Table of Content

05 March 2024, Volume 44 Issue 3

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Original Articles

Macrophage-to-myofibroblast transition promotes pulmonary fibrosis occurred in LPS-induced acute lung injury of mouse models

ZHAO Dong, ZHA Shiqian, WANG Yixuan, PAN Zhou, YU Wenzhen, HU Ke

2024, 44(3):  281-287.  doi:10.16352/j.issn.1001-6325.2024.03.0281

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Objective To explore the impact of macrophage-to-myofibroblast transition (MMT) on pulmonary fibrosis induced by acute lung injury by LPS. Methods Totally 21 male mice were randomly classified into 7 groups: control group, model group (LPS-PF) at different time points and intervention group of clodronate-liposomes (CL-LIP)treatement at different time points(n=3). Pulmonary fibrosis was identified by HE and Masson staining microscopy. The immuno-fluorescence technology was used for the evaluation of numbers of macrophage- to- myofibroblast transition cells (MMT cell which co-expressed CD68 and α-SMA). Bone marrow-derived macrophages (BMDMs) were randomly classified into two group: control (Ctrl) group and TGF-β1-treated group induced by transforming growthfactor-β1. α-SMA, FN and Col1 were detected by RT-qPCR. The expression of α-SMA, Smad3 and p-Smad3 protein was evaluated by Western blot. Results At day 7, the Ashcroft score of lung tissue in LPS-PF mouse model was significantly increased when compared with the Ctrl group (P＜0.01); While the score significantly declined when the model was pretreated with CL-LIP (P＜0.05). As detected by immuno-fluorescence staining, in CL-LIP group the number of CD68-positive cells co-labeled with α-SMA was obviously less then that of LPS-PF group of the corresponding time point(P＜0.01). When the BMDMs were stimulated by TGF-β1 at 24 h, 48 h and 96 h respectively, a higher expression of α-SMA,FN,Col1, were found in TGF-β1-treated group than that in Ctrl group at the corresponding time point (P＜0.01). The expression of Smad3, p-Smad3 significantly higher in LPS-PF group (at both day 7 and day 10) and TGF-β1-treated group (at both 48 h and 96 h) as compared to corresponding control group (P＜0.01). Conclusions MMT promotes pulmonary fibrosis induced by ALI via LPS. Smad3 is proved to be involved in the MMT process.

Regulatory effect of C12ORF66 on viability of MYCN amplified high-risk neuroblastoma cells

JIA Anna, ZHAN Shijia, ZHANG Xuan, GUO Jinxin, YU Yongbo, GUO Yongli, CHANG Yan

2024, 44(3):  288-294.  doi:10.16352/j.issn.1001-6325.2024.03.0288

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Objective To explore the effect of open reading frame 66 (C12ORF66) located at chromosome 12 on the viability of MYCN amplified NB cell lines. Methods DDatasets GSE16476 and GSE49710 in R2 database were analyzed for expression level of C12ORF66 in MYCN amplified and MYCN non-amplified NB cells and its potential correlation with the prognosis of pediatric patients. C12ORF66 mRNA expression level in normal tissue immortalized cell lines, MYCN amplified and MYCN non-amplified cell lines were detected by RT-qRCR. Transient or stable knockdown of C12ORF66 cell lines were constructed to compare the difference in real time cellular analysis (RTCA), colony formation, Ki67 positive cells between the control group and the C12ORF66 knockdown group. Results By analyzing R2 datasets, C12ORF66 level in MYCN amplified samples was significantly higher than that in MYCN non-amplified samples, and the expression of C12ORF66 was negatively correlated with the prognosis of pediatric patients(P＜0.05). C12ORF66 highly expressed in MYCN-amplified BE(2)-C and SK-N-BE(2) cell lines than in MYCN non-amplified CHLA-255 and SH-SY5Y cell lines (P＜0.001). Transient or stable knockdown of C12ORF66 resulted in significant slow down of proliferation of MYCN amplified NB cells (P＜0.001), the colony formation ability was significantly reduced (P＜0.001), and the proportion of Ki67 positive cells was significantly decreased (P＜0.05). Conclusions C12ORF66 was highly expressed in MYCN amplified clinical NB samples and cell lines which is believed to be correlated with poor prognosis of pediatric patients. C12ORF66 knockdown significantly inhibits cell viability of NB cells.

