[The expanding needs on lipid-lowering treatment in patients with acute coronary syndrome by applying newly issued definition of extreme high-risk by Chinese Society of Cardiology].

Objective: To assess the expanding needs on lipid-lowering treatment in patients with acute coronary syndrome (ACS) by applying newly issued definition of extreme high-risk, which is proposed by Chinese expert consensus on lipid management of extreme high-risk atherosclerotic cardiovascular disease (ASCVD) patients of Chinese Society of Cardiology (CSC). Methods: Data of this study was derived from the Improving Care for Cardiovascular Disease in China (CCC) project, which was a case-based nationwide registry study and launched as a collaborative initiative by the American Heart Association and the CSC. The project consecutively recruited ACS patients from158 tertiary hospitals and 82 second hospitals across China, and detailed clinical information of patients was collected. This study enrolled ACS inpatients in CCC project from November 2014 to July 2019. The proportion of extreme high-risk patients, their characteristics, mean LDL-C levels at admission, the gap between measured LDL-C level and the new target, and lipid-lowering therapy at discharge were assessed. Results: Among 104 516 ACS inpatients enrolled in this study, 75.1% (78 527/104 516) met the criteria of extreme high-risk and were expected to achieve the new LDL-C goal. Among patients at extreme high-risk, 21.2% (16 651/78 527) had multiple severe ASCVD events and 78.8% (61 876/78 527) had 1 severe ASCVD event and at least two high-risk factors. For the extreme high-risk patients, the mean level of LDL-C at admission was (2.8±1.0) mmol/L, prevalence of LDL-C ≥1.4 mmol/L was 93.4% (73 307/78 527) and the median gap between LDL-C level at admission and the target of 1.4 mmol/L was 1.3 (0.8, 2.0) mmol/L. If LDL-C could be further reduced to 50% of the admission level, we estimated that 55.6% (43 632/78 527) of the extreme high-risk patients would achieve the new LDL-C goal. Among 40 875 patients with information about discharge statin dosage, 93.5% (28 004/29 947) of the extreme high-risk patients were prescribed with statins at discharge, and among them 95.1% (26 632/28 004) received statin monotherapy and 91.1% (25 501/28 004) were at moderate doses of statins. Conclusion: About three fourth of inpatients with ACS were categorized as extreme high-risk based on the new definition of CSC expert consensuses, nine out of ten patients at extreme high-risk didn't achieve the new LDL-C target at admission, and the intensity of lipid-lowering therapy was insufficient in clinical practice. There are substantially expanding needs for implementing more intensive and effective lipid-lowering strategies.

[Association between smoking and the severity of coronary lesions among young and middle-aged female patients with acute coronary syndrome].

Objective: To investigate the association between smoking and the severity of coronary lesions among young and middle-aged female patients with acute coronary syndrome (ACS). Methods: Data of this study were derived from the Improving Care for Cardiovascular Disease in China (CCC)-ACS project, a collaborative study of the Chinese Society of Cardiology and the American Heart Association. Since 2014, the CCC-ACS project consecutively enrolled inpatients with ACS, systematically collected their clinical data and evaluated medical quality of these patients from 158 tertiary hospitals and 82 secondary hospitals across China. This study enrolled female patients less than 60 years old with initial ACS, who received coronary angiography in CCC-ACS project. Patients were divided into two groups according to smoking status. A multivariate logistic regression analysis was used to analyze the association between smoking and the severity of coronary lesions among young and middle-aged female patients with ACS. Results: A total of 2 863 female patients younger than 60 years old with initial ACS, who received coronary angiography, were enrolled. Among them, 12% (340 cases) was smokers. Proportion of patients younger than 45 years old was higher (13.2% (45/340) vs. 8.5% (215/2 523), P<0.01) and prevalence of hypertension (59.4% (202/340) vs. 66.7% (1 683/2 523), P<0.01) and diabetes (39.4% (134/340) vs. 44.2% (1 116/2 523), P=0.09) was lower in smoker group than in non-smoker group. However, prevalence of ST-elevation myocardial infarction (66.8% (227/340) vs. 53.7% (1 354/2 523), P<0.01), coronary multi-vessel lesions (39.1% (133/340) vs. 32.6% (822/2 523), P<0.01) and severe stenosis in either single-vessel (56.2% (109/194) vs. 46.1% (706/1 530), P<0.01) or multi-vessel (63.2% (84/133) vs. 58.2% (478/822), P=0.29) was significantly higher in smoker group than in non-smoker group. Multivariate logistic regression analyses showed that after adjusting for age, hypertension, diabetes, elevated low-density lipoprotein cholesterol, lower high-density lipoprotein cholesterol, elevated triglyceride, renal insufficiency, family history of coronary heart disease and types of ACS, smokers faced a higher risk of coronary multi-vessel lesions, coronary multi-vessel severe lesions and coronary severe lesions with the odds ratios and 95% confidence interval of 1.41 (1.11-1.79), 1.40 (1.10-1.78) and 1.78 (1.11-2.87), compared with non-smokers. Conclusions: Smoking is significantly associated with an increased risk of extensive and severe coronary lesions among young and middle-aged female patients with ACS. This study provides crucial evidence for further understanding the harms of smoking and the need to strengthen the tobacco control education and smoking cessation guidance for young and middle-aged women.

