// Fen Zhou 1,2 , Meiling Zhang 1,2 , Juan Han 1,2 , Jinjin Hao 1,2 , Yan Xiao 1,2 , Qin Liu 1,2 , Runming Jin 1,2 , Heng Mei 2 1 Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China 2 Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China Correspondence to: Runming Jin, email: // Heng Mei, email: // Keywords : skeletal abnormalities, SPECT, acute lymphoblastic leukemia, relapse Received : July 26, 2016 Accepted : May 08, 2017 Published : May 23, 2017 Abstract Objectives: Most children with acute lymphoblastic leukemia (ALL) exhibit skeletal abnormalities. This study aimed to investigate bone lesions detected by whole-body bone single-photon emission computed tomography (SPECT) and its prognostic value in children with ALL. Methods: A retrospective analysis was performed using whole-body bone SPECT scans obtained from children with ALL in our department between June 2008 and June 2012. A total of 166 children newly diagnosed with ALL were included, and the patients were divided into two groups: patients with positive and negative SPECT scans. We compared the clinical characteristics of the two groups and analyzed the relationship between the skeletal abnormalities detected by SPECT and prognosis. Results: Among the 166 patients, bone scintigraphic abnormalities was detected by SPECT scan in sixty-four patients (38.6%). The most common site was the limbs. There were no significant differences in age, gender, WBC count at diagnosis, risk group and minimal residual disease (MRD) level between SPECT-positive patients and their SPECT-negative counterparts. The event-free and overall survival rates were higher in SPECT-positive patients, but the difference was not statistically significant. However, patients with positive SPECT scans, especially those with multifocal abnormalities (≥3 sites), had a higher rate of relapse ( P < 0.05). Multivariate analyses identified that abnormal SPECT scan (HR = 3.547, P = 0.015) was an independent relapse risk. Conclusion: Children with ALL and multiple skeletal abnormalities will suffer from relapse. Abnormal SPECT scan was associated with increased relapse risk which might be a potential relapse marker for ALL children.
The accumulation of protoporphyrin IX in the liver caused by isoniazid and rifampicin through the disorder of heme biosynthesis was considered an important mechanism of anti-tuberculosis drug-induced liver injury (ATLI). Alanine synthase 1 (ALAS1) is a rate-limiting enzyme in the process of heme synthesis. This study aimed to investigate the association between ALAS1 gene polymorphism, serum ALAS1 level, and the risk of ATLI. This study was a case-control study including 58 ATLI cases and 192 controls. Four single nucleotide polymorphisms (SNPs) of the ALAS1 gene were selected for genotyping and serum ALAS1 concentrations were detected using ELISA kits. There was no significant difference in the genotype distribution of four SNPs between the ATLI cases and the controls under different genetic models. Patients carrying the GG genotype of SNP rs352163 in controls had higher baseline ALAS1 levels than those in ATLI cases (243.6 vs 290.2 ng/L, P = .034), and patients with baseline ALAS1 < 337.85 ng/L had a higher risk of ATLI than those with ALAS1 ≥ 337.85 ng/L (HR = 2.679, 95% CI: 1.360-5.278, P = .004). Our findings indicated that the serum ALAS1 concentrations in the ATLI cases were lower than those in the controls, and the lower baseline ALAS1 levels can be associated with higher ATLI risk.
CASP8 rs3834129 polymorphism (-652 6N insertion/deletion) is a genetic alteration which might affect the apoptosis pathway caspase enzyme. The impaired caspase enzyme would lead to the change of cancer risk. By now, the role of CASP8 rs3834129 polymorphism has been widely investigated. However, the relationship of this genetic variant on colorectal cancer (CRC) susceptibility still remains inconsistent. Therefore, we further investigated the role of rs3834129 polymorphism on CRC risk. Eligible published studies were retrieved from EMBASE, PubMed, CNKI and WANFANG database updates to March 2018. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the relationship strengths. In general, we successfully retrieved 13 studies (8 publications) involving 13058 cases and 14418 controls. The meta-analysis results demonstrated that rs3834129 polymorphism was associated with a decreased CRC risk in heterozygous model (ID vs. II: OR = 0.94, 95% CI = 0.88-0.99), but not the homozygous and allele models. Furthermore, significantly decreased risk was also found among Asian (ID vs. II: OR = 0.86, 95% CI = 0.76-0.98), and high quality score group (ID vs. II: OR = 0.90, 95% CI = 0.81-1.00) in the stratified analyses. Taken together, we showed that CASP8 rs3834129 polymorphism influences CRC susceptibility in a weak impact manner. More case-control studies are warranted to validate such relationship.
