BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

Objective: For patients with atrial fibrillation (AF) complicated with acute coronary syndrome (ACS), both anticoagulant and antiplatelet therapy should be applied, but the use of anticoagulation therapy is still poor in these patients in China. The purpose of this study was to explore the status and adherence of antithrombotic therapy in AF patients with ACS and the impact on 1 year clinical outcomes. Methods: Patients with AF hospitalized for ACS were retrospectively included from 6 tertiary hospitals in China between July 2015 and December 2020. According to the use of anticoagulant drugs at discharge, patients were divided into two groups: anticoagulant treatment group and non-anticoagulant treatment group. Logistic regression model was used to analyze the main factors influencing the use of anticoagulant drugs in patients with atrial fibrillation complicated with ACS. Major adverse cardiac events (MACEs) were defined as all-cause death, non-fatal myocardial infarction or coronary revascularization, and ischemic stroke and Bleeding Academic Research Consortium (BARC) 3 bleeding events were also collected at 1 year after discharge. After propensity score matching, Cox proportional hazards models and Kaplan-Meier analysis were used to evaluate the effect of anticoagulant treatment and non-anticoagulant treatment on 1-year prognosis. The patients were divided into different groups according to whether anticoagulation was performed at discharge and follow-up, and the sensitivity of the results was analyzed. Results: A total of 664 patients were enrolled, and 273 (41.1%) were treated with anticoagulant therapy, of whom 84 (30.8%) received triple antithrombotic therapy, 91 (33.3%) received double antithrombotic therapy (single antiplatelet combined with anticoagulant), and 98 (35.9%) received single anticoagulant therapy. Three hundred and ninety-one (58.9%) patients were treated with antiplatelet therapy, including 253 (64.7%) with dual antiplatelet therapy and 138 (35.3%) with single antiplatelet therapy. After 1∶1 propensity score matching between the anticoagulant group and the non-anticoagulant group, a total of 218 pairs were matched. Multivariate logistic regression analysis showed that history of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention were predictors of the absence of anticoagulant therapy, while history of ischemic stroke and persistent atrial fibrillation were predictors of anticoagulant therapy. At 1-year follow-up, 218 patients (79.9%) in the anticoagulant group continued to receive anticoagulant therapy, and 333 patients (85.2%) in the antiplatelet group continued to receive antiplatelet therapy. At 1-year follow-up, 36 MACEs events (13.2%) occurred in the anticoagulant group, and 81 MACEs events (20.7%) in the non-anticoagulant group. HR values and confidence intervals were calculated by Cox proportional risk model. Patients in the non-anticoagulant group faced a higher risk of MACEs (HR=1.802, 95%CI 1.112-2.921, P=0.017), and the risk of bleeding events was similar between the two group (HR=0.825,95%CI 0.397-1.715, P=0.607). Conclusions: History of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention are independent factors for the absence of anticoagulant therapy in patients with AF complicated with ACS. The incidence of MACEs, death and myocardial infarction is lower in the anticoagulant group, and the incidence of bleeding events is similar between the two groups. The risk of bleeding and ischemia/thrombosis should be dynamically assessed during follow-up and antithrombotic regiments should be adjusted accordingly.
Humans ; Atrial Fibrillation/drug therapy* ; Platelet Aggregation Inhibitors/adverse effects* ; Acute Coronary Syndrome/drug therapy* ; Fibrinolytic Agents/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Anticoagulants ; Myocardial Infarction/complications* ; Hemorrhage ; Percutaneous Coronary Intervention ; Ischemic Stroke/drug therapy* ; Stroke

BACKGROUND: Epigenetics, especially DNA methylation, plays an important role in the pathogenesis of primary Sjogren syndrome (pSS). Our study aimed to reveal the role of DNA methylation in peripheral monocytes of pSS patients. METHODS: A total of 11 pSS patients and five age-matched healthy controls (HCs) were included in this study. Monocytes were isolated from peripheral blood mononuclear cells using magnetic microbeads. DNA methylation profiles were generated using Human Methylation 850K BeadChips. RESULTS: In monocytes from pSS patients, we identified 2819 differentially methylated positions (DMPs), comprising 1977 hypomethylated- and 842 hypermethylated-DMPs, corresponding to 1313 unique genes when compared with HCs. IFI44L, MX1, PAARP9, and IFITM1, which influence the interferon (IFN) signaling pathway, were among the genes hypomethylated in pSS. Functional analysis of genes with a minimum of two DMPs showed involvement in antigen binding, transcriptional regulation, cell adhesion, IFN-γ pathway, type I IFN pathway, antigen presentation, Epstein-Barr virus infection, human T-lymphotropic virus type 1 virus infection, and metabolic disease-related pathways. In addition, patients with higher serum IgG levels exhibited enrichment in Notch signaling and metabolic-related pathways. Upon comparing monocytes with salivary gland epithelial cells, an important overlap was observed in the cell cycle, cell senescence, and interleukin-17 signaling pathways. The differentially methylated genes were more enriched in the ribosome- and AMP-activated protein kinase signaling pathway in anti-Ro/SSA and anti-La/SSB autoantibodies double-positive patients. CONCLUSION Genome-wide DNA methylation profiling revealed significant differences in DNA methylation in monocytes isolated from patients with pSS.
DNA Methylation/genetics* ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Humans ; Leukocytes, Mononuclear ; Monocytes ; Sjogren's Syndrome/genetics*

