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    Cell and Molecular Biology
    Mechanism of m6a methyltransferase METTL3 mediating the biological behavior of pituitary neuroendocrine tumor cells by regulating the expression of KAI1/CD82
    ZHENG Kai, LUO Xiuling, ZHANG Weihao, LIU Yuli, LI Yuming, LIAO Shanggao
    2023, 51 (8):  785-790.  doi: 10.11958/20221753
    Abstract ( 408 )   HTML ( 13 )   PDF (1195KB) ( 684 )  

    Objective To study the mechanism of m6a methyltransferase METL3 mediated proliferation, migration and invasion of pituitary neuroendocrine tumor cells by regulating the expression of KAI1/CD82. Methods The expression levels of METTL3 and KAI1/CD82 in rat pituitary cells, rat pituitary tumor cell lines GH3, and MMQ were determined by qPCR and Western blot assay. GH3 cells were cultured in vitro and randomly divided into the control group, the METL3 overexpression plasmid group, the METL3 empty plasmid group, the METL3 siRNA group and the METL3 siRNA negative control group. After grouping and transfection, the expression levels of METL3 and KAI1/CD82 of each cell group were detected by qPCR and Western blot assay. The cell viability of each group was detected by CCK-8 experiment. The cell migration and invasion in each group were detected by cell scratch and Transwell invasion experiment. The methylation modification of KAI1/CD82 m6A in each group was detected by methylated RNA immunoprecipitation (MeRIP) experiment. Results Compared with rat pituitary cells, the METL3 protein and mRNA expression level in rat pituitary tumor cell lines GH3 and MMQ were significantly increased (P<0.05). KAI1/CD82 protein and mRNA expression levels were significantly reduced (P<0.05). There were no significant differences in cell indicators between the control group, the METTL3 empty plasmid group and the METTL3 siRNA negative control group (P>0.05). Compared with the control group and the METTL3 empty plasmid group, the cell viability, migration distance, number of invaded cells, METL3 protein and mRNA expression level, KAI1/CD82 m6A methylation level increased in the METL3 overexpression plasmid group (P<0.05), and the KAI1/CD82 protein and mRNA expression levels decreased (P<0.05). Compared with the control group and the METTL3 siRNA negative control group, the cell viability, migration distance, number of invaded cells, METTL3 protein and mRNA expression level and KAI1/CD82 m6A methylation level decreased in the METTL3 siRNA group (P<0.05), and KAI1/CD82 protein and mRNA expression levels increased (P<0.05). Conclusion Down-regulating the expression of METTL3 can reduce the level of KAI1/CD82 m6A methylation, promote the transcriptional expression of KAI1/CD82 mRNA, reduce the proliferation, invasion and migration of pituitary tumor cells, and inhibit the occurrence and development of pituitary tumors.

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    The radiosensitizing effect of ginsenoside Rg3 on lung cancer cells by inhibiting mTOR pathway-mediated pentose phosphate pathway
    HUANG Lin, LI Bin, HU Zuowei
    2023, 51 (8):  791-796.  doi: 10.11958/20222018
    Abstract ( 394 )   HTML ( 6 )   PDF (969KB) ( 679 )  

    Objective To investigate the influence of ginsenoside Rg3 on the radiosensitivity of lung cancer cells by inhibiting the pentose phosphate pathway (PPP) mediated by mammalian target of rapamycin (mTOR) pathway. Methods A549 lung cancer cells were treated with 0, 10, 20, 40, 60, 80 mg/L ginsenoside Rg3. The proliferation of A549 cells was detected by MTT method. Cells were divided into the control group (normal culture, no irradiation), the radiation group (X-ray irradiation), the ginsenoside Rg3 group (60 mg/L ginsenoside Rg3, no irradiation), the combination group (X-ray irradiation +60 mg/L ginsenoside Rg3) and the activator group (X-ray irradiation +60 mg/L ginsenoside Rg3+100 nmol/L mTOR pathway activator MHY1485). All of groups were irradiated by 8 GyX ray after 48 h of culture with corresponding drugs. Plate cloning experiment was applied to detect the formation rate of cell clones in each group. Enzyme-linked immunosorbent assay (ELISA) was applied to determine levels of glucose-6-phosphate dehydrogenase (G6PD) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) in cell supernatant of each group. DCFH-DA fluorescent probe method was applied to detect the level of intracellular reactive oxygen species (ROS). Cell apoptosis was detected by flow cytometry. γ-H2AX immunofluorescence staining was applied to analyze DNA damage repair. Western blot assay was applied to detect expression levels of mTOR, p-mTOR, proliferating cell nuclear antigen (PCNA), Bcl-2-associated X protein (Bax), caspase-3 and γ-H2AX protein in cells. Results Ginsenoside Rg3 inhibited the proliferation of A549 cells in a dose-dependent manner (P<0.05). Compared with the control group, the cell clone formation rate, G6PD, ROS, NADPH levels, p-mTOR/mTOR and PCNA protein expressions were significantly decreased in the radiation group and the ginsenoside Rg3 group, and the cell apoptosis rate, γ-H2AX foci number, Bax, caspase-3, γ-H2AX protein expressions were significantly increased (P<0.05). Compared with the radiation group and the ginsenoside Rg3 group, the cell clone formation rate, G6PD, ROS, NADPH levels, p-mTOR/mTOR, and PCNA protein expressions were significantly decreased in the combination group, the cell apoptosis rate, γ-H2AX foci number, Bax, caspase-3, γ-H2AX protein expressions were significantly increased (P<0.05). Compared with the combination group, the cell clone formation rate, G6PD, ROS, NADPH levels, p-mTOR/mTOR and PCNA protein expressions were significantly increased in the activator group, and the cell apoptosis rate, γ-H2AX foci number, Bax, caspase-3, γ-H2AX protein expressions were significantly decreased (P<0.05). Conclusion The inhibitory effect of ginsenoside Rg3 on lung cancer cells may be realized through inhibition of PPP mediated by mTOR.

