Objective Advances in synthetic DNA technology have made it much easier to fake human DNA samples.There are literature reports that fake human DNA can be synthesized by different methods and implanted in the field to confuse the investigation or mislead the trial.Therefore,distinguishing authentic human DNA from synthetic DNA and performing individual identification has become a critical scientific challenge.Methods We define a novel composite genetic marker(methylation-microhaplotype)by combining CpG sites stably hypermethylated or hypomethylated in natural human DNA and nearby immediately adjacent microhaplotype sites.A total of 19 locis were obtained according to the screening criteria,and a composite detection system for methylation-microhaplotypes was established using MPS technology.Random volunteer DNA samples were extracted and synthetic DNA samples were prepared based on whole genome amplification techniques.Population DNA samples were analyzed to evaluate forensic parameters and methylation variability of the methylation-microhaplotype markers.Comparative analyses of human and synthetic DNA were conducted to assess the markers'ability to discriminate between the two and to detect/type both components in mixed mixed samples.Results The composite detection system composed of 19 locis demonstrated high individual identification ability,achieving a cumulative individual identification probability of 0.999 999 999 996 86.12 hypermethylated locis and 7 hypomethylated locis had relatively stable methylation levels in 57 human DNA samples.According to the allele methylation rate(Ram)value,the system can effectively identify natural and synthetic DNA samples.Meanwhile,for mixed DNA samples,the presence of human and synthetic DNA samples can be found and genotyped.Conclusion Methylation-microhaplotype genetic markers,which can discover human DNA and synthetic DNA and can detect the presence and genotyping of them from mixed samples,is a potential useful tool for forensic DNA analysis.

In recent years,the problem of population aging in China has been continuously intensifying.The mechanism of aging and its prevention and treatment have gradually become research hotspots.The successful establishment of aging animal models is an important part of aging-related research,and behavioral experiments can effectively evaluate these models.This article reviews the methods of constructing aging animal models from different aspects,analyzes the advantages and disadvantages of various behavioral evaluation experiments and their comparisons,with the aim of providing theoretical references for aging-related research.

In recent years,the problem of population aging in China has been continuously intensifying.The mechanism of aging and its prevention and treatment have gradually become research hotspots.The successful establishment of aging animal models is an important part of aging-related research,and behavioral experiments can effectively evaluate these models.This article reviews the methods of constructing aging animal models from different aspects,analyzes the advantages and disadvantages of various behavioral evaluation experiments and their comparisons,with the aim of providing theoretical references for aging-related research.

Objective Advances in synthetic DNA technology have made it much easier to fake human DNA samples.There are literature reports that fake human DNA can be synthesized by different methods and implanted in the field to confuse the investigation or mislead the trial.Therefore,distinguishing authentic human DNA from synthetic DNA and performing individual identification has become a critical scientific challenge.Methods We define a novel composite genetic marker(methylation-microhaplotype)by combining CpG sites stably hypermethylated or hypomethylated in natural human DNA and nearby immediately adjacent microhaplotype sites.A total of 19 locis were obtained according to the screening criteria,and a composite detection system for methylation-microhaplotypes was established using MPS technology.Random volunteer DNA samples were extracted and synthetic DNA samples were prepared based on whole genome amplification techniques.Population DNA samples were analyzed to evaluate forensic parameters and methylation variability of the methylation-microhaplotype markers.Comparative analyses of human and synthetic DNA were conducted to assess the markers'ability to discriminate between the two and to detect/type both components in mixed mixed samples.Results The composite detection system composed of 19 locis demonstrated high individual identification ability,achieving a cumulative individual identification probability of 0.999 999 999 996 86.12 hypermethylated locis and 7 hypomethylated locis had relatively stable methylation levels in 57 human DNA samples.According to the allele methylation rate(Ram)value,the system can effectively identify natural and synthetic DNA samples.Meanwhile,for mixed DNA samples,the presence of human and synthetic DNA samples can be found and genotyped.Conclusion Methylation-microhaplotype genetic markers,which can discover human DNA and synthetic DNA and can detect the presence and genotyping of them from mixed samples,is a potential useful tool for forensic DNA analysis.

