Cardiovascular and cerebrovascular diseases are one of the diseases with the highest mortality rate in the world, seriously affecting human health. Clinically, the abnormal values of myocardial injury markers are often detected to reflect the severity of myocardial injury and used as a reference index for screening, diagnosis, and prognosis of myocardial injury (abnormality). In this paper, the classification of metal-organic frameworks (MOFs) and their composites were introduced, and the research progress of electrochemical protein sensors, electrochemical immunosensors, and electrochemical aptamer sensors based on MOF composites for the detection of markers of myocardial injury was reviewed.

Functionalized nanomaterials combined and immobilized with recognition elements to construct biosensing interfaces are the core aspects of biosensor detection. By interfacially modifying functionalized nanomaterials with different properties, structures and morphologies, the application scope of nanomaterials can be expanded, such as metal-organic frameworks (MOFs), layered double hydroxides (LDHs), noble metal particles, magnetic materials, covalent organic frameworks (COFs), carbon-group materials, and conductive polymers. Based on these novel nanomaterials, a variety of biosensors with excellent performance have been developed. In this review paper, the types of functionalized nanocomposites and their progress in the application of constructed biosensors were summerized.

Objective: A label-free electrochemical immunosensor was developed for the detection of nuclear matrix protein-22 (NMP22) as a biomarker of bladder cancer. Methods: The study was based on the establishment and validation of the methodology. Urine samples were collected from 20 patients with bladder cancer and 20 controls in the affiliated Hongqi hospital of Mudanjiang medical university from September in 2017 to July in 2019 to validate the developed method. A screen-printed electrode (SPE) was modified with a film of a composite made from the reduced graphene oxide-tetraethylene pentamine (rGO-TEPA) immobilized Zn-based-Metal-organic frameworks deposited with Au nanoparticles (rGO-TEPA@Au-ZIF8). Primary antibody against NMP22 was immobilized on the Au nanoparticles on the surface of the modified SPE, which then was blocked with bovine serum albumin to elimiate nonspecific binding sites. The process of the construction of the proposed sensorwas characterized by cyclic voltammetry and electrochemical impedance spectroscopy. Differential pulse voltammetry was used to evaluate the linear range, recovery, precision, selectivity and stability. The data were analyzed by Mann-Whitney U test. Results: Under optimal conditions, the immunosensor exhibited a linear range of 0.01-1000 ng/mlwith a detection limit of 3.33 pg/ml (S/N=3) and a standard recovery of 97.65%-107.05%. The levels of NMP22 in urine samples from patients with bladder cancer [66.03 (4.34, 91.74)]ng/ml determined by the proposed sensor were significantly higher than those of controls 0.54(0.06, 8.84) ng/ml(P=0.001). Conclusion The immunosensor can achieve sensitive, rapid and acucurate detection of NMP22, and has potential application prospects in monitoring tumor markers.

