ObjectiveTo investigate the mechanism of Ershiwuwei Guijiu pill in preventing and treating postmenopausal osteoporosis （PMOP） by activating the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway and inhibiting excessive autophagy. MethodFemale SD rats were ovariectomized and randomly divided into the sham operation group （Sham）， the operation group （OVX）， the Ershiwuwei Guijiu pill （GJ） group， and the raloxifene hydrochloride （RLX） group， with 10 rats in each group. Enzyme-linked immunosorbent assay （ELISA） and colorimetric methods were used to detect the levels of estrogen， bone metabolism markers in serum， and total superoxide dismutase （T-SOD）， malondialdehyde （MDA）， and glutathione peroxidase （GSH-Px） in tibial tissue. Flow cytometry was used to detect reactive oxygen species （ROS） levels in bone marrow mesenchymal stem cells. Masson staining was used to observe pathological changes in the proximal tibia， and micro-computed tomography （Micro-CT） was used to observe changes in tibial microstructural parameters. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the expression of autophagy-related proteins Beclin1， microtubule-associated protein 1A/1B-light chain 3 （LC3）， autophagy-related 5 （Atg5）， as well as PI3K， Akt， and mTOR in tibial tissue. ResultCompared with the Sham group， the OVX group showed a significant decrease in serum levels of estradiol （E₂） and calcium ion （Ca²⁺）， and T-SOD， GSH-Px， PI3K， Akt， and mTOR mRNA levels in bone tissue （P<0.05， P<0.01）， significantly reduced bone mineral density （BMD）， bone surface/bone volume （BS/BV）， trabecular thickness （Tb.Th）， trabecular number （Tb.N）， and trabecular connectivity （Con） in the tibia （P<0.05， P<0.01）， thinner epiphyseal growth plate， and the bone marrow cavity filled with fat vacuoles. Moreover， the levels of phosphorus （P）， MDA， ROS， and mRNA and protein expression of Beclin1， LC3， and Atg5， as well as trabecular separation （Tb.Sp） were significantly elevated （P<0.05， P<0.01）. Compared with the OVX group， the GJ and RLX groups showed significant increases in serum E₂ and Ca²⁺， and bone tissue levels of SOD， GSH-Px， and the mRNA levels of PI3K， Akt， and mTOR （P<0.05， P<0.01）， significantly increased BMD， BS/BV， Tb.Th， Tb.N， and Con in the tibia， thickened epiphyseal growth plate， and significantly reduced fat vacuoles in the bone marrow cavity （P<0.05， P<0.01）. Additionally， the levels of P， MDA， ROS， Beclin1， LC3， Atg5 mRNA and proteins， and Tb.Sp were significantly decreased （P<0.05， P<0.01）. The ratios of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR， which were significantly reduced in the OVX group （P<0.01）， were significantly increased in the GJ and RLX groups （P<0.01）. ConclusionThe Ershiwuwei Guijiu pill reduces oxidative stress and inhibits autophagy， thereby preventing and treating postmenopausal osteoporosis. Its mechanism may be related to the activation of the PI3K/Akt/mTOR signaling pathway， which inhibits autophagy.

Objective:To analyze the effect of problem-based learning (PBL) combined with case-based learning (CBL) and clinical pathway (CP) teaching methods in standardized residency training in department of hepatobiliary surgery.Methods:A total of 64 residents who received the standardized residency training in the Department of Hepatobiliary Surgery in Shaanxi Provincial People's Hospital from July 2018 to July 2019 were selected and divided into the observation group and the control group. The control group used PBL + CBL teaching methods, while the observation group adopted PBL + CBL + CP teaching methods. The after-department examination scores and the teaching cognition scores of the two groups were compared. SPSS 15.0 was used for t-test and Chi-square test. Results:The after-department examination scores of the two groups were compared. Compared with the control group, the examination scores of professional theories, case analysis and operation skills in the observation group were significantly higher, and the difference was statistically significant ( t = 6.98, 7.85, 7.01, P < 0.05). In terms of recognition of teaching, the observation group was significantly higher than the control group, and the difference was statistically significant ( t = 9.14, P < 0.05). Conclusion:The PBL + CBL + CP teaching is conducive to the comprehensive and systematic mastery of knowledge and the rapid establishment of scientific clinical thinking. It has a strong scientific and systematic nature and is worthy of promotion.