BACKGROUND: Coronary artery disease (CAD) is the commonest cause of heart failure (HF), whereas pulmonary hypertension (PH) has not been established or reported in this patient population. Therefore, we assessed the prevalence, risk factors, and survival in CAD-associated HF (CAD-HF) complicated with PH. METHODS: Symptomatic CAD-HF patients were continuously enrolled in this prospective, multicenter registry study. Echocardiography, coronary arteriography, left and right heart catheterization (RHC), and other baseline clinical data were recorded. Patients were followed up and their survival was recorded. RESULTS: One hundred and eighty-two CAD-HF patients were enrolled, including 142 with HF with a preserved ejection fraction (heart failure with preserved ejection fraction [HFpEF]; left ventricular ejection fraction [LVEF] ≥50%) and 40 with a reduced ejection fraction (heart failure with reduced ejection fraction [HFrEF]; LVEF < 50%). PH was diagnosed with RHC in 77.5% of patients. Patients with PH showed worse hemodynamic parameters and higher mortality. HFrEF-PH patients had worse survival than HFpEF-PH patients. CAD-HF patients with an enlarged left ventricular end-diastolic diameter and reduced hemoglobin were at higher risk of PH. Nitrate treatment reduced the risk of PH. Elevated creatinine and mean pulmonary arterial pressure (mPAP), diastolic pressure gradient (DPG) ≥7 mmHg, and previous myocardial infarction (MI) entailed a higher risk of mortality in CAD-HF patients with PH. CONCLUSIONS: PH is common in CAD-HF and worsens the hemodynamics and survival in these patients. Left ventricle enlargement and anemia increase the risk of PH in CAD-HF. Patients may benefit from nitrate medications. Renal impairment, elevated mPAP, DPG ≥7 mmHg, and previous MI are strong predictors of mortality in CAD-HF-PH patients. TRIAL REGISTRATION ClinicalTrials.gov, NCT02164526.
Coronary Artery Disease/epidemiology* ; Creatinine ; Heart Failure/complications* ; Humans ; Hypertension, Pulmonary/complications* ; Nitrates ; Prevalence ; Prognosis ; Prospective Studies ; Registries ; Risk Factors ; Stroke Volume ; Ventricular Function, Left

Objective To analyze the clinical characteristics for hypertensive attack during operation and clinical experience of preoperative evaluation and preparation in patients with pheochromocytoma and paraganglioma(PHEO/PGL).Methods A total 219 PHEO/PGL cases from September 2016 to September 2018 were retrospectively reviewed.It included 99 males and 120 females,aged 13 to 76 (average 47) years old.The mean diameter of tumor was 5.3 cm (1.5-18.0 cm).140 cases were unilateral PHEO,6 cases were bilateral PHEO,68 cases were PGL(jugular,mediaphragm,heart,retroperitoneum,pelvic and bladder) and 5 cases were PHEO combined with PGL.Preoperative highest systolic blood pressure (SBP)was 240 mmHg(1 mmHg-0.133 kPa) and highest diastolic blood pressure (DBP) was 160 mmHg.20 cases were occult PHEO without hypertension.217 cases accepted preoperative preparation of alpha-blocker [phenoxy-benzamine,dosage ranging from 5 mg Q12h to 40 mg Q8h,maximum dosage not exceeding 1 mg/(kg· 24 h)].2 cases did not accept preoperative preparation.All cases accepted open or endoscope surgery.The patients were divided into 2 groups depending on the presence or absence of hypertensive attack at the time of surgery.Patient demographic characteristics and preoperative evaluations were assessed for their prognostic relevance with respect to hypertensive attack.Results Histopathological results showed that all cases were PHEO or PGL,while 205 cases were benign,14 cases were malignant.Hypertensive attack were recorded in 112 cases(51％).The diameter of tumors in the hypertensive attack group were larger than that in the non-hypertensive attack group[(6.70 ± 2.95)cm vs.(3.95 ± 1.70) cm,P =0.005].There was no significant difference between the two groups among age [(51.0 ± 10.8) years vs.(38.5 ± 17.6) years,P =0.105],preoperative catecholamine level [norepinephrine (111.20 ± 41.49) μg/24 h vs.(419.15 ± 154.81) μg/24 h,P =0.075],time of use of alpha blockers [(53.0 ± 7.5) d vs.(38.0 ± 6.4) d,P =0.139],daily dosage of alpha blocker [(40.0 ±7.2)mg vs.(27.1 ± 1.8) mg,P =0.111] and blood pressure at diagnosis[(173.75 ± 26.69) mmHg vs.(155.0 ± 20.75) mmHg,P =0.139].Among 219 cases,2 case had emergency hemostasis after operation,1 case had catecholamine cardiomyopathy after operation for occult pheochromocytoma,and no perioperative death occurred.Conclusions Patients with large tumor tend to have hypertensive attack during operation so that should be better prepared.

In the original publication Fig. 1D and supplementary material is incorrect. The correct figure and supplementary material is provided in this correction.

