[Advances in the role of autoimmune mechanisms in chronic obstructive pulmonary disease].

Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease whose pathogenesis mainly involves airway remodelling and alveolar destruction caused by inflammation, protease-antiprotease imbalance, oxidative stress, and imbalance between apoptosis and compensatory repair of lung tissue structure cells. In recent years, the role of the autoimmune response in COPD has attracted widespread attention, but there is still some controversy. This article reviewed the role of autoimmunity in COPD from different perspectives, starting with the relationship between autoimmunity and the pathogenesis of COPD.

[Metabolic reprogramming in pulmonary hypertension].

Pulmonary hypertension is a pathophysiological disorder with elevated pulmonary artery pressures that may involve multiple clinical conditions, yet the mechanism of pulmonary hypertension remains unclear. Metabolic reprogramming of structural cells (smooth muscle cells, endothelial cells, fibroblasts etc.) and immune cells (macrophages etc.) is a hallmark of pulmonary hypertension and leads to pulmonary vascular remodeling. Many studies have investigated the metabolic reprogramming in pulmonary hypertension and some potential therapeutic targets have been developed. In this review, recent work on metabolic programming in pulmonary hypertension is summarized.

[New progress of excimer laser corneal refractive surgery for presbyopia].

Presbyopia refers to the decline in the accommodation of eye that occurs with age, symptoms begin to appear after the age of 40 and the clarity of vision at near is insufficient to satisfy an individual's requirements. The correction of presbyopia include restoring natural accommodation and improving symptom. The former is still difficult to achieve at present, while the latter mainly involves wearing convex lens, and with more and more patients wanting to get rid of frame glasses, refractive surgery is gradually promoted and applied. Corneal refractive surgery, especially laser-assisted in situ keratomileusis, is one of the most common methods for surgical correction of presbyopia. We reviewed the recent literature to introduce the mechanism of corneal refractive surgery treating presbyopia and the efficacy of different surgical algorithms.

[Efficacy and safety of oral pyrotinib in HER2 positive metastatic breast cancer: real-world practice].

OBJECTIVE: Pyrotinib, a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor, showed promising antitumor activity and acceptable tolerability in phase II and phase III randomized clinical trials. We assessed the activity and safety of oral pyrotinib for human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer patients in the real world. METHODS: We retrospectively analyzed 72 HER2 positive metastatic breast cancer (MBC) patients who received oral pyrotinib based regimens at Beijing Cancer Hospital and other four hospitals (Peking University First Hospital, China-Japan Friendship Hospital, General Hospital of PLA, Peking University Third Hospital) from August 2018 to September 2019. Progression free survival (PFS), objective response rate (ORR), adverse events (AE) of pyrotinib were investigated. RESULTS: Seventy-two patients with HER2 positive MBC were enrolled. The median age of the patients was 55 years (range: 32-79 years). Sixty-nine (95.8%) patients had received anti-HER2 treatment in the metastatic and/or (neo) adjuvant settings; 61 (84.7%) patients had received anti-HER2 treatments in the metastatic setting in terms of trastuzumab 56 (77.8%) patients, lapatinib 36 (50.0%) patients, and T-DM1 4 (5.6%) patients. Among these 72 patients who received oral pyrotinib based regimens, 62 (86.1%) patients received pyrotinib (±trastuzumab) in combination with chemotherapy, 6 (8.3%) patients received pyrotinib (± trastuzumab) in combination with endocrine therapy and 4 (5.6%) patients received pyrotinib (±trastuzumab). Sixty-five (90.3%) patients received 400 mg pyrotinib once daily as initial dose, and 7 (9.7%) patients received 320 mg. OBJECTIVE response and safety to pyrotinib based therapy were evaluable in all the 72 patients. One (1.4%) patient achieved complete response (CR), 18 (25.0%) patients achieved partial response (PR), 41 (56.9%) patients had stable disease (SD), and 12 (16.7%) patients had progressive disease (PD). The ORR (CR+PR) was 26.4% and the median PFS was 7.6 months (95%CI: 5.5-9.7 months). Among the 36 patients with prior lapatinib therapy, the median PFS was 7.9 months (95%CI: 4.1-11.7 months). Among the 15 patients with brain metastasis, the median PFS was 6.0 months (95%CI: 2.2-9.8 months). The main toxicities related to pyrotinib were diarrhea in 57 (79.2%) cases, and 48 (66.7%) cases with grade 1-2 as well as 9 (12.5%) cases with grade 3. CONCLUSION: Pyrotinib based therapy is an effective treatment for patients with HER2 positive MBC, including patients with lapatinib treatment failure and brain metastasis, and the toxicities can be tolerated.