Objective:To analyze the serology and molecular typing of Listeriamonocytogenes isolated from patients in Henan, and to explore the epidemic situation of listeriosis, construct the molecular traceability database of patient isolates, so as to provide laboratory basis for listeriosis traceability. Methods:From January 2015 to July 2020, 71 positive Listeriamonocytogenes cases were monitored in 16 sentinel hospitals in Henan. Eighty samples of positive cases were collected for detection, and 71 positive strains were obtained for molecular typing. According to the Entry-exit Inspection and Quarantine Industry Standard of China (SN/T 2521-2010) and the instructions for the use of diagnostic serum of Listeriamonocytogenes, 80 strains of Listeriamonocytogenes were serotyped, and PFGE cluster analysis was performed according to the User Manual of National Foodborne Disease Molecular Traceability Network. Results:A total of 71 positive listeriosis cases were detected, of which 38 cases were perinatal cases and 33 cases were non-perinatal cases. Among the 80 positive cases of listeriosis, 58.75% (47/80) were from perinatal cases, 20.00% (16/80) were from non-perinatal cases with underlying diseases, the proportion of>1 month-≤5 years old,>5-≤60 years old and >60 years old was 7.50% (6/80), 12.50% (10/80) and 1.25% (1/80), respectively, in non-perinatal age group. There were 5 types of specimens, 73.75% (59/80) were blood, 15.00% (12/80) were cerebrospinal fluid, and 3.75% (3/80) were stool, intrauterine swab and sputum. 80 strains of Listeriamonocytogenes were classified into three serotypes, Type 1/2b, Type 1/2a and Type 4b accounted for 61.25% (49/80), 35.00% (28/80) and 3.75% (3/80) respectively. The 71 strains of Listeriamonocytogenes were digested by AscⅠ, and 58 bands were obtained. Each band type included 1-4 strains, and the similarity was 60.8%-100%. GX6A16HA0005, GX6A16HA0011, GX6A16HA0030, GX6A16HA0023, GX6A16HA0029 and GX6A16HA0054 were dominant bands, including 4, 4, 4, 3, 2 and 2 strains respectively. Four strains of GX6A16HA0005 from 2016, 2018 and 2020 were isolated. One strain from 2016 and one strain from 2018 were from Puyang City. Four strains of GX6A16HA0011 were isolated from samples of 2016, 2018 and 2020, including two strains of 2020 from Luoyang City. Four strains of GX6A16HA0030 were isolated from 2018 samples from Luoyang City, Shangqiu City and Zhengzhou City, respectively. Three strains of GX6A16HA0023 were isolated from 2017 and 2018 samples, of which one strain from 2017 and one strain from 2018 were from Luoyang City. Two strains of GX6A16HA0029 were isolated from 2018 samples, from Kaifeng City and Puyang City respectively. Two strains of GX6A16HA0054 were isolated from 2020 from Pingdingshan City and Anyang City, respectively. The PFGE patterns of 4 strains with different serotypes were the same. Conclusion:Listeriosis cases in Henan are mainly found in patients during the perinatal period, and in elderly, new-born, and low immunity population. The infection type is mainly invasive infection; the serotypes of epidemic strains are 1/2a, 1/2b and 4b, and the results of PFGE typing of strains are diverse. There is a consistent phenomenon of cross-year or different regions in the same year, different time zones in the same year and the same region; phenotyping and genotyping or different genotyping techniques should be combined in the traceability analysis.

