Objective To investigate the efficacy and safety of Urinary kallidinogenase(UK)combined with butylphthalide in patients with acute cardioembolic stroke(ACS).Methods A retrospective collection was performed for ACS patients diagnosed and treated in Hangzhou First People's Hospital from May 2022 to April 2023.According to the treatment protocol,ACS patients were divided into UK group and Butylphthalide+UK group.The clinical efficacy,neurological function,serum indexes(Hcy,NT-proBNP and VEGF)and prognosis of the two groups were compared after 2 weeks of treatment.Results A total of 86 ACS patients were included in the study,including 43 in the UK group and 43 in the Butylphthalide+UK group.After treatment,the total effective rate of treatment in the Butylphthalide+UK group was significantly higher than that in the UK group(P<0.05),and there was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).In addition,the expression levels of Hcy and NT-proBNP in ACS patients in the Butylphthalide+UK group were significantly lower than those in the UK group(P<0.05),while the expression levels of VEGF were significantly higher than those in the UK group(P<0.05).The NIHSS score and mRS score of ACS patients in the Butylphthalide+UK group were significantly lower than those in the UK group(P<0.05).The rate of collateral circulation establishment in the Butylphthalide+UK group was significantly higher than that in the UK group(P<0.05).Conclusion Butaphthalide combined with UK has significant efficacy and high safety in ACS patients,which may be achieved by regulating the expression levels of serum Hcy,NT-proBNP and VEGF,thereby improving neurological function and promoting the establishment of collateral circulation.

OBJECTIVE: To evaluate the storage stability of metabolites from actinomycetes Streptomyces nigrogriseolus XD 2-7 and the mollcuscicidal activity against Oncomelania hupensis in the laboratory, and to preliminarily explore the mechanisms of the molluscicidal activity. METHODS: The fermentation supernatant of S. nigrogriseolus XD 2-7 was prepared and stored at -20, 4 °C and 28 °C without light for 10 d; then, the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The fermentation supernatant was boiled in a 100 °C water bath for 30 min and recovered to room temperature, and then the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The pH values of the fermentation supernatant were adjusted to 4.0, 6.0 and 9.0 with concentrated hydrochloric acid and sodium hydroxide, and the fermentation supernatant was stilled at room temperature for 12 h, with its pH adjusted to 7.0; then, the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The fermentation product of S. nigrogriseolus XD 2-7was isolated and purified four times with macroporous resin, silica gel and octadecylsilane bonded silica gel. The final products were prepared into solutions at concentrations of 10.00, 5.00, 2.50, 1.25 mg/L and 0.63 mg/L, and the molluscicidal effect of the final productswas tested against O. hupensis following immersion for 72 h, while dechlorination water served as blank controls, and 0.10 mg/L niclosamide served as positive control. The adenosine triphosphate (ATP) and adenosine diphosphate (ADP) levels were measured in in O. hupensis soft tissues using high performance liquid chromatography (HPLC) following exposure to the final purified fermentation products of S. nigrogriseolus XD 2-7. RESULTS: After the fermentation supernatant of S. nigrogriseolus XD 2-7 was placed at -20, 4 °C and 28 °C without light for 10 d, immersion in the stock solution and solutions at 10- and 50-fold dilutions for 72 h resulted in a 100% (30/30) O. hupensis mortality. Following boiling at 100 °C for 30 min, immersion in the stock solution and solutions at 10- and 50-fold dilutions for 72 h resulted in a 100.00% (30/30) O. hupensis mortality. Following storage at pH values of 4.0 and 6.0 for 12 h, immersion in the fermentation supernatant of S. nigrogriseolus XD 2-7 for 72 h resulted in a 100.00% (30/30) O. hupensis mortality, and following storage at a pH value of 9.0 for 12 h, immersion in the fermentation supernatant of S. nigrogriseolus XD 2-7 for 72 h resulted in a 33.33% (10/30) O. hupensis mortality (χ² = 30.000, P < 0.05). The minimum concentration of the final purified fermentation products of S. nigrogriseolus XD 2-7 was 1.25 mg/L for achieving a 100% (30/30) O. hupensis mortality. The ATP level was significantly lower in O. hupensis soft tissues exposed to 0.10 mg/L and 1.00 mg/L of the final purified fermentation products of S. nigrogriseolus XD 2-7 than in controls (F = 7.274, P < 0.05), while no significant difference was detected in the ADP level between the treatment group and controls (F = 2.485, P > 0.05). CONCLUSIONS The active mollcuscicidal ingredients of the S. nigrogriseolus XD 2-7 metabolites are maintained stably at -20, 4 °C and 28 °C for 10 d, and are heat and acid resistant but not alkali resistant. The metabolites from S. nigrogriseolus XD 2-7 may cause energy metabolism disorders in O. hupensis, leading to O. hupensis death.
Adenosine Diphosphate/pharmacology* ; Adenosine Triphosphate ; Animals ; Molluscacides/pharmacology* ; Silica Gel/pharmacology* ; Snails ; Streptomyces ; Water

