Objective:To analyze the impact of lymph node dissection on textbook outcomes (TO) and the prognosis of intrahepatic cholangiocarcinoma (ICC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 376 ICC patients who underwent hepatectomy in 4 medical centers, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from December 2011 to December 2017 were collected. There were 242 males and 134 females, aged 57(range, 48-63)years. According to the criteria of TO, patients were classified as two cate-gories, including patients achieving TO and not achieving TO. Measurement data with normal distri-bution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were represented as absolute numbers, and comparison between groups was conducted using the chi-square test, Yates adjusted chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the non-parameter rank sum test. Univariate and multivariate analyses were conducted using the Logistic regression model. The Kaplan-Meier method was used to draw survival curve. Survival analysis was conducted using the Log-rank test. Results:(1) TO situations. Of the 376 ICC patients who underwent hepatectomy, 199 cases achieved TO, including 40 cases with lymph node dissection and 159 cases without lymph node dissection, 177 cases did not achieve TO, including 76 cases with lymph node dissection and 101 cases without lymph node dissection. (2) Influencing factors for TO after hepatectomy of ICC patients. Results of multivariate analysis showed that lymph node dissection, microvascular invasion, nerve invasion and the volume of intraoperative blood loss >800 mL were independent risk factors for achieving TO after hepatec-tomy of ICC patients ( odds ratio=2.22, 2.95, 3.58, 4.09,95% confidence interval as 1.34-3.69, 1.43-6.07, 1.40-9.17, 1.35-12.43, P<0.05). Of the 116 patients with lymph node dissection, 40 cases achieved TO, 103 cases achieved R 0 resection, 38 cases had postoperative complications, 67 cases had delayed hospital stay. The above indicators were 159, 255, 41, 65 of 260 patients without lymph node dissection. There were significant differences in the above indicators between patients with and without lymph node dissection ( χ2=22.90, 15.16, 13.95, 37.78, P<0.05). (3) Follow-up. All the 376 patients were followed up for 19(range, 1-74)months. Of 199 patients achieving TO, the 1-, 2-and 3-year survival rates of 40 patients with lymph node dissection were 54.0%, 36.6% and 26.1%, respectively, versus 67.7%, 42.7% and 34.4% of 159 patients without lymph node dissection, showing no significant difference between them ( χ2=1.89, P>0.05). Of 177 patients not achieving TO, the 1-, 2-and 3-year survival rates of 76 cases with lymph node dissection were 58.9%, 25.7% and 10.3%, respectively, versus 53.0%, 28.5% and 17.2% of 101 cases without lymph node dissection, showing no significant difference between them ( χ2=0.25, P>0.05). Conclusions:Lymph node dissec-tion, microvascular invasion, nerve invasion and the volume of intraoperative blood loss >800 mL are independent risk factors for achieving TO after hepatectomy of ICC patients. Lymph node dissec-tion may increase the postoperative complication rate, prolong the hospital stay and decrease the rate of achieving TO. However, it does not affect the prognosis of patients.