Effect and mechanism of Sitravatinib combined with Niraparib on proliferation, apoptosis and autophagy in mucosal melanoma cell lines

HU Zijin, KONG Yan, WU Xiaowen, GUO Qian, GUO Jun

2024, 44(3):  295-302.  doi:10.16352/j.issn.1001-6325.2024.03.0295

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Objective To investigate the effect of anti-angiogenic drug Sitravatinib combined with poly(adenosine diphosphate[ADP]-ribose) polymerase inhibitor(PARPi) Niraparib on mucosal melanoma cell lines and its possible mechanism. Methods The CCK8 assay was used to detect the maximal half inhibitory concentration (IC₅₀) of Sitravatinib and Niraparib targeting at mucosal melanoma (MM) cell lines. CompuSyn was used to detect the Combination Index (CI) in different concentrations of the two drugs. Flow cytometry was used to detect the effect of drugs on cell apoptosis. Colony formation assay was used to detect the effect of drugs on cell proliferation. Western blot was used to detect the protein expressions and RT-qPCR was used to detect mRNA expression. Results CI values was respectively 0.19 and 0.15 for Sitravatinib (2 μmol/L) in combination with Niraparib (20 μmol/L) in a human vaginal maligant melanoma cell line (HMVII) and a metastasis inguinal lymph node of vulvar malignant melanoma cell line (GAK). Compared with the control group and single-drug groups, the cell proliferation of the combination group was significantly reduced (P＜0.05 or P＜0.01 or P＜0.001). The cell apoptosis rate was significantly increased (P＜0.01 or P＜0.001). The protein and mRNA expression of apoptosis-related biomarkers significantly increased (P＜0.001); In addition, the protein and mRNA expression of cell autophagy biomarkers significantly increased (P＜0.01 or P＜0.001). The protein expression of DNA damage marker significantly increased. Moreover, compared with the control group, The expression of radiation sensitive protein 51 (RAD51) recombinase in the Sitravatinib single-drug group and combination group significantly reduced. As the dose of Sitravatinib gradually increased up to 2 μmol/L, the protein and mRNA expression of RAD51 both significantly reduced (P＜0.05 or P＜0.01), the mRNA expression of BRCA1 and BRCA2 also significantly reduced (P＜0.05 or P＜0.01 or P＜0.001). Conclusions Sitravatinib combined with Niraparib inhibits the proliferation of mucosal melanoma cells, induces cell apoptosis and promotes autophagy. The mechanism is potentially related to the inhibition of homology-dependent recombination repairs(HRR).

Correlation between PIK3CA mutation and clinicopathological features and prognosis of breast cancer

Yiheliman·MAIMAITI, CAO Yanzhen, WANG Cuicui, YUE Na, LIANG Liping

2024, 44(3):  303-307.  doi:10.16352/j.issn.1001-6325.2024.03.0303

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Objective To find the correlation between phosphatidylinositol kinase-3 catalytic subunit A gene (PIK3CA) mutation and pathological features as well as clinical prognosis of breast cancer. Methods The pathological data of 181 patients diagnosed with invasive breast cancer from January 2018 to January 2020 were collected. The estrogen receptor(ER), progestogen receptor(PR), human epidermal growth factor receptor-2(HER2), Ki67 were examined by immuno-histochemistry(IHC).Mutation of exon 9 and exon 20 of PIK3CA were examined by quantitative real-time PCR(qPCR). Results Among 181 cases of invasive breast cancer, 70 cases had PIK3CA mutation with 31 cases (44.28%) showed exon 9 mutations and 39 cases (55.71%) showed exon 20 mutations. The difference between PIK3CA mutation and their distribution in molecular typing of breast cancer was statistically significant(P＜0.05). The expression of PIK3CA mutation in breast cancer with different Ki67 expression was significantly different(P＜0.05). There were 34 cases (48.57%) showed PIK3CA mutations in the HR+/HER2 group and 36 cases (51.43%) of non HR+/HER2 group mutations. There was a statistically significant difference in the distribution of PIK3CA mutations between 2 groups(P＜0.05). The death rate of PIK3CA mutation cases was higher than that of PIK3CA wild type cases (P＜0.05). Conclusions PIK3CA mutation is associated with molecular typing, Ki67 increment index and prognosis of breast cancer. Detection of PIK3CA mutation provides potential support to the development of precise treatment of breast cancer patients.

