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Table of Content

    05 September 2022, Volume 42 Issue 9
    Original Articles
    C5a/C5aR1 mediates the IMQ-induced psoriatic skin inflammation via promoting IL-17A expression by γδ T cells in mice
    ZHENG Quan-you, LIANG Shen-ju,SHU Yong, ZHOU Shan, ZHONG Yu, SHENG Fen, TANG Ming-jun
    2022, 42(9):  1325-1332.  doi:10.16352/j.issn.1001-6325.2022.09.1325
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    Objective To explore the effects and underlying mechanism of C5a/C5aR1 pathway in mediating imiquimod (IMQ)-induced psoriatic skin inflammation by increasing IL-17A expression in γδ T cells. Methods C5aR1+/+ and C5aR1-/- mice were treated with IMQ or control Vasline cream for 6 consecutive days. The psoriatic skin inflammation was monitored. Inflammatory cells infiltration (T cells and neutrophils) and cytokines expression (IL-17A and TNF-α) were tested by immunohistochemistry (IHC). The percentages and cellular sources of IL-17A in both draining lymph nodes and skin lesions were analyzed by flow cytometry (FCM). Before IMQ application,C5aR1a peptide was injected into C5aR1+/+ mice and the psoriatic skin lesions as well as IL-17A expression were examined. Additionally, the isolated spleen lymphocytes were stimulated with C5a, IL23 or C5aR1a and then tested with FCM for the expression of IL-17A in γδ T cells. Results It was shown that C5aR1 deficiency clearly ameliorated IMQ induced psoriatic skin inflammation and was coupled with decreased keratinocytes proliferation, attenuated CD3 positive T cells and neutrophils, alleviated cytokines expression (IL-17A and TNF-α). FCM results indicated that C5aR1 loss significantly decreased the percentages of IL-17A positive cells in both draining lymph nodes and skin lesions, and γδ CD3+ TCR+ T cell was proved to be the major source of IL-17A. In consistent with that, blocking C5a/C5aR1 pathway with C5aR1a peptide remarkably alleviated IMQ induced skin lesions and IL-17A responses. Moreover, blocking C5a/C5aR1 with C5aR1a significantly down-regulated IL-17A expression in γδ T cells in vitro. Conclusions This study indicates that C5a/C5aR1 signaling plays an essential role in the pathogenesis of psoriatic lesions by enhancing IL-17A expression by γδ T cells. Blocking C5a/C5aR1 pathway is a promise strategy in the treatment of psoriasis patients.
    HMGB1 attenuates the mitigative effect to myocardial ischemia-reperfusion injury by tanshinone ⅡA in rats
    ZHONG Jin-peng, YANG Li, WANG Hui-bo,CHEN Hong-jian, LI Jin-wei, WEN Ming-hong, LYU Yun-bo
    2022, 42(9):  1333-1338.  doi:10.16352/j.issn.1001-6325.2022.09.1333
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    Objective To study the influence of exogenous high-mobility group box 1(HMGB1) on the mitigative effect of tanshinone ⅡA (TSA) to myocardial ischemia-reperfusion (I/R) injury. Methods Rats were divided into sham, I/R (ligation of left anterior descending coronary artery), TSA (I/R + TSA intravenous injection) and TSA+HMGB1 (I/R+TSA intravenous injection + recombination HMGB1 intraperitoneal injection) groups. Serum CK-MB was measured by ELISA. Myocardial infarct area was measured by TCC. The expression of inflammatory indicators were measured by RT-qPCR and Western blot. Results Compared with sham group, CK-MB, myocardial infarct area, transcription level of IL-6, IL-1β and TNF-α, expression of HMGB1, NLRP3 and caspase-1 all increased in I/R group(P<0.05). Compared with I/R group, CK-MB, myocardial infarct area, transcription levels of IL-6, IL-1β and TNF-α, expressions of HMGB1, NLRP3, caspase-1 and NF-κB decreased in TSA group (P<0.05). However, compared with TSA group, CK-MB, myocardial infarct area, transcription levels of IL-6, IL-1β and TNF-α, expressions of HMGB1, NLRP3, caspase-1 and NF-κB increased in TSA+HMGB1 group(P<0.05). Conclusions Exogenous HMGB1 attenuates the mitigative effect of tanshinone ⅡA to rat myocardial I/R injury through up-regulation the expressions of inflammatory factors.
    Establishment and identification of a medulloblastoma transplantable tumor strain PUMC-MBT1
    WANG Shi-zun, ZHANG Dan, GE Ming, FENG Hai-liang, LIU Yu-qin
    2022, 42(9):  1339-1343.  doi:10.16352/j.issn.1001-6325.2022.09.1339
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    Objective To establish a transplantable tumor strain of medulloblastoma in vivo from cell-line-derived xenograft (CDX) and to analyze the growth and pathological characteristics of the transplanted tumor model. Methods A previously established medulloblastoma cell line(PUMC-MB1) was utilized to construct CDX. The cultured cell suspension was injected into the right axilla of SCID mice subcutaneously with dosage as 5×106 cells/mouse. The mice were sacrificed when the diameter of CDX reached around 1.5 cm. The xenografts were harvested and transplanted to other mice with the same number of cells. The process was repeated 10 times. The growth characteristics of transplanted medulloblastoma and survival curve of tumor-bearing mice at passage 10 were observed. The pathological characteristics of transplanted tumor were analyzed. Results The transplantable strain of medullo- blastoma with stable in vivo properties was named PUMC-MBT1. The successful rate of tumor transplantation was 100% at passage 10. The subcutaneous mass could be palpated 14 days after injection. The diameters of subcutaneous xenograft could reach about 1.5 cm 29 days after injection. Tumor-bearing mice died 50 days after injection. HE sections demonstrated that the transplanted PUMC-MBT1 belonged to classic medulloblastoma and the positive rate of Ki-67, Syn and NeuN were 80%-90%, 40%-50% and 20%-30% respectively. Conclusions A successful animal model of medulloblastoma is established with easy manipulation, characteristic features of classic medulloblastoma, so it is a potential technology for in vivo research.
