Humans ; Glycated Hemoglobin ; Diabetes Mellitus, Type 1 ; Blood Glucose ; Diabetes Mellitus, Type 2

Abstract The COVID-19 pandemic has posed a series of complex challenges. COVID-19 in children and adolescents is generally less severe than in adults and the elderly; however, some children and adolescents may experience severe complications and adverse health effects even after mild or asymptomatic COVID-19 infections. The article focuses on gathering the epidemic characteristics, health impact, risk factors, prevention and control measures, and vaccination status of children and adolescents with COVID-19 infection to provide recommendations for protecting children and adolescents in the post COVID-19 era.

Objectives:To investigate the effect of inhibition of long non-coding RNA(lnc RNA)in human metastasis associated lung adenocarcinoma transcript 1(MALAT1)on glycolipitoxicity-induced human umbilical vein endothelial cell dysfunction. Methods:Human umbilical vein endothelial cells were treated with glucose and palmitic acid in vitro to establish the glycolipitoxic endothelial cell models.Following groups were examined:control group,high-glucose and high-fat group,high-glucose and high-fat + non-targeting RAN control group,high-glucose and high-lipid+MALAT1 siRNA group,and high-glucose and high-lipid+MAPK1 siRNA group.RT-qPCR was used to detect the mRNA expression of MALAT1 and MAPK1.Western blot was used to detect the expression levels of autophagy,mitochondrial fusion division,apoptosis,and pathway-related proteins.Immunofluorescence confocal localization was used to detect the fluorescence colocalization of autophagy and lysosome-related proteins.The number of autophagolysosomes in endothelial cells was observed by transmission electron microscopy.Mitochondrial probe staining was used to detect mitochondrial morphology,immunofluorescence was used to detect intracellular reactive oxygen species(ROS)production,flow cytometry was used to detect the apoptosis of cells in each group,cell proliferation and scratch assays were used to detect the proliferation and migration ability of cells in different groups at different time points.The angiogenesis was quantified by counting the number of new blood vessels in each group. Results:Compared with the control group,the expression of lncRNA MALAT1 mRNA and the expression of phosphorylated mito-activated protein kinase 1(p-MAPK1)were upregulated(both P＜0.05)and the expression of phosphorylated mammalian target protein(p-mTOR)was downregulated in the high-glucose and high-fat group and the high-sugar and high-fat control group(all P＜0.01).Compared with the high-glucose and high-fat non-targeting RNA control group,the expressions of microtubule-associated protein 1A/1B-light chain 3(LC3)and p62 were downregulated(P＜0.01,P＜0.05),LC3 and lysosome-associated membrane protein 2(LAMP2)protein co-localized positive fluorescence particles were increased(both P＜0.01),number of lysosomes were decreased,the expression of ROS was decreased(P＜0.01),the expression level of mitochondrial fusion protein optic nerve atrophin 1(OPA1)was increased(P＜0.05),the expressions of cleaved caspase-3 and BCL-2-related X protein(BAX)were decreased and BCL-2 was increased(all P＜0.05),cell proliferation,migration,and tube-forming ability were increased(all P＜0.01),and the expression of p-MAPK1 was decreased(P＜0.05)and p-mTOR expression was increased(both P＜0.05)in the high-glucose and high-lipid+si-MALAT1 group.Compared with the high-glucose and high-fat non-targeting RNA control group,the expression of p-MAPK1 in endothelial cells was decreased and the expression of p-mTOR was increased in the high-glucose and high-lipid+si-MAPK1 group(both P＜0.01). Conclusions:Inhibition of lncRNA MALAT1 expression can reduce the level of mitophagy in glycolipidotoxic environments,reduce apoptosis of endothelial cells and improve endothelial cell function,which may be related to the regulation of MAPK1/mTOR signaling pathway.

Thrombocytopenia is one of the common complications of cirrhotic patients, which can induce an increasing bleeding risk and closely correlate with bleeding following invasive procedures. Consequently, how to respond to thrombocytopenia is crucial for improving the prognosis of patients with cirrhosis. This article reviews the main mechanisms of cirrhosis concurrent with thrombocytopenia, as well as the corresponding clinical management strategies.

Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.