AP2M1 inhibits proliferation and invasion of diffuse large B-cell lymphoma cells

LI Yuanchun, YAN Xueqian, FAN Dan, JI Yueru, XIAO Fang, GAO Jing

2024, 44(3):  308-316.  doi:10.16352/j.issn.1001-6325.2024.03.0308

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Objective To evaluate the regulatory effect of the adaptor related protein complex 2 subunit μ1 (AP2M1) on proliferation and invasion of diffuse large B-cell lymphoma (DLBCL). Methods Human diffuse large B-cell lymphoma cell line OCI-LY8 was aliquoted into control group, NC-shRNA group, AP2M1-shRNA group, NC-LV group, and AP2M1-LV group. Lipofectamine 2000 was used for cell transfection. Cell proliferation was detected by tetramethylazolium salt (MTT) method, apoptosis was detected by flow cytometry and cell migration and invasion were detected by Transwell assay. The protein expression of AP2M1, epidermal growth factor receptor (EGFR), p-phosphatidylinositol 3 kinase (PI3K), PI3K, p-protein kinase B (Akt) and AKT was detected by Western blot. Results Compared with control group, the relative expression of AP2M1 mRNA and protein in the AP2M1-shRNA group was decreased (P＜0.05). The relative cell viability was increased (P＜0.05). The cell apoptosis rate was decreased (P＜0.05). The counting number of migrating and invading cells was increased (P＜0.05). The relative expression level of EGFR protein and the phosphorylation level of PI3K and AKT were increased(P＜0.05). Compared with Control group, the expression of AP2M1 mRNA and protein relative expression level in AP2M1-LV group was increased (P＜0.05). The relative cell viability was decreased (P＜0.05). The cell apoptosis rate was increased (P＜0.05). The number of migrating and invading cells was decreased(P＜0.05). The relative expression level of EGFR protein and the phosphorylation level of PI3K and AKT were all decreased (P＜0.05). Conclusions The over-expression of AP2M1 partially inhibits the proliferation and invasion of DLBCL cells by inhibiting the EGFR/PI3K/AKT signaling pathway.

Paricalcitol inhibition of oxidative stress alleviates the damage of hepatocyte tight junction in mice

ZHANG Weiwei, XIE Jing, LI Lihua

2024, 44(3):  317-324.  doi:10.16352/j.issn.1001-6325.2024.03.0317

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Objective To explore the impact of paricalcitol (Pal) on the oxidative stress-induced tight junction damage of mouse hepatocytes and its mechanism. Methods A model of cholestatic liver injury was created by routine bile duct ligation. The mice were randomly divided into control group (control), model group (BDL) and treatment group (BDL+Pal). HE staining microscopy was used to observe the morphological changes of liver tissues. The human hepatoma cell line HepG2 was cultured and divided into blank group, model group (400 μmol/L H₂O₂) and treatment group (400 μmol/L H₂O₂+20 nmol/L Pal). Western blot was used to examine the level of tight junction protein 1 (ZO-1), occludin, phosphorylated p65 (p-p65), phosphorylated ERK (p-ERK) and phosphorylated myosin II regulated light chain (p-MLC) protein were checked in each group. Results Compared with the control group, the level of p-p65, p-ERK and p-MLC in the model group was significantly increased (P＜0.000 1 or P＜0.01 or P＜0.001). The protein expression of ZO-1 and occludin was significantly decreased (P＜0.01). HE staining microscopy showed an increased hepatocyte necrosis and inflammatory cell infiltration. In contrast, the above levels in the treatment group showed an opposite trend relative to the model group. Conclusions Pal is able to alleviate the damage of hepatocyte tight junctions by inhibiting oxidative stress in cholestatic mice and HepG2 cells. Its mechanism is potentially related to the inhibition of reactive oxygen species and NF-κB/p65 and ERK signaling pathways.

Inhibition of prohibitin 2 enhances the sensitivity of non-small cell lung cancer cell line A549 to erlotinib

ZHANG Jing, YANG Zigeng, CAI Wenqin, CAO Weiwei, WEI Hongmei, XUE Xixi, WU Bin

2024, 44(3):  325-332.  doi:10.16352/j.issn.1001-6325.2024.03.0325

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Objective To explore the effects of prohibitin 2(PHB2) on sensitivity of non-small cell lung cancer cell line A549 to erlotinib (Erl) and its potential mechanisms. Methods RACK1-specific small interfering RNA was transfected in A549 cells for knocking-down of PHB2. The effects of PHB2 inhibition on cell proliferation and apoptosis induced by Erl were observed. The colocalization of microtuble-associated protein light chain 3 alpha (LC3) and mitochondria was visualized by MitoTracker staining and green fluorescent protein-microtuble-associated protein light chain 3 alpha (GFP-LC3) transfection. Cell proliferation was detected by 5-ethynyl-2′-deoxyuridine (EdU) staining. Cell colony formation was evaluated by colony forming assay. Apoptotic index of A549 cells was evaluated by TUNEL. Western blot was used to measure the expressions of PHB2 and LC3Ⅱ. Mitochondrial transmembrane potential, cytochrome c and respiratory chain complex Ⅰ/Ⅱ/Ⅴ activity were analyzed by the commercially available kits. Results Compared with the siPHB2 and siCtrl+Erl group, the EdU-positive A549 cells and the number of cell colonies decreased significantly (P＜0.05), while the TUNEL-positive A549 cells increased significantly(P＜0.05) in the siPHB2+Erl group. In addition, compared with the siPHB2 and siCtrl+Erl group, mitochondrial transmembrane potential and respiratory chain complex Ⅰ/Ⅱ/Ⅴ activity decreased significantly (all P＜0.05) and the levels of cytochrome c increased in mitochondrial fractions (P＜0.05) and decreased in cytosolic fractions(P＜0.05) in the siPHB2+Erl group. Conclusions PHB2 inhibition significantly improves sensitivity of A549 cells to Erl,which may be explained by inhibition of PHB2-mediated mitochondrial autophagy.

