1.Mechanism of programmed death-ligand 1 in regulating oral cancer metastasis based on bioinformatics and in vitro experiments
Tian WANG ; Xiaocui NIE ; Xiaotang WANG ; Jiping GAO ; Xiaona SONG ; Guohua SONG
Chinese Journal of Comparative Medicine 2025;35(9):50-59
Objective To analyze the role and mechanism of PD-L1 in oral cancer metastasis based on TCGA and GEO databases.Methods The expression characteristics and clinical significance of the PD-L1 in oral cancer were analyzed using the TCGA database.PD-L1 mRNA levels were detected by quantitative reverse transcription-polymerase chain reaction(RT-qPCR)in various oral cancer cell lines.CCK-8,scrath test,Transwell-migration,and matrigel-invasion assays were employed to assess the effects of PD-L1 on proliferation,migration,and invasion of oral cancer cells.The interaction network between PD-L1 and functional genes in patients with oral cancer was constructed using STRING software and the GEO database,and key pathways were screened by Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.The regulatory relationship between PD-L1 and key genes was validated by RT-qPCR.Results TCGA data revealed that PD-L1 was highly expressed in patients with oral cancer and was correlated with lymph node metastasis(P<0.01).PD-L1 was also highly expressed in oral cancer cell lines and its inhibition significantly inhibited the proliferation,migration,and invasion of Cal27 and SCC25 cells(P<0.05).KEGG analysis indicated that PD-L1 activated the Janus kinase(JAK)/signal transducer and activator of transcription(STAT)pathway by upregulating C-X-C motif chemokine ligand(CXCL)9 and CXCL10,thereby promoting STAT1 expression to regulate oral cancer metastasis.Inhibition of the JAK/STAT pathway further suppressed the proliferation,migration,invasion,and expression of STAT1,CXCL9,and CXCL10 in Cal27 and SCC25 cells(P<0.05).Conclusions PD-L1 may promote oral cancer cell proliferation,migration,and invasion by upregulating CXCL9 and CXCL10 to regulate the JAK/STAT pathway and enhance STAT1 expression,ultimately driving oral cancer growth and metastasis.
2.Mechanism of programmed death-ligand 1 in regulating oral cancer metastasis based on bioinformatics and in vitro experiments
Tian WANG ; Xiaocui NIE ; Xiaotang WANG ; Jiping GAO ; Xiaona SONG ; Guohua SONG
Chinese Journal of Comparative Medicine 2025;35(9):50-59
Objective To analyze the role and mechanism of PD-L1 in oral cancer metastasis based on TCGA and GEO databases.Methods The expression characteristics and clinical significance of the PD-L1 in oral cancer were analyzed using the TCGA database.PD-L1 mRNA levels were detected by quantitative reverse transcription-polymerase chain reaction(RT-qPCR)in various oral cancer cell lines.CCK-8,scrath test,Transwell-migration,and matrigel-invasion assays were employed to assess the effects of PD-L1 on proliferation,migration,and invasion of oral cancer cells.The interaction network between PD-L1 and functional genes in patients with oral cancer was constructed using STRING software and the GEO database,and key pathways were screened by Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.The regulatory relationship between PD-L1 and key genes was validated by RT-qPCR.Results TCGA data revealed that PD-L1 was highly expressed in patients with oral cancer and was correlated with lymph node metastasis(P<0.01).PD-L1 was also highly expressed in oral cancer cell lines and its inhibition significantly inhibited the proliferation,migration,and invasion of Cal27 and SCC25 cells(P<0.05).KEGG analysis indicated that PD-L1 activated the Janus kinase(JAK)/signal transducer and activator of transcription(STAT)pathway by upregulating C-X-C motif chemokine ligand(CXCL)9 and CXCL10,thereby promoting STAT1 expression to regulate oral cancer metastasis.Inhibition of the JAK/STAT pathway further suppressed the proliferation,migration,invasion,and expression of STAT1,CXCL9,and CXCL10 in Cal27 and SCC25 cells(P<0.05).Conclusions PD-L1 may promote oral cancer cell proliferation,migration,and invasion by upregulating CXCL9 and CXCL10 to regulate the JAK/STAT pathway and enhance STAT1 expression,ultimately driving oral cancer growth and metastasis.
