[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.

[Retrospective analysis of infliximab in the treatment of Kawasaki disease].

Objective: To investigate the efficacy and safety of infliximab (IFX) therapy for children with Kawasaki disease. Methods: Sixty-eight children with Kawasaki disease who received IFX therapy in Children's Hospital of Fudan University from January 2014 to April 2021 were enrolled. The indications for IFX administration, changes in laboratory parameters before and after IFX administration, response rate, drug adverse events and complications and outcomes of coronary artery aneurysms (CAA) were retrospectively analyzed. Comparisons between groups were performed with unpaired Student t test or Mann-Whitney U test or chi-square test. Results: Among 68 children with Kawasaki disease, 52 (76%) were males and 16 (24%) were females. The age of onset was 2.1 (0.5, 3.8) years. IFX was administered to: (1) 35 children (51%) with persistent fever who did not respond to intravenous immunoglobulin (IVIG) or steroids, 28 of the 35 children (80%) developed CAA before IFX therapy; (2) 32 children (47%) with continuous progression of CAA; (3) 1 child with persistent arthritis. In all cases, IFX was administered as an additional treatment (the time from the onset of illness to IFX therapy was 21 (15, 30) days) which consisted of second line therapy in 20 (29%), third line therapy in 20 (29%), and fourth (or more) line therapy in 28 (41%). C-reactive protein (8 (4, 15) vs. 16 (8, 43) mg/L, Z=-3.38, P=0.001), serum amyloid protein A (17 (10, 42) vs. 88 (11, 327) mg/L, Z=-2.36, P=0.018) and the percentage of neutrophils (0.39±0.20 vs. 0.49±0.21, t=2.63, P=0.010) decreased significantly after IFX administration. Fourteen children (21%) did not respond to IFX and received additional therapies mainly including steroids and cyclophosphamide. There was no significant difference in gender, age at IFX administration, time from the onset of illness to IFX administration, the maximum coronary Z value before IFX administration, and the incidence of systemic aneurysms between IFX-sensitive group and IFX-resistant group (all P>0.05). Infections occurred in 11 cases (16%) after IFX administration, including respiratory tract, digestive tract, urinary tract, skin and oral infections. One case had Calmette-Guérin bacillus-related adverse reactions 2 months after IFX administration. All of these adverse events were cured successfully. One child died of CAA rupture, 6 children were lost to follow up, the remaining 61 children were followed up for 6 (4, 15) months. No CAA occurred in 7 children before and after IFX treatment, while CAA occurred in 54 children before IFX treatment. CAA regressed in 23 (43%) children at the last follow-up, and the diameter of coronary artery recovered to normal in 10 children. Conclusion: IFX is an effective and safe therapeutic choice for children with Kawasaki disease who are refractory to IVIG or steroids therapy or with continuous progression of CAA.

The synergistic effect of palmitic acid and glucose on inducing endoplasmic reticulum stress-associated apoptosis in rat Schwann cells.

OBJECTIVE: Diabetic peripheral neuropathy (DPN) is a common long-term complication of diabetes mellitus accompanied with hyperglycemia and hyperlipidemia. Both high blood glucose and high blood lipids are key pathogenies for DPN. This research aims to investigate whether the combination of glucose (Glu) and palmitic acid (PA) played a synergistic role in the pathogenesis of DPN. MATERIALS AND METHODS: The proliferation rate of Rat Schwann cell line RSC96 cells stimulated by different concentrations of Glu and PA were analyzed by CCK-8 assay. After the IC50 was detected for each drug, the RSC96 cells were divided into control, Glu, Glu+PA, PA, and BSA groups. The apoptosis of RSC96 cells in different groups were detected by flow cytometry. The effects of Glu and/or PA on endoplasmic reticulum (ER) stress-associated apoptotic signaling pathways were determined by Western blot and qPCR. RESULTS: Both Glu and PA showed similar inhibition on the proliferation of RSC96 cells in a dose-dependent manner. However, PA induced stronger apoptosis of RSC96 cells than glucose and significantly increased the levels of X-box-binding protein-1 (XBP1), C/EBP homologous protein (CHOP), and eIF2α phosphorylation, which are key proteins regulating endoplasmic reticulum (ER) stress-associated apoptotic signaling pathways. The combination of Glu and PA induced the strongest apoptosis in RSC96 cells and also activated ER stress-associated apoptotic signaling pathways. These results verified the synergistic effect of Glu and PA on inducing ER stress-associated apoptosis in RSC96 cells, and PA even induced stronger apoptosis in RSC96 cells than Glu. CONCLUSIONS: The present research indicated that hyperglycemia and hyperlipidemia might exert a synergistic damage during the pathogenesis of DPN, suggesting that blood lipid control is as important as blood glucose control for DPN patients.