Objective:To analyze the effect of traditional Chinese medicine fasting therapy on atherogenic index of plasma and metabolic indices in patients with metabolic syndrome.Methods:A case-control study was conducted on 90 patients with metabolic syndrome who were treated at Wenzhou Traditional Chinese Medicine Hospital between June 2021 and June 2023. The patients were divided into two groups with 45 patients in each group using a random number table method. The control group was given a normal diet, while the observation group underwent traditional Chinese medicine fasting therapy. Blood lipid indexes, atherogenic index of plasma, Homeostasis Model Assessment of Insulin Resistance index, anthropometric indices, and oxidative stress response were compared between the two groups.Results:After treatment, the levels of low-density lipoprotein cholesterol, total cholesterol, and triglyceride in the observation group were (2.11 ± 0.26) mmol/L, (4.31 ± 0.26) mmol/L, and (1.39 ± 0.26) mmol/L, respectively. They were significantly lower than those in the control group [(2.95 ± 0.34) mmol/L, (5.24 ± 0.33) mmol/L, (2.68 ± 0.41) mmol/L, t = 13.16, 14.85, 17.82, all P < 0.05]. After treatment, the level of high-density lipoprotein cholesterol was significantly higher in the observation group than in the control group [(1.18 ± 0.09) mmol/L vs. (1.03 ± 0.04) mmol/L, t = 10.21, P < 0.001]. After treatment, atherogenic index of plasma and Homeostasis Model Assessment of Insulin Resistance index in the observation group were (0.10 ± 0.04) and (5.12 ± 0.42), respectively in the observation group. They were significantly lower than those in the control group [(0.28 ± 0.10), (5.80 ± 0.67), t = 11.21, 5.76, both P < 0.001]. After treatment, waist circumference, hip circumference, and visceral adiposity index in the observation group were (91.05 ± 4.26) cm, (98.16 ± 5.06) cm, and (3.94 ± 0.52), respectively. They were significantly lower than those in the control group [(95.55 ± 9.87) cm, (102.64 ± 9.84) cm, (5.66 ± 1.04), t = 2.80, 2.71, 9.92, all P < 0.05). After treatment, the level of superoxide dismutase in the observation group was significantly higher than that in the control group [(101.52 ± 13.52) U/mL vs. (80.01 ± 6.82) U/mL, t = 9.52, P < 0.001]. After treatment, the level of malondialdehyde in the observation group was significantly lower than that in the control group [(4.41±0.35) nmol/L vs. (6.26 ± 0.61) nmol/L, t = 17.64, P < 0.001). Conclusion:Traditional Chinese medicine fasting therapy can effectively reduce the atherogenic index of plasma, blood lipid level, waist circumference, hip circumference, and visceral adiposity index in patients with metabolic syndrome. It also reduces oxidative stress reactions and is highly effective.

AIM:Clopidogrel and aspirin are com-monly used drugs for the secondary prevention of cerebrovascular disease.Due to drug resistance,their preventive effect is often affected.This article explores the clinical value of clopidogrel and aspirin pharmacogenetic genetic testing in the secondary prevention of ischemic stroke.METHODS:220 pa-tients with mild ischemic stroke or TIA admitted to our hospital from 2021.7 to 2022.9 were included and randomly divided into individualized treatment group and clopidogrel conventional treatment group(control group).The patients were followed up for one year to observe stroke recurrence and hemorrhagic events.RESULTS:(1)Compared with the control group,the recurrence rate of ischemic stroke in the individualized treatment group after 1-year follow-up was slightly lower(5.82％vs.7.92％,P＞0.05),the risk of cerebral hemorrhage was simi-lar,but the risk of other occurrences was increased(6.79％vs.0.99％,P＜0.05).(2)COX regression analy-sis showed that ESRS(HR 2.576,95％CI 1.226-5.413,P=0.013)and history of hypertension(HR 5.517,95％CI 1.624-18.737,P=0.006)were associated with recurrence of ischemic stroke,independent of anti-thrombotic regimen(HR 0.918,95％CI 0.291-2.894,P=0.883).CONCLUSION:Aspirin GPIBA,PTGS1,and ITGB3 gene polymorphisms have limited signifi-cance in guiding antiplatelet medication.Selecting aspirin maintenance therapy for clopidogrel CYP2C19*2*3 allele carriers cannot significantly re-duce the risk of recurrence of minor ischemic stroke and may increase other bleeding risks.COX regression analysis shows that ESRS and history of hypertension are independent risk factors for stroke recurrence.

【Objective】 To investigate the gene frequency and polymorphism of RBC blood group systems in RhD negtive population in Hunan, so as to lay a foundation for clinical blood transfusion and construction of multiple rare blood group database. 【Methods】 Blood samples were taken from 300 RhD negative blood donors, confirmed by serological method, from June 2019 to June 2020,. RHD genotyping was performed by SSP-PCR. For blood donors with typing results as RhD negative plus RHD gene deletion, antigens genotyping of MNS, Duffy, Kell, Domrock, Diego, Kidd, Sciawnna, Colton, Lutheran and Yt RBC blood group systems were performed by SSP-PCR and analyzed by the chi square test of SPSS 20 statistical software. 【Results】 RHD gene deletions accounted for 58.67% (176 / 300) of serological D negative blood donors. The gene frequencies were as follows: MNS: GYPB^*S=0.045 5(8/176), GYPB^*s=0.954 5(168/176), GYP^*Dane=0.039 8(7/176); Duffy: FY^*A =0.965 6(170/176), FY^*B=0.034 1(6/176); Dombrock: DO^*A=0.082 4(14.5/176), DO^*B=0.917 6(161.5/176); Diego: DI^*A=0.025 6(4.5/176), DI^*B =0.974 4(171.5/176); Kidd: JK^*A=0.485 8(85.5/176), JK^*B=0.514 2(90.5/176); Kell: KP^*A=0.005 7(1/176), KP^*B=0.994 3(175/176); Lutheran: LU^*A=0.005 7(1/176), LU^*B=0.994 3(175/176); Yt: YT^*A=0.002 8(0.5/176), YT^*B=0.997 2(175.5/176). The genotypes of Kell(K+ /k+ ), Scianna and Colton blood groups were KEL^*02 /KEL^*02, SC^*01 /SC^*01 and CO^*A /CO^*B, respectively. The expected frequencies of the combination of type O, RhD negative and other blood group systems were between 1/100 000 to 1/10 000. 【Conclusion】 Among RhD negative blood donors in Hunan, the gene profiles of MNS, Duffy, Domrock, Diego, Kidd, Kell and Lutheran blood group system were polymorphic, and Kell (K+ /k+ ), Colton and Scianna were homozygous. The data of other RBC blood group systems from RhD negative blood donors is of great significance to establish local database of rare blood groups.

