[Association of ambient fine particulate air pollution with hospitalization costs and stays for depression in China: a multicity analysis].

Objective: To explore the effect of fine particulate matter (PM2.5) pollution on depression hospitalization cost and length of stay in 57 cities of China. Methods: A total of 84 207 patients with depression in 57 cities of China from January 2013 to December 2017 were selected as the subjects. The demographic characteristics and hospitalization status of the patients were obtained from the database of basic medical insurance for urban workers and urban residents in China. The environmental exposure data of the same period were obtained from the national air quality real-time release platform of China Environmental Monitoring Station. A generalized additive model based on quasi-Poisson distribution was used to analyze PM2.5 exposure effect in each city, and the nonlinear mixing of moving average temperature, relative humidity and date was controlled by natural smooth spline function. Results: Among the included cities, southern cities accounted for 50.88% (29), and the number of female inpatients, hospitalization costs and hospitalization days accounted for 62.65%, 63.50% and 60.85% (42 735 cases, 567.78 million yuan and 1.14 million days, respectively). The proportion of hospitalized cases, hospitalization cost and length of stay in the age group of 40 to 64 years old were 59.15% (40 346 cases), 53.92% (482.15 million yuan) and 52.07% (0.98 million days), respectively. PM2.5 level was positively correlated with the number of hospitalized cases with depression, hospitalization cost and length of stay. When the 3-day moving average of PM2.5 exposure level increased by 10 µg/m3, the number of hospitalization cases increased by 0.64%. The attributed percentage (95%CI) of hospitalized cases, hospitalization costs and length of stay were 3.35% (0.57%-6.04%), 3.04% (0.52%-5.48%) and 3.07% (0.49%-5.56%), respectively. Subgroup analysis showed that the attributed percentage of hospitalization cases, hospitalization cost and length of stay to PM2.5 exposure ranged from 3.97% to 4.68%, 4.04% to 4.33% and 4.13% to 4.30% in northern China, male and cold season, respectively. Conclusion: PM2.5 exposure is associated with the increase of hospitalization cost and length of stay among Chinese urban population with depression.

[Analysis on tissue-related biomarkers in patients with acute aortic dissection].

Objective: To explore the clinical implication of tissue-related biomarkers in patients with acute aortic dissection (AAD). Methods: It was a cross-sectional study. Ten Stanford Type A AAD patients, who were diagnosed and surgically treated in the Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, from December 2018 to August 2019, were selected as the case group. Meanwhile, 10 patients with atherosclerotic heart disease, who underwent coronary artery bypass grafting (CABG), were selected as control group. The ascending aorta tissue specimens from patients of the two groups were collected during the operation. Four-dimensional non-standard quantitative proteomics technology (4D-LFQ) was used to detect the protein profile of ascending aorta tissue specimens of the two groups and to screen out differentially expressed proteins and analyze their biological functions. Precise quantification of the selected target proteins was achieved by parallel response monitoring (PRM). Results: A total of 3 985 proteins were identified by 4D-LFQ technology, among which 3 350 proteins could be quantified. There were 39 proteins were significantly upregulated and 47 proteins were significantly downregulated in AAD group. The results of biological function analysis showed that most of the differentially expressed proteins were located in the extracellular, and their functions were mainly involved in cell migration and proliferation, inflammatory cell activation, cell contraction, and muscle organ development. The 15 selected proteins underwent precise quantification by PRM, and the results showed that integrin α-Ⅱb (ITGA2B), integrin α-M (ITGAM), integrin ß-2 (ITGB2), integrin ß-3 (ITGB3) were significantly upregulated in the ascending aorta tissue of AAD patients. Conclusion: ITGA2B, ITGAM, ITGB2, and ITGB3 are highly expressed in aortic tissues of patients with AAD, which may be used as biomarkers for the diagnosis of AAD patients.

[The correlation between coagulation function and prognosis in patients with acute respiratory distress syndrome caused by extrapulmonary sepsis or pulmonary infection].