Objective To test the activity of aromatic pyrrole-based compounds against cercariae of Schistosoma japonicum and test their acute toxicity to fish. Methods A series of aromatic pyrrole-based compounds were synthesized using 4-benzyl-5-(trifluoromethyl)-1H-pyrrole-3-nitrile as the lead compound. The synthesized compounds were prepared into solutions at concentrations of 10.00, 1.00, 0.10, 0.01 mg/L, and the activity of these solutions against S. japonicum cercariae was tested in 30 min, while 0.10 mg/L and 0.01 mg/L niclosamide solutions served as a positive control and dechlorinated water with 1% dimethyl sulfoxide (DMSO) was used as a negative control, with 10 to 30 cercariae of S. japonicum in each group. In addition, the compounds were prepared into solutions at concentrations of 0.50, 0.25, 0.12, 0.06, 0.03 mg/L, and their toxicity to zebrafish was tested in 72 h, while 0.15 mg/L and 0.30 mg/L niclosamide solutions served as a positive control and dechlorinated water with 1% DMSO was used as a negative control, with 10 zebrafishes in each group. Results A total of 7 aromatic pyrrole-based compounds were successfully synthesized. Treatment with compounds 102, 104 and 106 at a concentration of 0.01 mg/L for 30 min killed all S. japonicum cercariae, and compounds 105 and 107 showed no activity against cercariae. No death of cercariae was found in the blank control group, while treatment with 0.10 mg/L niclosamide for 10 min caused a 100% mortality rate of S. japonicum cercariae and 0.01 mg/L niclosamide failed to kill S. japonicum cercariae. No zebrafish death was found 72 h post-treatment with compounds 101, 104 and 105 at a concentration of 0.03 mg/L, and exposure to compounds 102, 103 and 106 at a concentration of 0.03 mg/L for 12 h resulted in a 100% mortality rate of zebrafish. No zebrafish death occurred 72 h post-treatment with 0.50 mg/L Compound 104, and no zebrafish death was found in the blank control group, while treatment with 0.30 mg/L niclosamide for 24 h resulted in a 100% mortality rate of zebrafish. Conclusions Compound 104 achieves a 100% mortality rate against S. japonicum cercariae at a concentration of 0.01 mg/L for 30 min, and causes no death of zebrafish at a concentration of 0.50 mg/L for 72 h, which may serve as a cercaricide candidate.

Mechanical stimulus is critical to cardiovascular development during embryogenesis period.The mechanoreceptors of endocardial cells and cardiac myocytes may sense mechanical signals and initiate signal transduction that induce gene expression at a cellular level,and then translate molecular-level events into tissue-level deformations,thus guiding embryo development.This review summarizes the regulatory roles of mechanical signals in the early cardiac development including the formation of heart tube,looping,valve and septal morphogenesis,ventricular development and maturation.Further,we discuss the potential mechanical transduction mechanisms of platelet endothelial cell adhesion molecule 1-vascular endothelial-cadherin-vascular endothelial growth factor receptor 2 complex,primary cilia,ion channels,and other mechanical sensors that affect some cardiac malformations.
Animals ; Heart/embryology* ; Humans ; Mechanotransduction, Cellular ; Myocytes, Cardiac/physiology* ; Vascular Endothelial Growth Factor A/metabolism*

