Glucuronic acid metabolites of phenolic acids target AKT-PH domain to improve glucose metabolism / 中草药·英文版

OBJECTIVE@#Phenolic acids widely exist in the human diet and exert beneficial effects such as improving glucose metabolism. It is not clear whether phenolic acids or their metabolites play a major role in vivo. In this study, caffeic acid (CA) and ferulic acid (FA), the two most ingested phenolic acids, and their glucuronic acid metabolites, caffeic-4'-O-glucuronide (CA4G) and ferulic-4'-O-glucuronide (FA4G), were investigated.@*METHODS@#Three insulin resistance models in vitro were established by using TNF-α, insulin and palmitic acid (PA) in HepG2 cells, respectively. We compared the effects of FA, FA4G, CA and CA4G on glucose metabolism in these models by measuring the glucose consumption levels. The potential targets and related pathways were predicted by network pharmacology. Fluorescence quenching measurement was used to analyze the binding between the compounds and the predicted target. To investigate the binding mode, molecular docking was performed. Then, we performed membrane recruitment assays of the AKT pleckstrin homology (PH) domain with the help of the PH-GFP plasmid. AKT enzymatic activity was determined to compare the effects between the metabolites with their parent compounds. Finally, the downstream signaling pathway of AKT was investigated by Western blot analysis.@*RESULTS@#The results showed that CA4G and FA4G were more potent than their parent compounds in increasing glucose consumption. AKT was predicted to be the key target of CA4G and FA4G by network pharmacology analysis. The fluorescence quenching test confirmed the more potent binding to AKT of the two metabolites compared to their parent compounds. The molecular docking results indicated that the carbonyl group in the glucuronic acid structure of CA4G and FA4G might bind to the PH domain of AKT at the key Arg-25 site. CA4G and FA4G inhibited the translocation of the AKT PH domain to the membrane, while increasing the activity of AKT. Western blot analysis demonstrated that the metabolites could increase the phosphorylation of AKT and downstream glycogen synthase kinase 3β in the AKT signaling pathway to increase glucose consumption.@*CONCLUSION@#In conclusion, our results suggested that the metabolites of phenolic acids, which contain glucuronic acid, are the key active substances and that they activate AKT by targeting the PH domain, thus improving glucose metabolism.

Clinical characteristics of plastic bronchitis and risk factors for recurrence in children / 中国当代儿科杂志

OBJECTIVES@#To study the clinical characteristics of plastic bronchitis (PB) in children and investigate the the risk factors for recurrence of PB.@*METHODS@#This was a retrospective analysis of medical data of children with PB who were hospitalized in Children's Hospital of Chongqing Medical University from January 2012 to July 2022. The children were divided into a single occurrence of PB group and a recurrent PB group and the risk factors for recurrence of PB were analyzed.@*RESULTS@#A total of 107 children with PB were included, including 61 males (57.0%) and 46 females (43.0%), with a median age of 5.0 years, and 78 cases (72.9%) were over 3 years old. All the children had cough, 96 children (89.7%) had fever, with high fever in 90 children. Seventy-three children (68.2%) had shortness of breath, and 64 children (59.8%) had respiratory failure. Sixty-six children (61.7%) had atelectasis and 52 children (48.6%) had pleural effusion. Forty-seven children (43.9%) had Mycoplasma pneumoniae infection, 28 children (26.2%) had adenovirus infection, and 17 children (15.9%) had influenza virus infection. Seventy-one children (66.4%) had a single occurrence of PB, and 36 cases (33.6%) had recurrent occurrence of PB (≥2 times). Multivariate logistic regression analysis showed that involvement of ≥2 lung lobes (OR=3.376) under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts (OR=3.275), and concomitant multi-organ dysfunction outside the lungs (OR=2.906) were independent risk factors for recurrent occurrence of PB (P<0.05).@*CONCLUSIONS@#Children with pneumonia accompanied by persistent high fever, shortness of breath, respiratory failure, atelectasis or pleural effusion should be highly suspected with PB. Involvement of ≥2 lung lobes under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts, and concomitant multi-organ dysfunction outside the lungs may be risk factors for recurrent occurrence of PB.