[Transplantation of compound tissue flap of toe to reconstruct the thumb with necrosis caused by electric burns in four patients].

From January 2010 to December 2017, 4 patients of thumb with necrosis caused by electric burns (all male, aged from 31 to 58 years) were admitted to our hospital, with 1 patient of second degree injury of right thumb, 2 patients of third degree injury of right thumb, and 1 patient of third degree injury of left thumb. Routine debridement under general anesthesia was performed within 7 days after injury. The compound tissue flap of contralateral second toe was transplanted to reconstruct the thumb with third degree defect, and compound tissue flap of ipsilateral distal hallex was transplanted to reconstruct the thumb with second degree defect. Dorsalis pedics artery was anastomosed with radial artery, saphenous vein or dorsalis pedics vein was anastomosed with cephalic vein. The donor site was transplanted with split-thickness skin graft from autologous thigh. All the tissue flaps and skin grafts survived in 2 weeks after surgery. Within 1 year of follow-up, the reconstructed thumbs can achieve radial abduction and palmar abduction with good function. Reconstruction of thumb with free transplantation of compound tissue flap of toe is a good method to repair thumb with necrosis caused by electric burn.

The sources and mechanisms of bioactive ingredients in coffee.

Coffee bioactive components include caffeine, chlorogenic acids (CGAs), trigonelline, tryptophan alkaloids, diterpenes and other secondary metabolites. During roasting, coffee metabolites undergo complex Maillard reactions, producing melanoidins and other degradation products, the most controversial among which is acrylamide, an ingredient widely found in baked food and listed as a second class carcinogen. Green and roasted coffee ingredients have good biological activities for the prevention of cardiovascular disease, and antibacterial, anti-diabetic, neuroprotection, and anti-cancer activities. To better understand the relationship between coffee ingredients and human health, and to effectively use the active ingredients, it is essential to understand the sources of coffee active ingredients and their mechanisms of action in the organism. This paper systematizes the available information and provides a critical overview of the sources of coffee active ingredients and the mechanisms of action in vivo or in vitro, and their combined effects on common human diseases.

Development of Aldrichina grahami (Diptera: Calliphoridae) at Constant Temperatures.

Aldrichina grahami (Aldrich) (Diptera: Calliphoridae) is a forensically important species mainly found in Asia and is one of the first species to colonize a corpse in early spring and late autumn when the ambient temperature is slightly lower. In this study, A. grahami was collected from the Yangtze River Delta region and reared at seven constant temperatures ranging from 16 to 34°C to investigate the indices of development duration, accumulated degree hours, and larval body length. Using these results, we generated an isomorphen diagram, thermal summation model, and isomegalen diagram for A. grahami. Equations of the variation in larval body length with time after hatching and variation in time after hatching with body length were also obtained. A. grahami can complete its life cycle in 16-28°C, while its development was incomplete at 31 and 34°C, where puparia failed to transform into adults and eggs failed to hatch, respectively. The mean (±SD) developmental durations of A. grahami from egg to adult at 16, 19, 22, 25, and 28°C were 685.5 ± 18.8, 540.3 ± 15.9, 454.3 ± 19.4, 388.8 ± 19.0, and 335.5 ± 8.7 h, respectively. The mean (±SE) developmental threshold temperature D0 and the thermal summation constant K were determined as 4.33 ± 0.21°C and 7,985.9 ± 104.5 degree hours, respectively. The results of this study provide fundamental development data for the use of A. grahami in minimum postmortem interval estimations.