    Up-regulation of miR-140 enhances the sensitivity of human CML cell strain KBM5R to imatinib
    ZHENG Yan, LI Lan, GAO Qiu-ying, NIU Ben, ZHANG Wei-hua
    2022, 42(9):  1344-1349.  doi:10.16352/j.issn.1001-6325.2022.09.1344
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    Objective To evaluate the effect of miR-140 on the sensitivity of imatinib(IM)-resistant chronic myeloid leukemia (CML) cell strain KBM5R to IM and potential underlying mechanism. Methods The expression level of miR-140 and Bcl-2 in CML cells KBM5 and IM resistant CML cells KBM5R were detected by RT-qPCR and Western blot, respectively. KBM5R cells were transfected with miR-NC or miR-140 mimic, and then incubated with 25-100 nmol/L IM for 24 h. Cell viability was examined by CCK-8 assay. KBM5R cells transfected with miR-NC or miR-140 mimic were examined with 100 nmol/L IM for 24 h then cell apoptosis was detected by flow cytometry; Mitochondrial membrane potential was detected by JC-1 staining, and cleaved caspase-3 expression was detected by Western blot.The targeting relation between miR-140 and Bcl-2 was verified by bioinformatics and fluorescence activity analysis. Results Compared with KBM5 cells, the expression of miR-140 in KBM5R cells was significantly decreased (P<0.01) and the expression of Bcl-2 was significantly increased(P<0.001). In the presence of IM, compared with the miR-NC group, the cell viability in miR-140 mimic group was significantly decreased (P<0.01 or P<0.001); Cell apoptosis was significantly increased(P<0.001); Mitochondrial membrane potential was significantly decreased (P<0.001), and cleaved caspase-3 expression was significantly increased(P<0.001). Bcl-2 was a target of miR-140. Conclusions miR-140 may increase the sensitivity of KBM5R cells to IM by inhibiting the target gene Bcl-2.
    Circ_0032821 is involved in sorafenib's inhibition of the proliferation, migration and invasion of breast cancer cell line T47D
    ZHANG Xiao-lei, LIU Jing, LI Chao-ping
    2022, 42(9):  1350-1354.  doi:10.16352/j.issn.1001-6325.2022.09.1350
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    Objective To investigate the effect and possible mechanism of sorafenib on the proliferation, migration and invasion of breast cancer cell line T47D. Methods Effects of sorafenib (2.5, 5 and 10 μmol/L) on T47D cells proliferation, colony formation, migration and invasion were detected by CCK-8 experiment, plate cloning experiment, scratch healing experiment and Transwell experiment. RT-qPCR was applied to detect circ_0032821 expression. The circ_0032821 small interfering RNA(si-circ_0032821) and circ_0032821 over-expression plasmid were transfected into T47D cells respectively. And the effect of interference with circ_0032821 or circ_0032821 over-expression combined with sorafenib on the malignant behavior of T47D cells was detected. Results The cell proliferation inhibition rate T47D cells were significantly increased after sorafenib treatment (P<0.05); The colony formation number, scratch healing rate, invasion number, and circ_0032821 expression were significantly decreased(P<0.05).After silencing with the expression of circ_0032821, the proliferation inhibition rate of T47D cells was significantly increased (P<0.05); The colony formation number, scratch healing rate and invasion number were significantly reduced(P<0.05). Circ_0032821 over-expression significantly reduced the effects of sorafenib on the proliferation, migration colony formation and invasion of T47D cells (P<0.05). Conclusions Sorafenib can inhibit T47D cell proliferation, migration and invasion. And the mechanism may be explained by the down-regulation of circ_0032821.
    Up-expression of FABP4 promotes the proliferation and migration of endometrial cancer cell line HEC-1-A
    HE Jing, LI Yan, WANG Yan-feng, BAO Hui
    2022, 42(9):  1356-1361.  doi:10.16352/j.issn.1001-6325.2022.09.1356
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    Objective To investigate the expression of fatty acid binding protein 4 (FABP4) in endometrial cancer and its effects on the proliferation, migration and invasion of endometrial cancer cells line HEC-1-A. Methods The expression level of FABP4 mRNA in endometrial cancer tissues and adjacent normal tissues was detected with RT-qPCR. The correlation between FABP4 mRNA expression and pathological changes of endometrial cancer was analyzed. HEC-1-A cells were cultured in vitro and were randomly divided into control group, FABP4 negative control (si-NC) group and interference FABP4 (si-FABP4) group. RT-qPCR, MTT and Transwell assays were used respectively to detect the FABP4 mRNA expression in HEC-1-A cells, the proliferation, migration and invasion of HEC-1-A cells. Western blot was used to detect the protein expression of FABP4, matrix metalloproteinase (MMP)-2 and MMP-9 of HEC-1-A cells in each group. Results The expression level of FABP4 mRNA in endometrial cancer tissues was significantly higher than that in tissues adjacent to cancer (P<0.05); The FABP4 mRNA expression was related to tumor TNM staging and lymph node metastasis (P<0.05).Interference with FABP4 expression could significantly inhibit the proliferation, migration and invasion of endometrial cancer cells. Conclusions Expression of FABP4 is up-regulated in endometrial cancer and interference with FABP4 expression can inhibit the proliferation, migration and invasion of endometrial cancer cells.
