Aim To investigate the mechanism by which sufentanil(Suf)improved hypoxia-reoxygen-ation(H/R)-induced myocardial cell injury by regula-ting hypoxia inducible factor-1α(HIF-1α)and KC-NQ1 opposite strand/antisense transcript 1(Kcnq1ot1).Methods Bioinformatics analysis was conducted to predict the interaction between HIF-1αand Kcnq1ot1.Subsequently,H9c2 cells were divided into multiple treatment groups:Ctrl group,H/R group,and Suf group.Further grouping was based on different transfection conditions,including oe-HIF-1α group,oe-HIF-1α+Suf group,sh-HIF-1α group,and sh-HIF-1α+Kcnq1ot1 group.Cell viability was detected u-sing the MTT assay,cell apoptosis was detected using the TUNEL assay,and the concentrations of CK-MB and HBDH in cell supernatants were measured using ELISA.HIF-1α protein expression in cellswas deter-mined by Western blot,and the mRNA expression level of Kcnq1ot1 was measured by reverse transcription quantitative PCR(RT-qPCR).Additionally,a rat model of myocardial is chemia reperfusion was con-structed to evaluate the therapeutic potential of Suf for myocardial ischemia reperfusion injury in vivo.Results The results of bioinformatics analysis showed a direct interaction between HIF-1α and Kcnq1ot1.Compared with the Ctrl group,the H/R group showed significantly reduced H9c2 cell viability,increased cell apoptosis,and significantly upregulated concentrations of CK-MB and HBDH,along with significantly enhanced expres-sion of HIF-1α and Kcnq1ot1(all P＜0.05).When H9c2 cells were transfected with oe-HIF-1 α,cell via-bility further decreased,apoptosis was worsened,and CK-MB and HBDH concentrations further increased(all P＜0.05);however,these adverse effects were significantly inhibited when combined with Suf inter-vention(all P＜0.05).Additionally,compared with the H/R group,the sh-HIF-1α group showed signifi-cantly improved cell viability,reduced apoptosis and decreased CK-MB and HBDH concentrations(all P＜0.05);however,these improvements were partially re-versed upon transfection with Kcnq1ot1(all P＜0.05).Animal experiments confirmed that Suf could improve myocardial ischemia-reperfusion injury in myo-cardial ischemia-reperfusion injury rats.Conclusions Suf improves myocardial H/R injury by inhibiting the HIF-1α-Kcnq1ot1.

Objective To observe the value of left atrial volume/mechanical coupling index(LACI)for predicting left atrial(LA)dysfunction in patients with chronic kidney disease(CKD).Methods Totally 213 CKD patients(CKD group)and 50 healthy controls(control group)were enrolled.Clinical data,laboratory indicators and echocardiographic parameters were compared between groups.According to quartile values of LACI,patients in CKD group were further divided into 4 subgroups,and their clinical,laboratory indicators and echocardiographic parameters were compared.The correlations between LACI and laboratory markers of myocardial injury as well as echocardiographic parameters were analyzed.Taken LAVI＞34 ml/m2 as LA dysfunction,the efficacy of LACI,LA strain and LA stiffness index(LASI)for predicting LA dysfunction in CKD patients were evaluated.Results Statistical differences of gender,blood pressure,creatinine,estimated glomerular filtration rate(eGFR),cardia troponinT(cTnT),creatine kinase isoenzymes(CK-MB)and N-terminal pro-B-type natriuretic peptide(NT-proBNP)were found between groups(all P＜0.05).In CKD group,with the increase of LACI,the prevalence of blood pressure and diabetes,the levels of cTnT and NT-proBNP in different subgroups showed increasing trend,while eGFR showed a decreasing trend.LACI was correlated with cTnT,CK-MB,NT-proBNP and multiple echocardiographic parameters(all P＜0.001).The AUC of LACI for predicting LA dysfunction in CKD patients was 0.884,higher than that of LA strain during reservoir phase,conduit phase,contraction phase and LASI(AUC=0.652,0.621,0.611,0.746,all P＜0.05).Conclusion LACI could be used to effectively predict LA dysfunction in CKD patients.