Aucubin inhibits the proliferation of human hepatocellular carcinoma cells line HepG2

AN Qi, QI Guangzhao, HAN Chao

2024, 44(3):  333-338.  doi:10.16352/j.issn.1001-6325.2024.03.0333

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Objective To investigate the effects of aucubin (AU) on the proliferation, apoptosis, and cell cycle of human liver cancer cells line HepG2 and its mechanism of action. Methods HepG2 cells were cultured in vitro, CCK-8 method was applied to screen the optimal dosage concentration of AU. HepG2 cells were randomly grouped into a control group, an AU 12.5 mg/L group (AU L group), an AU 62.5 mg/L group (AU H group), and an AU H+Akt pathway agonist (SC79) group(AU H+SC79 group). The cell proliferation was observed in each group; 5-Ethynyl-2′-deoxyuridine (EDU) method was applied to detect cell proliferation; Flow cytometry was applied to detect cell apoptosis and cell cycle; Western blot was applied to detect the expression levels of phosphorylated protein kinase B (p-Akt), Akt, p-MDM2, MDM2, p-p53, and p53 proteins. Results AU concentrations of 12.5 and 62.5 mg/L were selected for subsequent experiments.Compared with 0 mg/L AU, the proliferation of 12.5 and 62.5 mg/L AU cells was obviously reduced (P＜0.05);Compared with the control group, the number of suspended and exfoliated cells in the AU L and AU H groups gradually increased. Cells shrunk and became round. The proportion of G0/G1 phase cells, the proportion of EDU positive staining cells increased and the expression level of p-Akt/Akt and p-MDM2/MDM2 proteins decreased. The proportions of S and G2/M phase cells, the rate of cell apoptosis, and the expression level of p-p53/p53 protein all increased (P＜0.05). Compared with the AU H group, the above changes in the AU H+SC79 group were recovered(P＜0.05). After AU treatment, the tumor volume and weight of transplanted nude mice decreased. Conclusions AU may inhibit the proliferation of liver cancer cells, induce cell cycle arrest and apoptosis by regulating the Akt/MDM2/p53 signaling pathway.

Dexmedetomidine alleviates lung tissue injury of rat models with ventilator-associated lung injury

HAN Huijing, WU Hong, GE Yin, QIAO Juan

2024, 44(3):  339-345.  doi:10.16352/j.issn.1001-6325.2024.03.0339

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Objective To investigate the effect of dexmedetom idine (DEX) on lung tissue and Ras homolog gene family member A (RhoA)/Rho kinase 1 (ROCK1) signaling pathway in lung tissue of rats with ventilator-induced lung injury (VILI). Methods A VILI rat model was established and separated into control group, model group (VILI group), dexmedetomidine low and high dose groups (DEX-L,DEX-H group), and high dose dexmedetomidine+lysophosphatidic acid (LPA) group (DEX-H+LPA group). Determination of wet/dry mass ratio of rat lung tissue (W/D); HE staining microscopy was applied to observe morphology of lung tissue; ELISA kit was applied to detect the level of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF); TUNEL staining method was applied to detect lung epithelial cell death; Immunoblotting was applied to detect the expression levels of apoptosis-related proteins, and RhoA, ROCK1 proteins. Results DEX could reduce lung injury, lung injury score, W/D, apoptosis rate, levels of TNF-α, IL-1β, IL-6, and expression of Bax, cleaved caspase-3, RhoA, ROCK, α-SMA in VILI rats (P＜0.05), while increased the expression of Bcl-2(P＜0.05); LPA could aggravate lung injury and increase lung injury score, W/D, apoptosis rate, level of TNF-α, IL-1β, IL-6 and expressions of Bax, cleaved caspase-3, RhoA, ROCK and α-SMA(P＜0.05); Bcl-2 expression level was decreased (P＜0.05). Conclusions Dexmedetomidine may protect rats with ventilator-induced lung injury by the inhibition of RhoA/ROCK1 signaling pathway.