BACKGROUND:There are a lot of adipose-derived stem cel s in the vascular stroma. These cel s are shown to play a very important role in the fat granule transplantation.
OBJECTIVE:To explore the role of adipose-derived stem cel s in the fat granule transplantation.
METHODS:Normal adipose tissues were obtained from 10 male BALB/C mice, SPF grade. Adipose-derived stem cel s and fat granules were extracted from the abdominal fat tissues. Another 24 nude mice acted as recipients and were assigned into control, fat granule transplantation or mixed transplantation (adipose-derived stem cel s+fat granules) groups. In the latter two groups, fat granule suspension and suspension of fat granules and adipose-derived stem cel s were injected into the shoulder of rats, respectively. In the control group, the same volume of cel medium was injected. Four weeks later, separated plasma and grafts were taken out for indicator measurement.
RESULTS AND CONCLUSION:Compared with the fat granule transplantation group, the mixed transplantation could remarkably increase the weight of grafts, while reduce the absorption of grafted fat tissues (P<0.01). After transplantation, the highest level of vascular endothelial growth factor in the plasma was obtained in the mixed transplantation group fol owed by fat granule transplantation group and control group (P<0.01). Level of basic fibroblast growth factor and microvessel density were significantly higher in the mixed transplantation group than the fat granule transplantation group (P<0.01). Better cel morphology and higher number of fat droplets were found in the mixed transplantation group compared with the fat granule transplantation group. Al these results indicate that adipose-derived stem cel transplantation can remarkably promote the expression of basic fibroblast growth factor, improve graft microcirculation, and improve morphology and function of fat granules.

Objective To evaluate the level of regional public health development in Zhejiang Province,and to learn the development problems in order to provide suggestions for developing public health strategies.Methods The index system established for evaluation included 30 indexes of public health in 4 aspects,namely the health level of residents,the allocation of public health resource,the level of public health service and public health security.Based on the data in 2010,the comprehensive development index was calculated to evaluate the level and speed of public health development. Results The comprehensive development index of Zhejiang Province was 127. 31 in 2012,which was 9. 97 higher than thatof2011.Thespeedofdevelopmentwas108.50%,andthelevelofpublichealthdevelopmentinZhejiangProvincehas increased continuously.Among 1 1 cities,the highest and lowest comprehensive development index of public health development was 146. 35 and 101. 55 respectively.The fastest and slowest speed of development was 122. 76% and 104. 95% respectively.Conclusion The public health in Zhejiang Province kept the good momentum of development,but the unbalanced development still existed among different regions.

OBJECTIVETo assess the efficacy and safety of Gastrosis No.1 compound in the treatment of functional dyspepsia with Spleen (Pi) and Stomach (Wei) deficiency-cold syndrome.

METHODSA randomized, double-blind, placebo-controlled trial was performed in 5 centers. Patients with functional dyspepsia (FD) of Spleen-deficiency and qi-stagnation syndrome (162 cases) were randomly assigned to groups given Chinese herbal medicine (CHM) Gastrosis No.1 compound or placebo in a 2:1 ratio. This trial included a 4-week treatment period and a 4-week follow-up period. The outcomes were the dyspepsia symptom scores (measured by total dyspepsia symptom scale and single dyspepsia symptom scale) and syndromes of traditional Chinese medicine score (measured by traditional Chinese medicine syndrome scale). The outcomes were noted at weeks 0, 4 and 8.

RESULTSCompared with patients in the placebo group, patients in the CHM group showed significant improvement in the dyspepsia symptom scores as rated by patients and investigators (P <0.01), and also showed improvement in syndromes of traditional Chinese medicine score (P <0.01). No serious adverse event was reported. Safety tests obtained after 4 weeks of treatment showed no abnormal values.

CONCLUSIONCHM Gastrosis No.1 compound was effective and safe in the treatment of functional dyspepsia with Spleen and Stomach deficiency-cold syndrome.

Adult ; Double-Blind Method ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; therapeutic use ; Dyspepsia ; drug therapy ; physiopathology ; Female ; Humans ; Male ; Placebos ; Spleen ; drug effects ; physiopathology ; Stomach ; drug effects ; physiopathology ; Syndrome ; Treatment Outcome

The aim of the present study was to assess the ototoxicity of kanamycin sulfate (KM) in adult rats and its underlying mechanism. Forty male Sprague-Dawley rats (6-7 weeks old) were randomly divided into the experimental group and the control group. The animals in the experimental group were injected subcutaneously with KM (500 mg/kg per day) for two weeks, and the control group received equal volume of normal saline. To assess the ototoxicity of KM, the auditory brainstem response (ABR) was recorded to monitor the changes in hearing thresholds, and the density of spiral ganglion cells (SGCs) and morphology of cochlea were observed using surface preparations and frozen sections of cochlea. The results showed that the hearing threshold of rats in the experimental group was elevated by more than 60 dB across all the frequencies two weeks after the first administration of KM. And in the experimental group, the density of SGCs became lower, and organ of Corti suffered loss of hair cells. The loss of outer hair cells (OHCs) was more severe than that of inner hair cells (IHCs), correlated with the density decrease of SGCs. We conclude that the ototoxicity of KM in the adult rats was apparent and the underlying mechanism is associated with the loss of SGCs and hair cells.
Animals ; Cochlea ; drug effects ; pathology ; Evoked Potentials, Auditory, Brain Stem ; drug effects ; Hair Cells, Auditory, Outer ; cytology ; drug effects ; pathology ; Hearing Loss ; chemically induced ; physiopathology ; Kanamycin ; toxicity ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spiral Ganglion ; pathology ; physiology ; ultrastructure