Aim To investigate the mechanism by which sufentanil(Suf)improved hypoxia-reoxygen-ation(H/R)-induced myocardial cell injury by regula-ting hypoxia inducible factor-1α(HIF-1α)and KC-NQ1 opposite strand/antisense transcript 1(Kcnq1ot1).Methods Bioinformatics analysis was conducted to predict the interaction between HIF-1αand Kcnq1ot1.Subsequently,H9c2 cells were divided into multiple treatment groups:Ctrl group,H/R group,and Suf group.Further grouping was based on different transfection conditions,including oe-HIF-1α group,oe-HIF-1α+Suf group,sh-HIF-1α group,and sh-HIF-1α+Kcnq1ot1 group.Cell viability was detected u-sing the MTT assay,cell apoptosis was detected using the TUNEL assay,and the concentrations of CK-MB and HBDH in cell supernatants were measured using ELISA.HIF-1α protein expression in cellswas deter-mined by Western blot,and the mRNA expression level of Kcnq1ot1 was measured by reverse transcription quantitative PCR(RT-qPCR).Additionally,a rat model of myocardial is chemia reperfusion was con-structed to evaluate the therapeutic potential of Suf for myocardial ischemia reperfusion injury in vivo.Results The results of bioinformatics analysis showed a direct interaction between HIF-1α and Kcnq1ot1.Compared with the Ctrl group,the H/R group showed significantly reduced H9c2 cell viability,increased cell apoptosis,and significantly upregulated concentrations of CK-MB and HBDH,along with significantly enhanced expres-sion of HIF-1α and Kcnq1ot1(all P＜0.05).When H9c2 cells were transfected with oe-HIF-1 α,cell via-bility further decreased,apoptosis was worsened,and CK-MB and HBDH concentrations further increased(all P＜0.05);however,these adverse effects were significantly inhibited when combined with Suf inter-vention(all P＜0.05).Additionally,compared with the H/R group,the sh-HIF-1α group showed signifi-cantly improved cell viability,reduced apoptosis and decreased CK-MB and HBDH concentrations(all P＜0.05);however,these improvements were partially re-versed upon transfection with Kcnq1ot1(all P＜0.05).Animal experiments confirmed that Suf could improve myocardial ischemia-reperfusion injury in myo-cardial ischemia-reperfusion injury rats.Conclusions Suf improves myocardial H/R injury by inhibiting the HIF-1α-Kcnq1ot1.

Objective To observe the value of left atrial volume/mechanical coupling index(LACI)for predicting left atrial(LA)dysfunction in patients with chronic kidney disease(CKD).Methods Totally 213 CKD patients(CKD group)and 50 healthy controls(control group)were enrolled.Clinical data,laboratory indicators and echocardiographic parameters were compared between groups.According to quartile values of LACI,patients in CKD group were further divided into 4 subgroups,and their clinical,laboratory indicators and echocardiographic parameters were compared.The correlations between LACI and laboratory markers of myocardial injury as well as echocardiographic parameters were analyzed.Taken LAVI＞34 ml/m2 as LA dysfunction,the efficacy of LACI,LA strain and LA stiffness index(LASI)for predicting LA dysfunction in CKD patients were evaluated.Results Statistical differences of gender,blood pressure,creatinine,estimated glomerular filtration rate(eGFR),cardia troponinT(cTnT),creatine kinase isoenzymes(CK-MB)and N-terminal pro-B-type natriuretic peptide(NT-proBNP)were found between groups(all P＜0.05).In CKD group,with the increase of LACI,the prevalence of blood pressure and diabetes,the levels of cTnT and NT-proBNP in different subgroups showed increasing trend,while eGFR showed a decreasing trend.LACI was correlated with cTnT,CK-MB,NT-proBNP and multiple echocardiographic parameters(all P＜0.001).The AUC of LACI for predicting LA dysfunction in CKD patients was 0.884,higher than that of LA strain during reservoir phase,conduit phase,contraction phase and LASI(AUC=0.652,0.621,0.611,0.746,all P＜0.05).Conclusion LACI could be used to effectively predict LA dysfunction in CKD patients.