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    The mechanisms of circFAT1 on the biological process of GBM cells
    ZHANG Liqun, WURI Jimusi, ZHENG Xiaoming, WANG Lin, HAN Yuxiu, ZHANG Wei, YAN Tao
    2023, 51 (8):  797-802.  doi: 10.11958/20230224
    Abstract ( 392 )   HTML ( 5 )   PDF (1155KB) ( 654 )  

    Objective To investigate the regulation and mechanism of circFAT1 on proliferation, invasion and epithelial-mesenchymal transition (EMT) of glioblastoma (GBM). Methods Fifty GBM samples and 5 non-tumor brain tissue (NBT) samples were collected, and 3 GBM and 3 NBT samples were randomly selected for tissue RNA sequencing. The expression levels of circFAT1 in U87, U251, T98G, LN229 GBM cell lines and NHA astrocyte lines were detected by qRT-PCR. The cyclic properties of circFAT1 were determined by selective degradation of linear transcripts by RNase R. GBM cells were divided into the sh-control group and the sh-circFAT1 group. Cell proliferation, invasion and EMT were detected by colony formation assay, transwell assay and Western blot assay after lentivirus transfection. Fluorescence in situ hybridization (FISH) was used to detect the localization of circFAT1 in GBM cells, and the interaction between circFAT1 and miR-1182 was verified by dual-luciferase reporter and RNA immunocoprecipitation (RIP) assay. Finally, Western blot assay was performed to verify the regulatory effect of circFAT1 knockdown or inhibition of miR-1182 expression on TGF-β/Smad signaling pathway. Results The expression of circFAT1 was increased in GBM tissue and cells (P<0.05). RNase R reduced linear FAT1 expression without affecting circFAT1 (P<0.05). Knockout of circFAT1 inhibited the proliferation, invasion and EMT of GBM cells (P<0.05). Dual-luciferase reporter and RIP assay confirmed that circFAT1 targeting on miR-1182. The protein levels of TGFB2, p-SMAD2 and p-SMAD3 were decreased after circFAT1 knockdown, while protein expressions of TGFB2, p-SMAD2 and p-SMAD3 increased after inhibiting the expression of miR-1182 (all P<0.05). Conclusion Knockout of circFAT1 can inhibit proliferation, invasion and EMT of GBM cells, and its mechanism may be related to the regulation of TGF-β/Smad signaling pathway by sponge miR-1182.

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    Effects of polymer assisted deposition of Ta2O5 coating on the surface of TiO2 nanotubes on improving the biological activity of MC3T3-E1 cells
    WANG Feifan, WANG Qingfu, ZHANG Shuo, LI Guangzhong
    2023, 51 (8):  803-808.  doi: 10.11958/20230648
    Abstract ( 209 )   HTML ( 3 )   PDF (1087KB) ( 648 )  

    Objective To explore the effect of polymer assisted deposition of tantalum pentoxide (Ta2O5) coating on the surface of TiO2 nanotubes on the biological activity of mouse bone forming precursor cells, MC3T3-E1 cells. Methods Three sets of samples were prepared, including Ta/TiO2 nanotubes (the Ta/NT group), Ta2O5/pure titanium (the Ta2O5/PT group) and Ta2O5/ TiO2 nanotubes (the Ta2O5/NT group). The Ta2O5/PT group and the Ta2O5/NT group were prepared by polymer-assisted deposition. The three sets of samples were characterized and tested by scanning electron microscopy (SEM) to observe the surface morphology. X-ray photoelectron spectroscopy (XPS) was used to analyze surface element composition, and X-ray diffraction (XRD) was used to detect surface compounds. MC3T3-E1 cells were selected to explore the effect of three groups of samples on cell biological activity. Fluorescence microscope was used to observe the adhesion of cytoskeleton and nucleus. Cell activity was determined by CCK-8 method. Cell alkaline phosphatase (ALP) activity was detected. Calcium deposition was detected by alizarin red staining and semi-quantitative analysis. The expression levels of recombinant human bone morphogenetic protein-2 (BMP-2), ALP, osteocalcin (OCN) and osteopontin (OPN) were detected by real-time PCR. Results SEM images showed that on the surface of the Ta2O5/NT group, the TiO2 nanotube substrate was covered with a sheet-like, banded cross-linked micro-nano Ta2O5 coating structure. XRD showed that the TiO2 nanotubes in the Ta2O5/NT group presented a trace of demineralized titanium and rutile crystal structure. Compared with the Ta/NT group, the Ta2O5/NT group and the Ta2O5/PT group showed higher cell density, larger cytoskeletal mass and filamentous structure, more crosslinking and clusters, higher cytoskeletal tension and higher cell activity. The semi-quantitative analysis of alizarin red staining samples showed that calcium deposition decreased successively in the Ta2O5/NT group, the Ta/NT group and the Ta2O5/PT group (P<0.01). The ALP activity, calcium deposition and ALP, OCN and OPN mRNA contents on day 7 and 14 were decreased successively in the Ta2O5/NT group, the Ta/NT group and the Ta2O5/PT group, and the BMP-2 mRNA content on day 14 in the Ta2O5/NT group was the highest in the three groups (P<0.05). Conclusion Ta2O5/TiO2 nanotube composite coating can promote the adhesion of MC3T3-E1 cells, the expression of mineralization and osteogenic genes, and enhance the activities of cell and ALP, which is conducive to the play of biological activities.

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    Impacts of NGF/TrkA axis on proliferation, apoptosis and invasion of cervical cancer SiHa cells
    LONG Ying, HUANG Fangyi, WEI Yousheng
    2023, 51 (8):  809-813.  doi: 10.11958/20230318
    Abstract ( 366 )   HTML ( 4 )   PDF (1135KB) ( 676 )  