Epidemiological characteristics of hand, foot and mouth disease in Zhejiang Province from 2016 to 2019 / 预防医学

Objective@#To investigate the epidemiological characteristics of hand, foot and mouth disease ( HFMD ) in Zhejiang Province, so as to provide insights into HFMD control.@*Methods@#The incidence of HFMD in Zhejiang Province from 2016 to 2019 was collected from National Notifiable Disease Reporting System. The temporal distribution, human distribution, regional distribution and pathogenic typing of HFMD were descriptively analyzed in Zhejiang Province from 2016 to 2019.@*Results@#Totally 642 305 cases with HFMD were reported in Zhejiang Province from 2016 to 2019, including 121 severe cases and 9 fatal cases. The annual incidence of HFMD was 335.88/105, 147.76/105, 435.63/105 and 221.77/105, respectively. The incidence of HFMD peaked from May to July each year, and the three highest annual incidence included Ningbo, Jinhua and Wenzhou cities, while the lowest annual incidence was seen in Zhoushan City. The HFMD cases were predominantly found in children at ages of 1 to 5 years ( 537 738 cases, 83.72% ), and in children living at home ( 419 408 cases, 65.30% ). The average annual incidence of HFMD was higher in males than in females ( 328.23/105 vs. 239.99/105; P<0.05). The dominant pathogens gradually shifted from enterovirus 71 ( EV71 ) to Coxsachievirus A16 ( CA16 ), and other enteroviruses remained as the main pathogenic subtypes.@*Conclusions@#The incidence HFMD was high in summer and autumn in Zhejiang Province from 2016 to 2019. Children living at home are at a high risk of HFMD, and CA16 type gradually became the dominant pathogen of HFMD.

Neuro-protective effect of Levocarnitine on severe hand,foot and mouth disease after enterovirus 71 infection / 中华实用儿科临床杂志

Objective To observe the neuro-protective effect of Levocarnitine on severe hand,foot and mouth disease (HFMD) after enterovirus 71 (EV71) infection,to preliminarily explore the possible mechanism preliminarily.Methods One hundred and thirty-two children with EV71 infection and HFMD combined with serum S100 protein and neuronspecific enolase (NSE) abnormalities who were admitted to Chihlren's Hospital Affiliated to Zhengzhou University from March 2015 to July 2016 were enrolled in the study.They were divided into the routine group and the Levocarnitine group by the random number grouping method.The routine group (66 cases,including 32 males and 34 females,median age of 2 years and 3 months) was given symptomatic treatment such as antiviral therapy while the Levocarnitine group (66 cases,including 36 males and 30 females,median age of 2 years and 5 months) was treated with Levocarnitine for neuroprotection on the basis of routine group.Forty healthy children (23 males and 17 females,median age of 2 years and 6 months) who were examined at the Children's Hospital Affiliated to Zhengzhou University during the same period were selected as the healthy control group.The levels of S100,NSE,soluble apoptosis-related factors (sFas),soluble apoptosis-related factor l igands (sFasL),malondialdehyde (MDA),superoxide dismutase (SOD) in serum were compared between the healthy control group and children with HFMD.The levels of above-mentioned indexes in cerebrospinal fluid and serum,efficacy-related indicators such as duration of fever,white blood cell count on the 3rd day of treatment,time to remission of nervous system symptoms,time of disease progression and critical conversion rate were compared between 2 groups of children with HFMD.The correlation between sFas,sFasL,MDA,SOD and S100,NSEwas performed Results (1) The levels of S100 [(0.38:±:0.16) μg/Lvs.(0.06:±:0.23) μg/L],NSE [(43.70±8.80) μg/Lvs.10.10±3.60) μg/L],sFas [(6.61 ±1.86) μg/Lvs.(3.88±1.22) μg/L],sFasL [(101.40±20.7) μg/Lvs.(54.4±13.3) μg/L] and MDA[(11.98±2.54) nmol/Lvs.(4.08±1.45) nmol/L]in serum of HFMD group were significantly higher than those of the healthy control group (t =-12.245,-22.895,-8.273,-12.803,-17.960,all P ＜0.05),while the SOD level [(57.10 ± 10.40) kU/L vs.(70.3 ±14.4) kU/L] was significantly lower (t =5.457,P ＜ 0.05).(2) With the extension of treatment time for HFMD children in the two groups,S100 and NSE in cerebrospinal fluid,S100,NSE,sFas,sFasL and MDA in serum decreased,while SOD level increased.On the 3rd and 7th day after treatment,S100 (t3 =3.491,t7 =14.434),NSE (t3 =2.920,t7 =23.490) in cerebrospinal fluid,S100 (t3 =5.277,t7 =3.614),NSE (t3 =4.652,t7 =10.525),sFas (t3 =6.399,t7 =7.514),sFasL (t3 =11.155,t7 =8.804) and MDA (t3 =6.348,t7 =7.499) in serum of Levocarnitine group were significantly lower than those of routine group (all P ＜ O.05),while SOD (t3 =3.162,t7 =-3.529) was significantly higher than that of routine group (P ＜0.05).(3) The relief time of neurological symptom in levocarnitine group was significantly shorter than that in the routine group [(1.23 ± 0.65) d vs.(1.84 ± 0.47) d],and WBC on the 3rd day after treatment [(9.14 ± 2.93) × 109/L vs.(7.12 ± 2.58) × 109/L] and the progression time of the disease [(29.74 ± 7.85) h vs.(17.36 ± 8.73) h] were significantly better than the those in the routine group (t =-6.178,4.204,8.567,all P ＜ 0.05).The critical conversion rates of Levocarnitine group and the routine group were 7.58％ and 18.18％,respectively,and the difference in critical conversion rate was not statistically significant (x2 =2.316,P ＞0.05).(4)There was a positive correlation between S100 and sFas,sFasL,MDA in children with HFMD (r =0.373,0.735,0.334,P ＜ 0.05).NSE was positively correlated with sFas and sFasL (r =0.479,0.601,all P ＜0.05),while SOD and S100 were negatively correlated with NSE (r =-0.425,-0.460,all P ＜ 0.05).Conclusions Levocarnitine has good curative effect on severe HFMD in children infected by enterovirus EV71,which can effectively protect the cranial nerves.The mechanism may be related to scavenging oxygen free radicals and blocking nerve cell apoptosis.