Objective:To analyze the clinical characteristics,treatment,and prognosis of adult patients with early T-cell precursor acute lymphoblastic leukemia/lymphoma(ETP-ALL/LBL).Methods:Clinical data of 113 T lymphoblastic leukemia/lymphoma(T-ALL/LBL)patients from January 2006 to January 2019 were collected from three hematology research centers,including Peking University Third Hospital,the First Medical Center of Chinese PLA General Hospital and Institute of Hematology and Blood Diseases Hospital,Chinese Medical University.The clinical characteristics and prognosis of ETP-ALL/LBL patients were analyzed compared with non-ETP-ALL/LBL patients.Results:In 113 T-ALL/LBL patients,13 cases(11.5％)were diagnosed as ETP-ALL/LBL,including 11 males,with a median age of 28(18-53)years.Compared with non-ETP-ALL/LBL patients,there were no significant differences in age,sex,incidence of large mediastinal mass,clinical stage,international prognostic index(IPI)score,white blood cell(WBC)count and lactate dehydrogenase(LDH)level among ETP-ALL/LBL patients.Among 13 ETP-ALL/LBL patients,9 cases(69.2％)achieved complete remission(CR),and there was no statistically significant difference in response rate induced by chemotherapy between ETP-ALL/LBL patients and non-ETP-ALL/LBL patients.Among patients who received chemotherapy without allogeneic hematopoietic stem cell transplantation(allo-HSCT),ETP-ALL/LBL group had a worse 5-year overall survival(OS)rate compared with non-ETP-ALL/LBL group(0 vs 7.1％,P=0.008),while in patients with allo-HSCT,there was no significant difference for 5-year OS rate between the two group(37.5％vs 40.2％,P＞0.05).Multivariate Cox regression analysis showed that CR after induction therapy,allo-HSCT,and LDH level were independent prognostic factors affecting T-ALL/LBL patients.Conclusion:No significant difference in response rate induced by chemotherapy is observed between ETP-ALL/LBL and non-ETP-ALL/LBL patients.Allo-HSCT consolidation after induction of remission therapy may have significant favorable influence on OS for patients with ETP-ALL/LBL.

Objective ， To investigate the role of serum chemokines and oxidative and antioxidant biomarkers in occupational （ silicosis） Methods silicosis hereinafter referred to as . A total of 58 patients with stage Ⅰ silicosis were selected as the - （ ）， research subjects using convenient sampling method. The serum levels of nuclear factor erythroid 2 related factor 2 Nrf2 -（ - ） - （ - - ） - heme oxygenase 1 HO 1 and 8 isoprstaglandin F2α 8 iso PGF2α were determined by enzyme linked immunesorbent assay. （ ） （ - ） The serum levels of lipid peroxide LPO and total antioxidant capacity TAOC were determined by chemistry colorimetric method. - - （ - ）， Luminex flow fluorescence technology was used to detect the serum levels of interferon γ inducible protein10 IP10 macrophage （ ）- ， - - （ ） inflammatory protein MIP 1α MIP1β and macrophagederived chemokine MDC . The above indicators were analyzed by factor Results - analysis. The information extraction rate of the original indicators of the nine biomarkers was 58.5%96.5%. Four common ， ， （ ） ， factors were extracted including Nrf2 antioxidant signaling pathway helper T cell Th 1 dominant chemotaxis the total ， ， ， ， ， oxidation/antioxidant balance and Th2 dominant chemotaxis whose variance contribution rates were 32.2% 19.1% 16.4% ， ， Conclusion - and 11.8% respectively and the cumulative variance contribution rate was 79.5%. Both the oxidant antioxidant ， disturbance and the dominance chemotaxis are involved in the occurrence and development of silicosis and the Nrf2 antioxidant signaling pathway plays the most critical role.