Objective:To explore clinical evaluation and genetic analysis of patients with idiopathic hypogonadotropic hypogonadism (IHH).Methods:The clinical data and phenotypes of 22 patients with IHH diagnosed and treated in our department were reviewed and analyzed. Whole-exome sequencing(WES)and Sanger method were used for variant analysis and verification.Results:Among the 22 cases of IHH probands, 12 cases of Kalman syndrome (KS) and 10 cases of IHH (nIHH) with normal sense of smell. On physical examination, males showed short penis, small testicles, small or inconspicuous laryngeal knots, and a sharp voice. Mammary gland development, mammary gland dysplasia, primary amenorrhea, etc. in women. Sex hormone examination: Follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E2) levels are reduced or at the lower limit of normal. There were nine missense variants of CHD7 gene in 8 patients. Based on the American College of Medical Genetics and Genomics guidelines, the c. 307T>A(p.Ser103Thr), c.3143G>A(p.Gly1048Glu), c.6956G>T(p.Arg2319Leu) and c. 3145A>T(p.Ser1049Cys) variants of CHD7 gene were predicted to be likely pathogenic (PS1+ PP1+ PM2, PM2+ PM6+ PP2+ PP3, PM2+ PM5+ PM6+ PP2+ PP3 and PM2+ PM6+ PP2+ PP3), the remaining 14 cases of IHH patients had negative genetic screening. Conclusion:CHD7 gene variants may be related to IHH disease.

Objective: To explore the role and mechanism of long noncoding RNA(lncRNA) AC005062.1 in colorectal cancer(CRC) cell proliferation and apoptosis. Methods: The analysis of GSE84983 and GSE 104364 was used to indicate the expression level lncRNA AC005062.1 in CRC. The tumor tissues(tumor group) and adjacent tissues(control group) of patients undergoing CRC surgery in the hospital tumor surgery department were collected. Eight pairs of tissues were randomly selected, and qPCR was used to detect the expression of lncRNA AC005062.1 in CRC tissues and paired adjacent tissues in the two groups. After using siRNA to down-regulate the expression of lncRNA AC005062.1 in CRC cells, CCK-8 assay was used to detect cell proliferation in two groups, flow cytometry was used to detect cell cycle and apoptosis in two groups, wound scratch test was used to detect cell migration in two groups, and the lncRNA was determined. The database was used to compare the localization of lncRNA AC005062.1 and MACC1 genes on staining. The expression levels of MACC1 transcription and protein levels in the control group and tumor group were detected by qPCR and Western blot, respectively. The lncRNA AC005062.1 in CRC cells was down-regulated, and the expression levels of MACC1 transcription and protein levels in the two groups of cells were detected by qPCR and Western blot, respectively. Results: The database analysis of GSE84983 and GSE104364 and the detection results of the two groups indicated that the lncRNA AC005062.1 was highly expressed in CRC. After down-regulation of lncRNA AC005062.1, the results of CCK-8 experiments showed that the proliferation rate of HT29 cells in the down-regulation group decreased. Flow cytometry showed that the number of apoptosis of HT29 cells in the down-regulated group increased, the proportion of G1 phase increased, and the proportion of S phase and G2 phase decreased. Western blot experiments showed that the expressions of cleaved-caspase3 and Bax in the down-regulated HT29 cells increased, while the expression of Bcl-2 decreased. Wound scratch experiments showed that the migration rate of HT29 cells in the down-regulated group was lower than that in the control group. The analysis of UCSC to compare the location of lncRNA ac005062.1 and MACC1 on chromosomes showed that they were located very close together. MACC1 was highly expressed in CRC and down-regulated lncRNA AC005062.1 expression in HT29 cells could reduce the expression of MACC1. Conclusion lncRNA AC005062.1 can inhibit the proliferation, cycle and migration of HT29 cells, and promote its apoptosis by regulating the expression of MACC1 in CRC.