    Objective To investigate the impact of nerve growth factor (NGF)/tropomyosin receptor kinase A (TrkA) axis on the proliferation, apoptosis and invasion of cervical cancer SiHa cells. Methods Normal cervical epithelial cells HUCEC and cervical cancer cells SiHa were cultured in vitro. SiHa cells were grouped into the control group (normal culture), the L-NGF group (50 μg/L recombinant human NGF protein), the H-NGF group (100 μg/L recombinant human NGF protein), the H-NGF+L-K252a group (100 μg/L recombinant human NGF protein+50 μg/L K252a) and H-NGF+H-K252a group (100 μg/L recombinant human NGF protein+100 μg/L K252a). The protein expression levels of NGF, TrkA, E-cadherin, N-cadherin and Vimentin were detected by Western blot assay. The proliferation of SiHa cells was detected by CCK-8 method. Apoptosis of SiHa cells was detected by flow cytometry. Cell migration was determined by scratch healing test. Cell invasion was measured by Transwell assay. Results The levels of NGF and TrkA were obviously higher in SiHa cells than those in HUCEC cells (P<0.01). Compared with the control group, levels of NGF and TrkA, proliferative activity, migration rate, number of invasive cells and N-cadherin and Vimentin proteins were obviously higher in the L-NGF group and the H-NGF group (P<0.05), and the apoptosis rate and the level of E-cadherin protein were obviously lower (P<0.05). The above indexes were more obviously different in the H-NGF group than those of the L-NGF group (P<0.05). Compared with the H-NGF group, levels of NGF, TrkA, proliferative activity, migration rate, number of invasive cells and N-cadherin and Vimentin proteins were obviously lower in the H-NGF+L-K252a group and the H-NGF+H-K252a group (P<0.05), and the apoptosis rate and the level of E-cadherin protein were obviously higher (P<0.05). The above indexes in the H-NGF+H-K252a group were more obviously different than those in the H-NGF+L-K252a group (P<0.05). Conclusion Down-regulation of NGF/TrkA axis can inhibit the proliferation and invasion of cervical cancer SiHa cells and promote their apoptosis.

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    The effect of piceatannol on the migration and invasion of cervical cancer cells by regulating miR-106b-5p/RUNX3 axis
    WANG Yuning, SONG Juxing, TIAN Zhigang, HAO Guorong, SHEN Hao
    2023, 51 (8):  814-819.  doi: 10.11958/20221529
    Abstract ( 382 )   HTML ( 9 )   PDF (1254KB) ( 634 )  

    Objective To explore the effect of piceatannol (PIC) on migration and invasion of cervical cancer (CC) cells by regulating microRNA-106b-5p (miR-106b-5p)/RUNT-related transcription factor 3 (RUNX3) axis. Methods Firstly, human CC cells Hela were treated with culture media of different concentrations of PIC (0, 20, 40, 80 and 160 μmol/L), and the effect of PIC on cell proliferation was detected by CCK-8 assay to determine the optimal concentration of PIC. Hela cells were divided into the control group, the PIC group, the PIC+NC mimics group, the PIC+ miR-106b-5p mimics group, the NC inhibitor group, the miR-106b-5p inhibitor group, the miR-106b-5p inhibitor+si-RNA group and the miR-106b-5p inhibitor+si-RUNX3 group. qRT-PCR was used to detect the expression level of miR-106b-5p in Hela cells in each group. Transwell method was used to detect the migration and invasion abilities of Hela cells in each group. Western blot assay was used to detect the protein levels of RUNX3, MMP2 and MMP9 in Hela cells of each group. Dual luciferase reporter gene experiment was used to detect the targeting relationship between miR-106b-5p and RUNX3. Results The proliferation activity of Hela cells decreased with the increase of PIC treatment concentration (P<0.05). The inhibitory effect of 80 μmol/L PIC on Hela cells was nearly to half inhibitory concentration (IC50), so 80 μmol/L was selected as the PIC concentration for subsequent study. Compared with the control group, the expression levels of miR-106b-5p, MMP2 and MMP9 decreased in the PIC group, the numbers of migrating and invasive cells decreased, and the expression level of RUNX3 increased (P<0.05). Compared with the PIC+NC mimics group, the expression levels of miR-106b-5p, MMP2 and MMP9 increased in the PIC+miR-106b-5p mimics group, numbers of migrating and invasive cells increased, and the expression level of RUNX3 decreased (P<0.05). Double luciferase reporter gene assay confirmed RUNX3 as the target gene of miR-106b-5p. Compared with the NC inhibitor group, the expression level of RUNX3 increased in the miR-106b-5p inhibitor group, and the expression levels of miR-106b-5p, MMP2 and MMP9 decreased, and numbers of migrating and invasive cells decreased (P<0.05). Compared with the miR-106b-5p inhibitor+si-RNA group, the miR-106b-5p inhibitor+si-RUNX3 group showed lower RUNX3 expression level, increased miR-106b-5p, MMP2 and MMP9 expression levels, and increased numbers of migrating and invading cells (P<0.05). Conclusion PIC inhibits the miR-106b-5p expression and promotes RUNX3 expression to inhibit CC cell migration and invasion.

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    Experimental Research
    Study of ginsenoside Rg1 antagonizes sodium arsenite-induced nephrotoxicity in C57BL/6 mice
    YANG Yuan, SONG Shuang, CHEN Rong, LIU Yonglian, LIU Chunyan
    2023, 51 (8):  820-824.  doi: 10.11958/20221834
    Abstract ( 356 )   HTML ( 1 )   PDF (1200KB) ( 657 )  

    Objective To investigate the intervention effect of ginsenoside Rg1 (Rg1) against sodium arsenite (SA) induced nephrotoxicity in mice. Methods Twenty healthy male C57BL/6 mice were randomly divided into the control group (given deionized water by gavage), the SA exposure group (10.0 μg/g SA by gavage), the Rg1 intervention+SA exposure group (20.0 μg/g Rg1 was injected intraperitoneally 8 hours before SA exposure+10.0 μg/g SA gavage) and the Rg1 control group (20.0 μg/g Rg1 intraperitoneal injection). All of groups were given corresponding treatment once every other day for 14 days. HE staining was performed to observe pathological changes of renal tissue and renal tubular injury (TI) score. Serum creatinine (Scr) and renal glutathione (GSH), heme oxygenase-1 (HO-1) and malondialdehyde (MDA) were detected by enzyme-linked immunosorbent assay (ELISA). The expression levels of HO-1, phosphorylated mammalian target of rapamycin (p-mTOR), ubiquitin-binding protein P62 (SQSTM1/p62), unc-51-like kinase-1 (ULK1) and microtubule-associated protein light chain 3B (LC3-B) in renal tissue were detected by Western blot assay. LC3-B levels were detected by immunofluorescence staining. Results Compared with the control group, the TI score, Scr and expression levels of MDA, ULK1 and LC3-B in renal tissue were increased in the SA group, while expression levels of GSH and HO-1, p-mTOR and SQSTM1/p62 in renal tissue were decreased (P<0.05). The staining intensity of red spot LC3-B was enhanced and increased. Compared with the SA group, TI score, Scr and expression levels of MDA, ULK1 and LC3-B in renal tissue were decreased in the Rg1 +SA group, while expression levels of GSH, HO-1, p-mTOR and SQSTM1/p62 were increased (P<0.05). The immunofluorescence staining intensity of LC3-B was weakened and decreased. Conclusion Rg1 antagonizes SA-induced nephrotoxicity in mice, which may be associated with the activation of HO-1 signal and the inhibition of autophagy.