Objective:To investigate the role of umbilical cord mesenchymal stem cell-derived exosomes (ucMSC-exos) in acute skin wound healing in mice.Methods:ucMSC-exos were extracted by ultracentrifugation, and identified by transmission electron microscopy, Western blot analysis of exosome surface markers CD63 and TSG101, and particle size analysis. Firstly, in vitro cultured third- to fifth-passage human skin fibroblasts (HSF) were incubated with high-glucose Dulbecco′s modified Eagle′s medium (DMEM) containing 0, 1 and 2 μg/ml exosome suspension for 24 hours (negative control group, 1- and 2-μg/ml groups, respectively) , and cell counting kit-8 (CCK8) assay was performed to evaluate the effect of ucMSC-exos on the proliferative activity of HSF. Secondly, 24 male BALB/c mice aged 8 weeks were selected to construct a mouse model of full-thickness skin wound, and then divided into ucMSC-exos group and phosphate-buffered saline (PBS) group by using a random number table to be subcutaneously injected with exosome suspension and PBS respectively at multiple equidistant sites located about 1 mm apart from the wound edge. On days 0, 4, 7, 10 and 14 after operation, the wounds in mice were observed, and the percentage of residual wound area was calculated in the above two groups. On days 7 and 14 after operation, wound tissues were resected and subjected to hematoxylin and eosin (HE) and Masson staining to observe structural changes of skin tissues. On day 14 after operation, wound tissues were collected in the two groups, and real-time quantitative PCR (qRT-PCR) and Western blot analysis were performed to determine the mRNA and protein expression of type Ⅰ collagen, fibronectin and vascular endothelial growth factor, respectively. Statistical analysis was carried out by using one-way analysis of variance, least significant difference- t test, two-way repeated measures analysis of variance and unpaired t-test. Results:Under the transmission electron microscope, the ucMSC-exos were oval in shape with a diameter of about 100 nm; Western blot analysis showed positive expression of ucMSC-exos surface proteins CD63 and TSG101; particle size analysis showed that 96.2 % of the ucMSC-exos had diameters of 30 - 150 nm. CCK8 assay showed that the relative proliferative activity of HSF was significantly higher in the 1- and 2-μg/ml groups (0.97 ± 0.05, 1.08 ± 0.07, respectively) than in the negative control group (0.71 ± 0.04; t = 2.00, 7.05, respectively, both P < 0.05) , and significantly higher in the 2-μg/ml group than in the 1-μg/ml group ( t = 5.09, P < 0.05) . On days 4, 7, 10 and 14 after operation, the percentage of residual wound area was significantly lower in the ucMSC-exos group than in the PBS group (all P < 0.05) . HE and Masson staining showed increased numbers of hair follicles, glands and granulation tissues, more neovascularization, and neater arrangement of collagens in neonatal skin tissues of the mice in the ucMSC-exos group compared with the PBS group. qRT-PCR and Western blot analysis showed significantly increased mRNA and protein expression of type Ⅰ collagen, fibronectin and vascular endothelial growth factor in the ucMSC-exos group compared with the PBS group (all P < 0.01) . Conclusion:Subcutaneous injections of ucMSC-exos can promote acute skin wound healing in mice, likely by promoting the synthesis of extracellular matrix and vascular endothelial growth factor in wound tissues of mice and proliferation of HSF.

Objective:To establish and evaluate a nomogram for long-term survival of patients with intrahepatic cholangiocarcinoma (ICC) after radical resection.Methods:The data of ICC patients who underwent radical resection for the first time at Zhongshan Hospital, Fudan University from January 2014 to December 2017 were retrospectively analyzed. Of 167 patients who were enrolled, there were 104 males and 63 females, with the age of (60.3±10.9) years. Tumor tissues were collected for immunohistochemical staining and interpretation. Univariate Cox regression, LASSO regression and multivariate Cox regression were used to analyze influencing factors of postoperative long-term survival after ICC. R software was used to construct a nomogram in predicting ICC prognosis.Results:Cox regression analysis showed that TNM staging, poorly differentiated tumor, positive resection margin, positive mucin 5 expression and abnormal P53 expression to be independent risk factors associated with poor long-term survival after radical resection. The prognostic nomogram model of ICC was constructed based on these factors. The C-index was 0.821. The nomogram model consistency index had a high degree of prognostic differentiation. The 45° diagonal of the 3-year postoperative calibration curve which represented the actual survival fitted well with the segmented line which represented the predicted survival of the nomogram. The area under the receiver operating characteristic curve of the nomogram model was higher than that of AJCC TNM staging (0.894 vs. 0.803, z=4.10, P<0.001). The nomogram model was more effective in predicting postoperative survival of ICC patients than the TNM staging. Conclusion:TNM staging, poorly differentiated tumor, positive resection margin, positive mucin 5 expression and abnormal P53 expression were independent risk factors for postoperative survival of ICC. The nomogram model could better evaluate long-term prognosis of ICC patients after radical resection than the traditional TNM staging system.