Mechanism of treating hyperlipidemia with Ningzhi capsule based on network pharmacology and molecular docking technology

XIE Hao, LI Yaoyang, ZHAO Bin, YANG Dan, WU Qunli

2024, 44(3):  346-351.  doi:10.16352/j.issn.1001-6325.2024.03.0346

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Objective To screen the potential pharmacological targets of Ningzhi capsule, a lipid-lowering traditional Chinese medicine, and explore its mechanism of effect. Methods The components and predicted targets of Ningzhi capsule′s constituent drugs were obtained from BATMAN-TCM database. Hyperlipidemia-related targets were obtained from DisGeNET and GeneCards databases. The Venny2.1.0 tool was used to map drug targets and disease targets to obtain common targets as potential pharmacological targets. Protein-protein interaction analysis (STRING), gene ontology and pathway enrichment analysis (DAVID) were performed for the common targets. Finally, Swiss dock was used for molecular docking verification. Results A total of 1 432 predicted targets of Ningzhi capsule and 87 targets related to hyperlipidemia were found and 32 common targets were screened which covered 64 potential pharmacological ingredients of Ningzhi capsule. Potential pharmacological targets were most abundant for turmeric root-tuber, turmeric and cattail pollen, and potential pharmacological ingredients were most abundant for sickle senna seed, turmeric and turmeric root-tuber. Apolipoprotein E (APOE), nitric oxide synthase 3 (NOS3) and peroxisome proliferator activated receptor alpha (PPARA) had the highest hyperlipidemia correlation scores and more protein interactions, which were potential core targets. The biological processes related to DNA transcription were significantly enriched. Cholesterol metabolism, cGMP-PKG and PPAR signaling pathways were involved with APOE, NOS3 and PPARA, respectively. Molecular docking showed good binding activity. Conclusions There are many potential pharmacological ingredients of Ningzhi capsule and the key components for lowering lipids include turmeric root-tuber, turmeric, cattail pollen and sickle senna seed. APOE, NOS3 and PPARA are believed to be the key targets for lowering lipids with potential mechanism related to cholesterol metabolism, cGMP-PKG and PPAR signaling pathways.

Identification of the effect of cisplatin on the transcriptome of human hepatocellular carcinoma cell lines

GUO Xin, JI Mengdie, WANG Qi, LI Xueyuan, CHEN Yang

2024, 44(3):  352-360.  doi:10.16352/j.issn.1001-6325.2024.03.0352

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Objective To investigate the effect of cisplatin treatment on the transcriptional level of human liver cancer cells by conducting transcriptome sequencing analysis after treating human liver cancer cell lines with different concentrations of cisplatin (CDDP). Methods Liver cancer cell lines HepG2 and Huh7 were incubated with cisplatin at different final concentrations of 0,20,50,100 and 200 μmol/L. After 12 hours, cell viability, immunofluorescence and RNA-sequencing(RNA-seq) were performed. Differential gene expression analysis (DEG), KEGG pathway analysis, and protein-protein interaction network analysis were conducted. Results Cisplatin decreased cell viability and increased DNA damage in HepG2,Huh7 cells. Among the genes regulated after cisplatin treatment at different concentrations, 59 genes were commonly up-regulated in both HepG2 and Huh7 cells, while 81 genes were commonly down-regulated. The commonly upregulated genes were mainly enriched in cancer initiation and progression pathways.The 81 commonly down-regulated genes were mainly enriched in Rap1 signaling pathway, Ras signaling pathway, signaling pathways regulating pluripotency of stem cells, axon guidance, and cell adhesion-related pathways. Survival analysis of key nodes in the protein-protein interaction network of commonly upregulated and downregulated genes revealed a significant correlation between high expression of Jun proto-oncogene, AP-1 transcription factor subunit (JUN) and prolonged patient survival and a significant correlation between low expression of growth arrest and DNA damage inducible alpha (GADD45A) and prolonged patient survival. Conclusions The study revealed common transcriptional changes in liver cancer cells under cisplatin treatment. Differential expression of JUN and GADD45A is a potential core mechanism to explain drug resistance. This conclusion provides some important prognostic indicators for clinical treatment.

Identification of the causative variants in five Chinese families with tuberous sclerosis complex

LIU Siyi, YANG Yujiao, YANG Tao, ZHAO Xiuli

2024, 44(3):  361-367.  doi:10.16352/j.issn.1001-6325.2024.03.0361

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Objective To identify the causative variants in 5 Chinese families with tuberous sclerosis complex (TSC) to provide genetic counseling and prenatal diagnosis. Methods Genetic counseling and clinical diagnosis were performed in 8 patients from five unrelated TSC families by teleconsultation. With informed consent obtained from the participants, 3 to 5 mL peripheral blood samples were collected from the probands and their family members for the extraction of genomic DNA. Candidate pathogenic variants were screened by panel sequencing (PS). The candidate pathogenic variants found in TSC1 and TSC2 by PS were validated by PCR-Sanger sequencing and bioinformatics analysis. Results All the pathogenic mutations were identified in the probands and their available family members. Causative variants in TSC1 or TSC2 were detected in all patients, including three reported variants and two novel variants. The two novel variants, TSC2:c.245G＞ A and TSC2: c.235delG, which were predicted to cause the nonsense variant p.(Trp82^*) and the frameshift variant p.(Val79Lysfs27^*) respectively was believed to introduce premature stop codons. The analysis of family co-segregation and bioinformatics were identified as very positive factors for pathogenicity. Conclusions This result provides more evidences for the genetic counseling and prenatal diagnosis in these families and expand the spectrum of TSC2 pathogenic variants.