[The value of adenosine triphosphate in CD4(+)T lymphocytes in predicting repeated respiratory tract infections in silicosis patients].

Objective: To explore the value of the concentration of adenosine triphosphate (ATP) in CD4(+)T lymphocytes in predicting repeated respiratory tract infections (RRTI) in silicosis patients. Methods: In April 2020, 614 silicosis patients admitted from March 2016 to March 2018 were included in the study, and they were divided into the RRTI group (n=105) and the non RRTI group (n=509) according to whether the occurrence of RRTI, another 30 healthy cases taken from body check were served as control group, and the concentrations of ATP produced by CD4(+)T lymphocytes was measured by ImmuKnow assay, and were compared between the three groups. And drawed the receiver operating characteristic (ROC) curve, and the Logistic regression analysis was used to explore the risk factors of RRTI. Results: The incidence of RRTI in silicosis patients was 17.10% (105/614) . The concentration of ATP produced by CD4(+)T lymphocytes in the RRTI group [ (260.42±90.36) mg/L] was significantly lower than that in the non RRTI group [ (413.66±138.74) mg/L] (t=-10.849, P<0.01) . The area under the ROC curve was 0.834, the cutoff value was 284 mg/L, the sensitivity was 0.88, and the specificity was 0.83. Logistic regression analysis showed that the concentration of ATP produced by CD4(+)T lymphocytes≤284 mg/L, impaired pulmonary ventilation function, serum albumin<40 g/L and diabetes were the risk factors of RRTI in silicosis patients (OR=2.126, 1.217, 1.164, 1.125, P<0.05) . Conclusion: Low CD4(+)T lymphocyte ATP value was a risk factor of RRTI in silicosis patients, and can predict the risk of RRTI in patients with silicosis.

[Application of mendelian randomization methods in causal inference of observational study].

Mendelian randomization (MR) approach follows the Mendel's law of inheritance, which is called "Parental alleles randomly assigned to the offspring", and refers to use genetic variants as an instrumental variable to develop causal inference between the exposure factor and the outcome from observational study. In recent years, with the rapid development of genome-wide association study (GWAS) and various omics data,the disclosure of a large number of aggregated data provides an opportunity for the wide application of MR approach in causal inference. We introduce three methods widely used in MR and then apply them to explore causal relationship between blood metabolites and depressive. The advantages and disadvantages of three methods in causal inference are compared in order to provide reference for the application of MR in observational studies.

Loss of cane and sugar yield resulting from Ceratovacuna lanigera Zehntner damage in cane-growing regions in China.

Ceratovacuna lanigera Zehntner is a major leaf pest of sugarcane. Widely distributed, it affects both the yield and quality of sugarcane in China. This study aimed to assess real yield and sugar yield losses, and the effect of C. lanigera damage on emergence of newly planted and ratoon cane under current production levels. Field experiments were carried out from 2014 to 2016 in Yunnan Province China. At maturity, plants were harvested and weighed to determine yield, and the effect on sugarcane quality and sucrose content analyzed. Real yield decreased by average of 46,185 kg hm-2 (range: 37,545-61,845 kg hm-2) in damaged versus undamaged areas, with an average yield loss rate of 35.9% (28.5-45.7%). Juice yield decreased by an average of 3.01% (2.4-4.13%) and sucrose content by 6.38% (5.48-8.16%). Juice brix decreased by an average of 7.66°BX (6.95-9.05°BX) and juice gravity purity by 12.35% (8.43-19.97%). In contrast, the reducing sugar content increased by an average of 1.21% (1.01-1.3%). Emergence rates of newly planted cane decreased by an average of 26.0% (24.7-27.3%). The emergence number of ratoon cane decreased by 66,834 hm2 (57,429-76,238 hm-2) and relative emergence loss rates of ratoon cane decreased by an average of 57.8% (57.6-58.0%). These findings confirm that C. lanigera damage severely affects sugarcane yield and quality in Yunnan Province. The results will help the implementation of effective control measures, thereby supporting sustainable development of the Chinese sugar industry.

