Blood metabolites in preterm infants with retinopathy of prematurity based on tandem mass spectrometry: a preliminary study / 中国当代儿科杂志

OBJECTIVES@#To study new biomarkers for the early diagnosis of retinopathy of prematurity (ROP) by analyzing the differences in blood metabolites based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and metabolomics.@*METHODS@#Dried blood spots were collected from 21 infants with ROP (ROP group) and 21 infants without ROP (non-ROP group) who were hospitalized in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2013 to December 2016. LC-MS/MS was used to measure the metabolites, and orthogonal partial least squares-discriminant analysis was used to search for differentially expressed metabolites and biomarkers.@*RESULTS@#There was a significant difference in blood metabolic profiles between the ROP and non-ROP groups. The pattern recognition analysis, Score-plot, and weight analysis obtained 10 amino acids with a relatively large difference. Further statistical analysis showed that the ROP group had significant increases in blood levels of glutamic acid, leucine, aspartic acid, ornithine, and glycine compared with the non-ROP group (P<0.05). The receiver operating characteristic curve analysis showed that glutamic acid and ornithine had the highest value in diagnosing ROP.@*CONCLUSIONS@#Blood metabolites in preterm infants with ROP are different from those without ROP. Glutamic acid and ornithine are the metabolic markers for diagnosing ROP. LC-MS/MS combined with metabolomics analysis has a potential application value in the early identification and diagnosis of ROP.

Dose-response relationship of blood flow restriction training on isometric muscle strength, maximum strength and lower limb extensor strength: A meta-analysis.

Objective: To perform a meta-analysis on the efficacy and dose-response relationship of blood flow restriction training on muscle strength reported worldwide. Methods: Thirty-four eligible articles with a total sample size of 549 participants were included in the meta-analysis. This study was performed using the method recommended by the Cochrane Handbook (https://training.cochrane.org/handbook), and the effect size was estimated using the standardized mean difference (SMD) and using RevMan 5.3 software (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, 2014). Results: The meta-analysis showed that blood flow restriction training increased the lower limb extensor muscle strength [SMD = 0.72, 95%; confidence interval (CI): 0.43 to 1.00, p < 0.01], knee extensor isokinetic torque SMD = 0.48 [95% CI: 0.24 to 0.73, p < 0.01], knee flexor isokinetic torque SMD = 0.39 [95% CI: 0.11 to 0.67, p < 0.01], and squat one-repetition maximum [SMD = 0.28, 95% CI: 0.01 to 0.55, p < 0.01]. There was no publication bias. Evaluation of dose-response relationship showed that the training load, mode, frequency, duration, and maximum cuff pressure affected the muscle function. Conclusion: blood flow restriction training. 16 significantly improved lower limb muscle strength, and the optimal training conditions consisted of a weight load smaller or equal to 30% of one-repetition maximum, training duration longer than 4 weeks, frequency of more than 3 times/week, and maximum cuff pressure lower than 200 mmHg. Systematic Review Registration: website, identifier registration number.

Low peripheral blood lymphocyte count predicts poor prognosis in the intermediate-risk myelodyplastic syndrome / 中华检验医学杂志

Objective:This study is aimed to investigate the value of absolute lymphocyte count (ALC) in predicting the clinical prognosis of patients with myelodyplastic syndrome(MDS).Methods:245 patients with MDS who diagnosed in our hospital from 2009 to 2019 were analyzed retrospectively, re-diagnosed according to WHO 2016 standard, and 208 patients with intact IPSS-R were risk-stratified, all of the patients′ peripheral blood ALC were collected and analyzed, through the time dependent receiver operating characteristic curve (ROC) analysis in Survival ROC package of R language, the optimal threshold value of ALC was 1.0×10 9/L. The patients of MDS were divided into normal ALC group (ALC ≥1.0×10 9/L) and low ALC group (ALC<1.0×10 9/L). Pearson χ 2 test and Mann-Whitney U test was used to analyze the differences in general data between the two groups. The overall survival (OS) curve and leukemia-free survival (LFS) were plotted by Kaplan-Meier method and compared by Long-rank test. Factors influencing the prognosis of MDS were analyzed by Cox Regression Model. Results:There were 97 cases in low ALC group and 148 cases in normal ALC group. The low ALC group had lower OS (15 months vs 60 months, P<0.000 1) and higher IPSS-R score (5.0 vs 3.75, P = 0.001). Multivariate analysis showed that ALC (<1.0×10 9/L) (HR:0.374,95% CI:0.153-0.917, P = 0.032) was independent risk factor of OS in IPSS-R-intermediate-risk MDS patients. Conclusion:This study shows that ALC in peripheral blood is an independent risk factor in IPSS-R-intermediate-risk MDS patients, which provides clinical evidence for the influence of body immunity on the development of MDS.