[The epidemiology of myopia in primary school students of grade 1 to 3 in Hubei province].

Objective: To investigates the visual condition and myopia status in primary school students of grade 1 to 3 in Hubei province and to further analyze the influencing factors of myopia, so as to provide theoretical basis for prevention and control of myopia. Method: Cross-sectional study. A total of 18 532 primary school students from grade 1-3 in 26 primary schools from 17 prefecture-level cities in Hubei province were included in the study from March 2017 to July 2017, by using a random stratified cluster sampling method. In this study, 16 955 people were actually surveyed, with a response rate of 91.49%. All students' Visual acuity was measured, a further retinoscopy refraction test after application of Cyclopentolate Hydrochloride Eye Drops was conducted for those whose visual acuity was less than 5.0. The general situation and eye behavior of all students were investigated by questionnaires. Chi-square test was used to compare the prevalence of myopia between different grades, different regions and different genders, as well as the distribution of myopia correlation between different regions, and Logistic regression model was used to analyze the correlation between myopia and related factors. Results: The prevalence of myopia among primary school students of grade 1 to 3 in Hubei province is 24.15% with 12.67% in the first grade, 24.91% in the second grade, 34.95% in the third grade, and the difference was statistically significant (χ(2)=862.28, P<0.05). According to the study, mild myopia is the most prevailing condition among myopia students, with the prevalence rate of mild myopia, moderate myopia and severe myopia being 19.21%,4.29%, and 0.64% respectively, and the difference is statistically significant (χ(2)=155.62, P<0.05). In addition, the prevalence of myopia is different in each region, which was highest in provincial capitals, followed by non-provincial cities, and the lowest in rural areas, with statistically significant difference (χ(2)=539.57, P<0.05). Myopia is generally related to multiple factors, such as the grade, parents' myopia, outdoor activities, continuous closing reading, exposure to electronic products, and extracurricular reading time are related to myopia (P<0.05). Conclusions: Children's myopia is a public health problem that should not be ignored. The prevalence of myopia among 1-3 grade pupils is 24.15% with an increasing tendency with grade. The occurrence of myopia is related to heredity and eye behavior. (Chin J Ophthalmol, 2018, 54:756-761).

Baicalin inhibits Escherichia coli isolates in bovine mastitic milk and reduces antimicrobial resistance.

In this study, we aimed to evaluate the inhibitory effect of baicalin on Escherichia coli in vitro and the effects of baicalin treatment on antimicrobial resistance of the E. coli isolates. Through isolation, purification, and identification, a total of 56 E. coli strains were isolated from 341 mastitic milk samples. The study of inhibition effect of baicalin on the E. coli strains in vitro was focused on permeability and morphology of the isolates using an alkaline phosphatase kit and scanning electron microscopy. Furthermore, the resistance spectrum of the isolates to the common antimicrobial agents was tested at sub-minimum inhibitory concentrations of baicalin by the agar dilution method. Extended-spectrum ß-lactamase and plasmid-mediated quinolone resistance genes were amplified by PCR before and after incubation with baicalin. The results revealed that baicalin has certain inhibitory effects on the isolates in vitro. The alkaline phosphatase enzyme activity was significantly increased from 1.246 to 2.377 U/100 mL, and the surface of E. coli was concave and shriveled. Analysis of the resistance spectrum and PCR amplification showed that, after administration with baicalin, the sensitivity of most strains to the selected antimicrobial agents was enhanced. Strikingly, the drug-resistant genes from 71.43% (40/56) of these isolates were found to have drug-resistant genes to different extents. Altogether, the current study confirmed both the inhibitory effect on Escherichia coli in vitro and the reduction of antimicrobial resistance by baicalin. This is the first comprehensive study to report on baicalin, a traditional Chinese medicine that acts on E. coli isolated from the mastitic milk samples.

New two-dimensional global longitudinal strain and strain rate imaging for assessment of systemic right ventricular function.