    Tripterygium wilfordii glycosides reduce inflammation response in Sjgren's syndrome of mouse models
    LIU Jia-yan, MEI Rong, YANG Li-feng, ZHAO Wen-bin, HAN Cheng-long, ZHOU Hui, LI Er-long
    2022, 42(9):  1362-1366.  doi:10.16352/j.issn.1001-6325.2022.09.1362
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    Objective To investigate the effect of Tripterygium wilfordii polyglycosides(TWPS) on inflammatory response found in mouse models with Sjgren's syndrome(SS). Methods Mice were randomly divided into control group, Sjgren's syndrome model group, hydroxychloroquine sulfate treatment group (20 mg/kg hydroxychloroquine sulfate intragastric administration), TWPS low-dose, medium-dose and high-dose groups (10, 20, 30 mg/kg TWPS), TWPS + Wortmanin (PI3K/Akt/eNOS signaling pathway inhibitor) group (30 mg/kg TWPS and 0.6 mg/kg Wortmannin viajugular vein).Saliva flow rate, water intake, whole blood viscosity and plasma viscosity were recorded. Serum IL-6, IL-17, IgG and eNOS were detected by ELISA. Western blot was used to detect PI3K/Akt/eNOS pathway related proteins. Results Compared with control group, the saliva flow rate of the model group decreased and the quantity of drinking water increased(P<0.05). Compared with model group, saliva flow rate increased and water consumption decreased in low, medium and high dose TWPS groups, which alleviated the change of model group(P<0.05). Compared with the low, medium and high dose TWPS +Wortmanin groups, saliva flow rate decreased and water intake increased (P<0.05). The whole blood and plasma viscosity of model group increased compared with control group(P<0.05). The whole blood and plasma viscosity of TWPS low-dose, medium-dose and high-dose groups were lower than that of model group(P<0.05). The whole blood and plasma viscosity of TWPS+Wortmanin group was higher than that of low, medium and high dose TWPS groups(P<0.05). Compared with the control group, the levels of serum IL-6, IL-17 and IgG in model group were increased, while the level of eNOS was decreased(P<0.05). The serum levels of IL-6, IL-17 and IgG in TWPS low-dose, medium-dose and high-dose groups were lower than those in model group, while the levels of eNOS were higher than those in model group(P<0.05). The serum level of IL-6, IL-17 and IgG in TWPS +Wortmanin group increased as compared to those in low, medium and high dose TWPS +Wortmanin group, while the level of eNOS decreased as compared to those in low, medium and high dose TWPS +Wortmanin group(P<0.05). The level of p-PI3K/PI3K, p-Akt/Akt and p-ENOS /eNOS in model group was lower than those in control group(P<0.05). Compared with model group, p-PI3K/PI3K, p-Akt/Akt and p-ENOS/eNOS levels of TWPS in low, medium and high dose groups all increased(P<0.05); The level of p-PI3K/PI3K, p-Akt/Akt and p-ENOS /eNOS in TWPS +Wortmanin group was lower than those in low, medium and high dose TWPS groups(P<0.05). Conclusions TWPS alleviates inflammatory response and improves symptoms of mouse models with Sjgren's syndrome.
    Tamoxifen inhibits TGF-β/Smad pathway and reduces pathological proliferation of human dermal fibroblasts
    SHI Chun-tian, MAO Shu-ran, PENG Yi-xuan, XIAO Zhi-bo
    2022, 42(9):  1367-1373.  doi:10.16352/j.issn.1001-6325.2022.09.1367
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    Objective To explore the function and mechanism of tamoxifen, an estrogen receptor modulator, in the pathogenesis of hyperplatic scar. Methods Primary human fibroblasts were isolated and cultured for 4 generations and then aliquated into 3 groups: control group, TGF-β1 group and TGF-β1+ tamoxifen group. The effects of tamoxifen on human fibrogenic factor production, cell proliferation, migration and differentiation of TGF-β1-induced skin fibroblasts were detected by real-time quantitative polymerase chain reaction (RT-qPCR), MTS, cell scratch test, Western blot and immunofluorescence assay. Results Tamoxifen (10 μmol/L) inhibited the production of collagen 1, collagen 3 and α-SMA induced by TGF-β1 in fibroblasts. MTS results showed that the proliferation activity of TGF-β1 group was higher than that of tamoxifen group (P<0.05). Wound healing test verified that the migration ability of cells was reduced by tamoxifen intervention. Tamoxifen inhibited collagen secretion and differentiation of skin fibroblasts into muscle fibroblasts. Conclusions The estrogen receptor modulator tamoxifen inhibits pathological proliferation of fibroblasts, so it may be a potential novel strategy for the treatment of hyperplastic scar.