Objective: To explore the difference of coagulation function and its correlation with prognosis in patients with acute respiratory distress syndrome (ARDS) caused by extrapulmonary sepsis and pulmonary infection. Methods: ARDS patients caused by extrapulmonary sepsis and pulmonary infection admitted to the ICU were retrospectively analyzed at the First Affiliated Hospital of China Medical University from July 2017 to June 2019. The clinical characteristics were collected including sequential organ failure assessment (SOFA), coagulation parameters [prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (Fib), D-Dimer (D-D), fibrinogen degradation product (FDP), antithrombin Ⅲ(AT-Ⅲ), platelet (PLT)], duration of mechanical ventilation, length of stay (LOS) in ICU and 28-day mortality. According to the risk factors, the patients were divided into extrapulmonary sepsis group and pulmonary infection group. The correlation analysis between coagulation parameters and the prognosis of ARDS patients were analyzed by multivariate logistic regression analysis. Results: A total of 268 ARDS patients were screened and 28 cases were excluded. Finally, 240 ARDS patients were enrolled, including 145 caused by extrapulmonary sepsis and 95 by pulmonary infection. PT, INR and APTT in the extrapulmonary sepsis group were significantly higher than those in pulmonary infection group (P<0.05). AT-Ⅲ level was lower than that in pulmonary infection group (P<0.05). Ninty-three patients survived at 28 days in the non-pulmonary sepsis group, the mortality rate was 35.9% (52/145). PT, INR, APTT in patients who died at 28 days were significantly higher than those of the patients who survived (P<0.05), while AT-Ⅲ level was lower than those of the patients who survived (P<0.05). 49 patients survived at 28 days in the pulmonary infection group, the mortality rate was 48.4% (46/95). There was no significant difference in the coagulation parameters between two groups. Multivariate logistic regression analysis showed that SOFA score without PLT(OR=1.210,95%CI 1.067-1.372,P=0.003) and INR (OR=2.408,95%CI 1.007-5.760,P=0.048) were independent risk factors for 28-day mortality in extrapulmonary sepsis group. Coagulation parameters are not independent risk factors for 28-day mortality in ARDS patients related to pulmonary infection. Conclusion: There are significant differences in coagulation function between ARDS patients caused by extrapulmonary sepsis or pulmonary infection. INR is an independent risk factor for 28-day mortality in extrapulmonary sepsis group.

[The clinical application of blood routine and liver and kidney function test in COVID-19 disease prediction].

Objective: To explore the clinical application value of routine indicators such as blood routine and liver and kidney function in auxiliary diagnosis and prognosis of COVID-19 patients. Methods: SNK-q and other methods were used to retrospectively analyzed the differences of blood routine test, liver and kidney function and other inflammatory indexes of 30 patients with covid-19, 29 patients with other viral pneumonia, 35 patients with influenza A/B and 25 healthy persons from January 28 to February 14, 2020 in Xiangya Hospital of Central South University. Results: The neutrophils count increased gradually in COVID-19 group, influenza A/B group and other types of viral pneumonia group, and the difference between COVID-19 group and other viral pneumonia groups was statistically significant(H=-19.064,P<0.05); The lymphocyte count decreased gradually in the control group, influenza A/B group, other viral pneumonia group and COVID-19 group. In addition, DB, UA and GLU were also different among groups. Subgroup analysis showed that there were statistically significant differences in N(F=9.581,t=-0.152,P<0.05), N%(F=5.723,t=-0.600, P<0.05), NLR(F=4.773, t=-1.161, P<0.05), PCT(F=17.464, t=-1.477, P<0.05)and CRP(F=7.656, t=-1.973, P<0.05) between patients with lung involvement +-++ and patients with lung involvement +++-++++. There were statistically significant differences in NLR(F=63.931, t=-2.815, P<0.01), AST(F=15.704, t=-1.930, P<0.01), ALT(F=35.551, t=-2.199, P<0.01), LDH(F=7.715, t=-2.703, P<0.05) and GLU(F=6.306, t=-5.116, P<0.05) between the light+common subgroup and the heavy+critical subgroup of COVID-19 clinical classification. Correlation analysis showed that clinical stage and imaging credit period were significantly correlated with NLR (r=0.406, P=0.026; r=0.397, P=0.030), ALT (r=0.403, P=0.049; r=0.418, P=0.047), LDH (r=0.543, P<0.01; r=0.643, P<0.01) and GLU(r=0.750, P<0.01; r=0.471, P=0.042). A total of 5 principal components were extracted from all the included indicators, and the comprehensive information extraction rate was 82.86%. Indicators of a large load included Ur, PCT and CRP in PC1; ALT, AST and GLU in PC2; N%, L%, L and NLR in PC3. It indicated that the indicators of acute infection, liver function and blood routine had certein warning effect on disease surveillance. The results of ROC curve analysis showed that the combined detection of N+TB+Urea was the best practice to distinguish COVID-19 and other viral pneumonia, while the combined detection of N+L+UA was the most effective solution to make a distinction between COVID-19 and influenza A/B patients. In the aspect of disease evaluation, NL+LDH+GLU+ALT combined detection represent the best diagnostic performance to distinguish the clinical stage of light+common type and heavy+critical type, achieving the AUC (ROC) to 0.904, with the sensitivity 75% and the specificity 100% at the cut-off value of 0.477. Conclusion: In addition to etiology and imaging examination, doctors can also improve the routine laboratory tests such as blood routine test, liver and kidney function to assist diagnosis and disease prediction of patients with respiratory tract infection.