Objective To investigate the role and underlying mechanism of cathepsin B in myocar-dial injury in mice with diabetic cardiomyopathy(DCM).Methods Twenty 8-week-old male SPF C57BL/6 mice were randomly divided into wild-type(WT)group and WT DCM group,with 10 mice in each group.Another 20 8-week-old male SPF-grade mice with cathepsin B knockout(KO)were randomly and equally assigned to KO group and KO DCM group.HE staining was used to observe morphological changes,Prussian blue staining was employed to detect iron deposition,while immunohistochemical staining with 4-hydroxynonenal(4-HNE)was used to assess lipid peroxidation level in the myocardial tissues.Western blotting was performed to detect the expression of heme oxygenase-1(HO-1),superoxide dismutase 2(SOD2),and nuclear factor E2-related factor 2(Nrf2),while RT-PCR was applied to evaluate the expressions of Nrf-2,HO-1,and phospholipid hydroperoxide glutathione peroxidase 4(GPX4).Results Compared to the WT DCM group,the KO DCM group presented improved cell arrangement in cardiac tissues and sig-nificant reduction in inflammatory cell infiltration.Furthermore,the KO DCM group displayed a significant decrease in iron deposition compared to the WT DCM group.Additionally,the KO DCM group exhibited a significant reduction in 4-HNE expression compared to the WT DCM group.The protein levels of Nrf2,SOD2,and HO-1 were significant increased in the KO DCM group than the WT DCM group(0.68±0.21 vs 0.39±0.13,0.59±0.10 vs 0.28±0.09,1.03±0.10 vs 0.48±0.04,P＜0.05).Moreover,elevated mRNA levels of GPX4,Nrf2 and HO-1 were also observed in the KO DCM group than the WT DCM group(0.65±0.09 vs 0.40±0.10,0.61±0.11 vs 0.34±0.11,0.62±0.12 vs 0.39±0.09,P＜0.05).Conclusion Cathepsin B exacerbates myocardial injury in DCM mice through ferroptosis.

Despite complications were significantly reduced due to the popularity of percutaneous coronary intervention (PCI) in clinical trials, reperfusion injury and chronic cardiac remodeling significantly contribute to poor prognosis and rehabilitation in AMI patients. We revealed the effects of HSP47 on myocardial ischemia-reperfusion injury (IRI) and shed light on the underlying molecular mechanism. We generated adult mice with lentivirus-mediated or miRNA (mi1/133TS)-aided cardiac fibroblast-selective HSP47 overexpression. Myocardial IRI was induced by 45-min occlusion of the left anterior descending (LAD) artery followed by 24 h reperfusion in mice, while ischemia-mediated cardiac remodeling was induced by four weeks of reperfusion. Also, the role of HSP47 in fibrogenesis was evaluated in cardiac fibroblasts following hypoxia-reoxygenation (HR). Extensive HSP47 was observed in murine infarcted hearts, human ischemic hearts, and cardiac fibroblasts and accelerated oxidative stress and apoptosis after myocardial IRI. Cardiac fibroblast-selective HSP47 overexpression exacerbated cardiac dysfunction caused by chronic myocardial IRI and presented deteriorative fibrosis and cell proliferation. HSP47 upregulation in cardiac fibroblasts promoted TGFβ1-Smad4 pathway activation and Smad4 deubiquitination by recruiting ubiquitin-specific peptidase 10 (USP10) in fibroblasts. However, cardiac fibroblast specific USP10 deficiency abolished HSP47-mediated fibrogenesis in hearts. Moreover, blockage of HSP47 with Col003 disturbed fibrogenesis in fibroblasts following HR. Altogether, cardiac fibroblast HSP47 aggravates fibrosis post-myocardial IRI by enhancing USP10-dependent Smad4 deubiquitination, which provided a potential strategy for myocardial IRI and cardiac remodeling.