Objective: This study explored the thromboembolism risk of low-risk atrial fibrillation (AF) patients (CHA₂DS₂-VASc score of 0 or 1 for male and 1 or 2 for female) with different clinical characteristics to provide the basis for anticoagulation decision-making in these patients. Methods: We prospectively enrolled consecutive 2 862 nonvalvular low-risk AF patients between August 2011 to December 2018 in China-AF (China Atrial Fibrillation Registry) Study, their CHA₂DS₂-VASc score was 0 or 1 for male and 1 or 2 for female. According to their age, sex, presence or absence of hypertension, diabetes mellitus, congestive heart failure, and vascular disease at the time of enrolling, patients were divided into CHA₂DS₂-VASc score 0 score group, 1 score group, and 2 score group. Patients were followed up every 6 months by outpatient clinic visit or telephone interview. The outcome was a thromboembolic event, including ischemic stroke and systemic embolism. Univariate Cox regression analysis was used to compare the thromboembolism risk between the patients with different risk factors and CHA₂DS₂-VASc score 0 group. Results: A total of 2 862 low-risk atrial fibrillation patients were enrolled in this study. 915 patients (32.0%) were female, and age was (55.0±10.7) years old. There were 933 patients (32.6%) in CHA₂DS₂-VASc score 0 group, 1 401 patients (49.0%) in score 1 group and 528 patients (18.5%) in score 2 group. During follow-up (median 1.5 years, 5 811.82 person-years), 33 cases of thromboembolic events were recorded, the annual rate of thromboembolism was 0.57% (95%CI 0.40%~0.80%). The number of thromboembolic events in patients with CHA₂DS₂-VASc score 0, 1 and 2 were 8, 11 and 14, respectively, and the annual thromboembolism event rates were 0.40% (95%CI 0.20%-0.81%), 0.39% (95%CI 0.22%-0.71%) and 1.34% (95%CI 0.80%-2.27%), respectively. The risk of thromboembolism of CHA₂DS₂-VASc score 2 group (HR=3.53, 95%CI 1.48-8.44; P=0.005), especially female patients aged 65-74 years in CHA₂DS₂-VASc score 2 group (HR=2.67, 95%CI 1.63-4.38; P<0.000) was significantly higher than that in patients of CHA₂DS₂-VASc score 0 group. Conclusion: Low-Risk Atrial Fibrillation patients with CHA₂DS₂-VASc score 2, especially female patients aged 65-74 years old with CHA₂DS₂-VASc score 2 are at higher risk of thromboembolism in low-risk AF patients. For such patients, intensified oral anticoagulant therapy might be helpful to reduce the risk of thrombolism.
Adult ; Aged ; Anticoagulants ; Atrial Fibrillation ; China ; Female ; Humans ; Male ; Middle Aged ; Risk Assessment ; Risk Factors ; Stroke ; Thromboembolism

Objectives: This study explored the relationship between weight control and atrial fibrillation (AF) recurrence after catheter ablation in overweight and obese patients. Methods: We prospectively enrolled consecutive 333 overweight and obese patients aged 28 to 87 years old, who underwent catheter ablation for AF in Beijing Anzhen Hospital between October 2015 and February 2016. Data of patients′ characteristics, laboratory examination and treatment were collected at baseline. Each patient was followed up at 3, 6 and 12 months after ablation to collect information on weight, AF recurrence, stroke, major bleeding, hospitalization for cardiovascular reasons and death, etc. Patients were divided into weight controlled group (ΔBMI<-1 kg/m²) and weight uncontrolled group (ΔBMI≥-1 kg/m²), according to the changes in the most recent exposure BMI before AF recurrence in patients with recurrence or the BMI at 12 months′ follow-up in patients without recurrence and the BMI at baseline. Multivariate logistic regression was performed to adjust other known risk factors of AF recurrence and to explore the association between weight control and AF recurrence after catheter ablation. Results: There were 54 patients in weight controlled group and 279 patients in weight uncontrolled group. There were no significant differences in age, gender, education level, left atrial size and history of hypertension between the two groups (all P>0.05). The proportion of patients using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was higher in the weight controlled group (50.0%(27/54) vs. 34.8%(97/279), P=0.034). However, there was no significant difference in the proportion of patients with obesity (33.3% (18/54) vs. 29.7% (83/279)), paroxysmal AF (59.3% (32/54) vs. 56.6% (158/279)) and AF duration less than 5 years (76.9% (40/52) vs. 65.4% (178/272)) between the weight controlled group and the uncontrolled group. During 1-year follow-up after ablation, the recurrence rate of AF was significantly lower in the weight controlled group than that in the weight uncontrolled group (14.8% (8/54) vs. 32.6%(91/279), P=0.009). Multivariable logistic regression analysis shows that weight control is independently associated with a lower postoperative AF recurrence rate (OR=0.40, 95%CI 0.18-0.90, P=0.026). Conclusion Weight control is strongly associated with a lower AF recurrence rate after catheter ablation in overweight and obese patients.

