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.

Objective:To study the effects of Zuogui Pills on the expressions of miR-133b-3p and RhoA in osteoclasts of postmenopausal osteoporosis rats; To discuss its potential mechanism.Methods:SD female rats were randomly divided into normal group, model group, sham-operation group, and Zuogui Pills group using a random number table method, with 6 rats in each group. The model group and Zuogui Pills group were treated with oophorectomy to construct a rat model of osteoporosis. Zuogui Pills group was orally administered with Zuogui Pills decoction at a concentration of 10 g/kg for 12 consecutive weeks. Colorimetric method was used to measure the serum calcium and phosphorus levels of rats, and ELISA method was used to detect ALP levels. Bone density meter was used to measure the bone density of the femurs of rats in each group. The osteoclast of each group were cultured, and the expressions of RANKL and RUNX2 protein were detected by Western blot. MiRNA sequencing and differential expression analysis were performed on bone tissues of rats. Osteoclasts were treated with miR-133b-3p mimic and its negative control. The cell proliferation activity of osteoclasts was detected by cell counting kit-8 (CCK-8). The osteoclast differentiation activity was detected by the tartrate-resistant acid phosphatase staining. The dual-luciferase reporter assay was used to detect the relationship between miR-133b-3p and RhoA. The "rescue" experiment of miR-133b-3p mimic and RhoA co-expression were used to study the molecular regulatory mechanism of Zuogui Pills on osteoclast activity.Results:Compared with the model group, the bone mineral density of Zuogui Pills group significantly increased ( P<0.05, P<0.01), the levels of calcium and phosphorus in serum increased, the level of alkaline phosphatase ALP decreased ( P<0.05), the expression of RANKL protein decreased, and the expression of RUNX2 protein increased. Sequencing results showed that rno-miR-133b-3p was down-regulated in osteoclasts of postmenopausa osteoporosis rats treated with Zuogui Pills with the maximum difference ( P<0.01). Q-PCR results showed that the expression of miR-133b-3p in osteoclasts of Zuogui Pills group was significantly lower than that of the model group. The upregulation of miR-133b-3p could significantly promote the cell proliferation and differentiation of osteoclasts. RhoA overexpression could reverse the excessive proliferation and differentiation of osteoclasts caused by miR-133b-3p overexpression. Conclusions:RhoA is the target gene regulated by miR-133b-3p. Zuogui Pills can inhibit the activity of osteoclasts by regulating miR-133b-3p/RhoA axis, relieving the symptoms of osteoporosis.

South Africa is an ethnically and culturally diverse presidential republic country. The medical and health system consists of public and private medical care. AIDS, lower respiratory infections, neonatal diseases, and interpersonal violence and road injuries are the leading causes of adult death. South Africa has rich herbal resources, and a long history of traditional medicine, which is mainly black African traditional medicine. Until the establishment of diplomatic relations between China and South Africa in 1998, the development of TCM was significantly improved, and legislation of TCM was adopted by the government in 2000. Chinese herbal medicine has not yet formed industrial standardization, the TCM application and TCM education are insufficient. Therefore, it is suggested to accelerate the standardization of TCM, to strengthen the TCM education for professional TCM practitioners, and to form a large-scale, industrial and standardized development model. Only in these ways can TCM provide good medical services for residents in South African.

Objective: To explore the effect of insulin-like growth factor-Ⅰ (IGF-Ⅰ) receptor on radiosensitivity of HepG2 cells and the underlying mechanism. Methods: HepG2 cells were divided into the following groups: negative control group, siRNA group, irradiation group and combined group. HepG2 cells were transfected with IGF-Ⅰ receptor siRNA combined with irradiation therapy to investigate the effect on cell proliferation by methyl thiazolyl tetrazolium and cell cycle using flow cytometry. Expression of IGF-Ⅰ receptor, proliferating cell nuclear antigen (PCNA), cyclin-dependent kinases 1(CDK1) and Survivin were detected using Western blotting and Q-PCR. Results: The expression of IGF-Ⅰ receptor in HepG2 cells was decreased significantly after siRNA transfection compared with the control group. After the combinational therapy, cell viability was decreased significantly according with control group [(1.02±0.08) vs. (1.08± 0.10) vs. (0.60±0.07)]; In addition, cell cycle was arrested in G2/M[(20.3±0.3)% vs. (22.6±0.4)% vs. (34.7±0.5)%] and CDK1 expression was reduced significantly. The relative expression of Survivin in siRNA group was lower than negative control group, the difference was statistically significant (P<0.05). Conclusion Inhibition of IGF-Ⅰ receptor can enhance the radiosensitivity of HepG2 cells through cell cycle arrest.