Inhibition of triggering receptor expressed on myeloid cells-1(TREM-1) attenuates chronic intermittent hypoxia-induced atherosclerosis in mouse models

YU Hanqiao, LI Chao, YU Yubin, FENG Lina, SHENG Xiaosheng, YE Xiaoxia, WANG Linyan

2024, 44(3):  368-373.  doi:10.16352/j.issn.1001-6325.2024.03.0368

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Objective To investigate the role of triggering receptor expressed on myeloid cells-1(TREM-1) in atherosclerosis induced by chronic intermittent hypoxia (CIH). Methods ApoE^-/- mice were randomly divided into blank group, model group and experimental group. The mice in the model group and the experimental group were kept in a hypoxic environment and fed with a high-fat diet. After 4 weeks of high-fat feeding, mice in the experimental group were intraperitoneally injected with TREM-1 inhibitor LR12 (5 mg/kg) for 8 weeks. After 12 weeks of feeding, the level of serum total cholesterol (TC), low density lipoprotein (LDL), triglyceride (TG), tumor necrosis factor-α (TNF-α), interleukin-1β(IL-1β) and interleukin-10 (IL-10) were detected. Histological analysis of aortic TREM-1 expression, plaque area and macrophage level were examined. Results Compared with blank group, the expression of TREM-1 in the aorta of the model group significantly increased (P＜0.05). Compared with model group, the aortic plaque, the level of lipids in serum(TC, LDL, TG) and inflammatory factors (TNF-α, IL-1β, IL-10), aortic plaque, the expression of TREM-1 and infiltrating macrophages in aortic plaque of the experimental group were all significantly reduced (P＜0.05). Conclusions TREM-1 is involved in the development of CIH-induced AS. Inhibition of TREM-1 can alleviate CIH-induced AS and its mechanism is related to the inhibition of macrophage activation.

Clinical Sciences

Evaluation of ^99mTc-HYNIC-TOC and ¹³¹I-MIBG imaging in diagnosis of pheochromocytoma and paraganglioma

WANG Yu, TONG Anli, ZHOU Yue, ZHANG Wenqian, CUI Yunying, JING Hongli , LI Yuxiu

2024, 44(3):  374-378.  doi:10.16352/j.issn.1001-6325.2024.03.0374

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Objective To evaluate ^99mTc-HYNIC-TOC somatostatin receptor and ¹³¹I-MIBG imaging in clinical diag- nostic of pheochromocytoma and paraganglioma (PPGL). Methods This was a retrospective study.359 PPGL patients diagnosed by pathology microscopy were included. The diagnostic sensitivity and influencing factors on ^99mTc-HYNIC-TOC somatostatin receptor and ¹³¹I-MIBG imaging were analyzed. Results The positive rate of ^99mTc-HYNIC-TOC somatostatin receptor scintigraphy was 57.7%(184/319)and ¹³¹I-MIBG imaging was 83.2%(232/279). The positive rates of ^99mTc-HYNIC-TOC somatostatin receptor imaging in the adrenal glands, retroperitoneum, head and neck, heart and mediastinum, pelvis and bladder were 53.3%, 62.5%, 95.0%, 66.7%, 50.0% and 11.0% respectively and the positive rates of ¹³¹I-MIBG imaging were 86.7%, 88.5%, 45.4%, 50.0% ,75.0% and 33.3% respectively. The positive rate of the two imaging did not showed difference among patients with different genetic backgrounds (SDH,VHL,RET mutations). The median maximum diameter of tumors was 4.4(3.0, 6.1)cm.and the diagnostic sensitivity of somatostatin receptor imaging and ¹³¹I-MIBG imaging for larger tumors(≥4.4 cm) was significantly higher than those for the smaller tumor group (＜4.4 cm) (64.0% vs. 51.3%; 92.3% vs. 74.1%)(P＜0.01). Tumors in 19 patients (5.3%) failed to uptake neither imaging method. Conclusions This is the largest PPGL cohort in China concerning ^99mTc-HYNIC-TOC somatostatin receptor imaging and ¹³¹I-MIBG imaging. The sensitivity of¹³¹I-MIBG imaging is higher than that of ^99mTc-HYNIC-TOC somatostatin receptor imaging, but for some tumors, such as head and neck paraganglioma, the latter has obvious advantages. These two imagings technologies are complementary and the choice of them should depend the individual situation of patients.