Objectives This study explored the relationship between weight control and atrial fibrillation (AF) recurrence after catheter ablation in overweight and obese patients. Methods We prospectively enrolled consecutive 333 overweight and obese patients aged 28 to 87 years old, who underwent catheter ablation for AF in Beijing Anzhen Hospital between October 2015 and February 2016. Data of patients′ characteristics, laboratory examination and treatment were collected at baseline. Each patient was followed up at 3, 6 and 12 months after ablation to collect information on weight, AF recurrence, stroke, major bleeding, hospitalization for cardiovascular reasons and death, etc. Patients were divided into weight controlled group (ΔBMI<-1 kg/m2) and weight uncontrolled group (ΔBMI≥-1 kg/m2), according to the changes in the most recent exposure BMI before AF recurrence in patients with recurrence or the BMI at 12 months′ follow?up in patients without recurrence and the BMI at baseline. Multivariate logistic regression was performed to adjust other known risk factors of AF recurrence and to explore the association between weight control and AF recurrence after catheter ablation. Results There were 54 patients in weight controlled group and 279 patients in weight uncontrolled group. There were no significant differences in age, gender, education level, left atrial size and history of hypertension between the two groups (all P>0.05). The proportion of patients using angiotensin?converting enzyme inhibitors/angiotensin receptor blockers was higher in the weight controlled group (50.0%(27/54) vs. 34.8%(97/279), P=0.034). However, there was no significant difference in the proportion of patients with obesity (33.3% (18/54) vs. 29.7% (83/279)), paroxysmal AF (59.3% (32/54) vs. 56.6% (158/279)) and AF duration less than 5 years (76.9% (40/52) vs. 65.4% (178/272)) between the weight controlled group and the uncontrolled group. During 1?year follow?up after ablation, the recurrence rate of AF was significantly lower in the weight controlled group than that in the weight uncontrolled group (14.8% (8/54) vs. 32.6%(91/279), P=0.009). Multivariable logistic regression analysis shows that weight control is independently associated with a lower postoperative AF recurrence rate ( OR=0.40, 95%CI 0.18-0.90, P=0.026). Conclusion Weight control is strongly associated with a lower AF recurrence rate after catheter ablation in overweight and obese patients.

Objective The aim of our study was to investigate the influence of hexavalent chromium exposure on mRNA expression of cell cycle related genes in electroplating workers, and to provide population data for investigating the toxic mechanisms of hexavalent chromium. Methods A total of 155 cases of workers occupationally exposed to hexavalent chromium were selected, including 89 males and 66 females, and the average age of workers was 39.65±8.856 years old. Questionnaire was used to collect essential information of workers. Peripheral blood was collected from electroplating workers. The inductively couple plasma mass spectrometry (ICP-MAS) was used to measure total blood chromium content. The workers were divided into four groups according to the blood chromium content. After extracting total RNA from whole blood and reverse transcription, the mRNA expression levels of p16 and CDK6 genes were detected by real-time quantitative PCR. Meanwhile, the levels of blood chromium (BCr) and the mRNA expression of p16 and CDK6 genes were compared among four groups. The impact of BCr, smoking habits, drinking habits, gender on the mRNA expression of CDK6 gene was analyzed. Results The levels of BCr in group 1 to 4 were 0.04ppb, 0.47±0.29 ppb, 2.76±1.16 ppb, 9.36 ±4.38 ppb, respectively, and the difference between every two groups was significant (P<0.05) . The median of p16 gene expression in four groups was 4.22, 7.19, 7.47, and 14.60, respectively, and the difference between every two groups was not significant (P>0.05) . The mRNA expression levels of CDK6 gene in groups 2 to 4 were 15.05, 8.03 and 24.81, respectively, which were significantly higher than that in group 1 (P<0.05) . The results of logistic regression showed that the level of Bcr was the main influence factor, while smoking habits, drinking habits and gender had no obvious impact on the mRNA expression of CDK6 gene. Conclusions Long-term exposure of hexavalent chromium led to higher mRNA expression of CDK6 gene, and it may serve as a biomarker for workers occupationally exposed to hexavalent chromium.

