[Effects of retinopathy on visual function in type 2 diabetes mellitus].

Objective: To study the influence of the severity of diabetic retinopathy (DR) on the visual function of patients with type 2 diabetes, to provide scientific basis for the early prevention and control of DR. Methods: This study was designed as a cross-sectional study, recruiting already-diagnosed type 2 diabetes patients in four community health service centers in Guizhou Province between February and September 2022. Employing the Chinese version of the Visual Function Index-14 (VF-14), assess the participants' near vision, visual adaptation, subjective visual perception, and stereo vision, with higher scores indicating poorer visual function. Categorize the severity of each eye's damage into no diabetic retinopathy (DR), mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR, and proliferative diabetic retinopathy (PDR), and use a 5-level DR grading system to evaluate the overall severity of diabetic retinopathy in both eyes. Employing linear regression analysis to investigate the linear relationship between DR and visual function index. Local weighted regression evaluates the nonlinear relationship between the DR composite score and the scores of visual function, with a steeper slope indicating poorer visual function for that level. Results: A total of 542 patients with type 2 diabetes were investigated, including 244 (45.02%) males, 298 (54.98%) females, and 162 (29.89%) patients with DR. After adjusting for confounders, compared with those without DR, patients with binocular DR Had overall scores (ß=0.136, P=0.003), near vision (ß=0.163, P<0.001), visual adaptation (ß=0.092, P=0.042), subjective vision (ß=0.120, P=0.009) and stereo vision (ß=0.094, P=0.044) were higher than those without DR. There were no differences in visual functions between DR And monocular DR. The local weighted regression curve showed that near vision (slope: 23.78) and overall score (slope: 58.37) increased sharply from mild to moderate NPDR in both eyes. Visual adaptation (slope: 5.37, 7.72), subjective vision (slope: 6.53, 7.93), stereovision (slope: 0.74, 0.91) increased slowly in mild to moderate NPDR in both eyes and in moderate to severe NPDR/PDR in both eyes. Conclusion: Binocular DR is associated with impaired visual function, but there is no difference between monocular DR And non-DR visual function. The early damage of DR To visual function is mainly manifested in near vision. In the prevention and control of DR, more attention should be paid to visual function, especially the change of near vision, and retinal damage should not be assessed solely by visual status.

[Elemental and isotopic determination of lead in whole blood by ISIS-ICP-MS].

Objective: To establish a method for determination of lead and istope ratios in the blood by ISIS-ICP-MS. Methods: After wet digestion, the blood sample was on-line addition of thallium as internal standard and analyzed by ISIS-ICP-MS. Results: The limit of detection was 0.03 µg/L and the lower limit of quantification was 0.08 µg/L. The detection concentration was 0.45 µg/L and the minimum quantitative concentration was 1.49 µg/L. The relative standard deviations (RSD) were 0.3%~1.7%. The recovery was between 91.0% and 103.4%. The precision of the major lead isotope ratios was better than 0.3%. The calibrated isotope ratios of the standard liquid are close to the certificate. Conclusion: The method has a low detection limit, good precision and high accuracy, it is feasible for determination of lead concentration and isotope ratios in the bloune.

[Relationship between clopidogrel resistance and genetic variability in Kawasaki disease children with coronary artery lesions].