Objective To investigate the range of gray values of MRI local hyperintensity signals corresponding to the classification of partial tear of knee anterior cruciate ligament (ACL) under arthroscopy so as to evaluate its significance for diagnosis and treatment of acute partial ACL tear.Methods A retrospective analysis was conducted of 82 patients who had identical orthopaedic and MRI findings at Department of Orthopaedics and Traumatology,Shenzhen Baoan People's Hospital from January 2014 to June 2016.They were 49 males and 33 females;their ages ranged from 18 to 71 years,with an average of 39.6 years;27 left and 55 right knees were involved.Of them,67 were assigned into an ACL tear group in which both arthroscopic and MRI findings indicated diagnosis of acute ACL partial tear,and 15 into an ACL normal group in which both arthroscopic and MRI findings indicated diagnosis of normal ACL but injury to meniscus and/or articular cartilage.According to the arthroscopic grading,the 67 patients were rated as grade Ⅰ in 21 cases,as grade Ⅱ in 19,and as grade Ⅲ in 27.Software Photoshop CS4.0 was used to measure the gray values of local hyperintensity signals of the partial ACL tear in the MRI in the ACL tear group and the overall gray values of local hyperintensity signals of the normal ACL in MRI in the ACL normal group.The 2 groups were compared in terms of the range of gray values of MRI local hyperintensity signals and the proportion of ACL partial tear under arthroscopy.Results The range of gray values of MRI local hyperintensity signals in diagnosis of acute ACL partial tear was 20.24 ± 7.77 for the ACL normal group,67.54 ± 8.78 for the grade Ⅰ ACL partial tear,90.99 ± 7.21 for the grade Ⅱ tear,and 138.89 ± 32.40 for the grade Ⅲ tear,showing significant differences between the 4 groups and any 2 of the 4 groups as well (both P ＜ 0.05).The percentage of ACL partial tear under arthroscopy was 0 for the ACL normal group,0.22 ± 0.08 for the grade Ⅰ ACL partial tear,0.56 ± 0.08 for the grade Ⅱ tear,and 0.84 ± 0.064 for the grade Ⅲ tear,showing significant differences between the 4 groups and any 2 of the 4 groups as well (both P ＜ 0.05).Twenty-six patients (21 cases of grade Ⅰ and 5 ones of grade Ⅱ tear) received symptomatic treatment of the injury to the meniscus and/or articular cartilage without ACL reconstruction due to good function of residual ACL and stable knee joint.Forty-one patients (14 cases of grade Ⅱ and 27 ones of grade Ⅲ tear) underwent ACL reconstruction and treatment of co-morbidities because of poor function of residual ACL and instability of the knee joint.Conclusion The range of gray values of MRI local hyperintensity signals can be used to assist diagnosis and classification of acute ACL partial tear.

Objective: To analyze the gene mutations in the patients with myelodysplastic syndromes (MDS). Methods: Forty-seven patients with MDS newly diagnosed in Xiyuan Hospital, China Academy of Chinese Medical Sciences from January 2016 to July 2017 were enrolled. NGS 127-gene panel was used to detect the gene mutations, and the relationship between the gene mutations and the clinicopathological features was also analyzed. Results: Thirty-one (66.0 %) cases had gene mutations in 47 patients with MDS, and 23 gene mutations were detected with clinical significances. There were 7 mutant genes with a mutation frequency over 5 % in the population, including U2AF1 (23.4 %), SF3B1 (12.8 %), ASXL1 (10.6 %), TET2 (8.5 %), BCOR (8.5 %), TP53 (8.5 %) and DNMT3A (6.4 %) in turn. Among 31 patients with gene mutations, 16 (51.6 %) patients had ≥ 2 synergistic mutations, and 12 cases had synergistic mutations in different genetic functional groups, which was higher than that in same genetic functional groups (4 cases). There was a tendency of coexistence in IDH2-KRAS, IDH2-SRSF2, IDH2-STAG2, KRAS-SRSF2, KRAS-STAG2, RUNX1-PHF6, EZH2-ASXL1, EZH2-ZRSR2, and NPM1-NRAS (all P < 0.05). The variant allele frequency (VAF) of signaling pathway related genes including JAK2, KRAS, NRAS, SH2B3 was low in general and in a sub-clone status. JAK2 gene mutation was observed in 1 case with MDS-U. SH2B3 gene mutation was observed in a patient with very poor prognosis of karyotype. SETPB1 and EZH1 gene mutations were observed in two patients with high-risk revised international prognostic scoring system (IPSS-R). Conclusions The common mutated genes include U2AF1, SF3B1, ASXL1 and TET2. The genes in different genetic functional groups tend to synergistic mutations. Gene mutations can be used to predict the prognosis of diseases and become the target in the treatment of MDS.