Neutron depth profiling system at CARR.

A neutron depth profiling (NDP) device was developed on China advanced research reactor (CARR) of China Institute of Atomic Energy (CIAE). The CARR-NDP device uses cold neutron beams transmitted by a neutron guide from the cold neutron source of CARR, and it is composed of a neutron beam collimator, and a vacuum target chamber containing a beam stopper and a detection system. The neutron flux at 1 m from the end of neutron guide is about 4.8 × 108 n cm-2 s-1 under operating power of 15 MW. A standard reference material SRM-2137 sample and a multilayer film sample were utilized to verify the performances of the CARR-NDP device.

Construction of a mouse model of cblC type methylmalonic acidemia with W203X mutation based on the CRISPR/Cas9 technology / 中国当代儿科杂志

OBJECTIVE@#To construct a W203X-mutant mouse model of cblC type methylmalonic acidemia based on the CRISPR/Cas9 technology.@*METHODS@#At first, BLAST was used to compare the conservative nature of the cblC gene and protein sequences in humans and mice, and then, the CRISPR/Cas9 technology was used for microinjection of mouse fertilized eggs to obtain heterozygous F1 mice. Hybridization was performed for these mice to obtain homozygous W203X-mutant mice. The blood level of the metabolite propionyl carnitine (C3) was measured for homozygous mutant mice, heterozygous littermates, and wild-type mice.@*RESULTS@#The gene and protein sequences of MMACHC, the pathogenic gene for cblC type methylmalonic acidemia, were highly conserved in humans and mice. The homozygous W203X-mutant mice were successfully obtained by the CRISPR/Cas9 technology, and there was a significant increase in C3 in these mice at 24 hours after birth (P<0.001).@*CONCLUSIONS@#A W203X-mutant mouse model of cblC type methylmalonic acidemia is successfully constructed by the CRISPR/Cas9 technology.

Exposure to phthalates in house dust and associated allergies in children aged 6-12years.

Phthalates are widely used as plasticizers in household products. Several studies have reported an association between phthalate exposure and an increased risk of allergies. The present study estimated phthalate exposure in children aged 6-12years and assessed potential correlations with allergies. House dust samples were collected from floors and multi-surface objects >35cm above the floor. Urine samples were collected from the first morning void of the day. Daily phthalate intake (DIdust and DI) was estimated using both house dust and urinary metabolite concentrations. Exposure to di-2-ethylhexyl phthalate (DEHP) in floor dust was associated with parental-reported rhino-conjunctivitis. After stratification by gender, this trend was found to only occur in boys. Furthermore, urinary mono-isobutyl phthalate was inversely associated with parental-reported wheeze in boys. DIdust of benzyl butyl phthalate (BBzP) and DEHP were significantly correlated with DI_BBzP and DI_DEHP, respectively. These correlations were stronger with floor than with multi-surface dust. Our results suggest that, among Japanese children, house dust from low surfaces, such as living room floors, might play a meaningful role in the indoor environmental exposure pathway for BBzP and DEHP.

Comparisons of urinary phthalate metabolites and daily phthalate intakes among Japanese families.

