ObjectiveTo explore the mechanism of action of Paeoniae Radix Rubra and Aconiti Lateralis Radix Praeparata （CSFZ） in the treatment of acute-on-chronic liver failure （ACLF） through network pharmacology， molecular docking， and animal experiments. MethodsNetwork pharmacology was used to identify potential targets and related signaling pathways for the treatment of ACLF with CSFZ. Molecular docking was used to examine the binding activity of the core components with corresponding key targets. An ACLF rat model was established by subcutaneous and tail vein injections of bovine serum albumin combined with lipopolysaccharide （LPS） + D-galactosamine （D-GalN） intraperitoneal injection. A normal control group （NC）， a model group， a CSFZ group （CSFZ， 5.85 g·kg^-1）， and a hepatocyte growth-promoting granule group （HGFG， 4.05 g·kg^-1） were set up in this study. Pathological changes in rat liver tissue were observed using hematoxylin and eosin （HE） and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of interleukin-6 （IL-6）， B-cell lymphoma-2 （Bcl-2）， Caspase-3， and albumin （ALB）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to measure the mRNA and protein expression levels of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt）， phosphorylated PI3K （p-PI3K）， and phosphorylated Akt （p-Akt）. ResultsNetwork pharmacology screening identified 49 active ingredients of CSFZ， 103 action targets， and 3 317 targets related to ACLF. Among these， 74 targets overlapped with CSFZ drug targets. Key nodes in the protein-protein interaction （PPI） network included Akt1， tumor necrosis factor （TNF）， IL-6， Bcl-2， and Caspase-3. Gene Ontology （GO） functional analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis identified multiple signaling pathways， with the PI3K/Akt signaling pathway being the most frequent. Molecular docking showed that the core components of the drug exhibited good binding activity with the corresponding key targets. Animal experiments confirmed that CSFZ significantly improved liver tissue pathological damage in ACLF rats， reduced the release of inflammatory factors and liver cell apoptosis， and upregulated the expression levels of the PI3K/Akt signaling pathway. ConclusionThrough network pharmacology， molecular docking， and in vivo experiments， this study confirms the effect of CSFZ in reducing liver cell inflammatory damage and inhibiting liver cell apoptosis. The specific mechanism may be related to its involvement in regulating the PI3K/Akt signaling pathway.

Autoimmune hepatitis （AIH） is a chronic inflammatory liver disease. The pathogenesis of AIH remains unclear， but it is mainly autoimmune injury caused by the breakdown of autoimmune tolerance due to the abnormal activation of the immune system， while the specific molecular mechanism remains unknown. Recent studies have shown that abnormal amino acid metabolism plays an important role in the development and progression of AIH. This article reviews the research advances in amino acid metabolic reprogramming in AIH， in order to provide a theoretical basis for amino acid metabolism as a new target for the clinical diagnosis and treatment of AIH.

ObjectiveTo study the effect and mechanism of Shentong Zhuyutang in treating intervertebral disc degeneration （IDD） in rats. MethodsIn the cell experiment， male rats were administrated with normal saline or low-， medium-， and high-dose （3.38， 6.75，13.5 g·kg^-1， respectively） Shentong Zhuyutang by gavage， respectively， and serum samples were collected after 7 days of continuous administration. Another 10 male rats were selected for the isolation of nucleus pulposus cells. The cell model of IDD was established by treatment with interleukin （IL）-1β. The modeled cells were then treated with Shentong Zhuyutang-containing serum and the ferroptosis inhibitor ferrostatin-1 （Fer-1）， respectively， to investigate the effects of Shentong Zhuyutang-containing serum on the proliferation and ferroptosis of nucleus pulposus cells. To study the role of silent information regulator 1 （SIRT1）/nuclear factor erythroid 2-related factor 2 （Nrf2） in the regulation of ferroptosis in nucleus pulposus cells by Shentong Zhuyutang-containing serum， this study treated the cells with the SIRT1 inhibitor Ex 527 and the Nrf2 inhibitor ML385， respectively， in addition to the treatment with IL-1β and high-dose Shentong Zhuyutang-containing serum. The cell-counting kit-8 （CCK-8） assay and EdU staining were employed to measure the cell viability and proliferation， respectively. The Fe²⁺， glutathione （GSH）， and malondiadehyde （MDA） levels were measured by colorimetric assay. Western blot was employed to determine