The effects of rate pressure product at admission on cardiopulmonary function during hospitalization in patients with acute myocardial infarction.

OBJECTIVE: This study aimed to analyze the correlation between the rate pressure product (RPP) and cardiopulmonary function during hospitalization in patients with acute myocardial infarction (AMI). METHODS: A total of 362 patients with AMI were selected for the study, and the median admission RPP was used as the cutoff point to divide the patients into a low-RPP group (n = 181) and a high-RPP group (n = 181). The relationship between the RPP at admission and the cardiopulmonary function during hospitalization was analyzed. RESULTS: The patients in the high-RPP group had a higher body mass index (BMI) (p = 0.014), a higher prevalence of combined hypertension and diabetes mellitus (p < 0.001), a lower incidence of smoking (p = 0.044), and a higher incidence of oscillatory ventilation (6.1% vs. 1.7%, p = 0.029). The differences in RPP at rest, during warm-up, and within 1 and 4 minutes of recovery were statistically significant between the two groups (p < 0.01 on each occasion), while the differences in anaerobic threshold (AT) and watt max (Max) were not statistically significant (p > 0.05 for both). The patients in the low-RPP group had higher oxygen uptake (VO2 [AT]: 14.9 ± 3.4 vs. 14.2 ± 3.6, p = 0.048) and (VO2peak [Max]:18.2 ± 3.8 vs. 17.3 ± 3.8, p = 0.020). The RPP at admission was negatively correlated with VO2 (AT) and VO2peak (p < 0.05) using the regression Equation VO2peak = 33.682 + (-0.012 * RPP at admission/100) + (-0.105 * Age) + (-0.350 * BMI), while there was no correlation between the RPP at admission and VO2 (AT) (p = 0.149). CONCLUSION: The RPP at admission was negatively correlated with cardiopulmonary function during hospitalization in patients with AMI. Patients with a high RPP were more likely to have a combination of obesity, hypertension, diabetes mellitus, and reduced oxygen uptake during exercise, while a high RPP at admission appeared to affect their cardiovascular response indicators during exercise.

Design, Synthesis and Biological Evaluation of Glycosylated Derivatives of Silibinin as Potential Anti-Tumor Agents.

Objective: Silibinin, a natural product extracted from the seeds of the Silybum marianum, is versatile with various pharmacological effects. However, its clinical application was strongly hampered by its low bioavailability and poor water solubility. Herein, a series of glycosylated silibinin derivatives were identified as novel anti-tumor agents. Materials and Methods: The cell viability was evaluated by CCK8 assay. Furthermore, cell apoptosis and cell cycle progression were tested by flow cytometry. In addition, the pharmacokinetic assessment of compound 15 and silibinin through intravenous administration (i.v., 2 mg/kg) to ICR mice were performed. Results: The synthesized compounds showed better water solubilities than silibinin. Among them, compound 15 exhibited inhibitory activity against DU145 cells with IC50 value of 1.37 ± 0.140 µM. Moreover, it arrested cell cycle at G2/M phase and induced apoptosis in DU145 cells. Additionally, compound 15 also displayed longer half-life (T1/2 = 128.3 min) in liver microsomes than that of silibinin (T1/2 = 82.5 min) and appropriate pharmacokinetic parameters in mice. Conclusion: Overall, glycosylation of silibinin would be a valid strategy for the development of silibinin derivatives as anti-tumor agents.

Reduction in risk of contrast-induced nephropathy in patients with chronic kidney disease and diabetes mellitus by enhanced external counterpulsation.

Objective: To evaluate the efficacy of enhanced external counterpulsation (EECP) in the prevention of contrast-induced nephropathy (CIN) in patients with combined chronic kidney disease (CKD) and diabetes mellitus (DM) by comparing the changes in renal function-related indicators in patients before and after coronary angiography (CAG) or percutaneous coronary intervention (PCI). Methods: There were 230 subjects consecutively included in the study. Of these, 30 cases with DM underwent rehydration therapy, and 200 cases underwent EECP therapy in addition to rehydration therapy, comprising 53 patients with DM and 147 patients without. All the patients were tested to measure the renal function indicators before and after CAG/PCI. Results: The postoperative results of blood urea nitrogen (BUN), serum creatinine (Scr), estimated glomerular filtration rate (eGFR), B2 microglobulin, and high-sensitivity C-reactive protein in the three groups showed a statistically significant difference (P < 0.05). After EECP therapy, patients with DM showed a significant decrease in BUN (9.1 ± 4.2 vs. 7.2 ± 3.0, t = 3.899, P < 0.001) and a significant increase in eGFR (41.5 ± 12.7 vs. 44.0 ± 15.6, t = -2.031, P = 0.047), while the patients without DM showed a more significant difference (P < 0.001). Patients with DM showed a lower percentage of elevated Scr (66.7% vs. 43.4%, P = 0.042), a higher percentage of elevated eGFR (30.0% vs. 52.8%, P = 0.044), and a lower incidence of CIN (16.7% vs. 3.8%, P = 0.042) after EECP therapy. Conclusion: Treatment with EECP can reduce Scr in patients with combined CKD and DM post CAG/PCI, increase eGFR, and decrease the incidence of CIN.