[Predictive value of neutrophil/lymphocyte ratio on myocardial injury in severe COVID-19 patients].

Objective: To explore the predictive value of neutrophil/lymphocyte ratio (NLR) on myocardial injury in severe COVID-19 patients. Methods: In this single-center retrospective cohort study, we collected and analyzed data form 133 severe COVID-19 patients admitted to Renmin Hospital of Wuhan University (Eastern District) from January 30 to February 18, 2020. Patients were divided into myocardial injury group (n=29) and non-myocardial injury group (n=104) according the presence or absence of myocardial injury. The general information of patients was collected by electronic medical record database system. All patients were followed up for 30 days, the organ injury and/or dysfunction were monitored, the in-hospital death was compared between the two groups, and the disease progression was reevaluated and classified at 14 days after initial hospitalization. Logistic regression analysis was performed to identify risk factors of myocardial injury in severe COVID-19 patients. The ROC of NLR was calculated, and the AUC was determined to estimate the optimal cut-off value of NLR for predicting myocardial injury in severe cases of COVID-19. Results: There was statistical significance in age, respiratory frequency, systolic blood pressure, symptoms of dyspnea, previous chronic obstructive pulmonary disease, coronary heart disease history, white blood cells, neutrophils, lymphocytes, platelets, C-reactive protein, platelet counting, aspartate transaminase, albumin, total bilirubin, direct bilirubin, urea, estimated glomerular filtration rate, total cholesterol, low-density lipoprotein cholesterol, D-dimer, CD3+, CD4+, partial pressure of oxygen, partial pressure of CO2, blood oxygen saturation, other organ injury, clinical outcome and prognosis between patients with myocardial injury and without myocardial injury (all P<0.05). Multivariate logistic regression analysis showed that NLR was a risk factor for myocardial injury (OR=1.066，95%CI 1.021-1.111，P=0.033). ROC curve showed that NLR predicting AUC of myocardial injury in severe COVID-19 patients was 0.774 (95%CI 0.694-0.842), the optimal cut-off value of NLR was 5.768, with a sensitivity of 82.8%, and specificity of 69.5%. Conclusion: NLR may be used to predict myocardial injury in severe COVID-19 patients.

[Significance of micropapillary histopathological subtype of thyroid carcinoma].

Objective: To study the clinical and pathologic factors of papillary thyroid microcarcinoma (PTMC) and its significance as a histopathologic subtype of papillary thyroid carcinoma (PTC). Methods: A retrospective study of 719 patients with non-high-risk PTMC who underwent surgery for the first time in the Peking University People's Hospital from January 2007 to June 2019 was conducted, the relationship between clinicopathologic factors and lymph node metastasis, and the expression of four tumor markers CK19, HMBE1, Galectin-3 and CD56 by immunohistochemistry were evaluated. Some comparisons were made with PTC. Results: The peak patients' age was 40-49 years for both non-high-risk PTMC and PTC; the lymph node metastasis rate was higher in the 30-39 years age group than the 50-59 years age group (P<0.05); the lymph nodes metastasis rate was significantly higher for multiple lesions than for single lesion (P<0.05). Lymph node metastasis rate of PTMC with capsular invasion was significantly higher than those without (P<0.05). There was no significant correlation between lymph node metastasis of PTMC and patients' gender, tumor location, tumor size, and lymphocytic thyroiditis. The expression rates of CK19, HMBE1 and Galectin-3 both in PTMC and PTC were 100%, and the expression rates of CD56 were 25.6% (85/332) and 20.0% (70/350) respectively. Conclusion: As the main pathologic subtype of PTC, a variety of clinicopathologic factors of PTMC are related to lymph node metastasis, and it is highly recommended to pay close attention to PTMC. The expression of tumor marker CD56 alone cannot be used as a basis to exclude PTMC and PTC.

Scheduling nab-paclitaxel combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma.

BACKGROUND: Nab-paclitaxel plus gemcitabine (nabP+gemcitabine) offers modest survival gains for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Sequential scheduling of nabP+gemcitabine in a PDAC mouse model improved efficacy; this hypothesis was tested in a clinical trial. METHODS: Patients with previously untreated metastatic PDAC were randomised to receive nabP+gemcitabine administered either concomitantly on the same day, or sequentially, with gemcitabine administered 24 h after nabP. The primary outcome measure was progression-free survival (PFS). Secondary outcome measures were objective response rate (ORR), overall survival (OS), safety, quality of life (QoL) and predictive biomarkers. RESULTS: In total, 71 patients received sequential (SEQ) and 75 concomitant (CON) treatment. Six-month PFS was 46% with SEQ and 32% with CON scheduling. Median PFS (5.6 versus 4.0 months, hazard ratio [HR] 0.67, 95% confidence interval [95% CI] 0.47-0.95, p = 0.022) and ORR (52% versus 31%, p = 0.023) favoured the SEQ arm; median OS was 10.2 versus 8.2 months (HR 0.93, 95% CI 0.65-1.33, p = 0.70). CTCAE Grade ≥3 neutropaenia incidence doubled with SEQ therapy but was not detrimental to QoL. Strongly positive tumour epithelial cytidine deaminase (CDA) expression favoured benefit from SEQ therapy (PFS HR 0.31, 95% CI 0.13-0.70). CONCLUSIONS: SEQ delivery of nabP+gemcitabine improved PFS and ORR, with manageable toxicity, but did not significantly improve OS. CLINICAL TRIAL REGISTRATION: ISRCTN71070888; ClinialTrials.gov (NCT03529175).