Objective: To analyze the distribution of clopidogrel metabolism-related gene variability in Kawasaki disease (KD) children with coronary artery lesions (CAL) across different age groups and the impact of genetic variability on the efficacy of clopidogrel antiplatelet therapy. Methods: A retrospective cohort study was conducted. Clinical data were collected from 46 KD children with CAL who were hospitalized in the Cardiovascular Center of Children's Hospital of Fudan University between January 2021 and August 2022 and were treated with clopidogrel, including gender, age, body mass index, course of KD, CAL severity grade, and baseline platelet count. According to their age, the children were divided into ≥2-year-old group and <2-year-old group. Their platelet responsiveness was assessed by adenosine diphosphate-induced platelet inhibition rate (ADPi) calculated via thromboelastography, and children were categorized into high on-treatment platelet reactivity (HTPR) and normal on-treatment platelet reactivity (NTPR) groups. Genotypes of CYP2C19, PON1 and ABCB1 were detected. The t test, one-way analysis of variance and Chi-square test were used for intergroup comparison. Results: Among the 46 KD children with CAL, 34 were male and 12 were female; 37 were ≥2-year-old and 9 were <2-year-old; 25 cases were in the HTPR group and 21 cases were in the NTPR group, with 19 HTPR and 18 NTPR in the ≥2-year-old group, and 6 HTPR and 3 NTPR in the <2-year-old group. Genetic analysis showed that 92 alleles among the 46 children, with frequencies of CYP2C19*1, CYP2C19*2, CYP2C19*3, CYP2C19*17, PON1 192Q, PON1 192R, ABCB1 3435C, ABCB1 3435T at 59% (54/92), 32% (29/92), 9% (8/92), 1% (1/92), 36% (36/92), 64% (59/92), 63% (58/92) and 37% (34/92), respectively. Analysis of the impact of genotype on ADPi revealed that in children aged ≥2 years, those with CYP2C19*1/*3 genotype had significantly lower ADPi than those with CYP2C19*1/*1 genotype ((34±15)% vs. (61±29)%, t=2.18, P=0.036). There were also no significant difference in ADPi among children with PON1 192Q homozygous, PON1 192R heterozygote and PON1 192R homozygous genotypes ((40±22)% vs. (52±33)% vs. (65±27)%, F=2.17, P=0.130), or among those with ABCB1 3435C homozygous, ABCB1 3435T heterozygote and ABCB1 3435T homozygous genotypes ((55±34)% vs. (60±27)% vs. (49±24)%, F=0.33, P=0.719). In <2-year-old group, there were no significant differences in ADPi across CYP2C19*1/*1, CYP2C19*1/*2 and CYP2C19*2*2 genotypes ((40±20)% vs. (53±37)% vs. (34±16)%, F=0.37, P>0.05). There were no significant differences in ADPi across CYP2C19*1/*1 and CYP2C19*1/*3 genotypes ((44±27)% vs. (42±20)%, t=0.08, P>0.05). There were no significant differences in ADPi across PON1 192Q homozygous, PON1 192R heterozygote and PON1 192R homozygous genotypes (45% vs. (55±27)% vs. (24±5)%, F=1.83, P>0.05). There were no significant differences in ADPi across ABCB1 3435C homozygous, ABCB1 3435T heterozygote and ABCB1 3435T homozygous genotypes ((36±16)% vs. (50±35)% vs. 45%, F=0.29, P>0.05). The risk analysis of HTPR in different genotypes revealed that in children aged ≥2 years, carrying at least 1 or 2 loss-of-function alleles of CYP2C19 was a risk factor for HTPR (OR=4.69, 10.00, 95%CI 1.11-19.83, 0.84-119.32, P=0.033, 0.046, respectively), and PON1 192R homozygosity and carrying at least one PON1 192R allele were protective factors against HTPR (OR=0.08, 0.13, 95%CI 0.01-0.86, 0.01-1.19, P=0.019, 0.043, respectively). Conclusion: KD children aged ≥2 years carrying CYP2C19 loss-of-function alleles and PON1 192Q are more likely to develop HTPR.

Nano-TiO2 particles inhibit the biological behavior and mineralization of bone marrow mesenchymal stem cells transfected with CXCR4.

OBJECTIVE: Bone marrow mesenchymal stem cells (BMSC) are widely used as experimental cells with potential differentiation function. Nanomaterials are currently a research hotspot. We assessed nano-TiO2 particles' effect on the biological behavior and mineralization of CXCR4 transfected BMSCs. PATIENTS AND METHODS: After transfection of BMSC with CXCR4, cells were divided into blank group (no transfection), control group (transfection with CXCR4) and observe group (transfection with CXCR4 containing nanoparticles). Then, cell proliferation and ALP staining were measured along with analysis of Runx2 and BGP level by Western blot or RT-PCR and mineralization detection. RESULTS: With increased culture time, the observed fractionation on day 14 showed significantly reduced activity; 3 mn nano-TiO2 particles significantly inhibited cell proliferation and bone formation after CXCR4 transfection with an inhibitory effect on the osteogenic ability of CXCR4-transfected BMCS cells in a time-dependent manner. The longer the culture time, the more significantly inhibitory effect; 3 mn nano-TiO2 particles can inhibit the mineralization of BMSCs after transfection of CXCR4 to a certain extent. CONCLUSIONS: TiO2 nanoparticles have an inhibitory effect on the biological behavior and mineralization of BMSC cells transfected with CXCR4. The longer the culture time, the greater the inhibitory effect on osteogenic differentiation of BMSC cells transfected with CXCR4.

Changes of anti-ß2 glycoprotein I antibody IgA/G/M, platelet aggregation rate, plasma fibrinogen and d-dimer in guiding venous thrombosis during pregnancy.