A novel animal model of primary blast lung injury and its pathological changes in mice.

BACKGROUND: Primary blast lung injury (PBLI) is a major cause of death in military conflict and terrorist attacks on civilian populations. However, the mechanisms of PBLI are not well understood, and a standardized animal model is urgently needed. This study aimed to establish an animal model of PBLI for laboratory study. METHODS: The animal model of PBLI was established using a self-made mini shock tube simulation device. In brief, mice were randomly divided into two groups: the control group and the model group, the model group were suffered 0.5 bar shock pressures. Mice were sacrificed at 2 hours, 4 hours, 6 hours, 12 hours, and 24 hours after injury. Lung tissue gross observation, hematoxylin and eosin staining and lung pathology scoring were performed to evaluated lung tissue damage. Evans blue dye leakage and bronchoalveolar lavage fluid examination were performed to evaluated pulmonary edema. The relative expression levels of inflammation factors were measured by real-time quantitative polymerase chain reaction and Western blotting analysis. The release of neutrophil extracellular traps was observed by immunofluorescence stain. RESULTS: In the model group, the gross observation and hematoxylin and eosin staining assay showed the inflammatory cell infiltration, intra-alveolar hemorrhage, and damaged lung tissue structure. The Evans blue dye and bronchoalveolar lavage fluid examination revealed that the lung tissue permeability and edema was significantly increased after injury. Real-time quantitative polymerase chain reaction and Western blotting assays showed that IL-1ß, IL-6, TNF-α were upregulated in the model group. Immunofluorescence assay showed that the level of neutrophil extracellular traps in the lung tissue increased significantly in the model group. CONCLUSION: The self-made mini shock tube simulation device can be used to establish the animal model of PBLI successfully. Pathological changes of PBLI mice were characterized by mechanical damage and inflammatory response in lung tissue.

Design, synthesis, and biological evaluation of novel 3-(thiophen-2-ylthio)pyridine derivatives as potential multitarget anticancer agents.

A series of novel 3-(thiophen-2-ylthio)pyridine derivatives as insulin-like growth factor 1 receptor (IGF-1R) inhibitors was designed and synthesized. IGF-1R kinase inhibitory activities and cytotoxicities against HepG2 and WSU-DLCL2 cell lines were tested. For all of these compounds, potent cancer cell proliferation inhibitory activities were observed, but not through the inhibition of IGR-1R. Selected compounds were further screened against various kinases. Typical compound 22 (50% inhibitory concentration [IC50 ] values, HepG2: 2.98 ± 1.11 µM and WSU-DLCL2: 4.34 ± 0.84 µM) exhibited good inhibitory activities against fibroblast growth factor receptor-2 (FGFR2), FGFR3, epidermal growth factor receptor, Janus kinase, and RON (receptor originated from Nantes), with IC50 values ranging from 2.14 to 12.20 µM. Additionally, the cell-cycle analysis showed that compound 22 could arrest HepG2 cells in the G1/G0 phase. Taken together, all the experiments confirmed that the compounds in this series were multitarget anticancer agents worth further optimizing.

Transplantation of mesenchymal stem cells modulated Cx43 and Cx45 expression in rats with myocardial infarction.

At present, little is known about the influence of mesenchymal stem cell (MSC) transplantation on connexin43 (Cx43) and connexin45 (Cx45) remodeling in the ischemic heart. In this study, we investigated the effect of MSC transplantation on Cx43 and Cx45 remodeling in the ischemic heart. Wistar rats were subjected to left anterior descending artery ligation to induce myocardial infarction (MI) and then randomly allocated to receive an intramyocardial injection of PBS (MI group) or 5-azacytidine-induced MSCs (MSCs group). Histological examination and western blotting were performed 4 weeks after cell transplantation. We found that the MSCs exhibited plasticity by differentiating into cardiomyocyte-like cells. Gap junction remodeling after MI was characterized by a decrease in Cx43 expression and an increase in Cx45 expression. MSC transplantation modulated the MI-induced abnormalities by up-regulating Cx43 and down-regulating Cx45 expression. MSCs exhibited plasticity by differentiating into cardiomyocyte-like cells and modulated abnormal Cx43 and Cx45 remodeling following MI.