[The role of prophylactic use of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF) in breast cancer receiving adjuvant chemotherapy].

Objectives: To investigate the efficacy and safety of prophylactic use of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF) in breast cancer receiving docetaxel as adjuvant chemotherapy. Methods: A total of 58 patients with breast cancer receiving adjuvant chemotherapy with docetaxel were included between January 2014 to October 2017. Prophylactic use of PEG-rhG-CSF was administered.Patients were further divided into two groups according to the frequency of PEG-rhG-CSF use: frequent use group (≥3 cycles) and non-frequent use group (<3 cycles). Results: There were significant differences in the incidence rates of grade 3/4 neutropenia between the prophylactic group and non-prophylactic group in cycle 1-3(P<0.05). Less febrile neutropenia (FN) was also noted in the prophylactic group compared with the non-prophylactic group in cycle 1 and cycle 3 (P<0.05). Grade 3/4 neutropenia and FN were less in the frequent use of group compared with the non-frequent use group(P<0.001). The most common side effects of PEG-rhG-CSF included fatigue (10.2%), bone joint pain(50.8%), and 2 patients (3.4%) refused further treatment because of bone joint pain. Conclusions: PEG-rhG-CSF should be prophylactically used for preventing neutropenia and febrile neutropenia in breast cancer patients receiving adjuvant chemotherapy with docetaxel regimen.

[Clinicopathologic and molecular features of cribriform morular variant of papillary thyroid carcinoma].

Objective: To investigate the clinicopathologic and molecular features of the rare cribriform morular variant of papillary thyroid carcinoma (CMV-PTC). Methods: The clinicopathologic data of 10 patients with CMV-PTC were retrospectively reviewed. Immunohistochemical (IHC) staining was done using LSAB method. DNA sequencing for APC were applied using Sanger method. BRAF V600E mutation was examined using ARMS method. The cytological, morphological, IHC and molecular features were analyzed. Results: All patients were female at an average age of 27 years old. The tumors were mostly located in the right lobe of thyroid. Fine needle aspiration cytology was performed in three patients; two were diagnosed as suspicious for PTC and one as PTC. Nine tumors presented as solitary nodule and two as multiple nodules in both lobes. Infiltration was demonstrated in three cases. The average size was 2.6 cm. The neoplastic cells were arranged in papillary, cribriform, solid and glandular patterns, with rare or without colloid inside the lumen. The number of morula varied, ranging from zero to many. The neoplastic cells were variably enlarged, showing round, oval or spindle shape. Nuclear irregularity was identified as irregular membrane, nuclear grooves or pseudoinclusion, but no typical ground glass feature. Peculiar nuclear clearing could be observed in the morular cells. IHC staining showed the neoplastic cells were negative for thyroglobulin and p63, but positive for TTF1, cytokeratin 19 and estrogen receptor. Diffuse staining with cytokeratin was seen in the neoplastic cells and the morula. Specific cytoplasmic and nuclear staining of ß-catenin was seen in the neoplastic cells but not the morula. Ki-67 proliferation index was 1%-30%. No recurrence or metastasis was observed. One patient was demonstrated to harbor both somatic and germline mutations of the APC gene, who was found to have adenomatous polyposis and her mother died of colonic carcinoma. No BRAF V600E mutation was detected. Conclusions: CMV-PTC is rare and shows atypical cytological and clinicopathological features, and it is easily misdiagnosed.TG, TTF1, ER and ß-catenin are specific IHC markers for CMV-PTC. The morula is negative for cytokeratin 19, in contrast to squamous metaplasia. Although CMV-PTC has indolent clinical behavior, a definite diagnosis is necessary to rule out the possibility of APC gene mutation and related extra-thyroidal neoplasm, such as FAP and Gardner syndrome.

[Comparison of arterial stiffness in non-hypertensive and hypertensive population of various age groups].