We measured urinary phthalate metabolites, including di-n-butyl phthalate (DnBP), di-isobutyl phthalate, benzyl butyl phthalate (BBzP), and di(2-ethylhexyl) phthalate (DEHP), from 178 school-aged children and their 284 family members using gas chromatography-mass spectrometry, and we calculated daily phthalate intakes. The highest median levels of phthalate metabolites were for mono-isobutyl phthalate in all participants except schoolchildren, where the highest levels were for mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP). Comparing the schoolchildren with their parents, the schoolchildren had significantly higher urinary metabolites for MEOHP, mono-(2-ethyl-5-carboxypentyl) phthalate, and ΣDEHP. Regarding daily intakes, the schoolchildren had significantly higher daily intakes of DnBP, BBzP, and ΣDEHP. All phthalate metabolite and sums of metabolite levels in the schoolchildren were positively correlated with their mothers' levels, except for MEHP, whereas fathers were less correlated with their children. The DEHP intake in this study was higher than that of most other studies. Moreover, 10% of the children and 3% of the adults exceeded the Reference Dose (RfD) value (20µg/kg/day) of the U.S. Environmental Protection Agency, which indicates that it is important to focus on children's DEHP exposure because the children exceeded the RfD more than adults among the same families who shared similar exposure sources. Our results will contribute to considerations of the regulations for some phthalates and the actual phthalate exposure levels in the Japanese population.

Association of mechanical ventilation and flue use in heaters with asthma symptoms in Japanese schoolchildren: a cross-sectional study in Sapporo, Japan.

BACKGROUND: Use of fuel heaters is associated with childhood asthma. However, no studies have evaluated the associations of flue use and mechanical ventilation (ventilation) with asthma symptoms in schoolchildren. METHODS: This cross-sectional study investigated schoolchildren in grades 1 through 6 (age 6-12 years) in Sapporo, Japan. From November 2008 through January 2009, parents completed questionnaires regarding their home environment and their children's asthma symptoms. RESULTS: In total, 4445 (69.5%) parents of 6393 children returned the questionnaire. After excluding incomplete responses, data on 3874 children (60.6%) were analyzed. The prevalence of current asthma symptoms and ever asthma symptoms were 12.8% and 30.9%, respectively. As compared with electric heaters, current asthma symptoms was associated with use of flued heaters without ventilation (OR = 1.62; 95% CI, 1.03-2.64) and unflued heaters with ventilation (OR = 1.77; 95% CI, 1.09-2.95) or without ventilation (OR = 2.23; 95% CI, 1.31-3.85). Regardless of dampness, unflued heaters were significantly associated with current asthma symptoms in the presence and absence of ventilation. CONCLUSIONS: Use of unflued heaters was associated with current asthma symptoms, regardless of dampness. In particular, the prevalence of current asthma symptoms was higher in the absence of ventilation than in the presence of ventilation. Ever asthma symptoms was only associated with use of unflued heaters without ventilation. Consequently, use of fuel heaters, especially those that have no flue or ventilation, deserves attention, as their use might be associated with childhood asthma symptoms.

Detection and intake assessment of organophosphate flame retardants in house dust in Japanese dwellings.

The demand for phosphorus flame retardants (PFRs) has recently increased as an alternative to polybrominated diphenyl ether (PBDE). PFRs have been detected in house dust, but little is known about the concentrations of PFRs in private homes and the effects on human health. We measured the levels of 10 PFRs in indoor floor dust and upper surface dust from 128 Japanese dwellings of families with children in elementary school. The median (min-max) concentrations (µg/g) of PFRs were as follows: tris(2-butoxyethyl) phosphate (TBOEP), 30.88 (<0.61-936.65); tris(2-chloro-iso-propyl) phosphate (TCIPP), 0.74 (<0.56-392.52); and triphenyl phosphate (TPHP), 0.87 (<0.80-23.35). These values exceeded 50% detection rates, and the rates are median over the LOD in floor dust. The concentrations (µg/g) of TBOEP 26.55 (<0.61-1933.24), TCIPP 2.23 (<0.56-621.23), TPHP 3.13 (<0.80-27.47), tris(2-chloroethyl) phosphate (TCEP) 1.17 (<0.65-92.22), and tributyl phosphate (TNBP) 0.74 (<0.36-60.64) exceeded 50% detection rates in the upper surface dust. A significant positive correlation (P<0.05) between the concentrations of TCIPP and TBOEP was shown in floor dust and upper surface dust (n=48). Estimated median and 95th percentile daily intake was calculated for toddlers and elementary school children and was compared with reference dose values (RfD) from the literature. For TBOEP, the estimated 95th percentile intake from floor dust was 14% of RfD for toddlers and 4% for school children. The estimated intake from upper surface dust was somewhat lower. Estimated median intake of TBOEP and median intake for the other PFRs were less than 1% of the RfD. TBOEP, TCIPP and TPHP were the main PFRs in the dust. The median levels of PFRs are well below the RfD values.