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    Arctigenin alleviates neuronal damage of acute cerebral infarction in rats by inhibiting the HMGB1/TLR4/NF-κB pathway
    CHEN Xilong, WANG Hongjun, SONG Zhengyu, WANG Jing
    2023, 51 (8):  825-829.  doi: 10.11958/20221432
    Abstract ( 366 )   HTML ( 5 )   PDF (1014KB) ( 676 )  

    Objective To explore whether arctigenin (AG) can reduce neuronal damage of acute cerebral infarction in rats by inhibiting the expression of high mobility group box 1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway. Methods The rat model of acute cerebral infarction was established by middle cerebral artery embolism (MCAO). Fifty model rats were randomly separated into the model group, the nimodipine group (30 mg/kg), the low AG group (25 mg/kg), the medium AG group (50 mg/kg) and the high AG group (100 mg/kg), 10 rats in each group. Another 10 rats were used as the sham operation group (only anesthesia, dissociation of blood vessel, no thrombus insertion operation). Morris water maze experiment was used to assess cognitive function in rats. The serum TNF-ɑ, IL-1β and IL-6 contents were tested by ELISA. HE staining and TUNEL staining were performed to observe the pathological changes and neuronal apoptosis of cerebral cortex, and Western blot assay was performed to measure the protein expression of HMGB1, TLR4, p-NF-κB and NF-κB. Results Compared with the sham operation group, the cognitive function was declined in the model group, serum levels of TNF-ɑ, IL-1β and IL-6 were increased, neuronal apoptosis index, cortical HMGB1 and TLR4 protein expression and p-NF-κB/NF-κB ratio were increased (P<0.05). The neuron arrangement of cerebral cortex was disordered, serious vacuolation, edema and nuclear condensation occurred. Compared with the model group, cognitive function was partially restored in the AG groups and the nimodipine group. Serum levels of TNF-ɑ, IL-1β and IL-6 decreased. Neuronal apoptosis index, cortical HMGB1, TLR4 protein expression and p-NF-κB/NF-κB ratio were decreased (P<0.05). Cortical neuron damage was reduced. (P<0.05). Conclusion AG may inhibit the HMGB1/TLR4/NF-κB pathway to reduce neuronal damage in rats with acute cerebral infarction.

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    Study of effects of metformin on osteogenic differentiation of mesenchymal stem cells and bone tissue regeneration in type I osteogenesis imperfecta mice
    WANG Juan, ZHAO Yuxia, RU Yawei, WANG Zihan, FU Ting, LI Guang
    2023, 51 (8):  830-833.  doi: 10.11958/20221341
    Abstract ( 379 )   HTML ( 3 )   PDF (927KB) ( 664 )  

    Objective To evaluate the effect of metformin on the osteogenic differentiation of adipose derived mesenchymal stem cells of type I osteogenesis imperfecta mice (oimADSCs), and the therapeutic effect of metformin on bone tissue regeneration in oim mice. Methods The oimADSCs were isolated and cultured. Cell morphology observation, alkaline phosphatase staining and oil red O staining were used to validate the multiple differentiation potential of oimADSCs.After osteogenic induction,ALP staining and ALP activity were compared between groups. qPCR was applied to analyze the expression of osteogenic differentiation associated genes. Micro-CT was used to detect the femoral microstructure and analyze effects of metformin on bone regeneration in oim mice. Results Compared with the control group, ALP staining was more deeper and the ALP activity level was obviously increased in the osteogenesis+metformin group. The transcription levels of Bglap, Col1a1, Runx2 and BMP2 were significantly up-regulated. The micro-CT results revealed that after metformin treatment, BV/TV, trabecular number and Tb.Th of oim mice were increased. Conclusion Metformin can enhance osteogenic differentiation of oimADSCs in vitro and improve bone microstructure of oim mice in vivo.

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    Effects of berberine on skin damage in rats with chronic eczema by regulating PI3K/AKT/NF-κB signaling pathway
    QIN Zongbi, XU Aiqin, CAI Xiang, QIU Baiyi, WANG Shoufan, LI Linghua, ZHU Lihong
    2023, 51 (8):  834-840.  doi: 10.11958/20221627
    Abstract ( 376 )   HTML ( 3 )   PDF (1001KB) ( 669 )  

    Objective To investigate the effect of berberine on skin damage and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor-κB (NF-κB) signaling pathway in rats with chronic eczema. Methods Sixty SD rats were divided into the control group, the chronic eczema group, the berberine (low, medium and high dose) groups and the prednisone group (n=10 for each group). Except for the control group, the other groups of rats were treated with 2,4-dinitrochlorobenzene (DNCB) on back to establish chronic eczema model. Eczema area and severity index (EASI) scores were measured in groups. Serum levels of histamine, gastrin-releasing peptide (GRP), immunoglobulin E (IgE), interleukin (IL)-4, IL-6, tumor necrosis factor α (TNF-α) and γ interferon (IFN-γ) were detected by enzyme-linked immunosorbent assay (ELISA). Histopathological changes of skin lesions were observed by hematoxylin-eosin (HE) staining. Expression levels of PI3K/AKT/NF-κB signaling pathway-related proteins in skin lesions were detected by Western blot assay. Results Compared with the control group, skin lesions were seriously damaged in the chronic eczema group. Serum levels of histamine, GRP, IgE, IL-4, IL-6 and TNF-α, and protein expression levels of IL-4, IL-6 and TNF-α and p-PI3K/PI3K, p-AKT/AKT, p-NF-κB p65/NF-κB p65 and p-NF-κB inhibitor protein α (IκBα)/IκBα ratio in skin lesions were increased, serum and skin lesion IFN-γ decreased (P<0.05). Compared with the chronic eczema group, the pathological damage of skin lesions of rats was improved in the berberine groups and the prednisone group. EASI score, serum levels of histamine, GRP, IgE, IL-4, IL-6 and TNF-α levels, and protein expression levels of IL-4, IL-6 and TNF-α and p-PI3K/PI3K, p-AKT/AKT, p-NF-κB p65/NF-κB p65, p-IκBα/ IκBα ratio in skin lesions decreased, serum and skin lesion tissue IFN-γ increased (P<0.05). Serum IgE and IL-4 in skin lesions of rats decreased in the berberine groups (medium and high dose groups) and the prednisone group (P<0.05). The effect was better in the high dose berberine group. There were no significant differences in the above indexes between the high dose berberine group and the prednisone group (P>0.05). Conclusion Berberine, especially high dose berberine, can inhibit the activation of PI3K/AKT/NF-κB signaling pathway, reduce immune imbalance and inflammatory response, and improve skin damage in rats with chronic eczema.