    LncRNA PVT1 alleviates inflammation of airway via regulating miR-214/STAT6 axis in mouse models with asthma
    HUANG Hua, ZHOU Long, YAO Di, XU Yi
    2022, 42(9):  1374-1380.  doi:10.16352/j.issn.1001-6325.2022.09.1374
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    Objective To explore the effect of inhibiting the expression of lncRNA PVT1 on airway inflammation response and the effect on the miR-214/STAT6 axis in mice with bronchial asthma. Methods Mice were randomly divided into control group, model group [asthma induced by ovalbumin(OVA)], lncRNA PVT1 inhibitor group and lncRNA PVT1 NC group with 12 mice in each.Hemocytometer was used to count the total number of inflammatory cells, numbers of macrophages, neutrophils and lymphocytes in broncho-alveolar lavage fluid (BALF). ELISA kit was used to detect the concentration of interleukin-4(IL-4), interleukin-5 (IL-5) and interleukin-13 (IL-13) in the BALF supernatant. The kit was used to detect the level of IgE in serum. HE staining was used to observe and score the infiltration of inflammatory cells in lung tissue. RT-qPCR was used to detect the levels of miR-214 and STAT6 mRNA in lung tissue. Western blot was used to detect the expression of STAT6 and p-STAT6 proteins in lung tissue. The dual luciferase reporter gene detection was used to analyze the targeting relationship between lncRNA PVT1 and miR-214. Results Compared with the control group, the cell counting of inflammatory cells, macrophages, neutrophils and lymphocytes, level of IL-4, IL-5, IL-13 in BALF, serum IgE,inflammatory cell infiltration, STAT6 mRNA and protein phosphorylation in lung tissues of mice in the model group were all significantly increased (P<0.05).While the miR-214 level in lung tissue was significantly reduced (P<0.05). Compared with the model group and the lncRNA PVT1 NC group, the total number of inflammatory cells, macrophages, neutrophils and lymphocytes, IL-4, IL-5, IL-13 levels in BALF, and serum IgE ,inflammatory cell infiltration, STAT6 mRNA and protein phosphorylation in lung tissues in the lncRNA PVT1 inhibition group were all significantly reduced (P<0.05). But the miR-214 exprssion in lung tissue was significantly increased(P<0.05). miR-214 showed a significant targeting relationship with lncRNA PVT1 (P<0.05). Conclusions Inhibiting lncRNA PVT1 may increase expression of miR-214 ,inhibit the STAT6 phosphorylation pathway and reduce airway inflammation response of mouse with asthma.
    Clemastine fumarate attenuates intestinal ischemia-reperfusion injury in mice
    LIU Yang, LU Ya-peng, HAO Wei, ZHONG Hai-lian, LIU Jie-ting, WANG Ying-bin
    2022, 42(9):  1381-1384.  doi:10.16352/j.issn.1001-6325.2022.09.1381
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    Objective To observe the effect of clemastine fumarate(CLE) on intestinal ischemia-reperfusion(I/R) injury in Balb/c mouse models and its correlation with the activation of intestinal NOD-like receptor protein 3(NLRP3) inflammasomes. Methods Balb/c mice were randomly divided into sham operation group, I/R group (established superior mesenteric artery branch clipping model, ischemia 40 min, reperfusion 2 h) and CLE group (intraperitoneal injection of CLE 5 mg/kg, 1 h before surgery). The pathological changes of intestinal mucosa were evaluated by Chiu's score; The serum levels of TNF-α, IL-1β and IL-18 were detected by ELISA; Western blot was used to detect the expressions of NLRP3, caspase-1 and Gasdermin D proteins in intestinal tissue. Results Compared with the sham group, the Chiu's score in the I/R group significantly increased (P<0.05). The level of TNF-α, IL-1β and IL-18 in serum was increased (P<0.05). The expression of NLRP3, caspase-1 and gasdermin D(GSDMD) proteins in intestinal tissue was increased (P<0.05); Compared with the I/R group, the change of the above indexes from CLE group was alleviated(P<0.05). Conclusions CLE alleviates intestinal ischemia-reperfusion injury of mouse models and the mechanism may be related to regulation of NLRP3 inflammasome activation.
    Matrine alleviates paraquat-induced pulmonary fibrosis in mouse models
    LI Mei-qi, DENG Jun, WANG Song-ping
    2022, 42(9):  1385-1390.  doi:10.16352/j.issn.1001-6325.2022.09.1385
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    Objective To study the effect of matrine on paraquat(PQ)-induced pulmonary fibrosis in mice and its possible mechanism. Methods Mice were divided into the control group, the paraquat(PQ) group and the matrine group randomly. The pulmonary fibrosis model was induced by intraperitoneal injection of paraquat (18 mg/kg). Twenty-four hours after modeling, the treatment group was intragastrically administered with matrine (100 mg/kg). Twenty-eight days later, the lung tissues of each group were collected; HE staining and Masson staining were used to observe the severity of inflammation and fibrosis in the lung tissue; Ashcroft scale was used to evaluate pulmonary fibrosis, and the content of hydroxyproline(HYP) in lung tissue of mice was detected by alkaline water method; Western blot was used to detect the expression of collagen Ⅰ and collagen Ⅲ; The expression of epithelial-mesenchymal transition(EMT)-related proteins[ alpha-smooth muscle action(α-SMA), E-cardherin and vimentin] was detected by immunofluorescence staining. Results The pulmonary structure of paraquat group mice was damaged significantly with deposition of collagen fiber. Compared with the control group, Aschcroft scale of the model group significantly increased(P<0.001)and paraquat upregulated the expression of EMT-related proteins significantly. After matrine intervention, the pathological evidence of pulmonary fibrosis was decreased and the content of hydroxyproline, collagen Ⅰ and collagen Ⅲ in lung tissue was decreased(P<0.001). The protein expression of α-SMA and vimentin was inhibited(P<0.05,P<0.001). Conclusions Matrine has a protective effect on paraquat-induced pulmonary fibrosis in mice, which may be mediated by inhibition of EMT-related proteins.