the protein levels of glutathione peroxidase 4 （GPX4）， acyl-CoA synthetase long-chain family 4 （ACSL4）， Collagen Ⅱ， Aggrecan， SIRT1， and Nrf2. Immunofluorescence was used detect SIRT1 expression. In the animal experiment， male rats were treated with anulus puncture for the modeling of IDD. Rats were randomly assigned into sham operation， model， Shentong Zhuyutang-containing serum （13.5 g·kg^-1）， and positive control （nimesulide dispersible tablets， 0.18 mg·kg^-1） groups. Rats in the drug intervention groups were administrated with corresponding agents at 1 mL·kg^-1， and those in the sham operation and model groups were administrated with equal volumes of normal saline， once daily for 28 consecutive days. At the end of the last administration， the histopathological changes in the intervertebral discs of rats were observed by hematoxylin-eosin staining and scored by the Masuda method. Western blot was employed to determine the protein levels of SIRT1， Nrf2， GPX4， and Collagen Ⅱ in the nucleus pulposus tissue. ResultsCompared with the control group， the IL-1β group of nucleus pulposus cells showed elevated levels of Fe²⁺， MDA， and ACSL4 （P<0.05）， decreased cell viability， lowered GSH level， and down-regulated protein levels of GPX4， Collagen Ⅱ， and Aggrecan （P<0.05）. Shentong Zhuyutang-containing serum and Fer-1 reversed the effects of IL-1β on the viability and ferroptosis of nucleus pulposus cells and up-regulated the protein levels of Collagen Ⅱ and Aggrecan in nucleus pulposus cells （P<0.05）. Compared with the control group， the IL-1β group showcased down-regulated expression of Sirt1 and Nrf2 in nucleus pulposus cells （P<0.05）. Compared with the IL-1β group， the high-dose Shentong Zhuyutang-containing serum+IL-1β group showed up-regulated expression of SIRT1 and Nrf2 in nucleus pulposus cells （P<0.05）. Compared with the high-dose Shentong Zhuyutang-containing serum+IL-1β group， the ML385 group showed down-regulated protein levels of Nrf2 and GPX4， lowered GSH level， and elevated Fe²⁺ and MDA levels （P<0.05）. In addition， the Ex 527 group showed down-regulated protein levels of SIRT1， Nrf2， and GPX4 （P<0.05）. The results of the animal experiment showed that compared with the sham operation group， the model group had severe degeneration of the intervertebral disc tissue with increased pathological score， up-regulated protein level of ACSL4 （P<0.05）， and down-regulated protein levels of SIRT1， Nrf2， GPX4， and Collagen Ⅱ （P<0.05）. Compared with the model group， the Shentong Zhuyutang group showed alleviated IDD with declined pathological score， down-regulated protein level of ACSL4 （P<0.05）， and up-regulated protein levels of SIRT1， Nrf2， GPX4， and Collagen Ⅱ （P<0.05）. ConclusionShentong Zhuyutang may activate the SIRT1/Nrf2 signaling pathway to inhibit the ferroptosis of nucleus pulposus cells， thereby delaying the process of IDD in rats.

Aim To study the neuroprotective effects of Herba siegesbeckiae extract on cerebral ischemia/ reperfusion rats and its mechanism. Methods Sixty SD rats were randomly divided into model group, low, middle and high dose groups of Herba siegesbeckiae, and Sham operation group, and the drug was given continuously for seven days. The degree of neurologic impairment was evaluated by mNSS, and the infarct volume was measured by MRI. The number of Nissl-posi- tive cells was detected by Nissl staining, and the apop- tosis was accessed by Tunel staining. Furthermore, the expression of Bax, Bcl-2 and NeuN was observed by Western blot, and the expression of NeuN was detected by immunofluorescence staining. The expression of IL- 1β, TNF-α and IL-6 mRNA was performed by RT- qPCR. Results The mNSS score and the volume of ischemic cerebral infarction in the model group were significantly increased, and Herba siegesbeckiae extract treatment significantly decreased the mNSS score and infarct volume (P<0.05, P<0.01). Herba siegesbeckiae extract could increase the number of Nissl-pos- itive cells and the expression of NeuN (P<0.01), and reduce the number of Tunel-positive cells (P<0.01). Western blot showed that Herba siegesbeckiae extract inhibited the expression of Bax, increased Bcl-2 and NeuN in ischemic brain tissue (P<0.01). RT-qPCR showed that Herba siegesbeckiae extract inhibited the expression of IL-1 β, TNF-α and IL-6 mRNA in the is-chemic brain tissue (P<0.01). Conclusions Herba siegesbeckiae extract can reduce the cerebral infarction volume, improve the neurological function damage, inhibit the apoptosis of nerve cells and the expression of inflammatory factors and promote the expression of NeuN, there by exerting protective effects on MCAO rats.