[Establishment of mouse model and preliminary screening of serum biomarkers for Candidemia].

Objective: To establish mouse models of Candidemia, and investigates statistically significant polypeptide peaks to provide auxiliary diagnosis of this disease. Methods: A total of 170 specific pathogen free adult male ICR mice with body mass of 27-30 g were completely randomly divided into Candida albicans infection group (n=80), Candida parapsilosis infection group (n=80) and the normal control group (n=10), and the two kinds of Candidemia mouse models were established via tail vein injection. The serum samples were analyzed by Matrix-assisted laser desorption-ionization time of flight mass spectrometry and relevant software, and the polypeptide peaks with significant differences were screened to establish diagnostic models. Results: A total of 65 differential polypeptide peaks were obtained compared with the Candida albicans infection group and the normal control group. Combined with m/z 1 100.4, 1 581.0, 3 808.0 as differential polypeptide peaks to established the diagnostic model, the sensitivity was 95.24%(40/42), the specificity was 90.63%(29/32), the accuracy rate was 93.24%(69/74), and the AUC value of the ROC curve was 0.972(95%CI: 0.941-1.000). A total of 73 differential polypeptide peaks were obtained compared with Candida parapsilosis infection group and the normal control group. Combined with m/z 1 433.2, 1 148.5, 4 093.5, 4 522.2, 8 140.9, 8 234.6 as differential polypeptide peaks to established the diagnostic model, the sensitivity was 95%(38/40), the specificity was 81.25%(26/32), the accuracy rate was 88.89%(64/72), and the AUC value of the ROC curve was 0.953(95%CI: 0.903-1.000). A total of 78 differential polypeptide peaks were obtained compared with Candida albicans infection group and Candida parapsilosis infection group. Combined with m/z 2 736.9, 8 091.5, 8 153.7 as differential polypeptide peaks to established the diagnostic model, the accuracy of distinguishing C. albicans infection from C. parapsilosis infection was 98.78%(81/82). Conclusions: Successfully screened the differential polypeptides and established the related diagnostic models. Which is helpful to find serum biomarkers for the auxiliary diagnosis of Candidemia, and provides a basis for the early diagnosis and the rational use of drugs.

[Comparison on the 10 years risk for ischemic cardiovascular disease among Han, Uygur, Kazak population from Xinjiang Uygur Autonomous Region].

Objective: To compare the 10 years risk for ischemic cardiovascular disease among Han, Uygur, Kazak nationality residents of Xinjiang Uygur Autonomous Region. Methods: From October 2007 to October 2010,14 618 adult (aged ≥35 years) Han (n=5 757),Uygur (n=4 767) and Kazak (n=4 094) residents were selected to join this study through the four-stage stratified cluster sampling method from 7 cities and regions of Xinjiang Uygur Autonomous Region. The 10 years risk for ischemic cardiovascular disease was calculated according to the 10 years ischemic cardiovascular disease risk assessment form modified with Chinese characteristics and compared among the residents of 3 nationalities. Results: (1) There were significant differences in age, body mass index, systolic blood pressure, diastolic blood pressure,fasting blood glucose,triglycerides,total cholesterol,low-density lipoprotein,high-density lipoprotein cholesterol, smoking history, and drinking history among Han, Uygur, Kazak nationality population (all P< 0.001). (2) There were significant differences in 10 years risk for ischemic cardiovascular disease between different gender and age group including 35-39, 40-44, 45-49, 50-54, 55-59, and ≥60 years old between Han, Uygur, Kazak nationality population (all P<0.001). (3) There were significant differences in rates of 10%-20% and>20% of 10 years risk for ischemic cardiovascular disease between different gender in Han, Uygur, Kazak nationality population (P values were 0.013 and <0.001, respectively). There were no significant differences in rates of <5% and 5%-9% of 10 years risk for ischemic cardiovascular disease between different gender in Han,Uygur,Kazak nationality population (all P>0.05).(4) There were significant differences in detection rates of diabetes,hypertension,smoking,hypertriglyceridemia,and obesity in male and female Han,Uygur,Kazak nationality population with 10 years risk for ischemic cardiovascular disease ≥10% (P<0.01 or 0.05). Meanwhile,there was significant difference in detection rates of hypercholesteremia in male Han, Uygur, Kazak nationality adults(P<0.001). There were no significant differences in detection rates of elevated low density lipoprotein cholesterol and reduced high density lipoprotein cholesterol in male and female Han,Uygur,Kazak nationality adults (all P>0.05). Conclusion: There are gender and age differences in the 10 years risk for ischemic cardiovascular disease in ≥35 years old Han,Uygur,Kazak nationality adults from Xinjiang Uygur Autonomous Region.