[Effects of apolipoprotein E deficiency on sphingosine-1-phosphate distribution in plasma and lipoproteins of mice].

Objective: To investigate the effects of apolipoprotein E deficiency (Apo E(-/-)) on plasma and lipoprotein distribution of sphingosine-1-phosphate (S1P) in mice. Methods: Five male or female Apo E(-/-) or wild type (WT) mice were fed with chow diet and sacrificed at 32-week-age and plasma was collected. The constituents of lipoprotein(very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL)) were separated by ultracentrifuge. The protein concentration of constituents was detected by BCA protein quantitative kit, and the S1P concentration in plasma and various lipoprotein constituents was detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Western blot was used to determine the plasma, liver, and kidney protein expression of apolipoprotein M(Apo M), which is considered as specific ligand of S1P.The S1P concentration in plasma and various constituents of lipoprotein in the Apo E(-/-) mice was compared to respective WT mice. Results: (1)Plasma S1P content was significantly higher in the Apo E(-/-) groups than that of WT groups (male: (535.7±78.5)nmol/L vs. (263.3±22.0)nmol/L; female: (601.1±64.0)nmol/L vs. (279.0±33.9)nmol/L; all P<0.01). (2) Compared with WT mice, S1P content in non-HDL(LDL+ VLDL) was significantly higher in Apo E(-/-) mice (male: (504.9±52.8)nmol/L vs. (28.7±9.0)nmol/L; female: (427.7±27.4) vs. (27.8±4.7)nmol/L; after standardization of protein concentration, male: (385.0±41.2)pmol/mg protein vs. (71.4±6.6)pmol/mg protein; female: (330.2±22.0)pmol/mg protein vs. (67.2±12.1)pmol/mg protein; all P<0.01). (3) The expression of Apo M in plasma, liver and kidney was significantly higher in Apo E(-/-) groups than that of WT groups(all P<0.05). Conclusion: The deficiency of Apo E could lead to upregulated S1P expression in the non-HDL, the underlying mechanism might be the increased transfer of HDL into the non-HDL by Apo M-S1P.

[Advances in the research of basic study and clinical application of adipose-derived mesenchymal stem cells].

Since the discovery of adipose-derived mesenchymal stem cell (ADSC) in more than ten years, a great progress has been made from its basic research to clinical application. Compared with bone marrow mesenchymal stem cells, ADSCs are more abundant in reserve, easier to obtain with fewer injuries and less complications. These cells have multiple differentiation potential and can differentiate into adipocytes, chondrocytes and osteoblasts with the influence of different inducing factors. Early studies of ADSCs mainly focused on the ability of multi-directional differentiation, espe-cially on the regeneration of bone defects and cartilage tissue. At present, the researches mainly focus on immunoregulation and paracrine function of ADSCs. Although ADSCs have made a great progress in clinical application, the cell preparation, use pattern, and mechanisms in clinical treatment are not clear. This paper elaborates on these issues.

[Survey of the first case of Zika virus disease in the mainland of China].

OBJECTIVE: To analyze epidemiological characteristics of the first laboratory confirmed case of Zika virus disease in the mainland China, and provide evidence for the prevention and control of the spread of Zika virus disease. METHODS: Epidemiological survey was conducted for the first suspect case of Zika virus disease in China, and medical observation was conducted for the close contacts. The nucleic acid detection of Zika virus was conducted with Real-time RT-PCR by using blood and urine samples collected from the cases. RESULTS: The first case of Zika virus disease was confirmed. The case was cured and discharged on 18(th) day after the onset. The blood sample on 10(th) day after the onset and urine samples on 11-13(th) days after the onset were all positive for Zika virus. The case had the history of mosquito bites in the endemic country before the onset. The close contacts showed no Zika virus disease-like symptoms during the medical observation period. CONCLUSION: The case reported by Jiangxi province was the first imported case of Zika virus disease in the mainland of China. The infection was related with the mosquito bites in Venezuela where Zika virus disease in endemic.