A new Schiff base modified MCM-41 molecular sieve(N-MCM-41)was synthesized via post-grafting method with 2-pyridine formaldehyde for efficient removal of lead ions(Pb2+)from aqueous solution.X-ray diffraction(XRD),scanning electron microscopy(SEM),transmission electron microscopy(TEM),Fourier transform-infrared(FT-IR)spectroscopy,thermogravimetric analysis(TGA),and X-ray photoelectron spectroscopy(XPS)were employed to characterize the structure,morphology,surface functional groups and chemical states of N-MCM-41.Moreover,the adsorption behavior of Pb2+by N-MCM-41 was systematically studied.Batch adsorption studies revealed that N-MCM-41 showed the maximal adsorption capacity of 101.3 mg/g at 45℃and pH=5.5 under the initial Pb2+ concentration of 80 mg/L after 180 min adsorption.The adsorption process conformed to the Langmuir isotherm model and the pseudo-second-order kinetics model.The adsorption of Pb2+by N-MCM-41 was a spontaneous and endothermic process.Adsorption mechanism analyses suggested that functional groups on N-MCM-41 had strong coordination ability with Pb2+to improve the adsorption capacity.The synthesized N-MCM-41 adsorbent exhibited excellent reusability in five regeneration cycles.Overall,this study showed that the N-MCM-41 had good application prospect to remove Pb2+ from aqueous solution.

Objective To observe the clinical efficacy of acupuncture combined with rehabilitation training under the guidance of Chinese medicine-enhanced recovery after surgery(CMERAS)in postoperative rehabilitation of tibial plateau fracture.Methods Sixty patients with tibial plateau fracture in postoperative rehabilitation period were randomly divided into observation group and control group,30 cases in each group.The control group was given routine postoperative rehabilitation training,and the observation group was treated with combined acupuncture treatment on the basis of the rehabilitation training of the control group.Both groups were treated for 3 consecutive months.After 3 months of treatment,the clinical efficacy of the two groups was evaluated,and the changes in the Visual Analogue Scale(VAS)scores of pain were observed before and after treatment,and the changes in the knee scores of the Hospital for Special Surgery knee score(HSS)of the United States were compared before and after treatment between the two groups.As well as the time of fracture healing on the operative side of the two groups of patients,and the fracture healing rate within 3 months of the two groups of patients were compared.Results(1)After 1 week,1 month and 3 months of postoperative treatment,the VAS scores of patients in the two groups were significantly improved compared with the pre-treatment period(P＜0.05),and the observation group was significantly superior to the control group in improving the VAS scores,with a statistically significant difference(P＜0.05).(2)After treatment,the HSS scores of patients in the two groups were significantly improved compared with those before treatment(P＜0.05),and the observation group was significantly superior to the control group in improving the HSS scores,and the difference was statistically significant(P＜0.05).(3)After 3 months of treatment,the fracture healing rate was 56.67%(17/30)in the observation group and 30.00%(9/30)in the control group.The fracture healing rate of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(4)After 3 months of acupuncture treatment,the total effective rate was 96.67%(29/30)in the observation group and 73.33%(22/30)in the control group.The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).Conclusion The clinical efficacy of acupuncture in postoperative rehabilitation of tibial plateau fractures under the guidance of CMERAS is significant,which reduces the clinical symptom of postoperative pain of the patients,shortens the healing time of fracture breaks,and significantly improves the patients'knee joint function.