Humans ; Computed Tomography Angiography ; Deep Learning ; Coronary Angiography ; Coronary Artery Disease ; Tomography, X-Ray Computed ; Coronary Stenosis/diagnosis* ; Retrospective Studies ; Fractional Flow Reserve, Myocardial ; Predictive Value of Tests

Background: Interferon lambda receptor 1 (IFNLR1) is a type II cytokine receptor that clings to interleukins IL-28A, IL29B, and IL-29 referred to as type III IFNs (IFN-λs). IFN-λs act through the JAK-STAT signaling pathway to exert antiviral effects related to preventing and curing an infection. Although the immune function of IFN-λs in virus invasion has been described, the molecular mechanism of IFNLR1 in that process is unclear. Objectives: The purpose of this study was to elucidate the role of IFNLR1 in the pathogenesis and treatment of porcine reproductive and respiratory syndrome virus (PRRSV). Methods: The effects of IFNLR1 on the proliferation of porcine alveolar macrophages (PAMs) during PRRSV infection were investigated using interference and overexpression methods. Results: In this study, the expressions of the IFNLR1 gene in the liver, large intestine, small intestine, kidney, and lung tissues of Dapulian pigs were significantly higher than those in Landrace pigs. It was determined that porcine IFNLR1 overexpression suppresses PRRSV replication. The qRT-PCR results revealed that overexpression of IFNLR1 upregulated antiviral and IFN-stimulated genes. IFNLR1 overexpression inhibits the proliferation of PAMs and upregulation of p-STAT1. By contrast, knockdown of IFNLR1 expression promotes PAMs proliferation. The G0/G1 phase proportion in IFNLR1-overexpressing cells increased, and the opposite change was observed in IFNLR1-underexpressing cells. After inhibition of the JAK/STAT signaling pathway, the G2/M phase proportion in the IFNLR1-overexpressing cells showed a significant increasing trend. In conclusion, overexpression of IFNLR1 induces activation of the JAK/STAT pathway, thereby inhibiting the proliferation of PAMs infected with PRRSV. Conclusion Expression of the IFNLR1 gene has an important regulatory role in PRRSVinfected PAMs, indicating it has potential as a molecular target in developing a new strategy for the treatment of PRRSV.

Background: Interferon lambda receptor 1 (IFNLR1) is a type II cytokine receptor that clings to interleukins IL-28A, IL29B, and IL-29 referred to as type III IFNs (IFN-λs). IFN-λs act through the JAK-STAT signaling pathway to exert antiviral effects related to preventing and curing an infection. Although the immune function of IFN-λs in virus invasion has been described, the molecular mechanism of IFNLR1 in that process is unclear. Objectives: The purpose of this study was to elucidate the role of IFNLR1 in the pathogenesis and treatment of porcine reproductive and respiratory syndrome virus (PRRSV). Methods: The effects of IFNLR1 on the proliferation of porcine alveolar macrophages (PAMs) during PRRSV infection were investigated using interference and overexpression methods. Results: In this study, the expressions of the IFNLR1 gene in the liver, large intestine, small intestine, kidney, and lung tissues of Dapulian pigs were significantly higher than those in Landrace pigs. It was determined that porcine IFNLR1 overexpression suppresses PRRSV replication. The qRT-PCR results revealed that overexpression of IFNLR1 upregulated antiviral and IFN-stimulated genes. IFNLR1 overexpression inhibits the proliferation of PAMs and upregulation of p-STAT1. By contrast, knockdown of IFNLR1 expression promotes PAMs proliferation. The G0/G1 phase proportion in IFNLR1-overexpressing cells increased, and the opposite change was observed in IFNLR1-underexpressing cells. After inhibition of the JAK/STAT signaling pathway, the G2/M phase proportion in the IFNLR1-overexpressing cells showed a significant increasing trend. In conclusion, overexpression of IFNLR1 induces activation of the JAK/STAT pathway, thereby inhibiting the proliferation of PAMs infected with PRRSV. Conclusion Expression of the IFNLR1 gene has an important regulatory role in PRRSVinfected PAMs, indicating it has potential as a molecular target in developing a new strategy for the treatment of PRRSV.