Intensive phototherapy don't affect cellular immune function and short-term reactions after discharge in neonatal hyperbilirubinemia

LIU Zhen, WANG Dalian, ZHANG Jie, ZHANG Qixing, WANG Fei

2024, 44(3):  379-383.  doi:10.16352/j.issn.1001-6325.2024.03.0379

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Objective To investigate the effect of intensive phototherapy for neonatal hyperbilirubinemia on cellular immune function and short-term immune-related adverse effects. Methods Totally 180 infants with hyperbilirubinemia were treated with different light intensity, the efficacy, cellular immune function and immune adverse effects were followed up for six months after discharge. Results After phototherapy, serum interleukin-6 (IL-6) in both groups were decreased and CD4⁺ (%) and CD4⁺/CD8⁺ were increased than that before phototherapy. The decrease rate of total bilirubin in the intensive phototherapy group was significantly faster than that in the conventional phototherapy group, at the same time, the total duration of phototherapy and hospital stay were significantly shorter than that in the conventional phototherapy group (P＜0.05). No statistical significance in the incidence of diarrhea, rash, fever and hypo-calcemia during hospitalization and no immune-related adverse effects in 6 months after discharge were recorded. Conclusions Compared with conventional phototherapy, intensive phototherapy reduces serum bilirubin level more quickly and shorten the duration of phototherapy and hospital stay. No common adverse effects nor immune-related adverse effects are recorded during hospitalization and the period of six months after discharge.

Pulmonary manifestations of hemodialysis patients combined with COVID-19 based on computer scan score and blood routine

WANG Chao, YANG Xiaoguang

2024, 44(3):  384-388.  doi:10.16352/j.issn.1001-6325.2024.03.0384

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Objective To investigate the characteristics of blood routine, chest computed tomography (CT) imaging and short-term evolution of hemodialysis patients infected with Omicron variant of severe acute respiratory syndrom coronavirus 2(SARS-CoV-2). Methods A total of 204 patients diagnosed with Omicron variant infection in the First Hospital of Hohhot from September 2022 to September 2023 were retrospectively reviewed. Among them, 89 patients with end-stage renal disease (ESRD) who were receiving hemodialysis were included in the hemo-dialysis group. The remaining 115 patients were control group, and the first blood routine results chest computed tomography (CT) imaging data were observed. Thirty-four patients in the hemodialysis group and 29 patients in the control group had complete pulmonary CT imaging data on the day of admission, 5-6 days and 10-12 days after admission. The characteristics and chest CT scores of all cases were analyzed. Results 1)The percentage of monocytes,neutrophils, neutrophil/lymphocyte ratio and chest CT score of the hemo-dialysis group were higher than those of the control group, while the white blood cells, lymphocytes and lymphocyte percentage were lower than those of the control group. 2)The positive rate of first chest CT was 49.4% in hemo-dialysis group and 35.7% in control group. 3) The chest CT scores of the hemo-dialysis group and the control group on day 5 and day 6 were higher than those of first check. Chest CT was reexamined on days 10-12, and scores were higher in the hemo-dialysis group than in the control group. Conclusions Hemo-dialysis patients with COVID-19 have higher blood routine indexes, higher positive rate of lung CT and slower absorption than non-hemodialysis patients.

Mini Reviews

Research progress on P2X7 receptor in cancer pain

ZHANG Zhongwen, ZHAO Rui, ZHANG Haolong, YANG Yuting, BAI Jinxia, ZHANG Haoling WANG Wei

2024, 44(3):  389-392.  doi:10.16352/j.issn.1001-6325.2024.03.0389

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The activation of the P2X7 receptor as an ATP-gated ion channel, triggers the release of pro-inflammatory cytokines in tumor carring individuals and stimulate excitation of injury-causing neurons, thereby exacerbating the transmission of pain. In preclinical cancer pain models, it has the potential to serve as a new therapeutic target for cancer pain management.