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    Effects of Fufang Tengli Decoction drug-containing serum on proliferation, apoptosis and epithelial-mesenchymal transition of human glioma U251 cells
    WU Haibo, LIANG Yan, SHEN Lei, FAN Zhan, FU Guohui
    2023, 51 (8):  841-846.  doi: 10.11958/20221840
    Abstract ( 496 )   HTML ( 5 )   PDF (1108KB) ( 682 )  

    Objective To explore effects of Fufang Tengli Decoction drug-containing serum on the proliferation, apoptosis and epithelial-mesenchymal transition (EMT) of human glioma U251 cells. Methods A total of 24 male SD rats were divided into the control group, the low-dose, medium-dose and high-dose Fufang Tengli Decoction groups [6, 12, 24 g/(kg·d)], 6 rats in each group. After 10 d of continuous intragastric administration, blood samples was collected to prepare drug-containing serum, and human glioma U251 cells were treated for 24 h. The cells activity was detected by Cell Counting Kit-8. The cell cloning was detected by colony formation assay. The distribution of cells cycles and apoptosis were detected by flow cytometry. The expressions of proto-oncogene C-myc and cyclin D1 (CyclinD1) genes were detected by quantitative polymerase chain reaction. The expressions of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), cysteine aspartase-3 (caspase-3), caspase-8, β-catenin, epithelial cadherin (E-cadherin) and vimentin (Vimentin) were detected by Western blot assay. Results The drug-containing serum with 10% volume fraction was selected as the final dose. Compared with the control group, cells activity, number of clone formation and expression levels of C-myc, CyclinD1 mRNA and Vimentin were decreased, while numbers of cells in S phase and expression levels of Bax/Bcl-2 and Caspase-3 were increased in the low-dose, medium-dose and high-dose Fufang Tengli Decoction groups (P<0.05). The proportion of cells in G2 phase and expression level of β-catenin were decreased, while expression levels of Caspase-8 and E-cadherin were increased in the medium-dose and high-dose Fufang Tengli Decoction groups (P<0.05). Cell apoptosis rate was increased in the high-dose Fufang Tengli Decoction group (P<0.05). Conclusion Fufang Tengli Decoction drug-containing serum can block human glioma U251 cells in S phase, inhibit cell proliferation, induce apoptosis, regulate expressions of β-catenin, E-cadherin and Vimentin, and inhibit EMT.

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    Clinical Research
    Clinical efficacy of neoadjuvant chemotherapy combined with PD-1 inhibitor in the treatment of triple negative breast cancer
    ZHANG Xiaoyu, REN Yue, LIU Wei, MIAO Yanling, ZHANG Hui, JIN Lijun, ZHANG Hengle, KANG Xiaoning, BAI Jie, WANG Zunyi
    2023, 51 (8):  847-850.  doi: 10.11958/20221554
    Abstract ( 486 )   HTML ( 3 )   PDF (1234KB) ( 694 )  

    Objective To investigate the clinical efficacy of neoadjuvant chemotherapy combined with PD-1 inhibitor in the treatment of triple negative breast cancer and its effect on immune function. Methods Eighty patients with triple negative breast cancer were randomly divided into the control group and the observation group, with 40 cases in each group. The control group received sequential chemotherapy of doxorubicin liposome + cyclophosphamide + albumin paclitaxel (AC-T), and the observation group was treated with PD-1 inhibitor on the basis of the control group. The quality of life, clinical efficacy, operation time, intraoperative blood loss, immune function and adverse reactions were compared between the two groups. Results After treatment, the SF-36 score was significantly higher in the observation group (84.55±6.09) than that of the control group (75.93±6.12, P<0.05). After 8 courses of treatment, the complete response rate (CRR), CD4+, CD8+, CD4+/CD8+, immunoglobulin IgG, IgA and IgM levels were significantly better in the observation group than those in the control group (P<0.05). The operative time [(43.25±6.85) min vs. (82.53±8.53) min] and intraoperative bleeding [(136.52±8.74) mL vs. (241.63±8.32) mL] were significantly decreased in the observation group than those of the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion Neoadjuvant chemotherapy combined with PD-1 inhibitor in the treatment of triple negative breast cancer can improve the immune function and quality of life of patients, and ensure the safety of clinical treatment.

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    Correlation analysis between viral load and T lymphocyte subsets in HIV/AIDS patients co-infected with syphilis infection in Guizhou province
    QIN Dawen, YANG Xiucheng, HONG Zhangping, XIONG Qianyu, MENG Nan, HU Yong, YANG Xinglin
    2023, 51 (8):  851-854.  doi: 10.11958/20221797
    Abstract ( 335 )   HTML ( 2 )   PDF (773KB) ( 677 )  