OBJECTIVE: This study provides a theoretical basis for the prevention, treatment and diagnosis of venous thrombosis during pregnancy. PATIENTS AND METHODS: Sixty patients with venous thrombosis in gestation period were treated as the research group, including every 30 people in the middle and late pregnancy groups, and the control group randomly selected 33 healthy pregnant women during the same period. The anti-ß2 glycoprotein I antibody IgA/G/M, platelet aggregation rate, plasma fibrinogen, and D-dimer levels were measured in all subjects. RESULTS: Resistance-ß2 glycoprotein I antibody IgA/G/M, platelet aggregation rate, plasma fibrinogen, and compared with the control group, D-dimer levels were significantly increased (p<0.05), but for the middle pregnancy group and late pregnancy group, the difference was not statistically significant (p>0.05). In the control group of pregnant women anti-ß2 glycoprotein Ⅰ antibody IgA/G/M, platelet aggregation rate, plasma fibrinogen, and D-dimer no obvious correlation (p>0.05), Anti-ß2 glycoprotein Ⅰ antibody IgA/G/M, platelet aggregation rate, plasma fibrinogen, D-dimer entry equation are closely related risk factors for venous thrombosis during pregnancy (p<0.05), and D-dimer is the most important. CONCLUSIONS: Vein thrombosis during pregnancy patients anti-ß2 glycoprotein I antibody IgA/G/M, platelet aggregation rate, plasma fibrinogen, and D-dimer in pregnant women group increased significantly compared with the control group, suggesting these above indicators are closely related to Venous thrombosis in pregnant women and associated with the severity of the disease. Vascular endothelial injury plays an important role in phlebothrombosis in gestation period.

MiR-24 inhibits oligodendrocyte precursor cell differentiation after spinal injury by targeting adrenal medulla.

OBJECTIVE: Oligodendrocyte precursor cells (OPCs) differentiate into oligodendrocytes (OLs) that provide nutrients to neurons. Adrenal medulla is (ADM) involved in nerve damage. MiR-24 participates in various diseases. However, the regulation and mechanism of miR-24 in oligodendrocyte precursor cell differentiation after spinal injury is unclear. MATERIALS  AND METHODS: Wistar rats were divided into sham operation group and model group. Real Time-PCR detects miR-24, PDGFRa and NG2 and MBP expression. OPC cells were cultured and divided into control group, miR-24 group, and si-miR-24 group followed by analysis of miR-24 expression by Real Time-PCR, expression of PDGFRa, NG2 and MBP by Western blot, as well as ADM content and secretion of IL-6 and TNF-α by enzyme-linked immunosorbent assay (ELISA). RESULTS: Expression of miR-24, PDGFRa, and NG2 was increased in the model group and MBP and ADM expression was decreased with increased secretion of IL-6 and TNF-α. Compared with control group, the difference was statistically significant (p<0.05). Upregulation of miR-24 promoted the expression of PDGFRa and NG2, decreased MBP and ADM level, and increased IL-6 and TNF-α secretion. Compared with control group, the difference was statistically significant (p<0.05). Downregulation of miR-24 reversed the above changes, and the difference was statistically significant (p<0.05). CONCLUSIONS: MiR-24 expression is increased in spinal injury. Upregulation of miR-24 expression reduces adrenal medulla expression and inhibits oligodendrocyte precursor cell differentiation.

MiR-99a suppresses cell migration and invasion by regulating IGF1R in gastric cancer.

OBJECTIVE: Gastric cancer is a common kind of gastrointestinal malignancies. Increasing evidence indicates dysregulation of microRNA-99a (miR-99a) in gastric cancer, and has been extensively investigated in terms of cancer formation, progression, diagnosis, therapy, and prognosis. The purpose of this study is to explore how miR-99a worked in gastric cancer on migration and invasion. PATIENTS AND METHODS: The mRNA and protein levels of miR-99a and insulin-like growth factor 1 receptor (IGF1R) in gastric cancer were measured by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. Transwell assay was employed to analyze the migratory and invasive capacities. The Dual-Luciferase reporter assay was performed to confirm miR-99a mediated the expression of IGF1R by directly targeting its mRNA 3'-untranslated regions (3'-UTR) in gastric cancer cells. RESULTS: MiR-99a was discovered to be significantly downregulated while IGF1R was upregulated in gastric cancer tissues and cell lines. The expression of miR-99a had a negative correlation with the IGF1R expression in gastric cancer tissues. Moreover, miR-99a was low expressed in gastric cancer cells HGC-27 and MGC-803 compared to the normal cell line. MiR-99a suppressed the migration and invasion through directly binding to the 3'-UTR of IGF1R mRNA in HGC-27 cells. In addition, IGF1R could reverse partial roles of miR-99a on migration and invasion in gastric cancer. CONCLUSIONS: MiR-99a inhibited the migratory and invasive abilities by regulating the expression of IGF1R. MiR-99a was downregulated while IGF1R was upregulated in gastric cancer cell lines. The newly identified miR-99a/IGF1R axis provides novel insight into the pathogenesis of gastric cancer.