Objective: To investigate the impact of blood pressure and age on arterial stiffness in general population. Methods: Participants who took part in 2010, 2012 and 2014 Kailuan health examination were included. Data of brachial ankle pulse wave velocity (baPWV) examination were analyzed. According to the WHO criteria of age, participants were divided into 3 age groups: 18-44 years group (n=11 608), 45-59 years group (n=12 757), above 60 years group (n=5 002). Participants were further divided into hypertension group and non-hypertension group according to the diagnostic criteria for hypertension (2010 Chinese guidelines for the managemengt of hypertension). Multiple linear regression analysis was used to analyze the association between systolic blood pressure (SBP) with baPWV in the total participants and then stratified by age groups. Multivariate logistic regression model was used to analyze the influence of blood pressure on arterial stiffness (baPWV≥1 400 cm/s) of various groups. Results: (1)The baseline characteristics of all participants: 35 350 participants completed 2010, 2012 and 2014 Kailuan examinations and took part in baPWV examination. 2 237 participants without blood pressure measurement values were excluded, 1 569 participants with history of peripheral artery disease were excluded, we also excluded 1 016 participants with history of cardiac-cerebral vascular disease. Data from 29 367 participants were analyzed. The age was (48.0±12.4) years old, 21 305 were males (72.5%). (2) Distribution of baPWV in various age groups: baPWV increased with aging. In non-hypertension population, baPWV in 18-44 years group, 45-59 years group, above 60 years group were as follows: 1 299.3, 1 428.7 and 1 704.6 cm/s, respectively. For hypertension participants, the respective values of baPWV were: 1 498.4, 1 640.7 and 1 921.4 cm/s. BaPWV was significantly higher in hypertension group than non-hypertension group of respective age groups (P<0.05). (3) Multiple linear regression analysis defined risk factors of baPWV: Multivariate linear regression analysis showed that baPWV was positively correlated with SBP(t=39.30, P<0.001), and same results were found in the sub-age groups (t-value was 37.72, 27.30, 9.15, all P<0.001, respectively) after adjustment for other confounding factors, including age, sex, pulse pressure(PP), body mass index (BMI), fasting blood glucose (FBG), total cholesterol (TC), smoking, drinking, physical exercise, antihypertensive medications, lipid-lowering medication. (4) Multivariate logistic regression analysis of baPWV-related factors: After adjustment for other confounding factors, including age, sex, PP, BMI, FBG, TC, smoking, drinking, physical exercise, antihypertensive medication, lipid-lowering medication, multivariate logistic regression analysis showed that risks for increased arterial stiffness in hypertension group were higher than those in non-hypertension group, the OR in participants with hypertension was 2.54 (2.35-2.74) in the total participants, and same results were also found in sub-age groups, the ORs were 3.22(2.86-3.63), 2.48(2.23-2.76), and 1.91(1.42-2.56), respectively, in each sub-age group. Conclusion: SBP is positively related to arterial stiffness in different age groups, and hypertension is a risk factor for increased arterial stiffness in different age groups. Clinical Trial Registry Chinese Clinical Trial Registry, ChiCTR-TNC-11001489.

[Analysis on the gender-specific risk factors of new-onset cerebral hemorrhage].

Objective: To explore the gender-specific risk factors of new-onset cerebral hemorrhage. Methods: In this prospective cohort study,a total of 98 961 participants((51.1±12.6)years old), who underwent the 2006 to 2007 physical examination and met the inclusion criteria, were enrolled from the Kailuanstudy cohort. There were 78 908 (79.7%) male,and 20 053 (20.3%) female.The incidence of cerebral hemorrhage was observed once per year until December 31, 2016.The difference on the incidence of cerebral hemorrhage between male and female was compared. Multivariate Cox regression analysis was applied to analyze therisk factors of cerebral hemorrhage events among different genders. Results: The participants were followed up for(10.00±0.73) years,and 860 cerebral hemorrhage events were recorded during follow up. The incidence of cerebral hemorrhage in the population was 86.90/10 million person years (standardized incidence rate of 47.85/10 million person years). The incidence of cerebral hemorrhage was significantly higher in male (49.61/10 million person years) than in female (34.07/10 million person years, P<0.05). Multivariate Cox regression analysis showed that 45-59 years old, ≥ 60 years old, diabetes,and waist-hip ratio were more strongly related to new-onset of cerebral hemorrhage events in female than in male, and the hazard ratios(95%CI) were 2.33 (1.23-4.43) ,2.71 (1.30-5.66) ,2.16 (1.24-3.74) and 8.79 (1.42-54.32) in female versus 1.55 (1.21-1.97) ,2.16 (1.68-2.78) ,1.19 (0.93-1.53) and 3.21 (1.09-9.41) in male, respectively. The risk of male cerebral hemorrhage increased by 29% (HR=1.29, 95%CI 1.19-1.40) in male and 24% (HR=1.24, 95%CI 1.20-1.28) in female,when the systolic blood pressure increased 10 mmHg (1 mmHg=0.133 kPa). Conclusions: The incidence of cerebral hemorrhage is higher in male than in female in this cohort.The association between systolic blood pressure and cerebral hemorrhage is stronger in male than that in female.The associations between age, waist-hip ratio, diabetes and cerebral hemorrhage are stronger in female than in male. Trial Registration: Chinese Clinical Trail Registry, ChiCTR-TNC-11001489.