Objective: To investigate the factors related to cardiac dysfunctions during the percutaneous coronary intervention (PCI) in patients with non-ST segment elevation acute coronary syndrome (NSTEACS). Methods: Patients diagnosed as NSTEACS receiving PCI from September 2007 to June 2018 were collected in the data base of medical record management system in Qingdao Eighth People′s Hospital. Patients with cardiac dysfunctions (≥ Killip Ⅱ grade) within 1 week after PCI were included into the case group, while patients with normal cardiac function (Killip Ⅰ grade) within 1 week after PCI were included into the control group. Firstly, baseline data of age, gender, histories of hypertension, histories of type 2 diabetes, histories of high cholesterol, histories of smoking, histories of drinking, histories of myocardial infarction, NSTEACS risk stratifications, the application of platelet glycoprotein (GP)Ⅱb/Ⅲa receptor antagonists, coronary artery SYNTAX scores, the dose of contrast agent during PCI, the peak cardiac troponin (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) within 24 h after admission was compared between the two groups; then, factors with statistical differences (P < 0.05) were analyzed by the multivariate logistic regression; at last, variables screening was performed through the backward method and likelihood ratio test. Results: A total of 3927 patients with NSTEACS receiving PCI were enrolled. After patients with incomplete information were eliminated, 313 patients were admitted to the case group and 2 906 patients were admitted to the controlled group. After the analysis of multivariate logistic regression and variables screening, it showed that >80 years old (OR = 1.758, 95% CI 1.129 to 2.367, P = 0.014), increased dose of contrast agent (OR = 1.083, 95% CI 1.007 to 1.274, P = 0.020), the peak cTnT>0.2 μg/L (OR = 2.102, 95% CI 1.703 to 3.104, P = 0.031) and NT-proBNP>450 ng/L (OR = 2.243, 95% CI 1.863 to 3.257, P = 0.015) after admission were the risk factors of cardiac dysfunctions. Conclusions Advanced age (>80 years old), increased dose of contrast agent during PCI, the peak cTnT>0.2 μg/L and NT-proBNP>450 ng/L within 24 h after admission could raise the risk of cardiac dysfunctions in patients with NSTEACS after PCI.

Objective:To explore the possibility of CD 4+ T cells and CD 4+ /CD 8+ ratio in peripheral blood to predict the survival of patients with stage Ⅳ non-small cell lung cancer (NSCLC), and to establish a Nomogram prediction model. Methods:The influence of CD 4+ T cells and CD 4+ /CD 8+ ratio on the clinical factors and survival of 682 patients pathologically diagnosed with stage Ⅳ NSCLC with no history of cancer treatment was retrospectively analyzed and the Nomogram prediction model was established. Combined with the changes of immune cells levels in 110 patients after treatment, the prognostic and predictive values of CD 4+ T cells and CD 4+ /CD 8+ ratio were verified. Countable data were analyzed by t-test. The survival rate was calculated by Kaplan-Meier method, log-rank test or univariate analysis. The multivariate analysis was performed by Cox regression model. Results:Univariate analysis demonstrated that CD 4+ > 43.15% before treatment significantly prolonged the survival. By multivariate analysis of Cox regression model, CD 4+ >43.15% was an independent prognostic factor to prolong survival for stage Ⅳ NSCLC. The Nomogram model was established and verified that the predicted and actual overall survivals were highly consistent. Further analysis showed that 43.15% as the critical value of CD 4+ T cell level significantly prolonged survival when CD 4+ expressed at a high-level before treatment, after treatment, before and after treatment, or combined with CD 4+ /CD 8+ >1.65. Conclusions:The baseline level of CD 4+ T cells before treatment in peripheral blood is an independent prognostic factor for stage Ⅳ NSCLC. The CD 4+ /CD 8+ ratio before treatment has limited value in predicting the prognosis.

Objective:To explore the changes of CD 8+ T cells in stage Ⅲ-Ⅳ non-small cell lung cancer (NSCLC) patients before and after radiochemotherapy and evaluate its clinical value in predicting survival. Methods:A total of 795 patients with stage Ⅲ-Ⅳ NSCLC who completed CD 8+ T cell testing from January 2011 to December 2017 were recruited (249 patients completed 1-3 tests within 6 months after treatment). The survival difference of patients with different levels of CD 8+ T cells and the prognostic value of the changes in the CD 8+ T cell level were analyzed. The survival analysis was performed by Kaplan- Meier method and log-rank test or univariate analysis. The multivariate survival analysis was conducted by Cox’s regression model. Results:Before treatment, the levels of CD 8+ T cells in the peripheral blood did not significantly differ among patients with different clinical factors. The survival time of stage Ⅲ NSCLC patients with CD 8+ T cell levels of<26.44% was significantly prolonged ( P=0.043). After treatment, the levels of CD 8+ T cells were significantly higher than those before treatment. The levels were similar within 1-3 months, decreased after 4-6 months but still significantly higher than those before treatment. The median survival time of patients with CD 8+ cell levels of<43.90% after treatment was 22 months, significantly longer than 16 months of those with CD 8+ cell levels of ≥43.90%( P=0.032). Stratified analysis demonstrated no significant difference in the survival time at 1 month and 2-3 months after treatment ( P>0.05), whereas the survival time significantly differed at 4-6 months ( P=0.001). The multivariate survival analysis showed that CD 8+ cell levels of<43.90% after treatment was an independent prognostic factor ( HR=0.714, P=0.031). Conclusions:The effect of CD 8+ T cells on prognosis of patients with stage Ⅲ-Ⅳ NSCLC is limited. After treatment, CD 8+ T cell levels are increased significantly. A certain increase in the CD 8+ T cell levels can prolong the survival time. The detection of CD 8+ T cell subtypes plays a more significant role.