Purpose:The image information and technique of positron emitter nuclei generated by high energy X-ray photonuclear reactions with body tissues from MM50 is studied.It is explored to verify for dose delivery and location monitoring in tumor target after high energy photon radiation therapy with the image information.Materials and Methods:The technique is based on the photonuclear reactio-as in body tissues elemental composition ~(12)C,~(16)O and ~(14)N with high energy X-Ray,energies well above 20 MeV,resulting primarily in ~(11)C and ~(15)O but also ~(13)N.The induced positron activity distributions were scanned off-line in a PET/CT after irradiation.The activity distributions and position may be used to verify for dose delivery and location in tumor target.These radiations are similar to RT in three fields with some different dose delivery from TPS.The phantom began to be scanned off-line in a PET/CT a couple of minutes after irradiation.The scanning time is respectively 20 minutes and(2～5)mniutes for ~(12)C and ~(16)O.The levels of the beam energy are 10MV,25MV,50 MV.The extent of dose is 1.0 Gy～10.0 Gy.Since measured PET images change with time post irradiation,as a result of the different decay tim-es of the radionuclides,the signals from activated ~(12)C,~(16)O within the irradiated volume could be separated from each other.Most informationis obrained from the carbon and oxygen radionuclide's which the most abundant elements are in soft tissue.A brain phantom Rlade oneself was irradiated with high energy X-ray beams from IBA MM50.The 3D radiation treatment planning system,Nucletron-TPP 3.2,was used to calculate the delivered dose distributions.The phantom was directly simulated in the Nucletron-TPP after CT scan.PET/CT is fro-m GE Discovery LS Ⅱ.Resuits:It was confirmed that no activity was detected at 10 Mv X-ray energy,which was far below the energy threshold for photonuclear reactions.Totally 25 MV X-ray beams can produce photonuclear reactions and get to activity distributions images in PET/CT.It need to greater dose in order to good images information.For 50 MV X-ray beams,2 Gy-3 Gy dose,a normal RT dose,can get to activity distributions images.Conclusions:It was concluded that the PET-CT image acquired from the activity of the ~(15)O and ~(11)C positron emitter nuclei might provide the area and dose distribution information of 50 MV X-ray irradiation in a phantom.It can verify the in vivo dose delivery and location in tumor target after high energy X-ray RT.

BACKGROUNDThe enlarged prostate leads to obstruction and lower urinary tract symptoms (LUTS), which comprise frequency, urgency, weak stream, straining and nocturia. This study was conducted in a large series of patients to evaluate the relationship between LUTS as stipulated in the International Prostate Symptom Score (IPSS) and the objective parameters related to benign prostatic hyperplasia (BPH).

METHODSWe enrolled 1295 BPH patients from seven centers. The patients were either at first diagnosis of BPH or had discontinued medical treatment for at least 3 months. Those with several other diseases that may be potential risk factors affecting urinary symptoms were excluded from the study. Age, IPSS, prostate volume, peak flow rate, urine volume and post-voiding residual urine volume were measured. The relationship between IPSS and objective parameters were quantified by means of Spearman correlation coefficients. The differences in these parameters between the groups with mild, moderate or severe symptoms were also evaluated.

RESULTSStatistically significant correlations were found between IPSS and objective parameters by means of Spearman correlation coefficients. When the patients were divided into three groups with different severities of symptoms, there were significant differences in peak flow rate, urine volume, prostate volume, residue urine volume and quality of life, whereas average age and prostate-specific antigen levels were similar. However, there was evident overlap of these parameters between the groups. The same results were found when the irritative or obstructive subscore of IPSS was considered.

CONCLUSIONSThe correlation between objective parameters of BPH and LUTS is significant. However, it is hard to predict the severity of symptoms by these parameters.

Aged ; Aged, 80 and over ; Humans ; Male ; Middle Aged ; Prostatic Hyperplasia ; diagnosis ; psychology ; Quality of Life ; Urination Disorders ; etiology