With the promulgation of a series of laws and regulations in our country, the requirement for stand-ardized management of clinical research process are gradually clear, and higher requirements on the following-up review management of ethics committee also are put forward. Through concluding and summarizing 128 noncompli-ance/violation or protocol deviation reports accepted by a hospital in recent two years, this paper analyzed four main problems including that the researchers at management level failed to report or report timely; the researchers reported in irregular filling;the same type of violation/deviation program happened repeatedly and the rectification to the review opinions of ethics committee was ineffective, and also put forward the corresponding suggestions, in order to strengthen and perfect the standard management of noncompliance/violation or protocol deviation report.

Objective To study the clinical effect of treating mild and moderate hypertension in the elderly with flavored liuwei dihuang decoction.Methods From January 2016 to January 2017,120 cases of elderly patients of mild and moderate hypertension with the diagnosis and treatment in our hospital are divided into two groups, the control group was treated with nifedipine zyban, and the observation group was treated with flavored liuwei dihuang decoction;Record two groups of patients with various experiment data, make an analysis of the relevant data obtained and discuss the clinical effect of flavored liuwei dihuang decoction to treat the mild and moderate elderly hypertension.Results The clinical results of the treatment of observation group were better than that of the control group.The patients had fewer adverse reactions, and the differences between two groups were statistically significant (P< 0.05).Conclusion The treatment which using the flavored liuwei dihuang decoction in the mild and moderate elderly hypertension receives significant improvement in the clinical symptoms and little adverse reactions.It is worth using widely in clinical practice.

OBJECTIVE:To systematically review the efficacy and safety of different doses of canagliflozin in the treatment of type 2 diabetes,and provide evidence-based reference for the clinical treatment. METHODS:Retrieved from PubMed,Cochrane Library,Clinical Trails.gov,CJFD,Wangfang Database and VIP,randomized controlled trials (RCT) about different doses of canagliflozin in the treatment of type 2 diabetes were collected. Meta-analysis was performed by using Rev Man 5.3 software after data extract and quality evaluation by Cachrane 5.10. RESULTS:Totally 11 RCTs were enrolled,involving 5 399 patients. Results of Meta-analysis showed,canagliflozin 300 mg/d were superior to 100 mg/d in reducing HbA1c[MD=0.14,95%CI(0.09,0.19), P<0.001],FPG[MD=0.40,95%CI(0.20,0.61),P<0.001] and reduction rate of body mass[MD=0.69,95%CI(0.42,0.96),P<0.001],the differences were statistically significant;and there were no significant differences in the incidence of total adverse reac-tions [RR=0.97,95%CI(0.94,1.01),P=0.10],hypoglycemia [RR=1.02,95%CI(0.94,1.10),P=0.67],urinary tract infection[RR=0.96,95%CI (0.78,1.18),P=0.69] in 2 groups;There was significantly different of genital mycotic infection in 2 groups[RR=0.84,95%CI(0.70,1.00),P=0.04]. CONCLUSIONS:Canagliflozin 300 mg/d is better than 100 mg/d in controlling HbA1c,fasting blood glucose and body mass of patients with type 2 diabetes,and the genital mycotic infection should be attentioned.

OBJECTIVETo investigate the effects of nano-lead exposure on learning and memory and iron homeostasis in the brain of the offspring rats on postnatal day 21 (PND21) and postnatal day 42 (PND42).

METHODSTwenty adult pregnant female Sprague-Dawley rats were randomly divided into control group and nano-lead group. Rats in the nano-lead group were orally administrated 10 mg/kg nano-lead, while rats in the control group were administrated an equal volume of normal saline until PND21. On PND21, the offspring rats were weaned and given the same treatment as the pregnant rats until 42 days after birth. The learning and memory ability of offspring rats on PND21 and PND42 was evaluated by Morris water maze test. The hippocampus and cortex s amples of offspring rats on PND21 and PND42 were collected to determine iron and lead levels in the hippocampus and cortex by inductively coupled plasma-mass spectrometry. The distributions of iron in the hippocampus and cortex were observed by Perl's iron staining. The expression levels of ferritin, ferroportin 1 (FPN1), hephaestin (HP), and ceruloplasmin (CP) were measured by enzyme-linked immunosorbent assay.