Objective:To investigate the risk factors for death in patients with corona virus disease 2019 (COVID-19).Methods:The clinical data of 141 cases of patients diagnosed with COVID-19 at Renmin Hospital of Wuhan University from February 1 to February 26, 2020 were included in this retrospective analysis. The gender, age, time of hospitalization after the onset, clinical manifestations, underlying diseases, laboratory examination indicators (inculding white blood cell counts, neutrophil counts, lymphocyte counts, lymphocyte subsets, immunoglobulin, complement 3, complement 4, D-dimer, fibrinogen), and short term prognosis were compared between the death group and the survival group. Logistic regression was used to analyze the factors influencing the death of COVID-19 patients. The t test, Mann Whitney U test or chi-square test were used for comparison between groups. Results:Of the 141 COVID-19 patients, 52 died and 89 survived. The age, hypertension, chronic respiratory diseases, cardiovascular and cerebrovascular diseases, fever and wheeze of patients in the death group were all higher than those in the survival group, which were (70.7±13.3) years old vs (50.4±15.3) years old, 51.9%(27/52) vs 14.6%(13/89), 15.4%(8/52) vs 4.5%(4/89), 30.8%(16/52) vs 7.9%(7/89), 80.8%(42/52) vs 61.8%(55/89) and 50.0%(26/52) vs 25.8%(23/89), respectively. The differences were all statistically significant ( t=7.972, χ2=22.104, 3.615, 12.392, 5.503 and 8.447, respectively, all P<0.05). The white blood cell count, neutrophil count, CD4 + /CD8 + T lymphocyte, immunoglobulin E, D-dimer, fibrinogen, CD19 + T lymphocyte proportion and CD19 + T lymphocyte count of patients in the death group were all higher than those in the survival group, which were 8.20(5.26, 13.01)×10 9/L vs 5.29(3.96, 7.04)×10 9/L, 7.40(4.54, 11.46)×10 9/L vs 3.16(2.20, 5.01)×10 9/L, 2.32(1.77, 3.11) vs 1.63(1.25, 2.08), 125.0(42.6, 275.0) IU/mL vs 66.8(38.3, 143.0) IU/mL, 7.27(2.11, 16.21) mg/L vs 0.95(0.38, 2.54) mg/L, 4.37(2.72, 6.78) g/L vs 4.10(2.78, 4.97) g/L, (23.19±13.43)% vs (15.38±6.38)%, and (181.5±115.4)/μL vs (98.89±77.64)/μL, respectively. The differences were all statistically significant ( Z=3.944, 4.210, 2.834, 1.190, 5.497, 1.180, t=3.987, 3.411, respectively, all P<0.05). The lymphocyte count, CD3 + T lymphocyte proportion, CD3 + T lymphocyte count, CD8 + T lymphocyte proportion, CD8 + T lymphocyte count, CD16 + CD56 + T lymphocyte count and CD4 + T lymphocyte count were all lower than those in survival group, which were 0.47(0.37, 0.96)×10 9/L vs 1.33(0.90, 1.55)×10 9/L, 48.72%(42.31%, 76.92%) vs 69.91%(65.05%, 75.36%), 223.0(100.0, 403.0)/μL vs 761.0(499.0, 1 092.0)/μL, 13.82%(10.32%, 19.82%) vs 24.90%(20.87%, 29.57%), 55.5(30.5, 106.0)/μL vs 318.0(162.5, 443.5)/μL, 63.0(29.0, 99.5)/μL vs 140.0(69.5, 195.5)/μL and (209.74±140.13)/μL vs (487.61±232.02)/μL, respectively. The differences were all statistically significant ( Z=6.937, 3.944, 5.883, 3.924, 5.703, 3.517 and t=7.558, respectively, all P<0.01). Age, history of hypertension, white blood cell count, D-dimer, and fibrinogen were the risk factors for death of COVID-19 (odds ratio ( OR)=1.170, 10.405, 3.055, 1.128 and 1.343, respectively, all P<0.05). Conclusion:Age, underlying hypertension, white blood cell count, D-dimer and fibrinogen are independent prognostic factors for COVID-19.

Oxidative stress and cardiomyocyte apoptosis are involved in the pathogenesis of doxorubicin (DOX)-induced cardiotoxicity. Matrine is well-known for its powerful anti-oxidant and anti-apoptotic capacities. Our present study aimed to investigate the effect of matrine on DOX-induced cardiotoxicity and try to unearth the underlying mechanisms. Mice were exposed with DOX to generate DOX-induced cardiotoxicity or normal saline as control. H9C2 cells were used to verify the effect of matrine . DOX injection triggered increased generation of reactive oxygen species (ROS) and excessive cardiomyocyte apoptosis, which were significantly mitigated by matrine. Mechanistically, we found that matrine ameliorated DOX-induced uncoupling protein 2 (UCP2) downregulation, and UCP2 inhibition by genipin could blunt the protective effect of matrine on DOX-induced oxidative stress and cardiomyocyte apoptosis. Besides, 5'-AMP-activated protein kinase 2 () deficiency inhibited matrine-mediated UCP2 preservation and abolished the beneficial effect of matrine in mice. Besides, we observed that matrine incubation alleviated DOX-induced H9C2 cells apoptosis and oxidative stress level activating AMPK/UCP2, which were blunted by either AMPK or UCP2 inhibition with genetic or pharmacological methods. Matrine attenuated oxidative stress and cardiomyocyte apoptosis in DOX-induced cardiotoxicity maintaining AMPK/UCP2 pathway, and it might be a promising therapeutic agent for the treatment of DOX-induced cardiotoxicity.