    High expression of Ku70 promotes proliferation of ovarian cancer cell lines and is associated with a poor prognosis for patients
    WANG Juan, ZHANG Xiao-yan, ZHU Ai-hua, YU Hong-bo, FAN Xin-dan, TANG Chun-hui, YAO Xiu-fang
    2022, 42(9):  1391-1399.  doi:10.16352/j.issn.1001-6325.2022.09.1391
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    Objective To investigate the expression of X-ray-repaired cross complementary protein 6 (Ku70/XRCC6) in epithelial ovarian cancer(EOC) and its effects on the proliferation, apoptosis and migration of ovarian cancer cells. Methods Western blot was used to detect the expression of Ku70 in 9 ovarian cancer tissues of different grades and 3 normal ovarian tissues. Immunohistochemistry was used to detect the expression of Ku70 in 119 ovarian cancer tissues, and the relationship between Ku70 expression and clinicopathological parameters was analyzed. Kaplan-meier survival curve was used to analyze the relationship between Ku70 expression and 5-year survival. Colony formation and CCK-8 assay were used to analyze the effect of Ku70 expression on proliferation of ovarian cancer cells, and flow cytometry was used to detect the effect of Ku70 expression on apoptosis of ovarian cancer cells. The effect of Ku70 expression on ovarian cancer cell migration was analyzed by scratch test and Transwell chamber method. Results The expression of Ku70 in ovarian cancer tissues was higher than that in normal ovarian tissues. The expression of Ku70 was closely correlated with pathological features (P<0.05). The survival rate of ovarian cancer patients with high Ku70 expression was lower than that of patients with low Ku70 expression(P<0.05). Inhibiting the expression of Ku70 decreased poliferation and migration, and increased apoptosis of ovarian cancer cells (P<0.05). Conclusions The abnormal expression of Ku70 is closely related to the occurrence of ovarian cancer and so Ku70 is a potential therapeutic target for ovarian cancer treatment.
    Icariin ameliorates lung injury in severe acute pancreatitis of rat models
    GU Wen-hao, GUO Fei-xia,XU Yu-peng, LU Xin-yu, HU Qing-qing
    2022, 42(9):  1400-1405.  doi:10.16352/j.issn.1001-6325.2022.09.1400
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    Objective To evaluate the protective effect and inflammation inhibition mechanism of icariin (ICA) on lung injury in rat model with severe acute pancreatitis (SAP). Methods The rats were randomly divided into sham operation group (sham group), model group (SAP group, 5% sodium taurocholate was retrograde pumped into bile duct according to 0.1 mL/kg through micropump) and experimental group (ICA group, icariin 80 mg/kg intervention was given 2 hours before modeling). There were 6 rats in each group. Twenty-four hours after the establishment of the model, the inferior vena cava blood, pancreatic tissue and lung tissue were collected. The pathological injury of pancreas and lung was observed by HE staining; The activity of amylase, serum IL-6, IL-1β and TNF-α were measured by ELISA; The expression of inflammatory factors IL-6, IL-1β and TNF-α in lung tissue was determined by immunohistochemical staining; And the ratio of phosphorylated JNK/JNK to phosphorylated NF-κB/NF-κB in lung tissue was measured by Western blot. Results The pathological scores of pancreas and lung in SAP group were significantly higher than those in sham group; And the pathological scores of pancreas and lung in ICA group were significantly lower than those in SAP group. Serum amylase activity, serum IL-6, IL-1β and TNF-α content and the expression of IL-6, IL-1β and TNF-α in lung tissue in SAP group were significantly higher than those in sham group; While serum amylase activity, serum IL-6, IL-1β and TNF-α content and the expression of IL-6, IL-1β and TNF-α in lung tissue in ICA group were significantly lower than those in SAP group. The level of phosphorylated JNK and phosphorylated NF-κB in lung tissue of SAP group were significantly higher than those of sham group; While icariin might significantly reduce the level of phosphorylated JNK and phosphorylated NF-κB in lung tissue. Conclusions ICA ameliorates lung injury in SAP rat model by inhibiting acute inflammation response,which is potentially mediated by JNK/NF-κB signal pathway.