[Combined application of immunohistochemical markers to identify pathologic subtypes of ampullary carcinoma and its clinical significance].

Objective: To investigate the expression of immunomarkers CK7, CK20, CK17, CDX2, MUC1 and MUC2 in primary adenocarcinoma of the ampulla of Vater, to explore the role of these markers in the histopathologic subclassification of ampullary carcinoma; and to provide biologic basis for precision treatment of patients with different types of ampullary carcinoma. Methods: Forty-two cases of primary ampullary carcinoma were collected at Peking University People's Hospital, from 2012 to 2018 year. There were 22 males and 20 females. Aged range 42 to 88 years old, with mean aged (62±11) years. Among the patients, 6 was high differentiation, 19 median differentiation, and 17 low differentiation. Immunohistochemical studies on the expression of CK7, CK20, CK17, CDX2, MUC1 and MUC2 were performed in 42 cases of primary ampullary carcinoma. The relationship between different ampullary carcinoma subtypes and clinicopathologic survival data was analyzed using SPSS 16.0 statistical software. Results: Three histopathologic subtypes were observed. Among 42 cases, 8(19.0%)were classified as intestinal subtype, which showed a positive expression rate of 8/8 for both CK20 and CDX2, and 5/8 for MUC2. Both CK7 and CK17 were weakly expressed in one case (1/8). No expression was observed for MUC1 in this subtype. Twenty-two (52.4%,22/42) cases were classified as pancreaticobiliary subtype, which showed a positive expression rate of 100.0%(22/22) for both CK7 and MUC1, and 90.9% (20/22) for CK17. No expression was observed for CK20, CDX2 and MUC2.The remaining 12 (28.6%) cases were classified as mixed subtype, which showed variable expression patterns. The expression frequencies of these 6 immunomarkers in different subtypes of ampullary carcinoma did not correlate with various clinicopathologic factors such as patient gender and age, tumor size, histologic differentiation, pancreatic and bile duct invasion, or the depth of duodenal invasion. However, stage Ⅲ+Ⅳ diseases were more commonly seen in pancreaticobiliary type (63.6%,14/22) than intestinal type (2/8) and mixed type (3/9; χ(2)=6.508, P=0.039). Follow-up data showed a trend of better survival rate for patients with intestinal subtype than those with mixed and pancreaticobiliary subtypes. Conclusions: Ampullary carcinoma can be subclassified into three different subtypes using a panel of six immunomarkers, especially for the identification of subtypes of poorly differentiated carcinoma. CK7, CK17 and MUC1 are major markers of pancreaticobiliary subtype, whereas CK20, CDX2 and MUC2 are useful markers for intestinal subtype. The mixed subtype variably expresses these markers. The prognosis of patients with intestinal subtype appears better than that of pancreaticobiliary and mixed subtypes. Accurate subtyping of ampullary carcinoma is clinically important to patient management and prognosis assessment.

A multicentre, open-label, phase-I/randomised phase-II study to evaluate safety, pharmacokinetics, and efficacy of nintedanib vs. sorafenib in European patients with advanced hepatocellular carcinoma.

BACKGROUND: This multicentre, open-label, phase-I/randomised phase-II trial evaluated safety, pharmacokinetics, maximum-tolerated-dose (MTD) per dose-limiting toxicities (DLTs), and efficacy of nintedanib vs. sorafenib in European patients with unresectable advanced hepatocellular carcinoma (aHCC). METHODS: Phase I: Patients were stratified into two groups per baseline aminotransferase/alanine aminotransferase and Child-Pugh score; MTD was determined. Phase II: Patients were randomised 2:1 to nintedanib (MTD) or sorafenib (400-mg bid) in 28-day cycles until intolerance or disease progression. Time-to-progression (TTP, primary endpoint), overall survival (OS) and progression-free survival (PFS) were determined. RESULTS: Phase-I: no DLTs observed; nintedanib MTD in both groups was 200 mg bid. Phase-II: patients (N = 93) were randomised to nintedanib (n = 62) or sorafenib (n = 31); TTP was 5.5 vs. 4.6 months (HR = 1.44 [95% CI, 0.81-2.57]), OS was 11.9 vs. 11.4 months (HR = 0.88 [95% CI, 0.52-1.47]), PFS was 5.3 vs. 3.9 months (HR = 1.35 [95% CI, 0.78-2.34]), respectively (all medians). Dose intensity and tolerability favoured nintedanib. Fewer patients on nintedanib (87.1%) vs. sorafenib (96.8%) had drug-related adverse events (AEs) or grade ≥ 3 AEs (67.7% vs. 90.3%), but more patients on nintedanib (28 [45.2%]) had AEs leading to drug discontinuation than did those on sorafenib (7 [22.6%]). CONCLUSIONS: Nintedanib may have similar efficacy to sorafenib in aHCC.