OBJECTIVES: To determine the usefulness of new two-dimensional strain indices, based on speckle tracking imaging, for assessment of systemic right ventricular (RV) function after an atrial switch operation for transposition of the great arteries. DESIGN: Cross-sectional study. SETTING: Tertiary paediatric cardiac centre. METHODS: 26 patients, mean (SD) age 21.0 (3.6) years at 19.9 (3.2) years after an atrial switch operation, and 27 age-matched controls were studied. Two-dimensional imaging at the four-chamber view was obtained with tracing of the entire RV endocardial border. The RV global longitudinal strain (GLS) and GLS rate were derived using automated software (EchoPAC, GE Medical) and correlated with tissue Doppler-derived RV isovolumic acceleration (IVA), and, in the patient cohort, with cardiac magnetic resonance-derived RV ejection fraction. RESULTS: Intra- and interobserver variability for measurement of GLS, as determined from the mean (SD) of differences in two consecutive results from 20 studies, were 0.06 (1.39)% and 0.24 (1.77)%, respectively. Compared with controls, patients had lower RV GLS (17.1 (1.9)% vs 26.3 (2.9)%, p<0.001), a reduced GLS rate (0.78 (0.11)/s vs 1.33 (0.23)/s, p<0.001), lower RV IVA (1.10 (0.36) m/s(2) vs 1.56 (0.53) m/s(2), p<0.001) and increased RV myocardial performance index (0.52 (0.09) vs 0.38 (0.09), p<0.001). Both RV GLS and GLS rate correlated positively with RV IVA (r = 0.43, p = 0.001 and r = 0.46, p<0.001, respectively), and negatively with RV myocardial performance index (r = -0.65, p<0.001 and r = -0.57, p<0.001, respectively). In patients, the GLS rate correlated positively with RV ejection fraction (r = 0.62, p = 0.001). CONCLUSIONS: Two-dimensional RV GLS and GLS rate are new, potentially useful indices for assessment of systemic RV function.

[Effect of xianzhen tablet on Na(+)-K(+)-ATPase, Ca(2+)-Mg(2+)-ATPase, of red blood cell membrane in patients with non-insulin dependent diabetes mellitus].

OBJECTIVE: To assess the effect of Xianzhen tablet in treating non-insulin dependent diabetes mellitus (NIDDM). METHODS: Seventy-two cases of NIDDM patients with deficiency of both Qi and Yin, deficiency of the Kidney and blood stasis were selected, and the effects of treatment on Na(+)-K(+)-ATPase, Ca(2+)-Mg(2+)-ATPase, whole blood viscosity, blood sugar and clinical symptoms were observed. RESULTS: After treatment, the treated group showed increased activities that were statistically significant of Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase (P < 0.01, P < 0.02). The whole blood viscosity and symptoms showed improvement to an extent and the total effective rate of blood sugar lowering were as follows: fasting blood glucose (FBG) 77.8%, 2hr. postprandial plasma blood glucose (2hr. postprandial PBG)69.4%. Whereas, the placebo group showed no marked improvement in either whole blood viscosity or symptoms and the total effective rate of blood sugar lowering were FBG 41.7%, 2hr. postprandial PBG 38.9%. CONCLUSION: Xianzhen tablet is effective in improving the activities of Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase, as well as the whole blood viscosity, blood sugar lowering and in improving clinical symptoms, it could treat effectively NIDDM patients with deficiency of both Qi and Yin, deficiency of the Kidney and blood stasis.

[Study on relationship of lipid peroxide in coronary heart disease with and without diabetes].

Activity of erythrocyte superoxide dismutase (RBC-SOD), levels of serum malondialdehyde (MDA), plasma 6-keto-prostaglandin F 1 alpha (6-keto-PGF 1 alpha) and thromboxane B2(TXB2) were measured in 30 healthy subjects and 57 coronary heart desease (CHD) patients inoluding 21 cases complicated with diabetes and 36 without. Their characteristics of Syndrome Differentiation and typing were observed. The results showed that the activity of RBC-SOD, 6-keto-PGF 1 alpha in CHD patients were significantly lower than those in the healthy subjects, but the levels of TXB2, MDA were significantly higher. The levels of TXB2 in CHD patients with diabetes were significantly higher than tose without, but the activity of RBC-SOD were significantly lower. There were remarkably positive correlations between the levels of serum MDA and that of blood sugar, TXB2, TG and BMI in CHD patients with diabetes. There were remarkably negative correlations between the levels of serum MDA and plasma 6-keto-PGF 1 alpha. The results suggested that the metabolic abnormality of lipoperoxides was more serious in CHD patients with diabetes than without. The main Syndrome of CHD with diabetes was Qi-Yin Deficiency with Blood Stasis, while that of without diabetes was Qi Deficiency with Blood Stasis.

[Effect of jiangzhi zhongyao pian on serum lipid and antioxidation of hyperlipemic patients].

62 cases of hyperlipemic patients were divided into 2 groups, 31 treated with Chinese herbal medicine Jiangzhi Zhongyao Pian (JZZYP) and the control group (31 cases) treated with placebo. Serum lipid, RBC-superoxide dismutase (RBC-SOD), and MDA were observed before and after 2 months treatment. Result showed that total cholesterol (TC), triglyceride (TG), atherogenic index (AI) and malondialdehyde (MDA) of test group were apparently dropped and high density lipid-cholesterol (HDL-C), RBC-SOD activity obviously elevated after treatment, the difference between two groups was significant (P < 0.05-0.001). The total effective rate of JZZYP on TC was 68.8%, that on TG was 86.7%. The results suggested that JZZYP has the effect of serum lipid regulation, antioxidase activity elevation and lipid peroxide inhibition. JZZYP had no side effect.