Objective To analyze the clinical efficacy and safety of compound Qinghuang powder (compound QHP) for treatment of myelodysplastic syndromes (MDS) and its association with blood arsenic concentration (BAC). Methods 40 patients with MDS were treated with compound QHP, and the clinical efficacy, safety, and its association with BAC were evaluated after treatment for 6, 9 months, respectively. Results After treatment for 6 months, the rate of hematology improvement was 32.5 % (13/40), and the effective rate was 87.5%(35/40). 21 cases depended on the blood transfusion before treatment, after treatment 6 cases completely got rid of blood transfusion and the blood transfusion of another 6 cases was decreased by more than 50 %. The absolute neutrophil count was increased from (0.50±0.13)×109/L to (0.93±0.33)×109/L (t= 4.130, P= 0.0008). The hemoglobin content was increased from (71.06±14.82) g/L to (80.41±27.35) g/L (t= 2.233, P= 0.0321). After treatment for 9 months, 76.2 % (16/40) of the patients got rid of blood transfusion or blood transfusion reduction was more than 50%. The platelet count was increased from (45.04 ± 24.38)×109/L to (60.65±29.46)×109/L (t= 2.241, P= 0.0335). The incidence of abdominal pain and diarrhea after treatment for 1, 3 and 6 months were 12.5 % (5/40), 10.0 % (4/40) and 5.0 % (2/40), respectively, all belonging to mild level . Before treatment , there were 12 patients with abnormal liver function , including 6 cases back to normal after treatment, and 6 cases of significantly relieved, without new case with abnormal liver function. Before treatment, there were 10 cases with abnormal myocardial enzymes, including 1 cases back to normal after treatment and 9 cases significantly relieved, without new case with abnormal myocardial enzymes. No patient with abnormal renal function was observed before and after treatment. The BAC was (7.71±5.65) μg/L before treatment, which was significantly lower than that of 1, 3 and 6 months [(29.27±9.07)μg/L, (27.79 ±10.18) μg/L and (31.98 ±12.55) μg/L respectively, all P< 0.0001]. There was no significant change of BAC among the patients after treatment for 1, 3 and 6 months (P> 0.05). The BAC in efficacy group [(33.48 ±12.56) μg/L] was significantly higher than that in non-efficacy group [(21.46 ±6.00) μg/L] (t=2.089, P=0.035). 12.5% (5/40) of the patients had mild gastrointestinal side effects after treatment for 1 month, while the BAC of them [(16.93 ±1.80) μg/L] was significantly lower than that in patients without gastrointestinal side effects [(31.78±1.39 ) μg/L, P<0.0001]. The occurrence rate of abdominal pain and diarrhea was decreased after treatment for 3 and 6 months, while the BAC was increased gradually. Conclusions Compound QHP is effective in the treatment of MDS with mild adverse reactions. There is no damage to the heart, liver, and renal function. Besides, it shows that reducing the gastrointestinal adverse reactions and maintaining the effective concentration of BAC play a significant role in the effect of compound QHP in the treatment of MDS.

Objective To search for application ways for the safe and effective clinical methods of arsenic-containing Compound Qinghuang Powder (Compound QHP) for the treatment of myelodysplastic syndrome (MDS). Methods Totally 200 patients with MDS were included in the study and treated with Compound QHP. After one-month treatment, the 60 patients with the blood arsenic concentrations <20 μg/L were randomly divided into control group and treatment group, with 30 cases in each group. Control group was given stable treatment, while the treatment group was given increased dose of realgar; blood arsenic concentration was detected monthly; realgar 0.1 g was increased each time until blood arsenic concentrations ≥20 μg/L and realgar ≤0.3 g/d. The blood arsenic concentration, clinical efficacy and safety in the two groups were observed. Results Totally 24 cases in each group were included for evaluation finally. The average blood arsenic concentration of treatment group was significantly higher than those of control group (P<0.05). The rate of hematologic improvement was significantly higher in treatment group (54.2％, 13/24) than that in control group (29.2％, 7/24) , with significant difference (P<0.05). The Hb, ANC, and PLT significantly increased in treatment group after treatment (P<0.05). There was no significant difference of incidence rate of adverse reaction observed between treatment group and control group (P>0.05). Conclusion In application of Compound QHP, the blood arsenic concentration can be monitored to adjust the daily dose of realgar, thus to increase the effective blood arsenic concentration, and then improving efficacy without increasing the clinical toxicity.