    Over-expression of miR-217 regulates EZH2 to promote osteogenic differentiation of BM-MSCs in osteoporotic mouse models
    RUAN Feng, LI He-wei, GONG Yan-lin, LIU Jia-li, LIU Ping
    2022, 42(9):  1406-1413.  doi:10.16352/j.issn.1001-6325.2022.09.1406
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    Objective To explore the effect of microRNA-217 (miR-217) on the osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) in osteoporosis (OP) mouse model and potential regulatory mechanism. Methods The mice were divided into OP group and sham operation (sham) group with 12 in each group and both underwent bilateral oophorectomy. The OP mouse BM-MSCs were divided into control group, miR-NC group, miR-217mimics group, miR-217 mimics+pcDNA 3.1 group and miR-217 mimics+pcDNA 3.1-EZH2(enhancer of zeste homologe 2) group. The different groups were treated by transfection with miR-NC, miR-217 mimics, miR-217 mimics plus pcDNA 3.1, miR-217 mimics plus pcDNA 3.1-EZH2 respectively and then followed by osteogenic differentiation. The mRNA and protein expressions of miR-217, EZH2, OCN, Runx2, and collagen Ⅰ were detected by RT-qPCR/Western blot; The alkaline phosphatase (ALP) activity of BM-MSCs in each group was detected by microplate reader; Alizarin red S (ARS) staining assay was used to stain the BM-MSCs in each group for microscopy; The targeting relationship between miR-217 and EZH2 was verified by the dual luciferase reporter gene. Results The expression level of miR-217 in the bone tissue and BM-MSCs of the OP group was lower than that of the sham group (P<0.05), and the expression level of EZH2 mRNA was higher than that of the sham group(P<0.05). The expression level of miR-217 in BM-MSCs, the expression levels of OCN, Runx2, collagen Ⅰ mRNAs and proteins, and the ALP activity in the miR-217 mimics group were higher than those in the control group and in miR-NC group (P<0.05). The expression level of EZH2 mRNA and protein were lower than those of the control group and miR-NC group (P<0.05). And the degree of ARS staining was heavier than that of the control group and miR-NC group. The expression levels of EZH2 mRNA and protein in BM-MSCs in the miR-217 mimics+pcDNA 3.1-EZH2 group were higher than those in the miR-217 mimics group and miR-217 mimics+pcDNA 3.1 group (P<0.05). And the expression levels of OCN, Runx2, collagen Ⅰ mRNAs and proteins, and ALP activity were lower than those in miR-217 mimics group and miR-217 mimics+pcDNA 3.1 group (P<0.05). The degree of ARS staining was lighter than that in miR-217 mimics group and miR-217 mimics+pcDNA 3.1 group. There were binding sites between miR-217 and the 3′UTR region of EZH2 mRNA. The relative luciferase activity of WT-EZH2+miR-217 mimics group was lower than that of WT-EZH2+miR-NC group (P<0.05). Conclusions Over-expression of miR-217 can inhibit the expression of EZH2 and promote the osteogenic differentiation of BM-MSCs in OP mice, which could provide a new strategy for clinical prevention and treatment of OP.
    Risk factors and prognosis of the in-hospital death of aged patients with acute exacerbation of chronic obstructive pulmonary disease
    SUN Ai-hua, ZHAO Yan-qiu, WANG Ji-ling
    2022, 42(9):  1414-1418.  doi:10.16352/j.issn.1001-6325.2022.09.1414
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    Objective To evaluate clinical significance and application outcomes of using the neutrophil-to-lymphocyte count ratio (NLR) and C-reactive protein to albumin ratio (CRP/ALB) in the aged patients hospitalized with acute exacerbation of chronic obstructive pulmonary disease(AECOPD). Methods 172 aged patients with AECOPD who were hospitalized in the Department of Geriatrics and Department of Respiratory Medicine of the Second People's Hospital of Hefei from January 2016 to January 2020 were recruited. According to clinical outcomes, they were divided into survival group (n=155) and death group (n=17). Survival group was divided into groups according to hospitalization days of more or less than ten days. Parameters were got through contrast of clinical and laboratory test indexes of patients in each group. Logistic regression and receiver operating characteristic curve (ROC) were used to analyze the risk factors and their correlation with in-hospital mortality. Results Among 172 aged AECOPD in-patients, 17 patients died during hospitalization with mortality as 9.88%. There were differences between the death group and the survival group in NLR, CRP, CRP/ALB, red blood cell distribution width (RDW), cigarette consumption, community acquired pneumonia (CAP) and various comorbidities. Parameters above mentioned in the death group was higher than the survival group(P<0.01). At the same time, 155 aged patients with AECOPD who survived and discharged were divided into two subgroups according to the hospitalization ≥10 days and <10 days. It was found that NLR, CRP, CRP/ALB, RDW, smoking and CAP in group with hospitalization longer than ten days were significantly more common than those in group of less than ten days hospitalization(P<0.01). The Logistic regression analysis of NLR, CRP, CRP/ALB and RDW showed that NLR and CRP/ALB might be independent risk factors for in-hospital death. From the analysis of the ROC, the cut-off value of NLR was 11.04, the area under the curve was 77%, and the cut-off value of CRP/ALB was 1.12, and the area under the curve was 65%. Conclusions NLR and CRP/ALB may be the risk factors for in-hospital death of aged patients with AECOPD, which are associated with poor prognosis.
    Clinical Sciences
    Risk factors for perioperative allogeneic blood transfusion in adolescent scoliosis posterior correction surgery
    MA Man-jiao, MA Lu-lu, ZHANG Xiu-hua, ZHANG Jian-guo, SHEN Jian-xiong, ZHANG Ai-hua, CHEN Lin, LIU Chang-cheng
    2022, 42(9):  1419-1423.  doi:10.16352/j.issn.1001-6325.2022.09.1419
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    Objective To investigate the perioperative rate of allogeneic red blood cell (RBC) transfusion in adolescent scoliosis(AS) that underwent posterior correction surgeries, and to identify its risk factors. Methods This study was a retrospective cohort study. Anesthetic data of adolescent scoliosis patients who underwent posterior correction surgeries from January 2015 to May 2017 in Peking Union Medical College Hospital were collected and analyzed. The clinical variables were subsequently compared between patients who received allogeneic RBC transfusion(transfusion group) and those who did not (non-transfusion group). Binary logistic regression analysis was performed to identify risk factors in perioperative allogeneic RBC transfusion in these patients. Results The study enrolled 469 patients. The perioperative rate of allogeneic RBC transfusion was 30.5% and the independent risk factors leading to it included corrected body mass index (BMI) (OR=0.887, 95% CI: 0.815-0.966, P<0.01),other type of scoliosis (OR=3.847, 95% CI: 1.660-8.917, P<0.01) (compared with idiopathic scoliosis), preoperative anemia (OR=6.322, 95% CI: 2.053-19.473, P<0.01), the number of fused levels more than 12.5 (OR=3.554, 95% CI: 2.174-5.885, P<0.001), preoperative Cobb angle larger than 64.5° (OR=2.381, 95% CI: 1.356-4.178, P<0.01) and osteotomy (OR=7.551, 95% CI: 3.258-17.503,P<0.001). The postoperative transfer rate to intensive care unit(ICU)(P<0.001) in transfusion group was higher, with longer hospital stay length(P<0.001) and higher cost(P<0.001), than that in the non-transfusion group. Conclusions The risk factors for perioperative allogeneic RBC transfusion in AS include corrected BMI, other type of scoliosis, preoperative anemia, the number of fused levels more than 12.5, preoperative Cobb angle larger than 64.5° and osteotomy.