[The effects and related mechanism of salvianolate on rats with myocardial ischemia-reperfusion injury].

Objective: To investigate the effect and related mechanism of salvianolate on myocardial ischemia-reperfusion (I/R) injury in rats. Methods: Thirty-six adult Sprague-Dawley rats were divided into three groups (n=12 each) using random number table method: control group (coronary artery was not ligated) , I/R group (myocardial I/R model was established by ligation and opening of left anterior descending coronary artery) , and salvianolate+I/R group (5 mg/kg of salvianolate was injected through the tail vein at the time of reperfusion) .Triphenyltetrazolium chloride (TTC) stain was utilized to measure the myocardial infarct size. The ELISA method was used to detect myocardial necrotic markers, including cardiac troponin T (TnT) , creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) . Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was used to analyses the levels of apoptosis. The levels of cleaved Caspase-3 protein were analyzed with Western blot.Cold luminescence method was used to detect the ATP level of myocardial tissue. The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in myocardial tissue were detected by immunofluorescence. Results: (1) The infarct size in control group, I/R group and salvianolate+I/R group were 0, (23.90±5.66) %, and (12.06±5.97) %, respectively (P<0.01 or 0.05) . (2) The TnT level was (0.04±0.03) , (16.96±2.80) , and (6.95±2.31) ng/ml, the CK-MB level was (43.6±23.5) , (1 135.8±180.6) ,and (390.3±121.5) U/L, the LDH level was (119.0±58.6) , (1 838.6±543.8) , and (631.6±228.3) U/L in control group, I/R group and salvianolate+I/R group, all significantly lower in salvianolate+I/R group than in I/R group (all P<0.01) . (3) The rate of TUNEL positive myocardial cells were (1.07±1.16) %, (21.36±4.11) %,and (13.30±3.67) % in control group, I/R group,and salvianolate+I/R group (all P<0.01) . (4) The cleaved Caspase-3 expression was 0.11±0.05, 0.84±0.20,and 0.43±0.09 in control group, I/R group, and salvianolate+I/R group (all P<0.01) . (5) The ATP level of myocardial tissue was (100.0±0.0) %, (34.2±9.2) %,and (62.1±18.0) % respectively in control group, I/R group, and salvianolate+I/R group (all P<0.01) . (6) There was almost no 8-OHdG expression in the myocardial tissue of control group. The expression of 8-OHdG in the myocardial tissue of I/R group was greater than that of the control group. The expression of 8-OHdG in the myocardial tissue of salvianolate+I/R group was less than that of the I/R group. Conclusion: Salvianolate may alleviate myocardial I/R injury of rat through reducing the mitochondrial DNA oxidative damage, protecting mitochondrial function and inhibiting the apoptosis of myocardial cells.

[Salvianolate protects H9c2 cells from hypoxia/reoxygenation injury-induced apoptosis by attenuating mitochondrial DNA oxidative damage].