[An Epidemiological Survey on Echinococcosis in Yushu Prefecture of Qinghai Province].

Objective: To investigate the prevalence of echinococcosis in Yushu Prefecture of Qinghai Province in 2012. Methods: Two to three towns were selected in each of Chengduo, Nangqian, Qu malai, Yushu, Zaduo and Zhiduo Counties from June to August in 2012. Ultrasound examination was conducted for residents aged over 1 year, and ELISA was performed to detect serum antibody against Echinococcus. Visceral dissection was performed to detect hydatid infection in rodents and livestock. ELISA was used to detect Echinococcus antigen in collected dog feces. Results: A total of 7 025 residents received ultrasound examination, of whom 319 showed hydatid cysts with a morbidity rate of 4.54%. ELISA showed a serum antibody positive rate of 16.38% （457/2 790）. The mobidity of hydatid disease was highest in Chengduo County （7.41%, 181/2 444）, and the rate of serum antibody was highest in Yushu County （23.18%, 127/548）. The morbidity and serum antibody in males were 3.91% （118/3 018） and 13.93% （172/1 235） respectively, and those in females were 5.02% （201/4 007） and 18.33% （285/1 555）. In terms of age distribution, the morbidity was relatively higher in residents of 60- （8.39%, 38/453） and 40- years （6.61%, 67/1 014）; and the rate of serum antibody was highest in residents over 70 years （33.93%, 19/56）. In terms of occupation, the morbidity was relatively higher in herdsmen （5.28%, 252/4 777）, Herdsmen-peasants （6.52%, 24/368）, and religious workers（3.37%, 11/326）, while the rate of serum antibody was relatively higher in children（24%, 6/25）, religious workers （18.79%, 31/165） and herdsmen（18.34%, 328/1 788）. In terms of education level, the morbidity and the rate of serum antibody were both highest in the uneducated（5.04%, 41/4 779; 18.34%, 359/1 958, respectively）. In terms of residential pattern, the morbidity and the rate of serum antibody were both highest in those who were settled in winter and nomadic in summer （8.25%, 227/2 753; 19.48%, 158/811, respectively）. There were significant differences in the morbidity and the rate of serum antibody in aspects of residential region, sex, age, occupation, education level and residential pattern (P<0.05 or P<0.01). In 872 rodents detected, the Echinococcus hydatid rate was 0.46% （4/872）, while in 809 cattle and sheep detected, the Echinococcus hydatid rate was 10.14% （82/809）. The fecal antigen positive rate in 838 samples of dog feces was 10.74%（90/838）. Conclusion: It shows a high morbidity of hydatid diesease and serum antibody positive rate in residents, a high Echinococcus hydatid rate in cattle and sheep, and a high fecal antigen positive rate in dogs in Yushu Prefecture.

[Survey on Echinococcosis in Maqing County of Qinghai Province].

OBJECTIVE: To understand the status of echinococcosis in Maqing County of Qinghai Province in order to facilitate echinococcosis control in this region. METHODS: Ultrasonic scanning and indirect hemagglutination assay were used to detect echinococcosis infection in residents >1 year old, according to the People's Republic of China Health Industry Standard--Diagnostic Criteria for Hydatid Disease (WS257-2006). Meanwhile, ELISA was used o detect the Echinococcus antigen in dog's feces collected in Youyun, Dangluo and Xiadawu townships. RESULTS: Ultrasonic scanning showed that the prevalence of hydatid disease in the residents was 7.4% (116/1 561), cystic hydatid disease 5.3% (82/1 561), alveolar hydatid disease 2.2% (34/1 561). The serum positive rate in human population was 23.8%(307/1 288). Of the 82 cases of cystic hydatid disease, 23 cases (28.1%) had the hydatid cyst with a diameter of >10 cm. The prevalence in males and females in the county was 5.3% (40/753) and 9.4% (76/808), respectively (P<0.05). Among populations with different occupations, the highest prevalence of hydatid disease fell into houseworkers (11/61, 18.0%), monks (5/41, 12.2%) and herdsmen (84/758, 11.1%). Among the age groups, the groups of >60 years (24/132, 18.2%) and 30-40 years (31/302, 10.3%) had higher prevalence of hydatid disease. The three townships with the higher prevalence were Youyun (29/247, 11.7%), Changmahe (6/63, 9.5%) and Dangluo (54/645, 8.4%). Of the 199 samples of dog's feces, 54 were positive for Echinococcus antigens (27.1%), with a positive rate of 40.4% (23/57) in Youyun towship, being significantly higher than in the other two (P<0.05). CONCLUSION: Maqin county is a co-endemic area of cystic echinococcosis and alveolar echinococcosis. The prevalence is higher in females and those over 60 years-old.