3.Mechanism of Zuoguiwan in Inhibiting Osteoclast Activation Induced by Breast Cancer via Regulating p38 MAPK/ERK Signaling Pathway
Jianjiang FU ; Yinlong MEI ; Junchao MA ; Xiaocui ZHU ; Wei WANG ; Hong LYU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):1-9
ObjectiveTo investigate the effects of Zuoguiwan on osteoclast activation induced by breast cancer and its mechanism. MethodsTo simulate breast cancer-induced osteoclastic bone metastasis, RAW264.7 cells were cultured in conditioned medium containing 50% supernatant of MDA-MB-231 breast cancer cells. The dosages of Zuoguiwan used in the experiment were sera containing 5% and 10% Zuoguiwan. Tartrate-resistant acid phosphatase (TRAP) staining was used to detect osteoclast activation. Enzyme-linked immunosorbent assay (ELISA) was used to measure Cathepsin K secretion from RAW264.7 cells. Real-time quantitative polymerase chain reaction (PCR) was used to detect the mRNA expression levels of osteocalcin (OCN) and bone sialoprotein (BSP). Immunoprecipitation was employed to detect the interaction between Runt-related transcription factor 2 (Runx2) and core binding factor β subunit (CBF-β). Western blot was used to assess the protein expression of Runx2, phosphorylated Runx2 (p-Runx2), extracellular signal-regulated kinases 1/2 (ERK1/2), p-ERK1/2, p38 mitogen-activated protein kinase (MAPK), p-p38 MAPK, and CBF-β. ResultsCompared with the blank group, the MDA-MB-231 cell supernatant group showed a significant increase in TRAP-positive cell counts and Cathepsin K secretion. Meanwhile, the expression levels of p-Runx2, Runx2-CBF-β interaction, BSP and OCN mRNA, p-p38 MAPK, and p-ERK1/2 proteins were significantly decreased (P<0.01). Compared with the MDA-MB-231 cell supernatant group, Zuoguiwan-containing sera significantly reduced TRAP-positive cell counts and Cathepsin K secretion (P<0.01), significantly increased p-Runx2, BSP and OCN mRNA expression, as well as p-p38 MAPK and p-ERK1/2 protein levels, and promoted the interaction between Runx2 and CBF-β (P<0.01). No significant change in Runx2 expression was observed. Compared to the blank group, the BVD-523 group showed significantly lower expression of p-p38 MAPK and p-ERK1/2 proteins (P<0.01). Compared with the BVD-523 group, both low and high concentration Zuoguiwan-containing sera groups showed significantly higher p-p38 MAPK expression (P<0.01), and the high concentration Zuoguiwan group also exhibited a significant increase in p-ERK1/2 expression (P<0.01), while no statistical difference was found in the low-dose group. ConclusionZuoguiwan inhibits osteoclast activation by inducing phosphorylation of the key transcriptional regulator Runx2 in intra-osteoclast bone formation, and this process is closely associated with the activation of the p38 MAPK/ERK signaling pathway.
4.Study on the characteristic chromatogram of Shexiang Jiegu Capsule and determination of seven components by HPLC
Xiaocui YU ; Xiwen WANG ; Guiying ZHANG ; Junwei XU ; Yuwei ZHU ; Dan HU
Journal of Pharmaceutical Practice and Service 2025;43(8):395-399
Objective To establish the characteristic atlas of Shexiang Jiegu Capsule and determine the contents of seven active components (hydroxysafflor Yellow A, paeoniflorin, ferulic acid, naringin, ligustilide, catechin, epicatechin). Methods Octadecyl silane bonded silica gel was used as the filling agent, the mobile phase was composed of methanol-0.05% phosphoric acid by gradient elution, the detection wavelength was 245 nm, flow rate was 1.0 ml/min, column temperature was 30℃. The similarity of the fifteen batches of sample was evaluated in line with the TCM Chromatographic Fingerprint (2012 edition), and the contents of seven active components were determined. Results The HPLC fingerprint of Shexiang Jiegu Capsules was established. The similarity of fingerprint between fifteen batches of samples and control fingerprint was between 0.893 and 0.992. The results of methodological investigation for the determination of seven active components in fifteen batches of samples all met the requirements. Conclusion The established characteristic atlas of Shexiang Jiegu Capsules had high specificity and good repeatability, which could provide scientific basis for quality control of Shexiang Jiegu Capsules.