Objective To analyze the blood arsenic concentration and the safety of compound Qinghuang powder(compound QHP)in patients with myelodysplastic syndrome(MDS).Methods A total of 45 MDS patients received treatment with compound QHP (the treatment group, n=45). The concentration of blood arsenic in different time was determined by atomic fluorescence spectrometry. The clinical safety of compound QHP was evaluated by analyzing the symptoms of adverse reaction and organ function. The comparison were MDS patients with Qinghuang powder (QHP group, n=47) and healthy people. Results There was no significant difference of the blood arsenic concentration between the treatment group and the healthy control group (P=0.450),while after the treatment for 1 month those concentrations significantly increased (P=0.000). There were no significant difference between the blood arsenic concentration after treatment for 1, 3, and 6 months (P=0.240). The incidence of adverse reaction in the treatment group was significantly lower than that in QHP group(χ2=4.720, P=0.030). The incidence of adverse reactions in the digestive tract was significantly lower in the treatment group than that in QHP group (χ2=4.650, P=0.034). The blood arsenic concentration of patients with abdominal pain diarrhea was significantly lower than those without abdominal pain diarrhea (P=0.020). Before treatment in the compound QHP group, there were 21 cases with increased myocardial enzymes, 10 cases with abnormal liver function and 4 cases with renal dysfunction, respectively. After treatment at 6th month, these indicators returned to normal with 7 cases of myocardial enzymes, 6 cases of liver function and 1 case of renal function, respectively. There was no new case with abnormal myocardial enzymes, liver function and renal dysfunction, respectively. Conclusions Arsenic could be absorbed in the digestive tract into blood in MDS patients after treatment with arsenic-containing compound QHP, and the blood arsenic concentration remained stable during the course of treatment. The adverse reactions were mainly mild gastrointestinal symptoms, but no heart, liver or renal function damage was observed. The incidence of abdominal pain diarrhea in patients treated with compound QHP was significantly lower than that with QHP.

Recently, more research about the plant bioreactor expressing genes encoding human proteins was reported. In the present study, the cDNA of the human gene keratinocyte growth factor 2 (KGF2) was replaced with plant preferred codons by PCR, and the modified full-length cDNA was cloned into the plant expression vector pCAMBIA-YO containing the oil-body promoter. The fusion construct pCAMBIA-YO-KGF2 was transformed into Brassica napus by Agrobacterium tumefacien-mediated cotyledon transformation method. The transgenic seedlings were identified by PCR, Southern and western blot analysis all showed that KGF2 gene was successfully expressed in in transgenic Brassica napus.
Brassica napus ; genetics ; metabolism ; Cloning, Molecular ; DNA, Complementary ; genetics ; Fibroblast Growth Factor 7 ; biosynthesis ; genetics ; Genetic Vectors ; genetics ; Humans ; Plants, Genetically Modified ; genetics ; Rhizobium ; genetics ; Transformation, Genetic

Objective To investigate mutation patterns in core promoter(CP)region of hepatitis B virus(HBV).Methods HBV DNA was extracted from sera of patients with chronic HBV infection.The CP sequence was amplified by polymerase chain reaction(PCR)and cloned into pMD19 T vector.The positive clones were then sequenced.The sequences were compared with known HBV genome in GenBank to identify the mutation sites and patterns of patients with chronic HBV infection.Results There were 74 clones from 21 patients with chronic HBV infection which were sequenced.The sequence comparisons showed that there was a 234-nucleotide deletion in CP region of HBV genome in 54 clones and a 245-nucleotide deletion in one clone.These deletion regions included CP,HBeAg initiation codon and direct repeat sequence(DR)Ⅰ regions,which named CP deletion(CPD).A1585T replacement mutation was also found in HBV strain with CPD,which indicated that there was linkage between these two mutations.Conclusions A novel mechanism of HBeAg negative chronic hepatitis B is observed,which includes deletions of CP and HBeAg initiation codon.Meanwhile,a simple and useful PCR method is developed to detect CPD.