BACKGROUNDGlobally, the proportion of child deaths that occur in the neonatal period remains a high level of 37-41%. Differences of cause in neonate death exist in different regions as well as in different economic development countries. The specific aim of this study was to investigate the causes, characteristics, and differences of death in neonates during hospitalization in the tertiary Neonatal Intensive Care Unit (NICU) of China.

METHODSAll the dead neonates admitted to 26 NICUs were included between January l, 2011, and December 31, 2011. All the data were collected retrospectively from clinical records by a designed questionnaire. Data collected from each NICU were delivered to the leading institution where the results were analyzed.

RESULTSA total of 744 newborns died during the 1-year survey, accounting for 1.2% of all the neonates admitted to 26 NICUs and 37.6% of all the deaths in children under 5 years of age in these hospitals. Preterm neonate death accounted for 59.3% of all the death. The leading causes of death in preterm and term infants were pulmonary disease and infection, respectively. In early neonate period, pulmonary diseases (56.5%) occupied the largest proportion of preterm deaths while infection (27%) and neurologic diseases (22%) were the two main causes of term deaths. In late neonate period, infection was the leading cause of both preterm and term neonate deaths. About two-thirds of neonate death occurred after medical care withdrawal. Of the cases who might survive if receiving continuing treatment, parents' concern about the long-term outcomes was the main reason of medical care withdrawal.

CONCLUSIONSNeonate death still accounts for a high proportion of all the deaths in children under 5 years of age. Our study showed the majority of neonate death occurred in preterm infants. Cause of death varied with the age of death and gestational age. Accurate and prompt evaluation of the long-term outcomes should be carried out to guide the critical decision.

Cause of Death ; China ; Female ; Hospital Mortality ; Humans ; Infant ; Infant Mortality ; Infant, Newborn ; Infant, Newborn, Diseases ; mortality ; Intensive Care Units, Neonatal ; statistics & numerical data ; Male ; Perinatal Death ; Retrospective Studies

BACKGROUNDCompared to the Western countries, Chinese patients present a special primary disease spectrum, diverse valvular pathogenesis, and different postoperational anticoagulation strategy. This research aimed to evaluate the mid- to long-term clinical performance of Hancock II bioprosthesis in the Chinese population.

METHODSThis study retrospectively reviewed all patients who received surgical treatments with at least one Hancock II bioprosthesis implantation from January 2004 to December 2013 at a single center in China. Totally 647 patients were included in the clinical evaluation, and 629 patients were successfully discharge, among whom 605 patients were completely followed-up. The follow-up rate was 96.2%. The mean and median follow-up time was 62.0 ± 59.0 and 56.0 months, respectively. Postoperative outcomes of survival rates, reoperations and valve related morbidities were assessed. Continuous and categorical variables were compared using the t -test and Chi-square test, respectively. Survival and freedom from adverse events were calculated by using a Kaplan-Meier method.

RESULTSThe overall in-hospital mortality was 2.8% (18/647) while there were 34 deaths (5.6%, 34/605) in the follow-up stage after discharge. The overall survival rate was 94.6% and 82.7% at 5 years and 10 years, respectively. The cumulative survival rate of 10 years was 82.8% in AVR group, 84.4% in MVR group, and 78.4% in DVR group. The overall rate of freedom from reoperations was 95.5% at 5 years and 86.8% at 10 years. The freedom from reoperation at 10 years was 87.0%, 88.1%, and 84.0% in AVR, MVR, and DVR group, respectively. The freedom from morbidities at 10 years was: 90.3% for thromboembolism, 95.2% for hemorrhage, 97.5% for prosthesis endocarditis, 95.9% for paravalvular leak, and 94.6% for structural valve deterioration, respectively.

CONCLUSIONSHancock II bioprosthesis exhibited a satisfactory mid- to long-term durability and promising clinical performance in the Chinese population. The occurrence rates of death and other adverse events in this single-center study were overall coincident and quite acceptable when compared with existing data.

Adult ; Aged ; Aged, 80 and over ; Aortic Valve ; surgery ; Bioprosthesis ; adverse effects ; China ; Female ; Heart Valve Diseases ; surgery ; Heart Valve Prosthesis ; adverse effects ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate