Building a professional clinical research team inside hospitals is in favor improving their research abilities,accelerating the clinical discipline construction,improving their comprehensive influence.Also it fits the objective of general hospital development under gate-keeping system.Now in domestic,the percentage of professional research staff in large hospitals accounts was much less than the international level.The main reasons included the misunderstanding of constructing the research-oriented hospitals,insufficient human resources enrollment,less attractive environment to the highlevel researchers and the absence of relevant degree training programs.To enhance the construction of research-oriented hospitals,it's of key importance to build the professional research team in hospitals.Besides,the hospital has to update management conception,broaden the channels of talent cultivation,grasp the development of the subject accurately and interact with the basic medicine and public health subject,increase the financial investment and perfect the relevant management regulations.

Objective To establish Ad-hLIF transgenic feeder cells for the expansion of umbilical cord blood CD34+ HSPC in vitro and study the SCID mice model of hematopoietic stem/progenitor cell (HSPC) transplantation. Methods The expression of objective gene in Ad-hLIF transgenic feeder cells was detected by RT-PCR and ELISA. The purity of umbilical cord blood CD34+ HSPC separated by magnetic-activated cell sorting(MACS) was detected by the flow cytometry. After expanded with various combinant of cytokines and transgenic feeder layer cells for 28 d, the quantity of mono-nuclear cell (MNC) and CD34+ cells rate was detected in different time. MNC after expansion stained by CFDA SE was injected to the sublethally irradiated SCID mice. Humanize gene Alu was detected by RT-PCR and fluorescence microscope. Results The green fluorescence was observed in the transgenic cells infected with 50MOI( multiplicity of infection) Ad-hLIF, and the objective gene was confirmed by RT-PCR and ELISA. The purity of umbilical cord blood CD34+ HSPC separated by MACS could reach 95.60% ±2.58%, Ad-hLIF transgenic feeder cells and various cytokines system increased MNC by 356.95±0.87 fold, and maximal expansion of CD34+ cells was observed during 0-14 d of culture, then down-expansion gradually. Four weeks after transplanted in SCID mice, fluorescently-labeled humanize cells still can be observed. The existence of the humanized gene Alu was confirmed by RT-PCR. Conclusion Ad-hLIF transgenic feeder cells can effectively proliferate umbilical cord blood CD34+ HSPC in vitro and delay it differentiate, what's more, it has high transplant efficacy and haematogenesis activity.

Objective: To determine the frequency and extent of left ventricular amyloid deposition in patients aged over 85 years with heart failure and preserved ejection fraction (HFpEF). Methods: A total of 43 patients aged 85 to 100 years old were enrolled in this study based on the autopsy database of Beijing Hospital from February 1, 2003 to October 31, 2016. The frequency and extent of left ventricular amyloid deposition and myocardial fibrosis were determined in left ventricular specimens from patients with antemortem diagnosis of HFpEF without clinically apparent amyloid (n=28) and from control subjects (n=15) post Congo red staining and Masson's trichrome staining. Kappa test was used to evaluate the consistency of the myocardial amyloidosis and fibrosis. Results: The heart weight of the patients in HFpEF group and in control group were similar((452.7±107.7)g vs. (415.0±70.8)g, t=-1.218, P=0.23)). Positive Congo-red staining was found in 24 examples (24/28) in HFpEF group and 5 examples (5/15) in the control group; severe amyloid deposition was found in 7 examples (7/28) in HFpEF group, but not in the control group. Amyloid deposition was more severe in HFpEF group than in control group (χ²=12.205, P<0.01). Masson's trichrome staining evidenced moderate to severe fibrosis in 19 cases (19/28) in HFpEF group and 8 cases (8/15) in control group (χ²=1.019, P=0.35). A consistent evaluation of the degree of myocardial fibrosis and the degree of myocardial amyloid deposition in all selected participants was performed and results showed that these two parameters were not consistent (Kappa value=0.2, P=0.820). Conclusion Amyloid deposition is common in the elderly patients with heart failure and preserved ejection fraction, suggesting that myocardial amyloidosis may be related to the development of HFpEF. There is no significant correlation between myocardial amyloidosis and myocardial fibrosis in this cohort.

Objective:To explore the effects of genotypes of one-carbon metabolism (OCM)-related enzyme single nucleotide polymorphisms (SNPs) sites and anti-epileptic drugs on OCM metabolite levels in epileptic patients, and to screen valproic acid (VPA) teratogenic susceptibility genes.Methods:Three hundred and seventy-two epileptic patients, admitted to our hospital from January 2019 to December 2020, were enrolled in the study; patients taking VPA, levetiracetam (LEV), lamotrigine (LTG) or oxcarbazepine (OXC) for more than 6 months without attack during regular medication were classified as VPA group ( n=95), LEV group ( n=61), LTG group ( n=57) and OXC group ( n=70); firstly diagnosed epileptic patients who had never taken antiepileptic drugs or had not taken antiepileptic drugs in the previous 6 months were assigned into blank control group ( n=89). Plasma folic acid (FA), vitamin B12 (VitB 12) and homocysteine (Hcy) levels were determined by automatic chemiluminescence immunoassay, and genotypes of OCM-related enzyme SNPs sites were detected by Sequenom iPLEX. Results:(1) As compared with LEV group and blank control group, VPA group had significantly decreased FA level and significantly increased Hcy level ( P<0.05). (2) Patients with DNA methyltransferase (DNMT) 3a rs12987326(-178G>A) GA type had significantly higher Hcy level than those with GG type ( P<0.05); patients with DNMT1 rs2288350(82G>C) GC type had significantly higher Hcy level than those with GG type ( P<0.05); patients with DNMT1 rs75616428 (55850G>C) GC type had significantly lower VitB 12 level than those with GG type ( P<0.05). Patients with DNMT1 rs1863771(128G>A) GA+AA type had significantly higher FA level than those with GG type, patients with folate receptor 2 rs2298444(59T>C) CT+CC type had significantly higher Hcy level than those with TT type, patients with 5,10-methylenetetrahydrofolate reductase rs1801131(1298A>C) AC+CC type had significantly higher Hcy level than those with AA type, and patients with DNMT3a rs6722613(2327C>T) CT+TT type had significantly lower VitB 12 level than those with CC type ( P<0.05). Conclusions:Decreased FA and increased Hcy levels can be noted in epileptic patients who used VPA; some gene variations in SNPs of OCM also affect the OCM metabolite levels in epileptic patients. Epileptic patients during pregnancy should avoid using VPA or detecting SNPs genotypes before medication to reduce the incidence of fetal malformation.