Prognostic scores for sorafenib-treated hepatocellular carcinoma patients: A new application for the hepatoma arterial embolisation prognostic score.

BACKGROUND: No prognostic classification is currently used for patients treated with systemic therapies for Hepatocellular Carcinoma (HCC). METHODS: We retrospectively analysed data from patients treated with sorafenib for HCC from five centres in France and in the United Kingdom (UK). The training set comprised data from two centres and the validation set from three. Variables independently associated with Overall Survival (OS) in the training set were used to build the SAP (Sorafenib Advanced HCC Prognosis) score. The score was tested in the validation set, then compared with other prognostication systems. RESULTS: The training set and validation set included 370 and 468 patients respectively. In the training set, variables independently associated with OS in multivariable analysis were: performance status (PS) >0, alpha-fetoprotein (AFP) >400 ng/ml, tumour size >7 cm, bilirubin >17 µmol/l and albumin <36 g/l. The SAP score was built giving one point to each abnormal variable, and three classes were constructed. The SAP score was significantly associated with OS in the training set, with median OS of 14.9 months for SAP A, 7.2 months for SAP B and 2.5 months for SAP C (P < 0.001). In the validation set, the SAP score was significantly associated with OS, and showed greater discriminative abilities than Barcelona Clinic Liver Cancer (BCLC) and albumin-bilirubin (ALBI) scores. However, the hepatoma arterial embolisation prognostic (HAP) score showed greater discriminative abilities than the SAP score. CONCLUSION: In European patients treated with sorafenib, the HAP was the most discriminant prognostic score and may facilitate stratification in trials and inform clinical decision making.

[Effect and potential mechanism of ß3-adrenoceptor activation on fibrosis in cardiac fibroblast cell].

OBJECTIVE: To observe the effect of ß3 adrenergic receptor (ß3-AR) on fibrosis in cardiac fibroblasts(CFBs) and explore the related mechanisms. METHODS: Neonatal CFBs were divided into negative control group (N-CFC): CFBs without any intervention; group treated with ß3 adrenergic receptor agonist (AngⅡ-CFC-ß3-AR BRL): CFBs treated with 10(-6) mol/L angiotensin Ⅱ(AngⅡ), 1 hour later treated with 10(-5) mol/L ß3 adrenergic receptor agonist (ß3-AR BRL37344); group treated with ß3 adrenergic receptor antagonist (AngⅡ-CFC-ß3-AR SR): CFBs treated with 10(-6) mol/L AngⅡ, 1 hour later treated with 10(-5) mol/L ß3 adrenergic receptor antagonist (ß3-AR SR59230A); and positive control group (AngⅡ-CFC): CFBs treated with 10(-6) mol/L AngⅡonly. Proliferation of CFBs was detected by the method of WST-1. Protein expression of ß3-AR, transforming growth factor ß1 receptor (TGF-ß1-R), transforming growth factor ß1(TGF-ß1), Smad-2, phospho-Smad-2 (p-Smad-2), collagen-Ⅰ (COL-Ⅰ) and collagen-Ⅲ(COL-Ⅲ) was determined by Western blot assay. RESULTS: (1) The proliferation of CFBs was the highest in AngⅡ-CFC-ß3-AR BRL, followed by AngⅡ-CFC-ß3-AR SR and AngⅡ-CFC group (all P<0.05 vs. N-CFC group). (2) The protein expression level of ß3-AR, TGF-ß1-R, TGF-ß1 and p-Smad-2 was in the same order as proliferation of CFBs. (3) The expression level of COL-Ⅰ and COL-Ⅲ protein was also in the same order as proliferation of CFBs. CONCLUSION: Activation of ß3-AR may promote fibrosis of CFBs through the TGF-ß/Smad signaling pathway and thus aggravate myocardial remodeling.

[Role and related mechanism of S1P/S1P1 signal pathway during post conditioning of hypertrophic cardiomyocytes].