Plocabulin (PM060184) is a promising new anticancer drug as a microtubule inhibitor. The conformational structure and properties of plocabulin have been studied theoretically. The initial structure was screened by the B3LYP/3-21G* method, and then 32 unique conformations were further optimised with the B3LYP/6-311G* method. The single-point energies were determined at the M06-L/6-311G(2df,p) level. The UV excitation of the most stable plocabulin conformation in methanol was studied by the TD-CAM-B3LYP/6-311G(2df,p) method. High-quality human p-glycoprotein model was obtained through homology modelling. The binding interaction between p-glycoprotein and plocabulin was studied by docking and MD simulation. LEU65, TYR310, ILE340, THR945, PHE983, MET986, and GLN990 were found to be important amino acid residues in the interaction. From a certain perspective, the ‘reverse exclusion’ mechanism of plocabulin with p-glycoprotein was illustrated, and this mechanism provides theoretical guidance for the structural modification of plocabulin and for design of drug’s to avoid p-glycoprotein-mediated drug resistance.
ABSTRACT Background Coronavirus disease 2019 (COVID-19) has been declared as a threat to the global. Due to the lack of efficient treatments, indicators were urgently needed during the evolvement of disease to analyze the illness and prognosis, and prevent the aggravation of COVID-19. Methods Patients’ general information, clinical type, all CK values and outcome were collected. CK value of all cases during disease course started from different initial time were analyzed. Results All cases underwent 504 tests of CK since symptom onset and the median value was 51.7 (35.0-91.5) U/L. The first median value on the day 8 from exposure onset was 78.1 (69.1-85.8) U/L then showed an upward trend from the day 8 to the day 12 (reaching a peak of 279.3 U/L), finally showed a fluctuation decline after the day 12. The CK median value in critical cases reached the peak (625.5 U/L) on the transforming date, and then decreased rapidly to the normal range. Before death, the CK median value in dead cases firstly increased until the day −14 with a peak as 470.0 U/L, then decreased with fluctuation until day −2, and finally increased again on the day 0. Conclusions CK reached its peak on the day when it became critical type, dynamic detection of CK can guide clinical judgment of prognosis. The increase of CK is a high risk factor of death. Severe cell damage 2 weeks before death might determines the outcome of the disease even if CK drops to the normal range afterward.
To research the changes of blood parameters on different time points after micro-rHuEPO injection on young men and hope to provide evidences for Athletic Biological Passport (ABP) using in the detection of blood doping.Fourteen health young men were injected with micro-rHuEPO for 7 weeks, twice per one week.The subjects were treated with ferralia 105 mg every day during the injections.The control group was administrated with the same volume of saline solution injection and placebo 105 mg.The blood parameters (red blood cell, hemoglobin, reticulocyte, total hemoglobin, plasma volume, etc) were tested 11 times (7 days before the first injection, 3, 10, 17, 24, 31, 38 and 45 days after the first injection, 1, 2 and 3 weeks post the seventh week of last injection).By analyzed these total and concentration parameters, hope to know the effective of two kinds of parameters on ABP.The levels of RBC and[Hb] were increased sharply after two weeks of injection and reached the peak in 5-6 weeks (9-10%, P<0.01).It sustained till 3 weeks after the last injection.Total hemoglobin was increased significantly during the whole procedure of injections and reached the peak in week 5 (10%, P<0.01) till 1 week after the last injection.Red blood cell volume was increased with the EPO injection and reached the peak in week 5 (P<0.01), but blood volume wasn't increased significantly.Plasma volume was decreased with EPO injection and it was hemoconcentration.It can enhance the total and concentration parameters through 7-week micro-rHuEPO injections and the total haemoglobin is more sensitive.So tHb can be used to detect blood doping in ABP.At the end of the last injection, the total blood parameters, such as the total hemoglobin, returned to normal, while the concentration index remained highly, possibly as a result of blood concentration.
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