Investigation of PD-1H in DEN-induced mouse liver cancer model.

OBJECTIVE: Immune therapy has recently become a novel strategy for treating liver cancer, making it of critical importance to identify novel targets for treatment. Programmed death-1 homology (PD-1H) is one newly discovered negative co-stimulating molecule, and plays important regulatory roles in suppressing T cell activation. However, the expression or function of PD-1H in liver tumors has not been reported. MATERIALS AND METHODS: Liver cancer tissues were collected from The Cancer Genome Atlas (TCGA) (http://tcga-data.nci-nih.gov). This study then utilized diethylnitrosamine (DEN) induced liver cancer mice, on which PD-1H monoclonal antibody and PD-1H extra-cellular Fc domain fusion protein were injected intraperitoneal. General status, gross morphology of liver tissues was examined, followed by hematoxylin-eosin (HE) staining and plotting survival curve. RESULTS: Among TCGA samples, PD-1H expression was significantly elevated. Induced liver cancer mice showed depressed mental status, early onset of hepatitis and liver cirrhosis. Five mice dead in model group (mortality=33.33%). No natural death occurred in control group. Injection of PD-1H-Fc-Ig fusion and PD-1H monoclonal antibody improved the condition to certain extents, with morality at about 20%. Comparing to DEN group, combined treatment group showed significantly fewer tumor lesion on liver surface, with increased body weight and lower liver-body weight ratio. HE staining showed significantly elevated ratio of normal cells in combined treatment group, although large amounts of cancer cells still existed. CONCLUSIONS: Blocking of PD-1H signal pathway could suppress liver cancer cell growth, decrease mouse mortality, indicating promising application of PD-1H in tumor immune therapy.

Brain sensorimotor system atrophy during the early stage of spinal cord injury in humans.

Spinal cord injury (SCI) usually leads to severe sensory and motor deficits below the spinal lesion. Previous animal models have shown significant atrophic changes in the neural sensorimotor system following SCI. However, specific anatomical changes in the human brain following SCI remain poorly understood. The purpose of the present study was to investigate structural changes during the early stage of SCI, and to investigate further the association between the structural changes and patients' sensorimotor functions. The study participants included 20 patients with SCI and 30 matched healthy controls. The mean period post-SCI was 8.9±2.7weeks (range 4-12weeks). Voxel-based morphometry was used to investigate the regions with gray and white matter volume changes. Compared to healthy controls, patients with SCI showed significant gray matter atrophy in the primary motor cortex (M1), primary somatosensory cortex (S1), supplementary motor area (SMA), and thalamus, as well as white matter atrophy in the corticospinal tracts at the level of the bilateral cerebral peduncles. In addition, gray matter volume in the primary motor cortex was positively correlated with the total American Spinal Injury Association motor score in patients with SCI. In conclusion, our findings suggest that SCI causes significant anatomical changes in the human sensorimotor system, and that these anatomical changes may occur in the early phase of SCI. Future treatments that aim to restore sensorimotor functions following SCI need to attend to these anatomical changes in the brain.

A laser-Compton scattering prototype experiment at 100 MeV linac of Shanghai Institute of Applied Physics.

As a prototype of the Shanghai Laser Electron Gamma Source in the Shanghai Synchrotron Radiation Facility, an x-ray source based on laser-Compton scattering (LCS) has been installed at the terminal of the 100 MeV linac of the Shanghai Institute of Applied Physics. LCS x-rays are generated by interactions between Q-switched Nd:yttrium aluminum garnet laser pulses [with wavelength of 1064 nm and pulse width of 21 ns (full width at half maximum)] and electron bunches [with energy of 108 MeV and pulse width of 0.95 ns (rms)] at an angle of 42 degrees between laser and electron beam. In order to measure the energy spectrum of LCS x-rays, a Si(Li) detector along the electron beam line axis is positioned at 9.8 m away from a LCS chamber. After background subtraction, the LCS x-ray spectrum with the peak energy of 29.1+/-4.4|(stat)+/-2.1|(syst) keV and the peak width (rms) of 7.8+/-2.8|(stat)+/-0.4|(syst) keV is observed. Normally the 100 MeV linac operates with the electron macropulse charge of 1.0 nC/pulse, and the electron and laser collision repetition rate of 20 Hz. Therefore, the total LCS x-ray flux of (5.2+/-2.0) x 10(2) Hz can be achieved.