OBJECTIVE: To study the role and mechanism of sphingosine-1-phosphate (S1P)/ sphingosine-1-phosphate receptor 1(S1P1) signal pathway during post conditioning of hypertrophic cardiomyocytes. METHODS: Neonatal rat cardiomyocytes were isolated and cultured, then stimulated by norepinephrine (NE) to induce cardiomyocytes hypertrophy. Using tri-gas incubator to create hypoxia and reoxygenation enviroment to mimic ischemia-reperfusion and postconditioning. Hypertrophic cardiomyoctyes were divided into five groups according to the presence or absence of various drugs and postconditiong and relevant signal pathways changes were detected: (1) IPost group (hypoxia+ postconditioning); (2) IPost+ S1P group (cells were pretreated with S1P (1 µmol/L) for 2 h before IPost); (3) IPost+ W-146+ S1P group (cells in IPost+ W-146+ S1P group were pretreated with S1P1 inhibitor W-146 (0.4 µmol/L) for 20 min); (4) IPost+ PD98059+ S1P group (cells in IPost+ S1P group were pretreated with MAPK antagonist PD98059 (125 µmol/L) for 20 min); (5) IPost+ LY-294002+ S1P group (cells in IPost+ S1P group were pretreated with PI3K antagonist LY294002 (0.1 µmol/L) for 20 min). Apoptosis was detected by flow cytometry and protein expression of relevant signal pathways were detected by Western blot. RESULTS: (1)Apoptosis rate was significantly increased in hypoxia/reoxygenation (27.90±4.49)% group compared with normal control group (7.97±2.18)%, which could be significantly reduced in IPost group (15.90±1.77)% (all P<0.05). (2)Apoptosis rate and caspase-3 expression were both significantly lower in IPost+ S1P and IPost+ S1P+ LY-294002 groups than in IPost and IPost+ S1P+ W-146 and IPost+ S1P+ PD98059 group (all P<0.05). (3)p-ERK1/2 expression was significantly higher in IPost+ S1P and IPost+ S1P+ LY-294002 group than in IPost and IPost+ S1P+ W-146 group and IPost+ S1P+ PD98059 group (all P<0.05) while p-Akt expression was similar among IPost, IPost+ S1P+ W-146 and IPost+ S1P+ PD98059 groups. p-ERK1/2 and p-Akt levels in IPost+ S1P+ W-146 group and IPost+ S1P+ PD98059 were similar as in IPost group. CONCLUSIONS: S1P can play protective role on NE induced cardiomyocytes hypertrophy during post conditioning through downregulating caspase-3 expression and reducing apoptosis rate via targeting S1P1 and activating ERK1/2 signal pathway.

[A large-scale, multicenter, retrospective study on efficacy of bivalirudin use during peri-percutaneous coronary intervention period for Chinese patients with coronary heart disease].

OBJECTIVE: To observe the efficacy and safety of bivalirudin use in Chinese patients with coronary heart disease (CHD) during the peri-percutaneous coronary intervention(PCI) period. METHODS: A total of 3 271 patients who underwent PCI and received periprocedural bivalirudin treatment between July 2013 and October 2015 from 88 centers of China were involved in this study. The primary outcome was 30-day net adverse clinical events (NACE a composite of major adverse cardiac or cerebral events (MACE, all-cause death, reinfarction, urgent target vessel revascularization, or stroke) or bleeding), the secondary outcome was stent thrombosis at 30 days. RESULTS: The mean age of enrolled patients was (65.12±12.44) years old, 27.4%(889/3 244) of them were female. Percent of stable coronary disease (SCD), non-ST segment elevation acute coronary syndrome (NSTE-ACS) and ST elevation myocardial infarction (STEMI) was 5.0%(162/3 248), 44.6%(1 450/3 248) and 50.4%(1 636/3 248) respectively. Radial access was performed in 89.5% (2 879/3 271) patients, and 9.7% (316/3 271) and 34.1% (1 115/3 271) patients also received ticagrelor and tirofiban medication. 69.3% (2 266/3 271) patients received post-procedural bivalirudin infusion, in which 46.3% (1 050/2 266) was treated at PCI-does, with a median duration of 2.5(1.0, 4.0) h. During the 30-day follow-up, NACE occurred in 3.45% (103/2 988) patients, the incidence of MACE, death was 2.17% (65/2 994) and 1.03% (31/3 017), respectively and bleeding events were recorded in 1.37% (41/2 996) patients. Four cases (0.13%) of stent thrombosis (3 acute stent thrombosis) were recorded. CONCLUSION: Peri-PCI Bivalirudin use is safe and related with low bleeding risk in Chinese CHD patients.

[Current status regarding the cardiovascular disease-related risk levels among the hypertensive population of different ethnicities in Xinjiang Uygur Autonomous Region, China].