ARMS-PCR method for detecting multiple NPM1 mutations / 中国实验血液学杂志

This study was aimed to establish a simple, sensitive detection method for multiple NPM1 mutations, so as to reduce the omission ratio of NMP1 mutant detection. Recombinant plasmids containing wide-type NPM1 and the most common mutations (A, B, C, D) were constructed as the detection objects. The ARMS-PCR for detecting multiple NPM1 mutations was established through designing a pair of specific primers whose 3' end base matched with four mutants (A,B,C,D), but did not matched with wild type NPM1 according to the different base sequence of NPM1 mutants. The feasibility of the ARMS-PCR method was evaluated by assessing the detection range and the sensitivity and comparing with direct sequencing. The results showed that the recombinant plasmids were constructed successfully by restriction analysis and DNA sequencing. The four mutants but not wild type NPM1 were detected by using ARMS-PCR, the detection range of the method was 10(3) copies/ml -10(9) copies/ml and the sensitivity was 0.01%, while the direct sequencing method could not detect the mutations if mutation was less than 10%. It is concluded that the high sensitive ARMS-PCR is established for detecting the four mutations of NPM1 and more than 95% mutants can be detected by this method, providing a new detection method for clinical NPM1 gene mutant.

Sex-dependent association of phosphodiesterase 4D gene polymorphisms with ischemic stroke in Henan Han population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recent evidence has implicated the gene for phosphodiesterase 4D (PDE4D) as susceptibility gene for ischemic stroke (IS) in Icelandic population. However, there are few reports on the associations between PDE4D gene polymorphisms and IS in Chinese individuals. The present study aimed to investigate the possible association of genetic polymorphisms in PDE4D gene with IS in Henan Han population.</p><p><b>METHODS</b>A total of 400 patients with IS and 400 matched controls were examined using a case-control design. Two single nucleotide polymorphism (SNPs) (rs918592 and rs2910829) in PDE4D gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated to test the association between the genetic factors and IS. Genetic parameter and association studies were carried out with SPSS 16.0.</p><p><b>RESULTS</b>Among the two SNPs tested, the rs918592 was significantly associated with IS (OR: 1.351, 95%CI: 1.110 - 1.645), especially in male patients (OR: 1.427, 95%CI: 1.105 - 1.844). Haplotype analysis showed that A-T was associated with an increased risk of the IS (OR: 2.114, 95%CI: 2.005 - 2.230) while G-T was associated with decreased risk of IS (OR: 0.419, 95%CI: 0.302 - 0.583). Protecting effect of haplotype G-T was also significant in males (OR: 0.264, 95%CI: 0.162 - 0.431).</p><p><b>CONCLUSIONS</b>The present study demonstrated a strong association of rs918592 with IS. Haplotype A-T increased the risk of IS while haplotype G-T had a protective effect in Henan Han population. The association was sex-dependent with male patients showing stronger effect.</p>

Comparison of (18)F-FDG PET-CT and abdomen enhancement CT in diagnosing peritoneal metastases / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the diagnostic value of (18)F-FDG PET-CT with abdomen contrast CT in the diagnosis of peritoneal metastases.</p><p><b>METHODS</b>Between January 2008 and May 2011, imaging results of 97 patients with suspicious peritoneal metastases were retrospectively reviewed, and all the patients underwent both abdomen contrast CT and (18)F-FDG PET-CT imaging. Final diagnosis was made by histopathology or follow up.</p><p><b>RESULTS</b>Seventy-seven patients were verified as peritoneal metastases after pathological examination(n=88) or follow up(n=9), while the other 20 patients were absent. The sensitivity of (18)F-FDG PET-CT was 90.9%(70/77), the specificity 85.0%(17/20), and the accuracy 89.7%(87/97). There were 3 false positive and 7 false negative. The sensitivity of contrast CT was 66.2%(51/77), the specificity 80.0%(16/20), and the accuracy 69.1%(67/97). There were 4 false positive and 26 false negative. The difference in diagnostic accuracy was statistically significantly between these two methods(P<0.05).</p><p><b>CONCLUSION</b>The diagnostic value of (18)F-FDG PET-CT is significantly higher than that of abdominal enhanced CT for peritoneal metastases.</p>