[Clinical and experimental study on effect of jin-qi-jiang-tang-pian on qi-yin deficiency and hyperactivity of diabetes mellitus].

The purpose of this study was to verify the effect of Jin-Qi-Jiang-Tang-Pian (JQJTP) on fasting blood glucose (FBG), postcibal blood glucose (PBG), total cholesterol (TC), triglycerides (TG), acetylcholine esterase (AchE), insulin, RBC-superoxide dismutase (RBC-SOD) and malondialdehyde (MDA). Efficacy was observed in 40 cases of diabetes mellitus, 20 cases administered with Yu-Quan Pian (YQP) were taken as control. Each group took drugs for two months. After treatment with Jin-Pi-Jiang-Tang-Pian, FBG, PBG, AchE were apparently dropped and RBC-SOD increased, as compared with patients of the YQP group (P < 0.05-0.01), and major symptoms of diabetes were improved. In experimental study, model rats suffering from diabetes induced by alloxan were observed, the rats' blood sugar level above 11.1 mmol/L were chosen for observation. These rats were divided into JQJTP group, YQP group and control group. It was found that JQJTP was able to lower blood sugar, TG and MDA (P < 0.05-0.001) significantly, with a increase of the SOD/MDA, as compared with those of patients of the control groups.

[Effect of jiang-zhi zhong-yao-pian on total cholesterol, triglyceride, TXB2, 6-keto-PGF1 alpha in hyperlipemic patients].

The purpose of this study was to verify the effect of a Chinese herbal medicine Jiang-Zhi Zhong-Yao-Pian to reduce serum lipoid. Efficacy was observed in 30 cases of hyperlipemia; 20 cases administered with evening primose oil capsules were taken as controls. Each group took drugs for two or three months. The results were as follows: After treatment as compared with before treatment, the serum levels of TC, TG and TXB2 dropped from 264.28 +/- 70.52 mg%, 393.52 +/- 250.42 mg% and 110.75 +/- 43.52 pg/ml to 225.60 +/- 50.93 mg%, 264.97 +/- 252.81 mg% and 88.82 +/- 46.50 pg/ml respectively (P less than 0.001, less than 0.01, less than 0.05). However, in the group taking evening primrose oil capsules, TC, TG and TXB2 in comparing with the pre-treatment levels were changed from 251.33 +/- 58.24 mg%, 316.35 +/- 104.93 mg% and 131.53 +/- 49.77 pg/ml to 244.30 +/- 43.28 mg%, 272.10 +/- 92.52 mg% and 115.33 +/- 47.49 pg/ml respectively (P greater than 0.05, less than 0.05, greater than 0.05). This medicine had no side-effect. The results showed that the herbal formula might be useful to reduce serum TC, TG and TXB2.

[Effect of "Yiqi yangyin huoxue" prescription on hemorrheology of diabetics with symptoms of "qi, yin" deficiency and stasis of blood].

Hemorrheologic tests were studied in 68 cases of diabetes with symptoms of deficiency of both Qi and Yin and blood stasis. The results showed that whole blood viscosity, plasma viscosity, hematocrit and RBC filterability in diabetics were significantly higher than in normal controls, except for hematocrit in male patients. After treatment with "Yiqi Yangyin Huoxue" prescription by Prof. Zhu Shenyu, whole blood viscosity (at shear rates of 3.83 s-1, 38.3 s-1, 192 s-1), plasma viscosity, hematocrit and RBC filterability were apparently improved, with a decrease of fasting blood sugar, as compared with patients of the placebo group.

Effects of Chinese medicinal herbs on hemorheology in diabetics.

There was a statistically significant increase in whole blood viscosity, plasma viscosity, erythrocyte filterability index and hematocrit in diabetics with "Qi Yin deficiency and blood stasis" syndrome. After treatment with "Yi Qi Yang Yin Hou Xue" prescription there was a statistically significant improvement in hemorheological properties and a slight decrease in fasting blood glucose.

Ultrafast noncollinear second-harmonic-generation-based 4 x 4 optical switching array.

A noncollinear second-harmonic-generation-based 4 x 4 switchable computational array is experimentally demonstrated. Picosecond binary scalar and vector-matrix multiplication results are presented.

Compact picosecond Nd:glass mode-locked laser with variable cavity length from 5 to 21 m.

The design, performance, and characteristics of a compact mode-locked laser with effective cavity length from 5 to 21 m is described. The overall size of the laser is 1.7 m. Pulse-to-pulse spacing of ~35-140 ns is obtained. The laser parameters of energy, number of pulses, length of train, and stability of the cavity are described. The stability zone for the cavity is calculated using the matrix method. The pulse duration was measured to be 10 ps for the early pulses in the train using a streak camera system.