Cystic and alveolar echinococcosis: an epidemiological survey in a Tibetan population in southeast Qinghai, China.

An epidemiological investigation on echinococcosis was made in Jiuzhi County of Qinghai Province, western China. Ultrasonography and an indirect hemagglutination test revealed a morbidity of 8.0% (124/1,549) and a seroprevalence of 25.8% (287/1,113), respectively, in the Tibetan population. The morbidity in herdsmen (16.6%) and Buddhist priests (15%) was significantly higher than that in other occupation groups (3.2%), and it was higher in females (9.8%) than in males (6.2%). The ultrasound images showed a coexistence of cystic echinococcosis (CE) and alveolar echinococcosis (AE), occupying 69 and 31% of the cases, respectively. An Echinococcus Western blot assay was performed as a serological backup test for differentiating CE and AE. The assay revealed that serum samples from most cases with a positive AE image showed a specific antibody against antigen bands at 16/18 kDa. Autopsy proved that 9 out of 12 stray dogs were infected with Echinococcus granulosus (n = 8) and E. multilocularis (n = 1). Inspection at the abattoirs demonstrated a hydatid rate of 78.5% in yaks and 82.6% in sheep. The data indicate that Jiuzhi County is an important endemic area for both CE and AE, in both human and animal populations.

[An epidemiological survey on hydatid disease in Yushu Prefecture of Qinghai Province].

Local inhabitants in 8 towns/townships of the counties Yushu, Zhiduo and Chengduo were examined with serology and ultrasound in 2006. Among 2 251 people tested by indirect hemagglutination (IHA), 207 showed anti-hydatid IgG positive (9.2%). Ultrasound examination found 106 cases out of 2581 people, with a morbidity of 4.1%. Females showed higher sero-positive rate (11.3%) and morbidity rate (5.0%) than males (6.6% and 3.0% respectively). The highest sero-positive rate was in the group of 40-49 years old (16.4%). The morbidity rate increased with age, with the highest rate (15.5%) in the group of 60 years old and above. Occupationally, those involved in semi-agriculture and semi-animal husbandry showed highest sero-positive rate and morbidity rate, 21.5% and 11.4% respectively. The survey demonstrated that the prevalence of hydatid disease in human population is at a high level in Yushu Tibetan Autonomous Prefecture.

[An epidemiological survey on echinococcosis in Zhiduo County of Qinghai Province].

The survey was carried out in July, 2006 in Zhiduo County. The IHA and ELISA positive rate in human population was 4.5% (42/933) and 8.2% (76/931) respectively. Ultrasonography revealed a morbidity of 3.4% (33/979) with 3.2% Echinococcus granulosus and 0.2% of E. multilocularis respectively. Animal dissection showed an infection rate of 15.1% (14/93) in pikas with one infected by E. shiquicus proved by molecular biology. Coproantigen rate by ELISA was 62% (12/193) in dogs and 35.7% (5/14) in wolves. The results indicated that Zhiduo County is a mixed endemic area for echinococcosis.

Function of c-Fos-like and c-Jun-like proteins on trichostatin A-induced G2/M arrest in Physarum polycephalum.

The homologs of transcription factors c-Fos and c-Jun have been detected in slime mold Physarum polycephalum during progression of the synchronous cell cycle. Here we demonstrated that c-Fos-like and c-Jun-like proteins participated in G2/M transition by the regulation of the level of Cyclin B1 protein in P. polycephalum. The study of antibody neutralization revealed that interruption of the functions of c-Fos-like and c-Jun-like proteins resulted in G2/M transition arrest, implicating their functional roles in cell cycle control. When G2/M transition was blocked by histone deacetylase inhibitor trichostatin A, changes in c-Fos- and c-Jun-like protein levels, and hyperacetylation of c-Jun-like protein, were observed. The data suggest that in P. polycephalum, c-Fos- and c-Jun-like proteins may be the key factors in the regulation of histone acetylation-related G2/M transition, involving the coordinated expression and hyperacetylation of these proteins.