5.Mechanisms of Spermatogenic Dysfunction and Sperm Quality Degradation Induced by Propylthiouracil via Endoplasmic Reticulum Stress in Rats and Interventional Effect of Shugan Bushen Yulin Decoction
Yuhao MENG ; Xiaocui JIANG ; Min XIAO ; Chaoyang WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):79-89
ObjectiveTo investigate the mechanisms through which Shugan Bushen Yulin decoction ameliorates spermatogenic dysfunction and sperm quality degradation caused by propylthiouracil (PTU) via the endoplasmic reticulum stress pathway in rats. MethodsSixty male rats were randomly assigned into six groups: a control group, a model group, low- (6.75 g·kg-1), medium- (13.5 g·kg-1), and high-dose (27 g·kg-1) Shugan Bushen Yulin decoction groups, and an L-carnitine (0.27 g·kg-1) group, with ten rats in each group. Other groups except the control group were administrated with PTU (10 mg·kg-1) by gavage for 12 consecutive days. After the completion of modeling, rats were administrated with corresponding agents or normal saline (control group) via gavage for 28 consecutive days. Twenty-four hours after the last administration, rats were sacrificed, and the body and organ (testis, epididymis, and seminal vesicle) weights were measured to calculate the organ indices. Hematoxylin-eosin staining was employed to observe the pathological changes in the testes and epididymis, and the testicular spermatogenic function of rats was scored. Enzyme-linked immunosorbent assay was employed to measure the levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E2), and malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the rat serum. Terminal deoxynucleotidyl transferase dUTP nick end labeling was adopted to assess the rate of testicular cell apoptosis. Western blot was conducted to determine the expression levels of glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), phosphorylated protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), protein kinase RNA-like endoplasmic reticulum kinase (PERK), phosphorylated eukaryotic translation initiation factor 2α kinase (p-EIF2α), eukaryotic translation initiation factor 2α kinase (EIF2α), and activating transcription factor 4 (ATF4) in the testicular tissue of rats. ResultsCompared with the control group, the model group exhibited reductions in volumes and indexes of testes, epididymides, and seminal vesicles (P<0.01), pathological damage of testes and epididymides, and declines in spermatogenic function and sperm density and motility (P<0.01). In addition, the model group demonstrated elevated serum levels of TSH and MDA, lowered levels of T3, T4, FSH, LH, T, and E2, decreased activities of SOD and GSH-Px (P<0.05, P<0.01), an increased apoptosis rate of testicular cells (P<0.01), and up-regulated expression of GRP78, CHOP, p-PERK/PERK, p-EIF2α/EIF2α, and ATF4 in the testicular tissue (P<0.01). Compared with the model group, Shugan Bushen Yulin decoction at different doses improved the morphology and indexes of testes, epididymides, and seminal vesicles (P<0.05), restored the spermatogenic function (P<0.05, P<0.01), increased the sperm density and motility (P<0.05, P<0.01), and decreased the percentage of apoptotic testicular cells (P<0.05). Furthermore, the decoction lowered the serum level of MDA, elevated the serum levels of FSH, LH, T, and E2, and increased the activities of SOD and GSH-Px (P<0.05, P<0.01). Moreover, the expression levels of GRP78, CHOP, p-PERK/PERK, p-EIF2α/EIF2α, and ATF4 in the testicular tissue were down-regulated (P<0.05, P<0.01). ConclusionShugan Bushen Yulin decoction can ameliorate the spermatogenic dysfunction and sperm quality degradation induced by PTU in a rat model of hypothyroidism by repairing the testicular oxidative damage and regulating the PERK/EIF2α/ATF4 signaling pathway, thereby alleviating spermatogenic cell apoptosis.