Recently we have established a new culture condition enabling the derivation of extended pluripotent stem (EPS) cells, which, compared to conventional pluripotent stem cells, possess superior developmental potential and germline competence. However, it remains unclear whether this condition permits derivation of EPS cells from mouse strains that are refractory or non-permissive to pluripotent cell establishment. Here, we show that EPS cells can be robustly generated from non-permissive NOD-scid Il2rg mice through de novo derivation from blastocysts. Furthermore, these cells can also be efficiently generated by chemical reprogramming from embryonic NOD-scid Il2rg fibroblasts. NOD-scid Il2rg EPS cells can be expanded for more than 20 passages with genomic stability and can be genetically modified through gene targeting. Notably, these cells contribute to both embryonic and extraembryonic lineages in vivo. More importantly, they can produce chimeras and integrate into the E13.5 genital ridge. Our study demonstrates the feasibility of generating EPS cells from refractory mouse strains, which could potentially be a general strategy for deriving mouse pluripotent cells. The generation of NOD-scid Il2rg EPS cell lines permits sophisticated genetic modification in NOD-scid Il2rg mice, which may greatly advance the optimization of humanized mouse models for biomedical applications.

Objective: To investigate the radiological and histopathological features of giant cell tumor of bone treated with RANKL inhibitor denosumab. Methods: Eleven cases were retrieved from the surgical pathology records between March 2015 and June 2017 in Beijing Jishuitan Hospital. Formalin fixed, paraffin embedded specimens were collected and the histological features were evaluated. The imaging features including X ray, magnetic resonance imaging, and computed tomography were also reviewed. Results: These 11 cases of giant cell tumor of bone were derived from five female and six male patients, with age ranged from 20 to 62 years (mean age, 35 years). The tumors were located in the sacrum (6 cases), femur (2 cases), radius (1 case), tibia (1 case) and patella (1 case), respectively. Histologically, all cases showed depletion of giant cells, proliferation of mononuclear cells and different degrees of ossification 3 to 6 months after denosumab therapy. Radiography showed marked osteosclerosis and sclerotic rim formation. Three cases of the sacrum recurred after 5, 6 and 11 months of surgery, and the remaining cases showed no recurrence within follow-up of 1 to 14 months. Conclusions Denosumab treated giant cell tumors morphologically differ from untreated tumors. Careful attention to a history of denosumab administration is crucial to avoid misdiagnosis and to allow proper differentiation from other tumors and tumor-like lesions.

OBJECTIVE:To investigate clinical efficacy and safety of different dosages of bromocriptine in the treatment pro-lactinoma,and its effects on serum prolactin(PRL)and tumor volume. METHODS:A total of 60 patients with prolactinoma were selected from our hospital during Jan.-Dec. 2015 as research objects,and then divided into group A and B according to random number table,with 30 cases in each group. Both groups were given Bromocriptine mesilate tablets orally during meal. Group A was given medicine with initial dose of 2.5 mg/d,increasing to 3.75 mg/d 3 d later,increasing by 2.5 mg every week after 2-3 d,and then recovering to 3.75 mg/d till serum PRL level had been controlled. Group B was given medicine with initial dose of 1.25 mg/d, increasing to 2.5 mg/d 3 d later,increasing by 1.25-2.5 mg every week after 2-3 d,and then recovering to 2.5 mg/d till serum PRL level recovered to normal. Both groups were treated for consecutive 3 months. Clinical efficacies as well as serum level of PRL and tumor size were observed in 2 groups,and the occurrence of ADR was recorded. RESULTS:The total response rate of group A (83.33％) was higher than that of group B (66.67％),without statistical significance (P>0.05). Before treatment,there was no statistical significance in serum level of PRL and tumor size between 2 groups (P>0.05). After 1,2 months of treatment,serum levels of PRL in 2 groups were decreased significantly,and the group A was significantly lower than the group B,with statistical significance(P<0.05). After 3 months of treatment,serum levels of PRL in 2 groups were decreased significantly compared to be-fore treatment,but there was no statistical significance between 2 groups(P>0.05). After treatment,tumor size of 2 groups were decreased significantly,and large adenoma and giant adenoma size in group A were significantly smaller than group B,with statisti-cal significance(P<0.05). There was no statistical significance in microadenoma size between group A and B(P>0.05). The inci-dence of ADR in group A(12 cases,40.00％)was significantly higher than group B(5 cases,16.67％),with statistical signifi-cance(P<0.05). CONCLUSIONS:Increasing dosages of bromocriptine no significant influence on therapeutic effect of prolactino-ma,but it can shorten the time of serum PRL level back to normal,and reduce the tumor size. The incidence of adverse reactions in-crease with the dosage.