Objective:To analyze the clinical characteristics and prognostic factors in patients with new-onset acute heart failure (AHF) and acutely decompensated chronic heart failure (ADCHF).Methods:Patients with heart failure (HF) admitted to Beijing Hospital during January 2009 to December 2017 with follow-up records were retrospectively enrolled. According to the duration of heart failure, the patients were divided into new-onset AHF group (duration of HF<1 month) and ADCHF group (duration of HF ≥1 month). Clinical data were collected and endpoint events (all-cause death and cardiovascular death) were recorded. The Kaplan-Meier survival curve and the log-rank method was used to compare survival between different groups. The multivariate Cox regression model was used to analyze the independent risk factors for the end-point events in patients with new-onset AHF and ADCHF.Results:The study enrolled 562 patients,292 (52.0%) with new-onset AHF and 270 (48.0%) with ADCHF. Patients with new-onset AHF were more likely to have coronary heart disease, acute myocardial infarction, higher diastolic blood pressure and higher troponin I levels(χ2=12.999,15.018, t=-2.088, Z=-2.727; all P<0.05). Patients with ADCHF were more likely to have poor cardiac function, atrial fibrillation, larger left ventricle and left atrium diameter, higher proportion of patients with pulmonary hypertension(χ2=16.565, 15.688, t=2.714, 5.029, χ2=15.274; all P<0.05). There were 205 (36.5%) all-cause deaths and 132 (23.5%) cardiovascular deaths during 28 (14, 60) months of follow-up. All-cause mortality rate [33.2%(97/292) vs. 40.0%(108/270), log-rank P=0.010] and cardiovascular mortality rate [18.8%(55/292) vs. 28.5%(77/270), log-rank P=0.001]were significantly lower in patients with new-onset AHF than those in ADCHF group. Multivariate Cox regression analysis showed that low body mass index (BMI), reduced hemoglobin, reduced resting heart rate, enlarged left atrium, and segmental wall motion abnormalities were independent risk factors for poor prognosis in new-onset AHF patients. It was different with ADCHF patients. Conclusion:Patients with new-onset AHF are more likely to have coronary heart disease; and lower BMI, reduced hemoglobin, acute coronary disease are associated with poor prognosis of patients. It is necessary to identify the underlying diseases early and actively standardize treatment to avoid the deterioration of cardiac function and readmission.

Objective:We evaluated frailty in elderly hospitalized patients with atrial fibrillation and analyzed the relevance, consistency, and diagnostic power of different frailty tools.Methods:From September 2018 to April 2019, a total of 197 elderly patients with atrial fibrillation aged ≥ 65 years in Beijing Hospital, Chinese PLA General Hospital, and Beijing Tsinghua Changgung Hospital were prospectively enrolled.Five frailty tools, including the clinical frailty scale(CFS), FRAIL scale(FRAIL), Fried frailty phenotype(Fried), Edmonton frail scale(EFS), and comprehensive geriatric assessment-frailty index(CGA-FI), were used for frailty assessment.Results:A total of 197 hospitalized elderly patients with atrial fibrillation were enrolled, with an average age of(77.5±7.1)years old(57.4% male). The prevalence of frailty, according to the five frailty tools, were 25.4%(FRAIL), 27.9%(EFS), 34.5%(Fried), 40.6%(CFS), and 42.6%(CGA-FI), respectively.CFS had a good correlation(correlation coefficient 0.80)and and consistency(Kappa value 0.71, 95% CI 0.61~0.81)with CGA-FI.The combined frailty index was used as the gold standard for frailty diagnosis.The results showed that CFS and CGA-FI had high diagnostic sensitivity(95.9 % and 98.0 %, respectively)and specificity(77.7 % and 75.7 %, respectively). Conclusions:Frailty is common in elderly hospitalized patients with atrial fibrillation, showing multidimensional features, and physical weakness is not prominet.CFS and CGA-FI are recommended for the assessment of frailty in patients with atrial fibrillation, which had good correlation and consistency.

Exosomes are nanoscale vectors with a diameter of 30~100 nm secreted by living cells, and they are important media for intercellular communication. Recent studies have demonstrated that exosomes can not only serve as biomarkers for diagnosis, but also have great potential as natural drug delivery vectors. Exosomes can be loaded with therapeutic cargos, including small molecules, proteins, and oligonucleotides. Meanwhile, the unique biological compatibility, high stability, and tumor targeting of exosomes make them attractive in future tumor therapy. Though exosomes can effectively deliver bioactive materials to receptor cells, there is a wide gap between our current understanding of exosomes and their application as ideal drug delivery systems. In this review, we will briefly introduce the function and composition of exosomes, and mainly summarize the potential advantages and challenges of exosomes as drug carriers. Finally, this review is expected to provide new ideas for the development of exosome-based drug delivery systems.
Biomarkers ; Drug Carriers ; Drug Delivery Systems ; Exosomes ; Humans ; Neoplasms