6.Analysis of Surgical Treatment Outcomes in 709 Cases of Infective Endocarditis
Chaoji ZHANG ; Zining WU ; Xingrong LIU ; Guotao MA ; Shangdong XU ; Jianzhou LIU ; Sheng YANG ; Yanxue ZHAO ; Xinpei LIU ; Xiaocui WANG ; Xiaojun MA ; Ligang FANG ; Chunhua YU ; Huaiwu HE ; Qi MIAO ; Jun ZHENG
Medical Journal of Peking Union Medical College Hospital 2025;17(1):197-203
To review the clinical characteristics, short-term outcomes, and risk factors of patients with infective endocarditis(IE) who underwent surgical treatment at a single center, and to summarize treatment experience. Consecutive patients diagnosed with IE who underwent cardiac surgery at the Department of Cardiac Surgery, Peking Union Medical College Hospital between May 2012 and June 2024 were enrolled. Statistical analyses were performed on their baseline characteristics, comorbidities, IE predisposing factors, surgical indications, pathogen distribution, surgical strategies, short-term outcomes, and associated risk factors. A total of 709 IE patients meeting the inclusion and exclusion criteria were included. IE involved left-sided valves in 85.3% of cases. The median age was 48(35, 58) years, and 68.0% were male. Prosthetic valve endocarditis accounted for 8.7%. Patients with left-sided IE had a higher prevalence of comorbidities. Streptococcus was the causative pathogen in 43.2% of patients, while right-sided IE was more frequently associated with Significant differences in pathogen distribution were observed between patients with left-sided and right-sided IE. Heart failure was identified as an independent risk factor for both perioperative mortality and adverse outcomes in surgically treated patients. Through strict timing of surgical intervention and optimized perioperative management, surgical treatment may effectively reduce mortality and improve prognosis in patients with IE.
7.HPLC method for the simultaneous determination of hydroxyphenyl esters and quaternary ammonium bacteriostatic agents in eye drops
Jin GAO ; Dan HU ; Yi BAO ; Xiaocui YU ; Zexin WANG ; Jing LIU ; Guiying ZHANG ; Yingying ZHAO ; Zhenyu CAO ; Chunpu LI ; Xiaoxu HONG
Drug Standards of China 2024;25(3):234-243
Objective:To establish a general method for the simultaneous determination of hydroxyphenyl esters and quaternary ammonium bacteriostatic agents in eye drops.Methods:The chromatographic analysis was per-formed on an Agilent C18 column(4.6 mm ×250 mm,5 μm)with 1%triethylamine solution(pH adjusted to 5.0 with phosphoric acid)as mobile phase A and methanol as mobile phase B.Gradient elution was performed at col-umn temperature of 40 ℃.The detection wavelength was 214 nm,the flow rate was 1 mL·min-1,and the injec-tion volume was 20 μL.Results:Methylparaben,ethylparaben,propylparaben,butylparaben,benzalkonium chlo-ride and benzalkonium bromide were 0.11-559.0,0.10-513.0,0.10-258.8,0.11-270.5,1.07-537.0 and 1.03-512.8 μg·mL-1,respectively.The linear range was good(r>0.999).The average recoveries of meth-ylparaben,benzalkonium bromide and benzalkonium chloride were 104.7%(RSD=1.3%),102.6%(RSD=1.1%)and 100.9%(RSD=1.1%),respectively.The contents of bacteriostatic agent in 100 batches of eye drops from 36 varieties of 12 enterprises were determined,and the accurate results were obtained.Conclusion:This meth-od provides a reference for the content quality control and safety evaluation of bacteriostatic agents in eye drops.
