Objective To investigate the effect of parent-child alienation on depression in surface ship officers and soldiers based on the theory of"diathesis-stress",and the mediating role of resilience between parent-child alienation and depression in them.Methods A cross-sectional study was conducted on 599 officers and soldiers from a surface ship unit.The participants were surveyed with inventory of alienation toward parents,connor-davidson resilience scale and patient health questionnaire-9 to obtain and analyze their demographic-military characteristics of their depression scores.The participants with depression scores ≥5 were recruited as the subjects,and Spearman correlation analysis was used to explore the correlation among parent-child alienation,resilience and depression.On the basis of hierarchical regression analysis,AMOS software was used to establish a structural equation modelling of intermediary effects.Results The depression score was 1(0,4)in the participants,and the depression scores of those with service length ≥11 years were comparatively higher than those with shorter length.Our results indicated that parent-child alienation was positive correlated with depression(r=0.451,P＜0.001),while resilience was negatively correlated with depression and parent-child alienation(r=-0.412,-0.407,P＜0.001).Regression analysis revealed that parent-child alienation had a direct positive predictive value for depression(β=0.574,P＜0.001),and resilience showed a negative predictive value for depression(β=-0.211,P＜0.01).Model analysis displayed that resilience had a significant mediating role in the effect of parent-child alienation on depression among these surface ship officers and soldiers,with an effect value of 0.088,and accounting for 15.86％of the total effect.Conclusion Parent-child alienation has a significant influence on depression among surface ship officers and soldiers,with resilience playing a partial mediating role.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

OBJECTIVE: To detect the differential expressions of miR-451, ABCB1 and ABCC2 in drug-sensitive leukemia cell line K562 and drug-resistant cell line K562/A02, and explore the regulatory relationship between miR-451 and the expressions of ABCB1 and ABCC2 , and the mechanism of miR-451 involved in drug resistance in leukemia. METHODS: CCK-8 assay was used to detect the drug resistance of K562/A02 and K562 cells. Quantitative Real-time PCR (qRT-PCR) was used to verify the differential expressions of miR-451 in K562 and K562/A02 cells. MiR-451 mimic and negative control (miR-NC), miR-451 inhibitor and negative control (miR-inNC) were transfected into K562 and K562/A02 cells respectively, then qRT-PCR and Western blot were used to detect the expression levels of mRNA and protein of ABCB1 and ABCC2 in K562 and K562/A02 cells and the transfected groups. RESULTS: The drug resistance of K562/A02 cells to adriamycin was 177 times higher than that of its parent cell line K562. Compared with K562 cells, the expression of miR-451 in K562/A02 cells was significantly higher (P <0.001), and the mRNA and protein expression levels of ABCB1 and ABCC2 in K562/A02 cells were significantly higher than those in K562 cells (P <0.001). After transfected with miR-451 inhibitor, the expression of miR-451 was significantly down-regulated in K562/A02 cells (P <0.001), the sensitivity to chemotherapy drugs was significantly enhanced (P <0.05), and the mRNA and protein expressions of ABCB1 and ABCC2 were significantly decreased (P <0.01). After transfected with miR-451 mimic, the expression of miR-451 was significantly upregulated in K562 cells (P <0.001), and the mRNA and protein expressions of ABCB1 and ABCC2 were significantly increased (P <0.01). CONCLUSION There are significant differences in the expressions of miR-451, ABCB1 and ABCC2 between the drug-sensitive leukemia cell line K562 and drug-resistant cell line K562/A02, which suggests that miR-451 may affect the drug resistance of leukemia cells by regulating the expression of ABCB1 and ABCC2.
Humans ; K562 Cells ; Drug Resistance, Neoplasm/genetics* ; Drug Resistance, Multiple/genetics* ; Doxorubicin/pharmacology* ; MicroRNAs/genetics* ; Leukemia/genetics* ; RNA, Messenger