Objective:To investigate the regulatory effects of salidroside (Sal) on mice in an inflammatory state with polycystic ovary syndrome (PCOS) and the link with nuclear factor-κB (NF-κB) signaling pathway.Methods:Totally twenty-eight female C57B/6J mice aged 21 d were divided into control group, Sal group, PCOS group and PCOS+Sal group with 7 mice per group based on numbers randomly generated by computer and 21 d treatment was taken. Glucose tolerance test (GTT) was performed when the treatment was finished, ovarian tissues were taken for HE staining and morphological analysis, immunohistochemistry was used to detect tumor necrosis factor (TNF)-α and p-NF-κB p65 protein levels in the ovaries, and enzyme-linked immunsorbent assay (ELISA) was taken to detect the levels of serum sex hormones and inflammatory cytokines. Human ovarian granulosa cell line (KGN cells) were divided into four groups: control group, Sal (30 μmol/L) group, lipopolysaccharide (LPS) (0.5 mg/L) group and LPS (0.5 mg/L) +Sal (15 μmol/L, 30 μmol/L, 60 μmol/L) group. Inflammatory cytokines mRNA levels and nuclear factor (NF)-κB associated protein levels were detected after culture for 24 h.Results:The levels of testosterone [(2.11±0.60) μg/L vs. (0.77±0.06) μg/L, P<0.001], luteinizing hormone (LH) [(2.54±0.27) U/L vs. (1.07±0.21) U/L, P<0.001], LH/follicle-stimulating hormone (FSH) (0.12±0.01 vs. 0.05±0.01, P<0.001) and inflammatory cytokines interleukin (IL)-1β [(107.83±12.05) ng/L vs. (33.83±4.96) ng/L, P<0.001], IL-6 [(56.70±7.33) ng/L vs. (28.91±8.53) ng/L, P<0.001], TNF-α [(74.72±14.64) ng/L vs. (37.07±5.48) ng/L, P<0.001] increased in PCOS mice compared with control group, but the levels of testosterone [(1.47±0.25) μg/L, P=0.012], LH [(1.73±0.17) U/L, P<0.001], LH/FSH (0.08±0.01, P<0.001), IL-1β [(74.21±10.64) ng/L, P<0.001], IL-6 [(40.90±5.01) ng/L, P=0.002] and TNF-α [(55.42±8.78) ng/L, P=0.017] decreased significantly following Sal treatment. Immunohistochemical staining showed that TNF-α and p-NF-κB p65 protein levels in granulosa cells increased in PCOS mice but decreased after Sal treatment. Besides, IL-1β (1.76±0.09 vs. 0.50±0.20, P<0.001), IL-6 (1.79±0.20 vs. 0.80±0.10, P<0.001), TNF-α (1.56±0.19 vs. 0.70±0.30, P<0.001) mRNA levels increased significantly in LPS induced KGN cells, after Sal treatment (15 μmol/L, 30 μmol/L and 60 μmol/L), the mRNA levels of IL-1β (1.09±0.07, 1.00±0.02, 0.96±0.03, all P<0.001), IL-6 (1.47±0.12, 0.93±0.18, 0.91±0.27, P<0.001) and TNF-α (1.21±0.25, 0.94±0.35, 0.76±0.07, all P<0.001) apparently decreased. In addition, p-NF-κB p65 (0.49±0.07 vs. 0.31±0.03, P=0.013) and p-IκBα (0.48±0.06 vs. 0.26±0.04, P=0.012) protein levels increased apparently in LPS induced KGN cells, but the protein levels of p-NF-κB p65 (0.33±0.05, P=0.024) and p-IκBα (0.31±0.06, P=0.046) decreased following Sal treatment. Conclusion:Sal can attenuate inflammation levels in mice with PCOS by inhibiting NF-κB signaling pathway.