    Case Report
    Tuberous sclerosis complex as a rare cause of multiple nodular and cystic lung disease:a case report
    WANG Ping, XU Zuo-jun, XU Kai-feng
    2022, 42(9):  1424-1427.  doi:10.16352/j.issn.1001-6325.2022.09.1424
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    Objective To broaden the differential diagnosis thinking of diffuse cystic lung diseases and multiple nodular lung disease, and to deepen the understanding of clinical phenotypes of tuberous sclerosis complex (TSC). Methods A case of TSC with complaint of diffuse lung diseases detected during a routine check-up was presented and relevant literatures were reviewed. Results Further examination confirmed multisystem involvement in the patient including heart, kidney, liver and bone, mimicking metabolic malignant tumor. However, percutaneous renal mass biopsy showed angiomyolipoma, which suggested TSC combined with “Confetti” skin lesions found on physical examination. Peripheral blood whole exome sequencing confirmed the diagnosis of TSC. The pulmonary lesions were improved after treatment with sirolimus. Conclusions High clinical awareness of TSC is essential in the patients with diffuse cystic lung diseases and multiple nodular lung diseases, especially in women. In-depth knowledge of multisystem manifestation in TSC is critical for early diagnosis and treatment of this rare disease.
    Mini Reviews
    Research progress of PI3K signaling pathway regulating the pathogenesis of atherosclerosis
    LIU Zhen-zhu, LI Jing, HE Dan, QU Peng
    2022, 42(9):  1428-1432.  doi:10.16352/j.issn.1001-6325.2022.09.1428
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    Phosphatidylinositol 3-kinase(PI3K) signaling pathway is involved in the occurrence and development of atherosclerosis, tumor and immune system diseases. Regulation of PI3K can regulate apoptosis, autophagy, inflammatory response and other pathophysiological processes, which provides a new idea for the treatment of diseases.
    Progress in the treatment with dopamine receptor agonist-induced impulse control disorders
    ZHANG Rui, WU Xue-yan
    2022, 42(9):  1433-1437.  doi:10.16352/j.issn.1001-6325.2022.09.1433
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    It is found that patients with hyperprolactinemia may have impulse control disorder(ICD) when treated with dopamine receptor agonist(DA), such as pathological gambling, high sexual desire, high appetite and forced shopping. This phenomenon also occurs in patients with Parkinson's disease (PD) or other neurological diseases treated with dopamine agonists. The pathogenesis may be that DA overstimulates D3 receptor. Drug withdrawal is a well accepted treatment method, which may reach a better catabatic outcome.
    Advances in the study of the role of estrogen and its receptor combined with HPV in cervical cancer microenvironment
    LI He-tong, REN Jing-jing, WANG Wen-hao, HAO Min
    2022, 42(9):  1438-1442.  doi:10.16352/j.issn.1001-6325.2022.09.1438
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    Human papillomavirus (HPV) infection is related to cervical cancer. Estrogen and its receptor combined with HPV oncogene can promote the occurrence of cervical cancer. Moreover, high parity and the use of contraceptives incrcasing the risk of cervical cancer support estrogen and HPV infection synergistically promotes cervical cancer. Estrogen can both combine with HPV responsive elements to change viral gene expression accelerating the process of HPV infection, and develop HPV-positive cervical cancer by exerting immunomodulatory function in tumor microenvironment. Estrogen and its receptor play vital roles in cervical cancer and are expected to be a potential therapeutic target for treatment of cervical cancer.
    Influencing factors for recurrence after intermittent exotropia surgery
    WANG Ya-chen, ZHANG Wei-jia, FU Tao
    2022, 42(9):  1443-1448.  doi:10.16352/j.issn.1001-6325.2022.09.1443
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    Surgical operation is the most commonly used method to correct intermittent exotropia(IXT), and the results are relatively positive. However, after surgery, some patients will experience a recurrence of exotropia. The recurrence rate increases with time. At present, there is no unified conclusion on the factors in the recurrence after intermittent exotropia surgery. Age at onset and surgery, preoperative and initial postoperative deviation, abnormal visual function, type of intermittent exotropia, operation pathway and preoperative assessment method may all be the risk factors. This review presents a conclusion on different results of recent studies and indication of the interaction among factors in order to gain a better understanding of the surgical indication and provide guidance for future research directions.
    Research progress on roxadustat treatment for renal anemia
    HU Bao-li, HU Bin
    2022, 42(9):  1449-1453.  doi:10.16352/j.issn.1001-6325.2022.09.1449
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    Renal anemia is an independent risk factor for progression of chronic kidney disease (CKD).Roxadustat, a novel medicine for renal anemia, utilizes the body's native response to hypoxia for activating the hypoxia-induced signaling pathway, regulating endogenous erythropoietin(EPO) production and improving iron metabolism, so effectively corrects hemoglobin level and comprehensively regulates erythropoiesis.