    Objective To analyze the correlation between HIV-RNA load and T lymphocyte subsets in HIV/AIDS patients co-infected with syphilis in Guizhou province in recent three years. Methods A total of 2 869 newly diagnosed HIV/AIDS patients who did not receive antiretroviral therapy (ART) were selected in the public health rescue center of Guiyang from January 1, 2019 to December 31, 2021. According to results of syphilis testing, patients were divided into the simple HIV infection group (n= 2 289), the current HIV/syphilis infection group (n=333) and the previous HIV/syphilis infection group (n=247). The general demography data and the baseline data of laboratory test indicators were compared between the three groups of patients. The correlation between the HIV-RNA load and T lymphocyte subsets in different groups of HIV was analyzed. Results The age of the HIV/syphilis current infection group was lower than that of the HIV/syphilis simple infection group and the HIV/syphilis past infection group, and the proportion of males was higher than that of the HIV simple infection group and the HIV/syphilis past infection group (P<0.05). The HIV-RNA load was lower in the HIV/syphilis current infected group than that in the HIV-only infected group. CD4+ T cells, CD8+ T cells, and CD3+ T cells were higher in the HIV/syphilis current infected group than those of the HIV simple infection group (P<0.05). The HIV-RNA load was higher in the HIV/syphilis previous infection group than that in the HIV/syphilis current infection group, and CD4+ T cells, CD8+ T cells and CD3+ T cells were lower than those in the HIV/syphilis current infection group (P<0.05). There was no significant difference in the CD4/CD8 ratio between different HIV groups (P>0.05). The HIV-RNA load of grade Ⅰ, Ⅱ and Ⅲ decreased sequentially in the simple HIV infection group and the previous HIV/syphilis infection group (P<0.05). The HIV-RNA load of grade Ⅱ and Ⅲ in the HIV/syphilis current infection group was lower than that of grade Ⅰ (P<0.05). There was a negative correlation between HIV-RNA load and T lymphocyte subsets in the three groups of patients (P<0.01). Conclusion Changes in T lymphocyte subsets occur after HIV/syphilis co-infection. With changes in HIV-RNA load, there are also differences in the T lymphocyte subsets of HIV/syphilis co-infection.

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    Curative effect of CRRT combined with plasma exchange in the treatment of hyperlipidemic severe acute pancreatitis
    CHENG Jiongjiong, LI Linlin, ZHAO Haodong, HU Zhixu, CHEN Weidong, WANG Xingyu
    2023, 51 (8):  855-859.  doi: 10.11958/20221994
    Abstract ( 460 )   HTML ( 3 )   PDF (747KB) ( 683 )  

    Objective To analyze the curative effect of continuous renal replacement therapy (CRRT) combined with plasma exchange (PE) in patients with severe acute pancreatitis of hyperlipidemia. Methods According to different treatment methods, 109 patients with severe acute pancreatitis of hyperlipidemia were divided into the CRRT group (51 cases) and the combination group (CRRT combined with PE, 58 cases). The curative effect, disappearance time of symptoms and complications were compared between the two groups. The decline degree of triglyceride (TG) was calculated in the combination group after 72 h treatment. According to the decline degree of TG (60% as the limit), patients were divided into the high efficiency group (>60%, 37 cases) and the low efficiency group (≤60%, 21 cases). The influencing factors on the curative effect of CRRT combined with PE were analyzed by multivariate linear regression model. Results After 72 h of treatment, levels of total cholesterol (TC), TG, amylase (AMY), C-reactive protein (CRP) and procalcitonin (PCT) were lower in the combination group than those of the CRRT group (P < 0.05). The disappearance time of symptoms (abdominal pain, fever, nausea and vomiting), mechanical ventilation time and stay time in ICU were shorter in the combination group than those of the CRRT group (P < 0.05). Before treatment, levels of TC and TG were higher in the high efficiency group than those of the low efficiency group, while interval from onset to PE was shorter than that in the low efficiency group (P < 0.05). The results of multivariate linear regression analysis showed that the regression equation:TG decline =33.591+1.010×(TC before treatment)+2.088×(TG before treatment)-0.443×(interval from onset to PE). Conclusion CRRT combined with PE can effectively relieve symptoms, which is conducive to disease outcomes. The curative effect is related to TC and TG levels before treatment and the interval from onset to PE.

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    Early diagnostic value of serum miR-134-5p and miR-320a combined with pulmonary function index in coal worker pneumoconiosis patients
    XIONG Gaocai, YANG Yuanfeng, LI Jiasong, LIU Tingqian, HE Bingbing, LIU Zhuoling
    2023, 51 (8):  860-863.  doi: 10.11958/20221645
    Abstract ( 319 )   HTML ( 3 )   PDF (809KB) ( 661 )  

    Objective To explore the value of serum miR-134-5p and miR-320a combined with pulmonary function indexes in the early clinical diagnosis of pneumoconiosis. Methods Forty cases of coal workers' pneumoconiosis (CWP), 40 cases of coal mine dust exposed physical examination population and 40 cases of healthy physical examination population in the same period were included in this study. Expression levels of serum miR-134-5p and miR-320a were detected by qRT-PCR assay. Lung function indexes were detected in three groups, including maximum ventilation volume (MVV), forced vital capacity (FVC), forced expiratory volume 1 (FEV1), forced expiratory volume 3 (FEV3), FEV1/FVC, FEV3/FVC, maximum mid-expiratory flow (MMEF), peak expiratory flow (PEF), 75 % maximal expiratory flow (MEF75), 50% maximal expiratory flow (MEF50), 25% maximal expiratory flow (MEF25), residual volume (RV), RV/total lung capacity (TLC), functional residual capacity (FRC) and alveolar ventilation (VA). Logistic regression was used to analyze risk factors of CWP in coal mine dust-related operations. Receiver operating characteristic (ROC) curve was used to analyze the early diagnostic value of miRNA combined with pulmonary function index in patients with CWP. Results The expression levels of serum miR-134-5p, miR-320a, MVV, FEV1, FEV1/FVC, MMEF, MEF50, FRC and VA were decreased gradually in the control group, the dust exposure group and the CWP group (P<0.05). Multiple Logistic regression analysis showed that the decrease of FRC was an independent risk factor for CWP in coal mine dust exposure population (P<0.05). miR-134-5p and miR-320a combined with lung function index FRC showed high diagnostic efficacy in predicting CWP disease in coal mine dust-related operations, with an AUC of 0.975 (95%CI: 0.948-1.000). Conclusion The combination of serum miR-134-5p, miR-320a and lung function index FRC has important reference value for the clinical diagnosis in patients with early CWP.