Objective: To investigate the possible mechanism related to the protective effects of salvianolate in H9c2 cells underwent hypoxia/reoxygenation (H/R)-injury. Methods: H9c2 cells were divided into four groups: control group, salvianolate group (S group), H/R group, and salvianolate+ H/R group(S+ H/R group), in which the H9c2 cells were pretreated with salvianolate before H/R-treatment.Apoptotic cells were detected by Tunel assays and AnnexinⅤ-FITC apoptosis detection kit.The intracellular ATP level, the change of mitochondrial membrane potential and the mitochondrial DNA oxidative damage were also determined in these groups. Results: (1) The apoptosis rate of H/R group(26.36±5.14)% was significantly higher compared to control group(2.71±1.66)%(P=0.000 4), which could be significantly reduced in S+ H/R group(17.28±4.75)%(P=0.012 8 vs. H/R group , P=0.003 9 vs. control group). The ratio of AnnexinⅤ and PI double positive cells in H/R group(28.23±6.73)% was significantly higher compared to control group(3.53±2.83)%(P=0.001 1), which was significantly reduced in S+ H/R group(18.10±4.56)%(P=0.037 2 vs. H/R group, P=0.038 3 vs. control group). (2)The ATP level of H9c2 cells in H/R group(49.05±10.12)% was significantly lower than in control group 100%(P=0.000 5), which was significantly increased in S+ H/R group(68.67±13.32)%(P=0.019 9 vs. H/R group). Confocal microscope showed that red fluorescence was dominant in the control group, red fluorescence was significantly reduced, while green fluorescence was significantly increased in H9c2 cells of H/R group and the fluorescence ratio of red to green in H/R group((37.13±8.47)%) was significantly decreased compared to control group (100%, P=0.000 1), fluorescence ratio of red to green was significantly increased in S+ H/R group((63.77±12.32)% vs. H/R group, P=0.007 3). (3)The mitochondrial DNA oxidative damage in different groups: there was only few 8-hydroxyguanine (8-OHdG) expression, which marked as green, in control group, and 8-OHdG expression was significantly upregulated in H/R group, moreover, the 8-OHdG was co-localized with mitochondria.The expression of 8-OHdG was significantly lower in S+ H/R group compared to H/R group. Conclusion: Salvianolate can reduce mitochondrial DNA oxidative damage, and protect mitochondrial function, thus inhibit myocardial cell apoptosis and eventually reduce the myocardial H/R-injury in H9c2 cells.

Financial burden on the families of patients with hepatitis B virus-related liver diseases and the role of public health insurance in Yunnan province of China.

OBJECTIVE: To investigate the financial burden of patients who had various stages of hepatitis B virus-related diseases and the level of alleviation from financial burden by health insurance schemes in Yunnan province of China. STUDY DESIGN: A cross-sectional survey. METHODS: Patients' information was consecutively recorded at the First Affiliated Hospital of Kunming Medical University, from December 2012 to June 2013. Consecutive cases of hepatitis B virus (HBV) (520), compensated cirrhosis (91), decompensated cirrhosis (198) and hepatocellular carcinoma (HCC) (131) were recruited from the outpatient and inpatient departments. The total direct costs, hospital charge, outpatient costs, hospitalization fees being reimbursed and household catastrophic health expenditure were estimated for each disease group. RESULTS: The average annual direct costs for each disease group were 19,496 RMB for HBV, 28,466 RMB in compensated cirrhosis, 46,061 RMB for decompensated cirrhosis, and 33,044 RMB for HCC patients. Catastrophic health expenditure occurred in all four groups. Health insurance reimbursement released the financial burden incurred by medical expenses of patients under a high level of household economic status. Public health insurance schemes helped the patients to various extents. CONCLUSIONS: Among these patient groups, direct costs represent a significant economic burden. Health expenditure and financing systems must be considered to prevent the increase of household catastrophe, particularly among the poor.

[Lycopene protects against hypoxia/reoxygenation injury in mouse cardiomyocytes by inhibiting endoplasmic reticulum stress induced apoptosis].