[Effect of vanadium exposure on neurobehavioral function in workers].

OBJECTIVE: To establish the comprehensive indicators for neurobehavioral function test, and to investigate the possible adverse effect of long-time vanadium exposure on neurobehavioral function and its features in workers. METHODS: From July to November, 2012, The Neurobehavioral Core Test Battery(NCTB) recommended by WHO was used to conduct tests for 128 workers in vanadium exposure group and 128 workers in control group. The t-test and analysis of covariance were used to compare the differences in each indicator in NCTB between different populations, and the principal component analysis was used to establish the comprehensive neurobehavioral index(NBI) and investigate the effect of vanadium on workers' neurobehavioral function. RESULTS: The vanadium exposure group had significantly lower visual retention score(6.9±1.9), digit span(order) score(8.9±2.9), lifting and turning dexterity(the non-handed hand) score (14.1±3.6), pursuit aiming test(the number of correct dots) score(65.7±24.8), and digit symbol score (31.1±15.0) than the control group (8.2±1.3, 9.4±2.7, 15.5±3.0, 76.5±23.8, and 33.7±9.5)(all P<0.05). The vanadium exposure group also had a significantly lower NBI than the control group(-0.167±0.602 vs 0.168±0.564, P<0.05). CONCLUSION: Long-term vanadium exposure can influence the workers' neurobehavioral function, with the manifestations of decreased hearing and visual memory, movement velocity, accuracy, and coordination.

Impact of common SNPs in VEGF gene on the susceptibility of osteosarcoma.

We conducted a case-control study to assess the role of vascular endothelial growth factor (VEGF) -634G/C, +936C/T, and +1612G/A genetic variations in the development of osteosarcoma in a Chinese population. This hospital-based case-control study examined 130 patients with osteosarcoma and 130 age- and gender-matched healthy controls from March 2011 and March 2013. Polymerase chain reaction-restriction fragment length polymorphism was applied to assess the VEGF -634G/C, +936C/T, and +1612G/A gene polymorphisms. Using conditional regression analysis, individuals carrying the TT genotype of VEGF +936C/T were found to be correlated with an elevated risk of osteosarcoma, with an adjusted odds ratio (95% confidence interval) of 2.70 (1.02-8.28). In conclusion, our study suggests that the TT genotype of VEGF +936C/T genetic variants is associated with an increased risk of osteosarcoma.

The relationship between tumour necrosis factor-α gene polymorphism and susceptibility and clearance of the persistent hepatitis B virus infection in a Chinese population: a meta-analysis.

To date, many studies conducted in the Chinese population have determined the correlation between the tumour necrosis factor-α (TNF-α)-238G/A, -308G/A, -857C/T and -863C/A polymorphisms and persistent hepatitis B virus (HBV) infection. However, their results remain inconclusive. With the aim of confirming this correlation, we performed a meta-analysis of 19 studies. The dichotomous data are presented as the OR with a 95% CI. The results of our study indicate that carriers of the TNF-α-857T allele among the pooled Chinese population were more likely to show spontaneous clearance of HBV (T vs C: OR = 0.824, 95% CI = 0.713-0.953, p 0.009; TT vs CC: OR = 0.701, 95% CI = 0.507-0.970, p 0.032; TC vs CC: OR = 0.804, 95% CI = 0.683-0.947, p 0.009; TT + TC vs CC: OR = 0.835, 95% CI = 0.716-0.974, p 0.021). The TNF-α-308A allele was associated with significantly reduced persistent HBV infection risk in the Chinese (A vs G: OR = 0.585, 95% CI = 0.456-0.751, p 0.002; AG vs GG: OR = 0.519, 95% CI = 0.341-0.789, p <0.000; AA + AG vs GG: OR = 0.512, 95% CI = 0.339-0.772, p 0.001). Persistent HBV infection susceptibility is associated with the TNF-α-308G/A gene polymorphism in the Chinese population, whereas HBV clearance is associated with the TNF-α-857C/T gene polymorphism.