Objective To explore the molecular mechanism of Atractylodes macrocephala in the treatment of Ulcerative colitis(UC)based on network pharmacology,and verify it with animal experiments.Methods The active components of Atractylodes macrocephala was screened from the TCMSP database,the TCM-ID database,and in combination with relevant references,and the corresponding targets were obtained through Swiss database.The relevant targets of UC were obtained from GeneCards database,construct the"drug-component-target-disease"network diagram and"pathway-active ingredient-target"network diagram and draw PPI network diagram;GO function enrichment analysis and KEGG signal pathway annotation analysis were carried out.Autodock software is used for molecular docking of active components and targets.Then,the experimental validation of the network pharmacology prediction was carried out.The mouse UC model was induced by dextran sodium sulfate(DSS).The pathological changes of the colon tissue,the number of goblet cells,and the positive expression of inflammatory factorswere detected by HE staining,AB-PAS staining and immunohistochemistry in colon tissue of UC mice.Results The results have shown 30 active ingredients including atractylolactone I,II and III were screened,and 591 corresponding targets were obtained,of which the key target was IL-1β、TNF-α and so on.Molecular docking show that the core components had good binding affinity with the key targets.And the results of animal experiments showed that the alcohol extract of Atractylodes macrocephala could significantly increase the colon length,reduce the DAI score,improve the pathological changes of colon tissue of UC mice,increase the number of goblet cells,and inhibit the expression of IL-1β,TNF-α in colon tissue.Conclusion This study indicated that Atractylodes macrocephala could regulate the release of inflammatory factors through multiple components,multi-target and multi-channel,which could inhibit inflammatory reaction and play a role in improving UC.

Objective:To explore the distribution characteristics and antibiotic resistance of pathogen in children with hematological disorders and cancers complicated with sepsis in pediatric intensive care unit (PICU).Methods:The clinical data of children with hematological disorders and cancers complicated with sepsis hospitalized at Shenzhen Children′s Hospital affiliated to China Medical University from January 2016 to August 2023 were retrospectively analyzed. Patients were divided into survival group and death group based on the outcome of sepsis on 28 days after diagnosis.Results:A total of 202 sepsis episodes occurred in 176 children were enrolled in this study. Among all, 144 (71.3%) cases of bloodstream infection, 59 (29.2%) cases of pulmonary infection, 21 (10.4%) cases of abdominal infection, 9 (4.5%) cases of soft tissue infection, 9 (4.5%) cases of nervous system infection, and 3 (1.5%) cases of urinary tract infection. A total of 244 pathogenic strains were identified, in which 74 (30.3%) cases were gram-positive bacteria. The top 3 pathogens isolated were Coagulase negative Staphylococcus (21 strains), Staphylococcus aureus (19 strains) and Streptococcus pneumoniae (13 strains). Gram-negative bacteria accounted for 122 (50.0%) strains, in which top 3 were Klebsiella pneumonia (33 strains), Escherichia coli (25 strains), and Pseudomonas aeruginosa (23 strains). Fungi comprised 48 (19.7%) strains:the top 3 were Candida tropicalis (14 strains), Candida albicans (10 strains), Aspergillus and Pneumocystis jirovecii (7 strains each). The incidence of Acinetobacter baumannii, Stenotrophomonas maltophilia, and Pseudomonas aeruginosa were significantly higher in death group compared to survival group[9.0%（6/67）vs. 2.3%（4/177）, χ2＝3.971 ，P＝0.046; 9.0%（6/67）vs. 1.1%（2/177）, χ2＝7.080 ，P＝0.008;16.4%（11/67）vs. 6.8%（12/177）, χ2＝5.288 ，P＝0.021]. The samples of 57 cases were simultaneously detected by both culture and metagenomic next-generation sequencing (mNGS). Pathogens were detected in 25 cases by both culture and mNGS. In 30 cases, pathogen detection were mNGS positive but culture negative. Two cases showed positive results only with culture. A total of 79 (46.8%) strains were multi-drug resistant bacteria, including 27 (34.2%) strains of gram-positive bacteria and 52 (65.8%) strains of gram-negative bacteria. A total of 174 (86.1%) children with sepsis received empirical anti-infective drugs within 24 hours of fever onset. A total of 124 (61.4%) cases were appropriately covered by the initial empirical antibiotics, while 40 (19.8%) cases were not adequately covered and 10 (5.0%) cases had incomplete coverage. Despite the inclusion of pathogenic in the coverage, resistance to initial antibiotics was observed in 22 (10.9%) cases. Fifty-one patients died. Conclusion:The predominant pathogens responsible for sepsis in PICU with hematological disorders and cancers is gram-negative bacteria, followed by gram-positive bacteria and fungi. In comparison to healthy children with sepsis, there is a higher incidence of fungal infections among hematological disorders and cancers. The proportion of multi-drug resistant bacteria infection is high. Early identification and combination of local etiological distribution and drug resistance, along with the empirical selection of appropriate anti-infection treatment strategies, can greatly enhance survival rate.