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

Objective:To observe the effect of Fangji Huangqitang （FJHQT） on collagen induced arthritis （CIA） and synovial angiogenesis in DBA/1 mice. Method:DBA/1 mice were randomly divided into normal group， CIA group and FJHQT group. DBA/1 mice in CIA group and FJHQT group were immunized with bovine type Ⅱ collagen and complete Freund's adjuvant on the first day， and DBA/1 mice were immunized with bovine type Ⅱ collagen and incomplete Freund's adjuvant on the 21^st day to establish CIA model. On the day of the second immunization， the drug was given by gavage once a day for 28 days. On the 22^nd day， the arthritis score and other symptoms of CIA mice were observed. On the 49^th day， Hematoxylin eosin （HE） staining was carried out to observe the angiogenesis in the synovium of CIA mice， the expression of vascular endothelial cell marker platelet endothelial cell adhesion molecule-1 （CD31） and vascular endothelial growth factor （VEGF） in the synovium of CIA mice were detected. Immunofluorescence double staining was used to detect the mature and immature vessels in the synovium of CIA mice. And the microvascular growth of the rat thoracic aortic ring was induced by VEGF （20 μg·L^-1）. The effects of FJHQT （0.25， 0.5， 1 g·L^-1） at different concentrations were observed under microscope. Result:Compared with the normal group， the inflammation， joints， red and swelling of the inflammatory joints of the CIA group were significantly increased （P<0.01）. The scores of clinical arthritis， the incidence rate， synovial inflammation and angiogenesis were significantly increased （P<0.01）. The density of blood vessels， the positive expression of CD31 and VEGF， the number of immature vessels in synovial membrane were significantly increased （P<0.01）. And compared with the CIA group， the inflammation， joint swelling， and malformation of the FJHQT group were significantly improved， the clinical arthritis score， incidence rate， synovial inflammation and angiogenesis were significantly reduced （P<0.01）. The vascular density， the positive expression of CD31 and VEGF， and the number of immature blood vessels in synovial membrane were significantly increased （P<0.01）. Compared with blank group， VEGF could significantly induce the growth of microvasculature in rat thoracic aortic ring （P<0.01）. Compared with VEGF group， FJHQT（0.25， 0.5， 1 g·L^-1） could significantly inhibit the formation of microvasculature in rat thoracic aortic ring （P<0.01）. Conclusion:FJHQT can effectively alleviate the clinical symptoms and condition of CIA mice， reduce the clinical arthritis score and incidence rate，and inhibit the synovial angiogenesis of CIA mice joints and VEGF induced microvascular formation in rat thoracic aortic rings.

Objective:To study the protective effect of Ficus pandurata extract on acute alcoholic liver injury based on pyroptosis mechanism.Method:The 56 male C57BL/6 mice were randomly divided into normal control group， model control group， positive control group（60 mg·kg^-1）， fresh medicine water extract group（48 g·kg^-1）， dry drug water extract group（48 g·kg^-1），dry drug 50% alcohol extract group（48 g·kg^-1） and dry drug 95% alcohol extract group （48 g·kg^-1）， 8 mice in each group.Positive control and different solvent extract groups of Ficus tenuifolia were intragastrically administrated for 18 days，once a day，while normal group and model group were given the same volume of pure water intragastrically. After 15 days of continuous gavage， mice received 50％ ethanol（12 mL·kg^-1）intragastrically for 3 days to induce acute alcoholic liver injury model except for the normal control group. At 14 h after the last treatment，serum and liver samples were obtained，the serum content of alanine aminotransferase （ALT） and aspartate transaminase（AST） were determined， the histopathologic changes of the hepatic tissues were observed by hematoxylin ecosin（HE） staining.The content of malondialdehyde (MDA) in liver was determined by thiobarbituric acid (TBA) and the content of lactate dehydrogenase (LDH) was determined by microplate method. Western blot and TUNEL assay kit was used to detect the cell pyroptosis rate.Result:Compared with normal group， ALT， AST， MDA and LDH levels in the model group were significantly increased， liver index was significantly increased，TUNEL staining positive， inflammatory factors and pyroptosis related protein expressions were significantly increased （P<0.05）. Compared with model control group， the ALT，AST ，MDA and LDH of the drug intervention group decreased significantly （P<0.05）. The liver index decreased in different degrees， and the expression of inflammatory factors and pyroptosis related protein in the water extract treatment group decreased significantly （P<0.05）.Conclusion:The root extract of Ficus pandurata Hance has protective effect on acute alcoholic liver injury， and the mechanism of water extract might relate to inhibiting hepatocyte pyroptosis.