Research progress on the mechanism of annexin A family members in breast cancer

NAN Lu, GUO Menjie, GAO Yanan, JIA Hongyan

2024, 44(3):  393-397.  doi:10.16352/j.issn.1001-6325.2024.03.0393

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The annexins(ANX) family is widely present in the cell membrane, cytoplasm or extracellular matrix. As key tumor regulatory molecules, annexins A (ANX A) family can promote or inhibit invasion and metastasis of breast cancer cells by influencing cell membrane and cytoskeleton formation and participating in signaling pathways. ANX A family also plays a role in the apoptosis of breast cancer cells by regulation of pro-apoptotic proteins and cell cycle independent kinases (CDKs) and related pathways. In addition, ANX A family can also promote therapeutic resistance to a large number of drugs. For instance,ANX A1 enhances triple-negative breast cancer resistance by inducing epithelial-mesenchymal transformation. ANX A4 induces resistance by forming ANX A4-Fhit complexes and secretion of exosomes containing ANX A6 promotes paclitaxel resistance in breast cancer cells in a YAP1-dependent manner. So ANX A family may be a new target for breast cancer treatment.

Research progress on the role of transmembrane proteins in malignant tumors

WANG Zihao, XIA Xiaochao, LI Shun

2024, 44(3):  398-402.  doi:10.16352/j.issn.1001-6325.2024.03.0398

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Transmembrane proteins (TMEMs) are a class of family proteins that span lipid bilayers, serving as crucial channel proteins on biological membranes, playing essential physiological roles. TMEMs′ over-expression in malignant tumors, such as TMEM16A and TMEM206, has been linked to the promotion of malignancy. Conversely, down-regulation of TMEM100 expression has been associated with tumor progression. TMEM98, whose expression varies across different malignancies.TMEMs has shown promise as both a therapeutic target and a prognostic marker in cancer.Additionally, TMEMs play a vital role in various malignancies by modulating the Wnt and AKT signaling pathways through interaction with different upstream and downstream regulatory factors. Furthermore, research has provided additional insights into their role in cisplatin-related chemoresistance in specific malignant tumor cell populations.

Research progress on the role of NMES1 gene in malignant tumors

WU Yuhong, YU Caiyuan, YE Shicai

2024, 44(3):  403-407.  doi:10.16352/j.issn.1001-6325.2024.03.0403

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The normal esophageal mucosa specific 1 gene (NMES1) is considered as a tumor suppressor gene which significantly reduces expression of various malignant tumors. The NMES1 can affect various cellular biological behaviors such as proliferation, apoptosis and migration of tumor cells. These findings provide new strategies for searching early biomarkers or therapeutic targets of malignant tumors and support the evaluation of disease progression and prognosis.

Postoperative complications and related risk factors in COVID-19 patients

ZHANG Yi, SHEN Le

2024, 44(3):  408-411.  doi:10.16352/j.issn.1001-6325.2024.03.0408

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The incidence of postoperative multi-system complications, such as pulmonary complications and sepsis, as well as mortality of patients with COVID-19. Therefore, patients with COVID-19 should be fully recovered before elective surgery and a minimum of 7 weeks recovery time is routinely recommen-ded. At the same time, the occurrence of adverse outcomes such as postoperative complications in patients with COVID-19 should be considered in a multidimensional manner, taking into account the related risk factors such as age, severity of the disease, type of surgery, anesthesia method, underlying comorbidities, type of viral strain, vaccination status and other related risk factors.

Medical Education

Qualitative research on anxiety status and coping strategies of clinical postgraduates

LIU Junxiang, DONG Meizhen

2024, 44(3):  412-417.  doi:10.16352/j.issn.1001-6325.2024.03.0412

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Objective To explore the anxiety status and coping strategies of clinical postgraduates, and to provide practical approaches to promote their mental health. Methods Using the phenomenological research method of qualitative research, 12 subjects were interviewed in a semi-structured way. Using the 7-step analysis method of Colaizzi phenomenology, the original data were analyzed and summarized. Results Five themes were extracted, including stress sources and psychological condition, interpersonal relationship, adjustment to cope with stress, self-understanding, career understanding and future vision. Clinical work, scientific research and economic pressures were the main causes of anxiety to the interviewees, who made cognitive, psychological, attitudes and behaviors adjustments, they hope to achieve a good work-life balance in the future. Conclusions Effective measures should be taken in view point of individual, school, family and social dimensions to alleviate anxiety and promote their physical and mental health.

Establishment and application of the clinical case database in vascular surgery teaching

YANG Genhuan, SHEN Chenyang

2024, 44(3):  418-420.  doi:10.16352/j.issn.1001-6325.2024.03.0418

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Vascular surgery is an emerging clinical discipline with a wide range of categories and disease types. In theoretical teaching, a large amount of vivid imaging materials and vascular reconstruction photos are needed to effectively display the clinical manifestation. During internship training, there are not enough patients in the ward to cover common or frequently-occurring diseases of vascular surgery. As a result, development of a clinical case database is of great significance for the teaching of vascular surgery. This article mainly introduces the establishment and preliminary application of a clinical case database in vascular surgery teaching at Beijing Tiantan Hospital affiliated to Capital Medical University.