Objective We aimed to investigate the effects of Biejiajian Pills on MHCC-97H hepatoma cells and whether Biejiajian Pills regulate the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway through miR-885-5p.Methods SPF SD rats (n = 10) were randomly divided into the blank group and the Biejiajian Pills (1.1 g/kg) group to prepare blank and Biejiajian Pills-containing serum. MHCC-97H cells in the logarithmic growth phase were divided into the model group, blank serum groups with different concentrations (5％, 10％, 15％, and 20％), the serum containing Biejiajian Pills group, and the blank group without cells. Cell proliferation was detected by the CCK-8 assay, and the optimal intervention time and concentration of drug-containing serum were screened. MHCC-97H cells were divided into the blank control group (no intervention), the Biejiajian Pills-containing serum group (20％ Biejiajian Pills-containing serum), the miR-885-5p mimics group (transfected with miR-885-5p mimics), the miR-NC group (transfected with miR-885-5p NC), and the Biejiajian Pills-containing serum + miR-885-5p mimics group (treated with 20％ Biejiajian Pills-containing serum and transfected with miR-885-5p mimics). Cells in each group were cultured for 72 hours. A dual luciferase reporter assay was conducted to verify the targeting relationship between miR-885-5p and EGFR. Cell proliferation was detected by the CCK-8 assay, cell migration and invasion abilities were detected by the cell scratch assay and the Transwell invasion assay. Annexin V-APC/PI double staining was performed to detect the apoptosis level, and real-time fluorescence quantitative PCR (RT-qPCR) analysis was conducted to determine the mRNA expression levels of miR-885-5p, EGFR, MEK, and ERK1/2. The expression levels of EGFR, p-EGFR, MEK, p-MEK, ERK1/2, p-ERK1/2, matrix metalloproteinase 1 (MMP1), and CyclinD1 were determined by Western blotting analysis. The subcutaneous tumor model of MHCC-97H hepatoma cells in nude mice was established by subcutaneous injection to observe the inhibitory effect of Biejiajian Pills of different doses(0.55,1.1,2.2 g/kg).Results The optimal concentration and intervention time of Biejiajian Pills-containing serum were 20％ and 72 hours, respectively. Meanwhile, the dual luciferase reporter assay showed that miR-885-5p could directly target EGFR. No statistical significances between the blank control group and the miR-NC group were observed (P>0.05). Compared with the blank control group, the proliferation rates of MHCC-97H hepatoma cells in the Biejiajian Pills-containing serum group, the miR-885-5p mimics group, and the Biejiajian Pills-containing serum + miR-885-5p mimics group were significantly decreased (P<0.01), and their migration and invasion abilities were significantly decreased (P<0.05, P<0.01). At the same time, the protein expression levels of CyclinD1 and MMP1, which are closely related to cell proliferation and invasion, were significantly downregulated (P<0.05, P<0.01). The proportions of late apoptotic cells and the proportion of total apoptotic cells were significantly increased (P<0.01). In the Biejiajian Pills-containing serum group, the miR-885-5p mimics group, and the Biejiajian Pills-containing serum + miR-885-5p mimics group, miR-885-5p mRNA was significantly upregulated (P<0.01) and EGFR, MEK, and ERK1/2 were significantly downregulated at the mRNA level (P<0.05, P<0.01). EGFR, MEK, and ERK1/2 phosphorylation was inhibited (P<0.01), and the Biejiajian Pills-containing serum + miR-885-5p mimics group showed the best effect (P<0.05, P<0.01). The subcutaneous liver tumor model in nude mice verified that Biejiajian Pills can inhibit tumor growth in a dose-dependent manner. Conclusion Biejiajian Pills can promote apoptosis of MHCC-97H hepatoma cells and inhibit their proliferation, invasion, and migration. The mechanism may be related to the targeted regulation of the EGFR/MAPK/ERK signaling pathway by miR-885-5p.

