian tissue. Therefore, this paper proposes optimized methods for vitrification of ovarian tissues based on sodium alginate hydrogel encapsulation and magnetic induction nanowarming technology. MethodsFirstly, the study investigated the effects of sodium alginate concentration, the sequence of hydrogel encapsulation and CPAs loading on vitrification efficiency of encapsulated ovarian tissue. Additionally, the capability of sodium alginate hydrogel encapsulation to reduce the required concentration of CPAs was validated. Secondly, a platform combining water bath and magnetic induction nanowarming was established to rewarm ovarian tissue under various concentrations of magnetic nanoparticles and magnetic field strengths. The post-warming follicle survival rate, antioxidant capacity, and ovarian tissue integrity were evaluated to assess the efficacy of the method. ResultsThe study found that ovarian tissue encapsulated with 2% sodium alginate hydrogel exhibited the highest follicle survival rate after vitrification. The method of loading CPAs prior to encapsulation proved more suitable for ovarian tissue cryopreservation, effectively reducing the required concentration of CPAs by 50%. A combination of 8 g/L Fe₃O₄ nanoparticles and an alternating magnetic field of 300 Gs showed optimal warming effectiveness for ovarian tissue. Combining water bath rewarming with magnetic induction nanowarming yielded the highest follicle survival rate, enhanced antioxidant capacity, and preserved tissue morphology. ConclusionSodium alginate hydrogel encapsulation of ovarian tissue reduces the concentration of CPAs required during the freezing process. The combination of magnetic induction nanowarming with water bath provides an efficient method ovarian tissue rewarming. This study offers novel approaches to optimize ovarian tissues vitrification.

BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

Objective:This study aimed to construct a prediction model for diagnosis of proliferative lupus nephritis based on a machine learning algorithm. Additionally, a user-friendly platform was developed to propose a non-invasive method to assist the pathologic classification of lupus nephritis.Methods:A retrospective analysis was conducted on clinical and pathological data of lupus nephritis patients confirmed by renal biopsy at Zhengzhou University People′s Hospital from January 2017 to August 2023. The study population was randomly divided into training and testing sets in a 7∶3 ratio. Utilizing six machine learning algorithms, classification models were developed. The predictive performance of each model was assessed using metrics such as accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC). The optimal model, once identified, was deployed as a web-based calculator for convenient model application. SPSS 25.0 and R 4.2.2 were used to analyze the data.Results:The study included a total of 212 patients, with 138 cases with proliferative lupus nephritis and 74 cases with non-proliferative lupus nephritis. The AUC values for the six models, namely logistic regression, decision tree, random forest, support vector machine, extreme gradient boosting, and light gradient boosting machine, were 0.79, 0.62, 0.79, 0.88, 0.81, and 0.77, respectively; the accuracy rates were 82.54%, 65.08%, 74.60%, 85.71%, 69.84%, 71.43%, respectively. Among them, the support vector machine model demonstrated the optimal performance. This model had deployed as a web-based calculator. Based on feature importance scores, the top 10 influencing factors were identified, including anti URNP antibody, immunoglobulin G, serum globulin, estimated glomerular filtration rate, anti Smith antibody, BMI index, anti dsDNA antibody, uric acid, anti-Rib.p antibody, and gender.Conclusion:A prediction model based on machine learning algorithms was successfully established, and a web calculator was developed to offer a simple and non-invasive method for diagnosing proliferative lupus nephritis. This can assist clinicians in evaluating the risk-benefit ratio of kidney biopsy in patients with lupus nephritis.

Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.

OBJECTIVE: Glucocorticoid-induced osteoporosis (GIOP) is a common complication of prolonged glucocorticoid therapy. Chlorogenic acid (CGA), a polyphenol with antioxidant properties that is extracted from traditional Chinese medicines such as Eucommiae Cortex, has potential anti-osteoporotic activity. This study aimed to investigate the possible effects of CGA on GIOP in mice and murine long bone osteocyte Y4 (MLO-Y4) cells and explore the underlying molecular mechanisms. METHODS: The protective effects of CGA were initially evaluated in the GIOP mouse model induced by dexamethasone (Dex). The micro-computed tomography, hematoxylin-eosin staining, silver nitrate staining, and serum detection were used to assess the efficacy of CGA for improving bone formation in vivo. Then, network pharmacology analysis was used to predict the potential targets and molecular mechanisms underlying the therapeutic efficacy of CGA against GIOP. After that, 2',7'-dichlorofluorescein diacetate staining, flow cytometry, real-time quantitative reverse transcription polymerase chain reaction, and Western blotting were used to verify the mechanisms of CGA against GIOP in vitro. RESULTS: Animal experiments showed that CGA treatment effectively attenuated Dex-induced decreases in bone mass and strength and improved disrupted osteocyte morphology in mice. The protein-protein interaction analysis highlighted erb-b2 receptor tyrosine kinase (ERBB2), which is also known as human epidermal growth factor receptor 2 (HER2), caspase-3, kinase insert domain receptor, matrix metallopeptidase 9, matrix metallopeptidase 2, proto-oncogene tyrosine-protein kinase Src, and epidermal growth factor receptor as core targets. The Kyoto Encyclopedia of Genes and Genomes analysis revealed several significantly enriched pathways (P < 0.05), including the ERBB, phosphoinositide 3 kinase-AKT serine/threonine kinase 1 (AKT), and mechanistic target of rapamycin kinase (mTOR) pathways. Cellular experiments verified that CGA enhanced bone formation and promoted autophagy while inhibiting apoptosis in MLO-Y4 cells exposed to Dex, which was associated with the upregulated expression of HER2 and activation of the HER2/AKT/mTOR signaling pathway. CONCLUSION CGA exerted anti-osteoporotic effects against GIOP, partially through targeting osteocytes and modulating the HER2/AKT/mTOR signaling pathway. Please cite this article as: Xie AN, Zhang SZY, Zhang Y, Cao JL, Wang CL, Wang LB, Wu HJ, Zhang J, Dai WW. Chlorogenic acid mitigates glucocorticoid-induced osteoporosis via modulation of HER2/AKT/mTOR signaling pathway. J Integr Med. 2025; 23(6):670-682.
Animals ; Chlorogenic Acid/therapeutic use* ; Osteoporosis/metabolism* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Mice ; Glucocorticoids/adverse effects* ; Receptor, ErbB-2/metabolism* ; Proto-Oncogene Mas ; Dexamethasone/adverse effects* ; Osteocytes/drug effects* ; Osteogenesis/drug effects* ; Male ; Cell Line ; Mice, Inbred C57BL ; Humans