Objective:To investigate the regulatory effects of salidroside (Sal) on mice in an inflammatory state with polycystic ovary syndrome (PCOS) and the link with nuclear factor-κB (NF-κB) signaling pathway.Methods:Totally twenty-eight female C57B/6J mice aged 21 d were divided into control group, Sal group, PCOS group and PCOS+Sal group with 7 mice per group based on numbers randomly generated by computer and 21 d treatment was taken. Glucose tolerance test (GTT) was performed when the treatment was finished, ovarian tissues were taken for HE staining and morphological analysis, immunohistochemistry was used to detect tumor necrosis factor (TNF)-α and p-NF-κB p65 protein levels in the ovaries, and enzyme-linked immunsorbent assay (ELISA) was taken to detect the levels of serum sex hormones and inflammatory cytokines. Human ovarian granulosa cell line (KGN cells) were divided into four groups: control group, Sal (30 μmol/L) group, lipopolysaccharide (LPS) (0.5 mg/L) group and LPS (0.5 mg/L) +Sal (15 μmol/L, 30 μmol/L, 60 μmol/L) group. Inflammatory cytokines mRNA levels and nuclear factor (NF)-κB associated protein levels were detected after culture for 24 h.Results:The levels of testosterone [(2.11±0.60) μg/L vs. (0.77±0.06) μg/L, P<0.001], luteinizing hormone (LH) [(2.54±0.27) U/L vs. (1.07±0.21) U/L, P<0.001], LH/follicle-stimulating hormone (FSH) (0.12±0.01 vs. 0.05±0.01, P<0.001) and inflammatory cytokines interleukin (IL)-1β [(107.83±12.05) ng/L vs. (33.83±4.96) ng/L, P<0.001], IL-6 [(56.70±7.33) ng/L vs. (28.91±8.53) ng/L, P<0.001], TNF-α [(74.72±14.64) ng/L vs. (37.07±5.48) ng/L, P<0.001] increased in PCOS mice compared with control group, but the levels of testosterone [(1.47±0.25) μg/L, P=0.012], LH [(1.73±0.17) U/L, P<0.001], LH/FSH (0.08±0.01, P<0.001), IL-1β [(74.21±10.64) ng/L, P<0.001], IL-6 [(40.90±5.01) ng/L, P=0.002] and TNF-α [(55.42±8.78) ng/L, P=0.017] decreased significantly following Sal treatment. Immunohistochemical staining showed that TNF-α and p-NF-κB p65 protein levels in granulosa cells increased in PCOS mice but decreased after Sal treatment. Besides, IL-1β (1.76±0.09 vs. 0.50±0.20, P<0.001), IL-6 (1.79±0.20 vs. 0.80±0.10, P<0.001), TNF-α (1.56±0.19 vs. 0.70±0.30, P<0.001) mRNA levels increased significantly in LPS induced KGN cells, after Sal treatment (15 μmol/L, 30 μmol/L and 60 μmol/L), the mRNA levels of IL-1β (1.09±0.07, 1.00±0.02, 0.96±0.03, all P<0.001), IL-6 (1.47±0.12, 0.93±0.18, 0.91±0.27, P<0.001) and TNF-α (1.21±0.25, 0.94±0.35, 0.76±0.07, all P<0.001) apparently decreased. In addition, p-NF-κB p65 (0.49±0.07 vs. 0.31±0.03, P=0.013) and p-IκBα (0.48±0.06 vs. 0.26±0.04, P=0.012) protein levels increased apparently in LPS induced KGN cells, but the protein levels of p-NF-κB p65 (0.33±0.05, P=0.024) and p-IκBα (0.31±0.06, P=0.046) decreased following Sal treatment. Conclusion:Sal can attenuate inflammation levels in mice with PCOS by inhibiting NF-κB signaling pathway.