    Injury of renal epithelial cell and the formation of Randall's plaque in kidney stones
    YANG Xiong, JIN Xiao-xiao, HE Wen-qiang
    2022, 42(9):  1454-1458.  doi:10.16352/j.issn.1001-6325.2022.09.1454
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    Kidney stone has a high incidence and recurrence rate, which is one of the common diseases in urology.At present, Randall's plaque theory is a widely accepted mechanism for the formation of kidney stones. Studies on Randall's plaque are of great significance for the prevention and treatment of kidney stones. Renal epithelial cell damage promotes the formation of Randall's plaque.In this paper, the research progress of osteogenic changes in renal epithelial cells, reactive oxygen species and oxidative stress, phagocytosis of macrophages, and non-coding RNA changes are reviewed.
    Application of speckle tracking imaging in diagnosis of ischemic heart disease
    ZHU Bing, WANG Xu
    2022, 42(9):  1459-1463.  doi:10.16352/j.issn.1001-6325.2022.09.1459
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    In recent years, the incidence of ischemic heart disease(IHD) has gradually increased. Speckle tracking imaging(STI) can overcome the limitation of angle dependence of traditional Doppler tissue imaging(DTI), and identify the incoordination of local or global myocardial movement or the decline of cardiac function in the early stage of the disease. Early intervention and early treatment can significantly improve the prognosis. In addition, the STI can also observe the clinical therapeutic effect of the disease and support the prediction of prognosis.
    Medical Education
    Cloudy hybrid teaching mode in the training course of biochemistry experiment for international students
    HU Bo, YAN Jing, FENG Chen, WANG Hua-qin
    2022, 42(9):  1464-1469.  doi:10.16352/j.issn.1001-6325.2022.09.1464
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    Objective To implement and evaluate an online hybrid teaching mode as “rain classroom—directed self-study—scientific research design—home experiment” in the cloud experimental course of medical biochemistry for international students. Methods Research design and home experiments were introduced through revised design of teaching contents to develop a new online hybrid teaching mode. A total of 105 international students majoring in clinical medicine (MBBS, 89 students) and dentistry (BDS, 16 students) were selected to join the online the teaching mode during COVID-19 pandemic. Results Compared with the traditional experimental class, the cloud hybrid teaching model effectively stimulated students' enthusiasm and encouraged their participation in experimental course. Students used the existing teaching and online resources to complete the self-study independently, built capacity of research logical thinking, research methodology and then initiated research design and home experiments. Conclusions The training of research design and home experiments can support online experiment teaching in order to cultivate students' innovative thinking and capacity building of experiment technology, and to improve the teaching effect of online biochemistry experiments.
    Opening pattern of key laboratory improves the innovation ability of medical students
    ZHANG Qian, LI Mei, XIA Wei-bo
    2022, 42(9):  1470-1473.  doi:10.16352/j.issn.1001-6325.2022.09.1470
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    The laboratory of medical college and affiliated hospital is an important teaching field, which plays an important role in training experimental skills and scientific innovation abilities of medical students. As a research base and talent training base, this paper elucidates the necessity of strengthening the opening pattern of the key laboratory from the laboratory management and training of medical students' experimental skills. Further, it discusses how to construct the open management mode and the specific implementation plan suitable for medical students in their early training of scientific research practice.
    Discussion on teaching mode of theoretical knowledge in obstetrics and gynecology for clinical medical students
    YIN Jie, ZHOU Ying
    2022, 42(9):  1474-1477.  doi:10.16352/j.issn.1001-6325.2022.09.1474
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    Objective To compare the classroom teaching mode and on-line live teaching mode of theoretical knowledge in obstetrics and gynecology for clinical medical students. Methods A prospective cohort study was designed. Eight-year medical students of 2014 and 2015 classes in Peking Union Medical College were divided into group A and group B. Both two groups got the same obstetric and gynecological theory from the same professors but with different teaching modes. Group A was classroom teaching mode and group B was on-line live teaching mode. Course satisfaction survey and close computer test were completed in one week. T test was used to analyze the score of the two groups. Results Compared with group B, the average score of group A was better (82.89 vs. 79.45,P<0.01). And students in group A could get more great grades in subjective questions than group B (P<0.001). However, students in both groups achieved almost the same scores in objective questions. All students were satisfied with theoretical teaching in obstetrics and gynecology they received. Most of students thought that few conversations with professors were the main shortage of on-line live teaching mode. Most of students thought that the two teaching modes should be combined in theoretical knowledge teaching of obstetrics and gynecology. Conclusions Students could better understand theory of obstetrics and gynecology through classroom teaching. But there is no difference in objective conception memory between students accepting classroom teaching and those accepting on-line live teaching.
    Training of doctor-patient communication skill in clinical teaching practice of oral medicine
    DONG Hai-tao, ZHAO Ji-zhi, GUO Chun-lan, WU Xuan, ZHANG Xiao-wei, YANG Wen-dong
    2022, 42(9):  1478-1480.  doi:10.16352/j.issn.1001-6325.2022.09.1478
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    Doctor-patient communication is an important part in the process of stomatology diagnosis and treatment. The training of doctor-patient communication skill should be emphasized in clinical teaching of stomatology. Through improving the clinical skills of medical students, strengthening the training of doctor-patient communication skills, establishing the concept of law and optimizing the teaching management, it can be realized to cultivate the doctor-patient communication skill of the stomatological students during clinical training and to speed up the growth to be a qualified modern dentist.