Objective To investigate the factors related to slow-flow (SF) or no-reflow (NR) during the percutaneous coronary intervention (PCI) in patients with non-ST segment elevation acute coronary sydrome (NSTEACS). Methods Patients diagnosed as NSTEACS who received PCI from September 2007 to June 2018 were collected through the data base of medical record management system in Qingdao Eighth People′s Hospital.The blood flow≤TIMI 2 grade during PCI was defined as slow-flow (SF) or no-reflow(NR). Patients with SF or NR were included into the case group and patients without SF or NR were included into the controlled group. Factors of age, gender, history of hypertension, history of type 2 diabetes, history of high cholesterol, history of smoking, history of drinking, NSTEACS risk stratification, the application of platelet glycoprotein (GP) ⅡB/ⅢA receptor antagonist, coronary artery SYNTAX score, culprit blood vessels, times of balloon dilatation, the burden of thrombus and the preoperative TIMI grade of blood flow were analyzed by multivariate Logistic regression. Then, variables screening was performed through backward method and likelihood ratio test. Results A total of 3 927 patients with NSTEACS receiving PCI were enrolled. After patients with incomplete information were eliminated, 143 patients were admitted to the case group and 3 588 patients were admitted to the control group. After the analysis of multivariate Logistic regression and variables screening, it was showed that times of balloon dilatation ≥ 3 ( OR＝1.725, 95% CI 1.211－2.358, P＝0.014) and high burden of thrombus ( OR＝1.821, 95% CI 1.322-2.511, P＜0.01) were the risk factors of SF or NR, while the application of GPⅡB/ⅢA receptor antagonist ( OR＝0.623, 95% CI 0.382-0.855, P＝0.012) was the protective factor of SF or NR. Conclusions Multiple balloon dilatation and high burden of thrombus increased the risk of SF or NR, while the application of GPⅡB/ⅢA receptor antagonists could inhibit the occurrence of SF or NR.

Objective To evaluate the value of left ventricular energy loss (EL) in the systolic left ventricular hemodynamic changes in hypertensive patients by ultrasonic flow vector imaging (VFM). Methods Ninty-eight hypertensive patients were divided into non left ventricular hypertrophy group (NLVH group) and left ventricular hypertrophy group (LVH group) according to the left ventricular mass index(LVMI).Thirty-one healthy adults were erolled as control group.The average total energy loss (EL-T),basal energy loss (EL-B),middle energy loss (EL-M) and apical energy loss (EL-A) of each isovolumic contraction phase,fast ejection phase and slow ejection phase were obtained by VFM,the difference among the three groups were compared.Results ①EL-T and EL-B in isovolumic phase,rapid ejection phase and slow ejection phase in NLVH group were higher than those in control group ( P <0.05 or P <0.01);EL-T,EL-B,EL-M and EL-A in isovolumic phase,rapid ejection phase and slow ejection phase in LVH group were all higher than those in control group ( P <0.05 or P <0.01);EL-M in isovolumic phase and rapid ejection phase,EL-T,EL-B,EL-M and EL-A in slow ejection phase in LVH group were higher than those in the NLVH group ( P <0.05 or P <0.01).② There was a positive correlation between EL-T and LVMI (r=0.311, P < 0.01),EL-B and LVMI ( r = 0.219, P < 0.05),EL-M and LVMI( r = 0.207, P <0.05),EL-T and LVEF( r = 0.340, P < 0.05),EL-B and LVEF( r = 0.367, P < 0.01) in isovolumic contraction phase.There was a positive correlation between EL-B and LVEF( r = 0.359, P < 0.01) in rapid ejection phase.There was a positive relation between EL-B and LVEF( r =0.352,P <0.05) in slow ejection phase.Conclusions The EL of systolic peroid in hypertensive patients increased,which suggests that the left ventricular hemodynamic changes abnormally,VFM can accurately evaluate the changes of hemodynamic during systole.