OBJECTIVE: To assess the status of the cardiovascular disease associated risk levels among hypertensive population of Han, Uygur and Kazakh ethnicities, in Xinjiang Uygur Autonornous Region, to guide hypertension prevention and treatment in different ethnicities. METHODS: Four stages random cluster sampling method was used, and all the data was collected from Xinjiang local residents aged over 18 between October 2007 and March 2010. RESULTS: A total of 14 618 subjects completed this survey, in which 2 654 Han, 1 612 Uygur and 2034 Kazakh people diagnosed with hypertension was included in this research. Most of them were"grade 1 hypertension", and the percentage of grade 3 hypertension was Han (19.1%), Uygur (17.3%) and Kazakh (32.3%), respectively. Majority hypertensive people accompanied with 1 risk factor. The risk proportions of low, medium, high and very high in hypertension population of different ethnicities were Han (19.4%, 34.6%, 46.1%), Uygur (17.7%, 37.6%, 44.7%), Kazakh (12.5%, 38.0%, 49.4%) respectively. In Han, Uygur and Kazakh ethnicities, the percentage of high risk and very high risk was highest in hypertensive men aged over 60 years old.The percentages of hypertension awareness were 42.0%, 45.6%, 46.5% and percentages of medicine therapy were 29.6%, 23.4%, 25.2% for Han, Uygur and Kazakh ethnicities, respectively. CONCLUSIONS: Hypertensive people among Han, Uygur and Kazakh ethnicities in Xinjiang are mainly under high risk and very high risk situation of cardiovascular disease, especially in men aged ≥60. The percentage of hypertension awareness and medicine therapy in high risk and very high risk population is the highest, while percentage of awareness in medium risk population is low.

Optimal waist-to-height ratio cutoff values for predicting cardio-metabolic risk in Han and Uygur adults in northwest part of China.

BACKGROUND/OBJECTIVES: Optimal obesity indices in predicting cardio-metabolic risk are less studied in Asian. We evaluated optimal waist-to-height ratio (WHtR) for predicting hypertension, dyslipidemia and diabetes in Han and Uygur populations in Xinjiang, a northwest part of China. SUBJECTS/METHODS: This study involved 5603 Han and 4657 Uyghur participants. Anthropometric data, blood pressure, serum total cholesterol (TC), triglyceride, low-density lipoprotein, high-density lipoprotein and fasting glucose were determined. The cutoff values of WHtR were calculated; the relation between WHtR and prevalence of cardio-metabolic risks was evaluated. RESULTS: There was a positive correlation between WHtR and blood pressure, TC, triglycerides and fasting glucose in both Han and Uygur participants (all P<0.001). The prevalence of hypertension, dyslipidemia and diabetes was higher with increased WHtR for both ethnic groups after adjusted by age. Calculated cutoff values of WHtR for predicting hypertension, dyslipidemia, diabetes or ⩾ 2 of these risk factors were 0.54 for both men and women in Han and 0.55 in male and 0.57 in female Uygur participants. A significant difference in blood pressure, triglycerides and fasting glucose between subgroups with WHtR either above or below the cutoff values was observed in both men and women of the two ethnicities. CONCLUSIONS: The optimal cutoff value of WHtR is a useful screen tool for predicting cardio-metabolic risks in Han and Uygur population in Xinjiang, northwest part of China.

Genetic polymorphisms of serum amyloid A1 and coronary artery disease risk.

Serum amyloid A (SAA) protein is not only an inflammatory factor but also an apolipoprotein that can replace apolipoprotein A1 (apoA1) as the major apolipoprotein of high-density lipoprotein cholesterol (HDL-C). However, the relationship between genetic polymorphisms of SAA and coronary artery disease (CAD) remains unclear. A total of four single nucleotide polymorphisms (rs12218, rs4638289, rs7131332, and rs11603089) of the SAA gene were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in two independent case-control studies, one of the Han population (1416 CAD patients and 1373 control subjects) and the other of the Uygur population (588 CAD patients and 529 control subjects). We found that the rs12218 CC genotype was more frequent among the CAD patients than among the controls in both the Han (8.3% vs. 4.8%, P < 0.001) and Uygur populations (15.5% vs. 11.3%, P < 0.05). After adjustments for confounding factors, such as sex, age, smoking, drinking, hypertension, diabetes, and serum levels of triglycerides, total cholesterol, HDL, and plasma SAA, the differences remained significant in the Han (CC vs. CT+TT, P < 0.001, OR = 3.863, 95% CI: 1.755-12.477) and Uygur groups (CC vs. CT+TT, P = 0.031, OR = 3.022, 95% CI: 1.033-8.840). Genetic polymorphisms in SAA1 are associated with CAD in the Han and Uygur populations in western China.