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    Analysis of the drug efficacy and safety before ICSI from different sources of sperm in patients with obstructive azoospermia
    CHEN Qigui, LI Dawen, CHENG Junping, HUANG Taishuai
    2023, 51 (8):  864-868.  doi: 10.11958/20221780
    Abstract ( 380 )   HTML ( 1 )   PDF (747KB) ( 654 )  

    Objective To investigate the efficacy, safety and the influence on pregnancy outcome of L-carnitine before intracytoplasmic sperm injection (ICSI) from different sources of sperm in patients with obstructive azoospermia (OA). Methods A total of 141 patients with OA were treated with L-carnitine for three months, and sperms were obtained by testicular sperm aspiration (TESA) and percutaneous epididymal sperm aspiration (PESA) respectively. According to the source of sperm, they were divided into the two groups: the TESA group (n=78) and the PESA group (n=63). The general clinical data, sperm quality, embryonic development and clinical outcome of the two groups were compared. Results In the TESA/PESA group, sperm DFI and sperm spontaneous acrosome reaction rate were significantly lower than those before treatment, and sperm acrosome integrity rate was significantly higher than that before treatment (P<0.05). There were no significant differences in sperm DFI, sperm acrosome integrity rate and sperm spontaneous acrosome reaction rate between the two groups(P>0.05). There were no significant differences in the fertilization rate, 2PN fertilization rate, cleavage rate, excellent embryo rate, implantation rate, clinical pregnancy rate, live birth rate, premature birth rate, abortion rate and neonatal malformation rate between the two groups (P>0.05). A total of 103 fresh transplant cycles, 989 MII oocytes, 773 zygotes, 49 clinical pregnancies and 39 live births were obtained (including 17 in the TESA group and 22 in the PESA group). During a 3-month follow-up after birth, it was found that one newborn had cardiac abnormalities in the TESA group, while the other newborns had no abnormalities. Conclusion In OA patients, L-carnitine before TESA-ICSI and PESA-ICSI can improve the sperm quality, optimize clinical outcome, and the medication is safe.

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    Correlation between macular retinal thickness and urinary protein in adult patients with nephrotic syndrome
    GUO Yufeng, LIU Yumei, BI Xiuzeng, GUO Junlin, SUN Li, WANG Weixiu, YANG Dingwei
    2023, 51 (8):  869-872.  doi: 10.11958/20221421
    Abstract ( 295 )   HTML ( 2 )   PDF (991KB) ( 663 )  

    Objective To investigate the correlation between retinal thickness in macular area and urinary protein in adult patients with nephrotic syndrome. Methods A total of 112 inpatients admitted to the internal medicine department were selected and divided into the normal urine protein group (28 cases, 56 eyes), the mildly abnormal urine protein group (30 cases, 58 eyes), the moderately abnormal urine protein group (27 cases, 51 eyes) and the nephrotic syndrome group (27 cases, 53 eyes) according to results of urine protein detection. Optical coherence tomography (OCT) was used to measure the average retinal thickness of the nine divisions in the macula regions, including the central region (Center), temporal side of the inner ring (InT), superior the inner ring (InS), nasal side of the inner ring (InN), inferior the inner ring (InI), temporal side of the outer ring (OutT), superior the outer ring (OutS), inferior the outer ring (OutI) and nasal side of the outer ring (OutN). The correlation ratio E2 was used to analyze the correlation between the mean retinal thickness of different macular regions and the grading of urinary protein in each group. Results The mean retinal thickness of Center, InT, InN and InI in the macular area was higher in the mildly abnormal urine protein group than that in the normal urine protein group. The mean retinal thickness of Center, InT, InS, InN, InI and OutN in the macular area was lower in the moderately abnormal urine protein group than that in the mildly abnormal urine protein group, and the mean retinal thickness of InT, InS, InN and InI in the macular area was higher in the nephrotic syndrome group than that in the moderately abnormal urinary protein group (All P<0.05). The mean retinal thickness of InT, InS, InN and InI in macular area was moderately correlated with the severity of urinary protein group (0.06≤E2<0.16), while the mean retinal thickness of Center and OutN in macular area was weakly correlated with the severity of urinary protein group (E2<0.06). Conclusion The mean retinal thickness of InT, InS, InN and InI in macular area may be biomarkers of early lesions of adult nephrotic syndrome.

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    Clinical characteristics of COVID-19 complicated with pulmonary thromboembolism
    GU Songtao, JIA Wei, LI Yuechuan, ZHANG Dongrui, ZHANG Yating, GAO Shulian, LI Na
    2023, 51 (8):  873-877.  doi: 10.11958/20230161
    Abstract ( 430 )   HTML ( 2 )   PDF (1093KB) ( 656 )  

    Objective To study the clinical features of novel coronavirus pneumonia (COVID-19) complicated with pulmonary thromboembolism. Methods A total of 27 patients with COVID-19 complicated with pulmonary thromboembolism were collected from December 2022 to January 2023 in the department of respiratory and critical care medicine, Tianjin Chest Hospital. The clinical features and prognosis of patients were summarized based on clinical information, laboratory tests, electrocardiogram, echocardiography, CT images, diagnosis and treatment. Results Among the 27 patients, 12 were males and 15 were females. The mean age was (71.78±9.21) years, ranged in age from 64 to 93 years old. There were 7 cases of coronary heart disease, 7 cases of malignant tumor, 4 cases of chronic obstructive pulmonary disease, 2 cases of pulmonary tuberculosis and 1 case of pulmonary interstitial fibrosis. The main clinical manifestations were shortness of breath, cough, fever and pleural effusion. The electrocardiogram of most patients showed that T-wave of chest lead was inverted (12/27). Ultrasonography revealed deep venous thrombosis of lower extremity (13/27). The main CT findings were multiple ground-glass opacity (21/27), consolidation (17/27), segmental pulmonary embolism (23/27) and subsegmental pulmonary embolism (10/27). There were 11 patients accompanied by right ventricular dysfunction (RVD) and 2 died within 30 days after admission. All of them were elderly patients. Conclusion When patients with malignant tumors and chronic cardiopulmonary diseases have unexplained dyspnea and other manifestations, the possibility of COVID-19 combined with pulmonary thromboembolism should be considered. The imaging findings are mostly segmental and subsegmental pulmonary embolism with ground-glass opacity of both lungs. The prognosis of elderly patients with right ventricular dysfunction is not good.