T cell recognition of the A2 domain of coagulation factor VIII in hemophilia patients and healthy subjects.

Hemophilia A patients treated with coagulation factor VIII (FVIII), and also some healthy subjects, may develop anti-FVIII antibodies (Ab), whose synthesis is driven by FVIII-specific CD4+ T cells. Some Ab block the procoagulant function of FVIII (inhibitors). Many inhibitors recognize epitopes on the FVIII A2 domain. Here, we have sought to identify A2 epitopes recognized by CD4+ T cells. We tested the proliferative response of CD4+ blood lymphocytes (BL) from hemophilia patients and healthy subjects, to overlapping synthetic peptides spanning the A2 domain sequence. Many A2 peptides induced proliferative responses of CD4+ BL from one or more subjects. The peptide-induced responses were strongest in hemophilia patients with inhibitors, weakest in healthy subjects. A2 peptides comprising residues 371-400, 621-650 and 671-690 elicited frequent and strong responses in hemophilia A patients, and especially in those with inhibitors. Healthy subjects recognized frequently only the sequence 371-400. A three-dimensional model of the A2 domain suggests that these CD4+ epitope sequences have structural features typical of 'universal' CD4+ T epitopes.

Recognition of coagulation factor VIII by CD4+ T cells of healthy humans.

Hemophilia A patients treated with coagulation factor (F)VIII may develop an anti-FVIII immune response. Anti-FVIII antibodies may occur also in healthy subjects. To understand the extent to which an immune response to FVIII occurs in healthy subjects, we investigated the proliferative response of blood CD4+ T cells from 90 blood donors to FVIII and to pools of overlapping synthetic peptides spanning the sequences of individual FVIII domains (A1-A3, C1-C2). Most subjects responded to FVIII and several FVIII domains. Men had stronger responses to FVIII than women, and older subjects than younger subjects. The domain-induced responses were weaker than the FVIII-induced responses, yet their intensity in individual subjects correlated with that of the response to FVIII. We examined whether Th1 and/or Th2 cells responded to FVIII in 68 subjects, by determining the CD4+ T cells that secreted interferon-gamma (IFN-gamma) or interleukin (IL)-5 after stimulation with FVIII: 25 subjects had FVIII-specific IFN-gamma-secreting cells, and seven of them had also FVIII-specific IL-5-secreting cells. None had only IL-5-secreting cells. Thus, a CD4+ T cell response to FVIII, which first involves Th1 cells, is common among subjects with a normal procoagulant function.

ELF magnetic fields induce internalization of gap junction protein connexin 43 in Chinese hamster lung cells.

We have previously demonstrated that exposure of Chinese hamster lung (CHL) cells to 50 Hz magnetic fields (MFs) and/or 12-O-tetradecanoylphorbol-3-acetate (TPA)-inhibited gap junctional intercellular communication (GJIC). To explore and compare the mechanisms of GJIC inhibition induced by extremely low frequency (ELF) MF and TPA, the number and localization of connexin 43 (C x 43) were studied. The localization of C x 43 was determined with indirect immunofluorescence histochemical analysis and detected by confocal microscopy after exposing CHL cells to 50 Hz sinusoidal magnetic field at 0.8 mT for 24 h without or with TPA (5 ng/ml) for the last 1 h. The C x 43 levels in nuclei and in cytoplasm were examined by Western blotting analysis. The results showed that the cells exposed to MF and/or TPA displayed individual plaques at regions of intercellular contact, which were fewer than the normal cells in number, while the number of C x 43 in cytoplasm increased and congregated near the nuclei. Western blot analysis further demonstrated the quantity of changes in location of Cx43. These results suggest that reduction of C x 43 at regions of intercellular contact may be one of the mechanisms of GJIC inhibition induced by ELF MF.

Helicobacter pylori cagA and vacA cytotoxin genes in Changsha, China.