Objective To investigate the effect and mechanism of Panax notoginseng saponins(PNS)in inhibiting c-Jun N-terminal protein kinase(JNK)/c-Jun signaling pathway activation to alleviate calcific aortic valve disease(CAVD)in mice.Methods Twenty-one male ApoE-/-mice aged 6 to 8 weeks were randomly divided into the model,PNS high-dose(60 mg/kg),and PNS low-dose(30 mg/kg)groups using the random number table method,with seven mice per group.Nine male C57BL/6 mice aged 6 to 8 weeks were used as the control group.Mice in the control group were fed a normal diet,whereas ApoE-/-mice were fed a high-fat diet for 12 weeks.After 12 weeks,three C57BL/6 and three ApoE-/-mice(one ApoE-/-mice from each group)were randomly selected to evaluate the CAVD modeling effect.After confirming successful modeling,the PNS high-and low-dose groups received daily intragastric PNS administration.The control and model groups were administered an equal volume of stroke-physiological saline solution by gavage for 4 consecutive weeks.The valve annulus diameter and peak velocity of the mice in each group were then detected using ultrasound.The degree of aortic valve calcification was evaluated using von Kossa and Alizarin Red S staining.The serum triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were detected by biochemical method.Inflammatory factor interleukin-4(IL-4),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-10(IL-10)levels were determined using an enzyme-linked immunosorbent assay.The expressions of calcification markers,runt-related transcription factor 2(RUNX2),and bone morphogenetic protein 2(BMP2)were detected using immunohistochemistry.Aortic valve cell apoptosis was evaluated using TUNEL staining,and JNK/c-Jun signaling pathway-related mRNA and mean fluorescence intensity were detected using quantitative real-time PCR and immunofluorescence,respectively.Results Compared with the control group,the mice in the model group showed an increase in serum TC,TG,LDL-C,TNF-α,and IL-1β levels,a decrease in IL-4 and IL-10 levels,a decrease in annulus diameter,an increase in peak flow velocity,and an increase in von Kossa and Alizarin Red S staining-positive areas.Additionally,the model group showed an increase in aortic valve cell apoptosis rate,an increase in BMP2 and RUNX2-positive rates,and an increase in JNK and c-Jun mRNA expression levels and p-JNK/JNK and p-c-Jun/c-Jun(P<0.05).Compared to the model group,the PNS low-dose group showed a decrease in serum TC,LDL-C,and TNF-α levels,an increase in annulus diameter,a decrease in peak flow velocity,and a decrease in positive area in Alizarin Red S staining.Furthermore,the PNS low-dose group showed a decrease in BMP2 and RUNX2-positive rates,JNK and c-Jun mRNA expression levels,and p-JNK/JNK and p-c-Jun/c-Jun(P<0.05).The PNS high-dose group showed an increase in HDL-C,IL-4 and IL-10 levels,a decrease in serum TC,LDL-C,TNF-α,and IL-1β levels,an increase in annulus diameter,a decrease in peak flow velocity,and a decrease in von Kossa and Alizarin Red S staining-positive areas and cell apoptosis rate.The PNS high-dose group also showed a decrease in BMP2 and RUNX2 positive staining rates,JNK and c-Jun mRNA expression levels,and p-JNK/JNK and p-c-Jun/c-Jun(P<0.05).Conclusion PNS may reduce valvular cell apoptosis,alleviate inflammation,and protect against aortic valve calcification in mice by inhibiting the activation of JNK/c-Jun signaling pathway.