Objective To investigate the improvement effect and mechanism of marmesin on cognitive impairment in Alzheimer's disease(AD)mice.Methods Fifty mice were randomly divided into five groups:blank group,model group,low-and high-dose marmesin groups and donepezil(positive drug)group,with 10 mice in each group.After 21 days of continuous administration,except for the blank group,the mice in other groups were given intraperitoneal injection of scopolamine to establish the AD model.Network pharmacology was used to construct the protein-protein interaction(PPI)network of common targets of marmesin in the treatment of AD,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed to provide further research direction.The cognitive function of AD model mice was evaluated by Morris water maze,open field test and new object recognition test.Nissl staining was used to observe the damage of hippocampal neurons.The levels of acetylcholine(Ach),acetylcholine transferase(ChAT),acetylcholinesterase(AChE),reactive oxygen species(ROS),malondialdehyde(MDA)and catalase(CAT)in hippocampus of mice were detected by kit.The protein expression levels of interleukin 6(IL-6),interleukin 1β(IL-1 β),tumor necrosis factor α(TNF-α),nuclear factor E2-related factor 2(NRF2),silent information regulator homologous protein 3(SIRT3),Kelch-like ECH-associated protein 1(KEAP1),quinone oxidoreductase 1(NQO1)and heme oxygenase 1(HO-1)in hippocampus were detected by Western Blot.Results Compared with the model group,the latency of Morris water maze test was significantly shortened in the high-dose marmesin group,the time of entering the target area in the open field new object test and the movement distance in the central area of the open field were prolonged,the number of neurons in the hippocampal CA1 and CA3 regions was significantly increased,the levels of ChAT and Ach in the hippocampus were significantly increased,AChE level was significantly decreased,CAT level was significantly increased,ROS and MDA levels were significantly decreased,TNF-α expression level was decreased,SIRT3 and HO-1 expression levels were increased,and KE AP1 protein expression level was decreased,the differences being statistically significant(P＜0.05 or P＜0.01 or P＜0.001).Conclusion Marmesin can effectively improve the learning and memory impairment of AD mice,and its mechanism may be related to the activation of NRF2/SIRT3 signaling pathway,thereby alleviating oxidative stress level and neuroinflammation,and repairing cholinergic neuron function.

[ Abstract] Objective To study the effect of sulodexide on the repair of diabetic retinopathy and the regulation of MAPK pathway in rats. Methods Totally 72 rats were randomly divided into normal control group, diabetic retinopathy group, low, middle and high dose of sulodexide group and metformin hydrochloride group. Except normal control group, other rats were intraperitoneally injected with streptozotocin to establish the rat model of diabetic retinopathy. Rats in the low, middle and high dose sulodexide groups were given sulodexide by intragastric administration of 10 mg / kg,20 mg / kg and 40 mg / kg, respectively. Metformin hydrochloride group was given metformin hydrochloride of 200 mg / kg, once a day for 12 weeks. The levels of fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c) and serum levels of advanced glycation end products (AGEs), interleukin-6 (IL-6), IL-1β, and levels of glucose transporter 1 (GLUT-1), glucose transporter 3(GLUT-3), superoxide dismutase (SOD) and malondialdehyde (MDA) in retina were detected. The levels of p38 MAPK and phosphorylated p38 MAPK (p-p38 MAPK) in retina were detected by immunohistochemistry and Western blotting. Retinal pathological changes and ganglion cell count were examined by HE staining. Results The levels of FBG and HbA1c, serum AGEs, IL-6, IL-1 β, GLUT-1, GLUT-3, MDA and p38 MAPK mRNA, p38 MAPK, p-p38 MAPK / p38 MAPK and immunohistochemical integral optical density of retina in sulodexide group were significantly lower than those in diabetic retinopathy group (P < 0. 05), while the SOD level and ganglion cell number in retinal tissue were significantly higher than those in diabetic retinopathy group (P < 0. 05) . Conclusion Sulodexide can regulate blood glucose level and retinal glucose metabolism in diabetic retinopathy rats, and repair retinal pathological damage, and its mechanism may be related to the regulation of MAPK pathway.

Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.
Adolescent ; Body Mass Index ; Child ; Child, Preschool ; China/epidemiology* ; Cross-Sectional Studies ; Female ; Humans ; Male ; Obesity/epidemiology* ; Overweight/epidemiology* ; Puberty ; Puberty, Precocious ; Sexual Development

AIM:To investigate whether ceramide kinase-like protein(CERKL)alleviates oxidative stress injury of retinal pigment epithelial(RPE)cells induced by blue light via activating the silent information regulator 1(SIRT1)/E2F transcription factor 1(E2F1)axis. METHODS:Cultured human retinal pigment epithelial-19(ARPE-19)cells were irradiated with blue light to observe the morphological changes, and the expression of CERKL was detected by PCR and Western blot. ARPE-19 cells were transfected with siRNA-CERKL and pcDNA3.1-CERKL respectively. After exposure to blue light, cell viability was determined by MTT assay, apoptosis was detected by TUNEL assay, content of oxidative stress markers and the expression of SIRT1/E2F1 axis was analyzed. Then siRNA-SIRT1 was transfected into ARPE-19 cells, and the oxidative stress damage of ARPE-19 cells under blue light irradiation was detected again.RESULTS:ARPE-19 cells gradually contracted into spheres and appeared vacuoles after exposure to blue light. Blue light irradiation led to the increase of CERKL expression level(P<0.05), meanwhile, the rate of cell viability was decreased(P<0.05), the rate of the apoptosis was increased(P<0.05), contents of reactive oxygen species, malondialdehyde and 8-hydroxydeoxyguanosine were increased(P<0.05). Silence of CERKL aggravated this phenomenon, while up-regulation of CERKL could alleviate this change(P<0.05). Up-regulation of CERKL also activated the expression of SIRT1 and promoted the deacetylation of E2F1(P<0.05). Silencing SIRT1 could reverse the alleviating effect of up-regulating CERKL on oxidative stress injury of ARPE-19 cells induced by blue light(P<0.05). CONCLUSION: CERKL can reduce oxidative stress damage of ARPE-19 cells induced by blue light via activating SIRT1 expression and promoting the deacetylation of E2F1.

OBJECTIVE: Through analysis of ABO blood group gene typing technology, to assist in the identification of difficult clinical serological specimens. METHODS: A total of 10 forwardreverse typing ambiguous samples were collected from January 2021 to August 2021 in our hospital.ABO genotypes were analysed by gene sequencing. RESULTS: The genotypes of 10 ABO ambiguous blood group samples were A102/BW11, A102/BW12, O02/O02, A102/B303, A102/B101, BW11/O02, B101/O04, BW11/O01, BW11/O01, A101/O02, respectively. The genotype results of 6 cases was consistent with the serological phenotype, and the serological phenotype of 4 cases were different from the geno sequencing. CONCLUSION ABO blood groups genotyping technology combined with serological typing can be used for accurate typing of ambiguous blood group, and better ensure the safety of blood transfusion.
ABO Blood-Group System/genetics* ; Alleles ; Blood Grouping and Crossmatching ; Exons ; Genotype ; Phenotype

Objective:To establish a method for qualitative analysis of components in Perilla frutescens leaves and stalks by liquid chromatography-mass spectrometry (LC-MS)，so as to explore the substance basis of pharmacodynamics differences between P.frutescens leaves and stalks.Method:P. frutescens leaves and stalks were extracted by 80% methanol-water ultrasound. The samples were analyzed by UPLC-Q-Exactive-Orbitrap-MS comprehensively. Halo-C₁₈ column (2.1 mm×100 mm，2.7 μm) was used for gradient elution with 0.05% formic acid aqueous-0.05% acetonitrile formate as mobile phase in positive and negative ion modes. The flow rate was 0.3 mL·min^-1，the column temperature was 40 ℃，and the injection volume was 5 μL.Result:The chemical compound in P. frutescens was deduced and identified based on the retention time of chromatography，and the exact molecular weight，excimer ion peaks，fragment ions and reference materials in Xcalibur software. The chemical composition of P. frutescens was identified by Mass Frontier 7.0 software. Totally 4 amino acids，7 phenylpropanoids，10 flavonoids，12 triterpenoids，7 organic acids，4 fatty acids，10 unknown compounds and 54 compounds were identified. Among them，6 triterpene acids, including glochidone, were identified in P. frutescens for the first time. The structures of five characteristic compounds were analyzed. There were 45 constituents in P.frutescens leaves and 32 constituents in P. frutescens stalks. They had 23 common constituents.Conclusion:LC-MS can identify the components of P. frutescens rapidly and effectively. This study provides an important theoretical basis for the quality control of different parts of P. frutescens and the development and utilization of P. frutescens.