RESULTSAfter nano-lead exposure, the iron content in the cortex of offspring rats on PND21 and PND42 in the nano-lead group was significantly higher than those in the control group (32.63 ± 6.03 µg/g vs 27.04 ± 5.82 µg/g, P<0.05; 46.20 ±10.60 µg/g vs 36.61 ± 10.2µg/g, P<0.05). The iron content in the hippocampus of offspring rats on PND42 in the nano-lead group was significantly higher than that in the control group (56.9 ± 4.37µg/g vs 37.71 ± 6.92µg/g, P<0.05). The Perl's staining showed massive iron deposition in the cortex and hippocampus in the nano-lead group. FPNl level in the cotfex of offspring rats on PND21 in the nano-lead group was significantly lower than that in the control group (3.64 ± 0.23 ng/g vs 4.99 ± 0.95 ng/g, P<0.05). FPN1 level in the hippocampus of offspring rats on PND42 in the nano-lead group was significantly lower than that in the control group (2.28 ± 0.51 ng/g vs 3.69 ± 0.69 ng/g, P<0.05). The escape latencies of offspring rats on PND21 and PND42 in the nano-lead group were longer than those in the control group (15.54 ± 2.89 s vs 9.01 ± 4.66 s; 6.16 ± 1.42 s vs 4.26 ± 1.51 s). The numbers of platform crossings of offspring rats on PND21 and PND42 in the nano- lead group were significantly lower than those in the control group (7.77 ± 2.16 times vs 11.2 ± 1.61 times, P<0.05; 8.12 ± 1.51 times vs 13.0 ± 2.21 times, P<0.05).

ONCLUSIONn Nano-lead exposure can result in iron homeostasis disorders in the hippocampus and cortex of offspring rats and affect their learning and memory ability.

Animals ; Cerebral Cortex ; drug effects ; metabolism ; Female ; Hippocampus ; drug effects ; metabolism ; Homeostasis ; Iron ; metabolism ; Lead ; toxicity ; Learning ; drug effects ; Maternal Exposure ; adverse effects ; Memory ; drug effects ; Pregnancy ; Rats ; Rats, Sprague-Dawley

BACKGROUND:Clinicaly, patients with constipation often have depression and depression is often associated with symptoms of constipation, but the mechanisms remain unclear. OBJECTIVE:To observe the relation between constipation and depression by establishing animal models. METHODS:A total of 60 specific-pathogen-free rats were divided randomly into three groups: normal group, chronic stress-induced depression model group and slow transit constipation model group. Slow transit constipation model was created by giving the solution of compound diphenoxlate 8 mg/kg daily, for 120 consecutive days. On day 100, chronic stress model rats were subjected to successive unforeseen stimulus for 21 days. Rats in the normal group were regularly housed. Fecal number, dry weight of feces and body weight were recorded once a week. After successful model establishment, fecal number, dry weight of feces, time of first dark stools defecation, sucrose preference, open-field behavior score and forced swim time were detected in each group, and statisticaly analyzed. RESULTS AND CONCLUSION:Fecal number was less in the chronic stress-induced depression model group than in the normal group (P = 0.00), and time of first dark stools defecation was longer (P = 0.00). Fecal number was more in the chronic stress-induced depression model group than in the slow transit constipation model group (P = 0.00), but time of first dark stools defecation was shorter (P = 0.00). No significant difference in fluid consumption, sucrose preference, horizontal and vertical scores of open-field test, and forced swim time was detected between slow transit constipation model group and normal group (P > 0.05). However, above indexes were higher in the slow transit constipation model group than in the chronic stress-induced depression model group (P < 0.01). Results verified that constipation was observed in chronic stress-induced rat model, but depression was not observed in slow transit constipation rat model, suggesting that depression can induce constipation, but constipation does not necessarily lead to depression.

Objective To investigate the effect of early intervention on general movements (GM) in preterm infants during fidgety movement. Methods 315 preterm infants during fidgety movement period were divided into intervention group (n=160) and control group (n= 155). The intervention group accepted very early intervention program consisted of hospital intervention and family intervention, and the control group accepted routine treatment and nursing. The incidences of different kinds of GMs were compared. Results There is no statistical difference (χ2=0.641, P=0.726) in writhing movement before intervention, and the fidgety movement presented more in the intervention group than in the control group (χ2=8.710, P=0.003), while the absence of fidgety movement was significantly fewer (χ2=5.685, P=0.017) after intervention. Conclusion Very early intervention can reduce the incidence of absence of fidgety movement and improve fidgety movement.