OBJECTIVE: To investigate the effects of lycopene on primary cultured neonatal mouse cardiomyocytes with hypoxia/reoxgenation (H/R) injury and explore related mechanism. METHODS: Primary cultured neonatal mouse cardiomyocytes were randomly divided to control group (control); lycopene group (5 µmol/L, lyc); H/R group (4 hours hypoxia followed by 6 hours reoxgenation); lycopene+ H/R group (lyc+ H/R, the cardiomyocytes were incubated with 5 µmol/L lycopene for 4 hours before H/R treatment). The cell viability of cardiomyocytes was assessed by CCK-8 assay. The apoptotic rate of cardiomyocytes was evaluated by flow cytometry using AnnexinV-PI double staining. Western blot was used to determine the GRP78, CHOP, Bax and Bcl-2 protein expression in cardiomyocytes. The mRNA expressions of ATF6、eIF2α and sXbp-1 were detected by real-time PCR. The fluorescence intensity for reactive oxygen species (ROS) in cardiomyocytes was measured with Olympus fluorescence microscope. RESULTS: Compared to control group, the cell viability of cardiomyocytes was significantly reduced ((64.28±6.12)% vs. (100.00±4.98)%, P<0.01), the apoptotic rate ((24.42±1.76)% vs. (5.16±1.31)%, P<0.01) and ratio of Bax/Bcl-2 (2.33±0.20 vs. 1.00±0.09, P<0.01) significantly increased, the ATF6, eIF2α and sXbp-1 mRNA expression, the CHOP and GRP78 protein expression (1.98±0.15 vs. 1.00±0.12, 2.09±0.11 vs. 1.00±0.09) as well as fluorescence intensity for ROS ((262.13±22.03)% vs. (100.00±12.35)%) were markedly increased in H/R group (all P<0.01). Compared to the H/R group, pretreatment with lycopene markedly improved the cell viability of cardiomyocytes ((81.75±6.85)%, P<0.01), significantly decreased the apoptotic rate ((17.24±2.02)%, P<0.01) and ratio of Bax/Bcl-2(1.64±0.13, P<0.01), significantly down-regulated the mRNA expression levels of ATF6, eIF2α and sXbp-1, and the protein expression levels of CHOP (1.54±0.12) and GRP78 (1.53±0.12), significantly reduced the fluorescence intensity for ROS ((171.18±19.09)%, all P<0.01). CONCLUSIONS: Lycopene could attenuate hypoxia/reoxygenation-injury in primary cultured neonatal mouse cardiomyocytes, possibly through inhibiting the ER stress and alleviating the ER stress-induced apoptosis.

[Association between the office, visit-to-visit and 24-hour ambulatory systolic blood pressure and vascular damages in the elderly].

OBJECTIVE: To investigate the association between different kinds of systolic blood pressure (SBP, including office, visit-to-visit, 24-hour ambulatory) and vascular damages (represented by carotid intima-media thickness, CIMT; brachial-ankle pulse wave velocity, baPWV) in the elderly. METHODS: A total of 2 814 participants aged of ≥60 years old and retired employees were selected with random sampling method from the individuals who took part in 2006-2007, 2008-2009, 2010-2011 health examination in Tangshan Kailuan Hospital, Kailuan Linxi Hospital, Kailuan Zhaogezhuang Hospital and with 24-hour ambulatory blood pressure monitoring data, CIMT and baPWV.Finally, 2 146 participants (1 438 males, average age (67.3±6.0) years old) were included to the analysis.Multivariable regression analysis was used to analyze association between the office, visit-to-visit, 24-hour, day-time, night-time SBP and CIMT and baPWV, respectively. RESULTS: (1) The average SBP, DBP, CIMT and baPWV were (137.0±20.4) mmHg(1 mmHg=0.133 kPa), (83.5±11.0) mmHg, (0.92±0.18)mm and (1 781.7±353.2)cm/s.(2) The participants were divided into high and low level groups according to the median of different SBPs, respectively.The results indicated that CIMT and baPWV were significantly higher in high level groups than in low level groups (all P<0.01). (3) After adjusting for gender and age, the partial correlate analysis showed that the office, visit-to-visit, 24-hour, day-time, night-time SBP positively associated with CIMT and baPWV (all P<0.01). (4) After adjusting for confounding factors, multivariable regression analysis showed that the office, visit-to-visit, 24-hour, day-time, night-time SBP were positively and linearly associated with CIMT and baPWV in total cohort, and standard regression coefficients were 0.157, 0.208, 0.175, 0.169, 0.163, 0.479, 0.420, 0.401, 0.389 and 0.354, respectively.In addition, similar results were observed in male and female participants but there was no significance between night-time SBP and CIMT in female participants. CONCLUSIONS: Office, visit-to-visit, 24-hour, day-time, night-time SBP are associated with vascular damages, and the best associations are observed between visit-to-visit SBP and vascular function damage. CLINICAL TRIAL REGISTRY: Chinese CLINICAL TRIAL REGISTRY, ChiCTR-TNC-1100 1489.