Cytotoxin-associated protein (cagA) and the vacuolating cytotoxin (vacA) encoded by cagA and vacA genes are virulence determinants of Helicobacter pylori. In earlier studies among Chinese patients, all H. pylori strains were cagA-positive and vacAs1a/m2 type. Here, we determine the cagA, vacA and allele status of H. pylori strains isolated from patients with upper gastrointestinal symptoms in Changsha, China. Forty strains of H. pylori isolated from patients with peptic ulcer disease between March 1997 and August 1999 were recovered from storage at -80 degrees C and studied by the polymerase chain reaction (PCR) for cagA and vacA genotypes. cagA was positive in 75% of H. pylori isolates. Patients with peptic ulcer demonstrated cagA in 83% (15/18), compared with 68% (15/22) patients with superficial gastritis. vacAs1 allele was carried in 82.5% (33/40) isolates, of which 52.5% (21/40) were subtype vacAs1a/m2 and 17.5% (7/40) were subtype vacAs1b/m2.

ELF magnetic field inhibits gap junctional intercellular communication and induces hyperphosphorylation of connexin43 in NIH3T3 cells.

The effects of extremely low frequency (ELF) magnetic field on gap junctional intercellular communication (GJIC), protein levels, and phosphorylation of connexin43 (Cx43) were studied in NIH3T3 cells. The suppression of GJIC by 24 h, 50 Hz, 0.8 mT ELF magnetic field, 2 h, 3 ng/ml 12-O-tetradecanoylphorbol-13-acetate (TPA), or ELF combined with TPA treatment was confirmed by the fluorescence recovery after photobleaching (FRAP) analysis with a confocal microscope. The results showed that ELF or TPA exposure induced 50-60% inhibition of GJIC (P < 0.01). ELF combined with TPA enhanced the inhibition of GJIC. Western blot analysis using Cx43 specific antibodies showed obviously decreasing non phosphorylated Cx43 (P(0)) induced by ELF and/or TPA exposure. On the other hand, cells treated with ELF and/or TPA displayed a hyperphosphorylated Cx43 band (P(3)). However, there was no obvious changes in the level of Cx43 protein. The results implied that the P(3) band appeared to result from phosphorylation of P(0). But it remains possible that upon the ELF exposure P(0) is converted to P(1), P(2) or both and that P(3) is formed from P(1) or P(2) resulting in the observed hyperphosphorylation pattern. From the present study, we conclude that ELF magnetic field inhibits GJIC and the main mechanism is the hyperphosphorylation of Cx43.

Polycolonization of Helicobacter pylori among Chinese subjects.

OBJECTIVE: To investigate the situation among Chinese patients with regard to infection with multiple strains of Helicobacter pylori. METHODS: Biopsy specimens for culture of H. pylori were obtained from gastric antrum, body and fundus of 20 patients during endoscopic investigation of upper gastrointestinal symptoms. H. pylori was identified by culture from one site in 16 and two or more sites in 10 of the 16 patients. Five isolated colonies of six strains of H. pylori from gastric antrum were subcultured and used for further analysis. Antibiotic susceptibility to metronidazole and clarithromycin was determined by disk diffusion test. Protein profiles of isolates were compared by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE). DNA diversity of the isolates was determined by arbitrarily primed polymerase chain reaction (AP-PCR) fingerprinting. RESULTS: Of the 10 patients with multiple isolates, 70% (7/10) exhibited variation in susceptibility to metronidazole and 20% (2/10) to clarithromycin between different sites. In 83% of (5/6) single colonies, no variability was seen in metronidazole and clarithromycin susceptibility; they were either susceptible or resistant. Protein profiles of all isolates by SDS-PAGE were similar. Isolates from different patients produced clearly different AP-PCR fingerprints. In 50% of H. pylori strains isolated from different sites of the stomach, genetic diversity was demonstrated by different AP-PCR fingerprints. In 67% (4/6) strains, five single-colony fingerprints were similar. CONCLUSIONS: Genetic variability has been found in H. pylori strains. Individual patients are infected with a single predominant genotype at a single site but can be colonized by multiple strains, and they may show different antibiotic susceptibilities. Individual colonies of the H. pylori population from a single site may not always yield identical DNA fingerprints and antibiotic sensitivities.