8.Incidence and influencing factors of refeeding syndrome in critically ill patients:a Meta-analysis
Xiaocui ZOU ; Xiaorong MAO ; Lixue WANG ; Xiaojuan YANG ; Qing WEN
Chinese Journal of Nursing 2024;59(21):2640-2648
Objective To systematically review the incidence and influencing factors of refeeding syndrome(RFS)in critically ill patients,and provide references for early identification of RFS and formulation of preventive measures.Methods Computerized searches were conducted for studies on RFS in critically ill patients in the databases of China National Knowledge Infrastructure(CNKI),Wanfang,VIP,CBM,PubMed,Embase,Web of Science,CINAHL,Cochrane Library from inception to May 29th,2024.Data analysis was performed using Stata 16.0 software.Results A total of 29 articles with 5 720 participants were included.The Meta-analysis showed that the incidence of RFS in critically ill patients was 33.68%.The subgroup analysis showed that the incidence of RFS in critically ill patients was higher in studies conducted in 2020 or later(38.22%),in the Americas(36.39%),and with only electrolyte changes as the diagnostic basis(37.51%).Risk factors for RFS in critically ill patients included higher acute physiological and chronic health evaluation Ⅱ scores(OR=1.41),higher sequential organ failure assessment scores(OR=1.29),initiation of feeding within 48 h of ICU admission(OR=3.36),age ≥60 years(OR=2.82),diabetes mellitus(OR=3.53),pre-albumin concentration<150 g/L(OR=5.53),albumin concentration<30 g/L(OR=3.26),caloric intake>25%standard calories(OR=2.86),enteral solution temperature of 36~38 ℃(OR=2.32),feeding rate>50 ml/h(OR=3.76),fasting time ≥2 d before feeding(OR=2.46),history of alcoholism(OR=2.64).Conclusion The incidence of RFS in critically ill patients is high and there are many influencing factors.Nurses should improve their awareness and attention to RFS,accurately identify high-risk groups and risk factors,and adopt a multidisciplinary collaborative model to develop whole-course,detailed and personalized intervention measures to prevent RFS.
9.Research progress of thrombus permeability in acute ischemic stroke
Xiaocui WANG ; Shuai YU ; Hang ZHANG ; Guodong XIAO
Chinese Journal of Neurology 2024;57(3):298-302
In patients with acute ischemic stroke, there is a wide variation in the composition of blood clots that block the blood vessels. Some imaging features are associated with the components of the clot, such as thrombus permeability, which is related to higher red blood cell density and lower fibrinogen density. The different components and mechanical properties of the clot may have an impact on treatment effectiveness and risk. Therefore, this article aims to summarize the correlation between thrombus permeability and biological, imaging characteristics, and explore the clinical significance of thrombus permeability in the treatment of patients with acute ischemic stroke, providing reference and assistance for neurologists.
10.Clinical Study on the Analgesic Effect of Electroacupuncture Combined with Indomethacin Suppository in Transvaginal Ultra-sound-Guided Oocyte Retrieval
Yixin WANG ; Yanyun YIN ; Yujia KOU ; Yumeng DONG ; Yanni ZHANG ; Zhihao GAO ; Xiaocui LIU
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(6):628-632
OBJECTIVE To observe the auxiliary analgesic effect of electroacupuncture at Hegu and Neiguan combined with in-domethacin suppository in patients undergoing transvaginal ultrasound-guided oocyte retrieval(TUGOR and its effect on the outcome of in vitro fertilization(IVF.METHODS 64 IVF-ET patients undergoing TUGOR were randomly divided into a treatment group and a control group,32 cases in each group.One case dropped out of the treatment group during the treatment.The control group was given indomethacin suppository rectal administration,and the treatment group was given electroacupuncture at Hegu and Neiguan in addition to the treatment of the control group.The patients'tenderness threshold,VAS score,pain grade score,respiratory rate,and pulse rate were evaluated before and after TUGOR operation.The number of oocytes obtained,the rate of two pronuclei(2PN,embryo utiliza-tion rate,and high-quality embryo rate were evaluated after TUGOR operation.The adverse reactions of the two groups were monitored during and after operation.RESULTS After TUGOR operation,the VAS score and pain grade of the treatment group were signifi-cantly lower than those of the control group(P<0.01;the tenderness threshold of the two groups was significantly reduced after opera-tion(P<0.05,P<0.01,and the treatment group was better than the control group(P<0.05;the incidence of nausea during opera-tion,abdominal distension and nausea 48 h after operation in the treatment group were better than those in the control group(P<0.05;the high-quality embryo rate in the treatment group was better than that in the control group(P<0.05.CONCLUSION Electroacupuncture at Hegu and Neiguan combined with indomethacin suppository can effectively assist in analgesia,and can reduce the incidence of adverse reactions during and after TUGOR to varying degrees,and may have certain advantages in improving the rate of high-quality embryos.

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