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    The difference between simple membranous nephropathy and simple membranous nephropathy combined with unknown monoclonal immunoglobulinemia
    GAO Ge, ZHANG Xinyue, DONG Yijun, CHENG Genyang
    2023, 51 (8):  878-882.  doi: 10.11958/20221789
    Abstract ( 378 )   HTML ( 1 )   PDF (794KB) ( 679 )  

    Objective To explore the difference in clinical pathological characteristics and short-term prognosis between patients with simple membranous nephropathy (MN) and patients with MN complicated with monoclonal gammopathy of undetermined significance (MGUS). Methods Forty-one patients diagnosed with MN combined with MGUS (the MN combined with MGUS group) and 81 patients with simple MN (the simple MN group) diagnosed by renal biopsy were selected in this study. General data and laboratory indicators were collected in the two groups, including white blood cell count (WBC), hemoglobin (Hb), platelet (PLT), urea nitrogen (BUN), serum creatinine (Scr), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and glomerular filtration rate (eGFR). Indirect immunofluorescence assay was used to detect serum anti-M-type phospholipase A2 receptor (PLA2R) antibody. M protein typing in patients with MN and MGUS was determined by immunofixation electrophoresis. The difference of pathological data was compared between the two groups. The treatment effect and adverse reactions of patients were followed up. Results Compared with the simple MN group, Hb, PLT, eGFR anti-PLA2R antibody were lower in the MN combined with MGUS group, while expression levels of BUN, Scr, CRP and ESR were higher (P<0.05). Most monoclonal immunoglobulins in patients with MN complicated with MGUS were IgG type [41.5% (17/41)]. There was no significant difference in pathological data between the two groups (P>0.05). Thirty-five patients in the MN combined with MGUS group and 74 patients in the simple MN group were followed up respectively. The remission rate after treatment in the MN combined with MGUS group was lower than that in the simple MN group [62.9% (22/35) vs. 78.4% (58/74), χ2=3.884, P<0.05]. The Kaplan-Meier curve showed that the cumulative complete remission rate of the MN combined with MGUS group was lower than that of the simple MN group (Log-rank χ2=8.943, P<0.01). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion Compared with simple MN patients, patients with MN and MGUS have worse baseline renal function and a lower post-treatment renal response rates.

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    Applied Research
    Study of rhenium sulfide nanoparticles in spectral CT imaging and photothermal therapy
    WANG Xiaoyi, WANG Xinyu, ZHANG Xuening, LI Jing
    2023, 51 (8):  883-887.  doi: 10.11958/20230209
    Abstract ( 363 )   HTML ( 2 )   PDF (1147KB) ( 658 )  

    Objective To investigate the spectral CT imaging performance of Rhenium sulfide (ReS2) nanoparticles and their effect on photothermal therapy in breast cancer cells. Methods ReS2 nanoparticles were synthesized by one-pot method at room temperature. The basic materialistic properties of ReS2 nanoparticles were characterized by X-ray photoelectron spectroscopy, high-resolution transmission electron microscopy and UV absorption spectroscopy. The spectral CT imaging capability of ReS2 nanoparticles with the same molar concentration of iodine at different energies (60-140 keV) was compared. The photothermal conversion ability of nanoparticles was evaluated by measuring the in vitro photothermal warming of aqueous solutions of ReS2 nanoparticles with different mass concentrations (0、20、40、80 and 100 mg/L). Mouse breast cancer cells 4T1 were co-incubated with different mass concentrations of ReS2 nanoparticle aqueous solution (0, 20, 40, 80 and 100 mg/L). The cytotoxicity of nanoparticles was evaluated by MTT experiment and cell photothermal killing experiment. The photothermal cell killing effect of ReS2 nanoparticles was visually observed and analyzed by cytofluorescent staining. Results High-resolution transmission electron microscopy observed that the particle size of the prepared nanoparticles was less than 10 nm. The UV absorption spectrum confirmed the strong absorption of ReS2 at 808 nm. When the energy was in the range of 60-140 keV, the CT imaging effect of ReS2 nanoparticles at equivalent molar concentration was significantly better than that of iohexol solution. The temperature of 500 mg/L ReS2 solution could be increased by 44.90 °C ± 1.2 °C under 808 nm laser irradiation with a power density of 3 W/cm2, while the temperature of pure water was only increased by 9.27 °C ± 0.74 °C under the same conditions. Cellular experiments showed that in the absence of laser irradiation, the survival rate of 4T1 cells treated with ReS2 nanoparticles at concentrations of 40-100 mg/L were all greater than 85%. The cell survival rate was also reduced at ReS2 nanoparticle concentrations of 40-100 mg/L compared to the 0-40 mg/L case under laser irradiation, but the survival rate was already less than 30%. Conclusion ReS2 nanoparticles are simple to prepare, have good biocompatibility and photothermal therapeutic properties, and have strong killing effect on breast cancer cells under NIR laser irradiation, which have good clinical translation potential.

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    Review
    Research progress of myocardial strain detection technique in myocardial injury of non-alcoholic fatty liver disease
    MA Yunting, ZHENG Yue, WANG Lujing, SHA Lihui, ZHAO Xinxiang
    2023, 51 (8):  888-891.  doi: 10.11958/20221772
    Abstract ( 402 )   HTML ( 2 )   PDF (779KB) ( 651 )  

    Non-alcoholic fatty liver disease (NAFLD) can lead to myocardial damage and is a risk factor for cardiac insufficiency. Myocardial strain (MS) detection is a new technique that has been rapidly developed in recent years and has become a common tool for quantifying myocardial deformation and diagnosing and predicting subclinical myocardial injury. MS can not only accurately assess local and global myocardial injury, but also detect changes of cardiac function in NAFLD patients with normal ejection fraction. Understanding myocardial injury caused by NAFLD, timely detection, diagnosis and prediction of cardiac dysfunction in patients with NAFLD by MS detection technique are of great clinical significance in preventing the progression of irreversible heart failure. This article reviews the pathophysiological mechanisms of myocardial injury caused by NAFLD, MS detection techniques and the use of MS detection techniques in atria and ventricle in patients with NAFLD.

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    Research progress on the role of potassium channels and drug intervention in hypoxic pulmonary hypertension
    ZHANG Zhaoxia, NAN Xingmei, LI Zhanqiang, LU Dianxiang
    2023, 51 (8):  892-896.  doi: 10.11958/20221822
    Abstract ( 405 )   HTML ( 7 )   PDF (758KB) ( 664 )  

    Potassium ion (K+) channel is a transmembrane protein located on cell membrane. The K+ channels of vascular smooth muscle cells play an important role in regulating vascular tension, cell excitability and proliferation through membrane potential. The dysfunction of K+ channels in pulmonary artery smooth muscle cells (PASMCs) is closely related to the pathological process of hypoxic pulmonary hypertension (HPH), and K+ channels are expected to become the therapeutic target of HPH. In this artical, types of K+ channels in PASMCs, the research progress of K+ channels in HPH and drugs that interfere with HPH were reviewed, in order to provide new ideas for the pathogenesis research and drug development of HPH.

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