The T-Box transcription factor family plays a crucial role during heart development. A large amount of clinical evidence showed TBX 1, 2, 5, 18, 20 proteins to be strongly associated with human congenital heart diseases including atrial septal defect, mitral valve disease, and tetralogy of Fallot. Among these, TBX20 has attracted much attention. This article gives a brief review for the progress made in the research on TBX20 and cardiovascular disease.
Cardiovascular Diseases ; prevention & control ; Gene Expression Regulation ; Humans ; T-Box Domain Proteins ; genetics

Objective To investigate the expression of PLP2 protein in the process of cardiac remodeling.Methods Mice were subjected to left anterior descending coronary artery ligation to induce cardiac remodeling model.Mice were subjected to isoproterenol (ISO) subcutaneous injection for 2 weeks to establish acute cardiac injury model.Mice were subjected to aortic banding (AB) surgery to establish a myocardial hypertrophy model.Cardiac myocytes hypertrophy model was induced by phenylephrine (PE) stimulation.Transforming growth factor (TGF) beta was used to stimulate cardiac fibroblasts.The PLP2 transcription level was detected by RT-PCR.Results PLP2 expression was significantly increased in 2 weeks after myocardial infarction (P ＜ 0.05),as well as in acute cardiac injury induced by ISO injection (P ＜ 0.05).After 1 week of AB surgery,the PLP2 expression began to increase (P ＜ 0.05),peaked at 2 weeks post AB (P ＜ 0.05),preserved to 8 weeks after AB (P ＜ 0.05).The expression of PLP2 in PE stimulated cardiomyocytes was increased as well as TGFβ stimulated fibroblast.Conclusion The expression of PLP2 were dynamically changed significantly in different cardiac remodeling model,suggesting that it may be involved in the occurrence and development of cardiac remodeling.

Objective:To investigate the protective effect of evodiamine on cardiomyocytes hypoxia injury. Methods:H9c2 myo-cardial cells were exposed to hypoxia for 24 h to induce myocardial cell injury model. The cells were pretreated with different concentra-tions of evodiamine for 12 h. The cardiomyoctes viability was detected by CCK-8 assay. The transcription of inflammatory cytokines was detected by RT-PCR. The cardiomyocyte apoptosis was detected with Tunel staining. The alteration of signal pathway was detected by immunoblotting. Results:Four concentrations of evodiamine did not affect the activity of cardiomyocytes in the basal condition (P>0.05). After 24-hour hypoxia,the viability of cardiomyocytes decreased significantly when compared with that in the control group with significant difference (P<0.05) among 1,5 and 10 μmol·L-1evodia in a dose-dependent manner. The transcription of pro-inflam-matory cytokines(TNF-α,IL-1 and IL-6) significantly increased and the cells apoptosis increased. Evodiamine pretreatment increased the cell viability after hypoxia injury, reduced the transcription of inflammatory cytokines and reduced the number of apoptotic cells when compared with that in the control group with significant differences(P<0.05) between 1 μmol·L-1and 10 μmol·L-1evodia. The results of western blot showed that evodiamine activated AMPKα and AKT, inhibited the activity of NF- kappa B, and compared with the control group,there were significant differences(P<0.05) between 1 μmol·L-1and 10 μmol·L-1of evodia. Conclusion:Evodiamine can protect cardiomyocytes from hypoxia injury and may become a new anti-myocardial ischemia drug.