Value of abnormal HLA-DR expression on CD14+ monocytes in estimating immune function status and clinical prognosis of patients with hand, foot and mouth disease / 中华微生物学和免疫学杂志

Objective To investigate the value of abnormal expression of HLA-DR on peripheral blood monocytes in evaluating the immune function status, clinical prognosis and severity of patients with hand, foot and mouth disease (HFMD). Methods From June 2017 to October 2018, 100 cases of mild HFMD, 80 cases of severe HFMD, 32 cases of critical HFMD and 40 healthy children (control group) were recruited in this study. The patients were divided into two groups, lower DR group (DR-L, HLA-DR expres-sion<30％ ) and normal DR group (DR-N,HLA-DR expression>30％ ) according to the HLA-DR expression on monocytes. Flow cytometry was used to detect the CD14+ monocytes expressing HLA-DR and the absolute count of lymphocyte subsets. Immunoturbidimetry was used to detect the levels of IgG, IgM and IgA in plas-ma samples. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of IFN-γ and IL-10 in plasma samples. Pediatric critical illness score ( PCIS) and the pediatric risk of mortality Ⅲ(PRISM Ⅲ) were used to estimate the severity of HFMD. Results ① There were significant differences in HLA-DR expression on monocytes among children with mild, severe and critical HFMD (F = 47. 102, P<0. 05). Patients with critical HFMD had the lowest HLA-DR expression (P<0. 05). ② The numbers of CD14+ monocytes, CD3+T cells, CD4+T cells, CD8+T cells, B cells and NK cells in peripheral blood of the DR-L group were significantly lower than those of the DR-N group and the normal group, especially in pa-tients with severe or critical HFMD (P<0. 05). ③ There was no significant difference in the level of IgG, IgA or IgM among the DR-L, DR-N and control groups (P>0. 05). ④ Compared with the DR-N group, the DR-L group showed decreased IFN-γ level and increased IL-10 level in plasma (P<0. 05). The ratio of IFN-γ/ IL-10 of the DR-L group was lower than that of the DR-N group and control group (P<0. 05). HLA-DR expression was negatively correlated with the concentration of IL-10 in plasma (r= -0. 704, P<0. 05), and positively correlated with the IFN-γ/ IL-10 ratio (r = 0. 773, P<0. 05). ⑤ Compared with the DR-N group, the DR-L group showed lower PCIS and higher PRISM Ⅲ. HLA-DR expression was positively corre-lated with PCIS (r=0. 715, P=0. 00) and negatively correlated with PRISM Ⅲ (r = -0. 610, P = 0. 00).⑥ The incidence of pulmonary edema, pulmonary hemorrhage and cardiopulmonary failure and the mortality of HFMD patients in the DR-L group were significantly higher than those in the DR-N group (P<0. 05).Conclusions Patients with severe or critical HFMD had cellular immune dysfunction and abnormal HLA-DR expression on CD14+ monocytes. Assessing the expression of HLA-DR on monocytes could be used to evaluate the cellular immunity of patients with severe or critical HFMD. Lower expression of HLA-DR on CD14+ monocytes might be associated with severe HFMD and poor prognosis.

Neuro-protective effect of Levocarnitine on severe hand, foot and mouth disease after enterovirus 71 infection / 中华实用儿科临床杂志

Objective@#To observe the neuro-protective effect of Levocarnitine on severe hand, foot and mouth disease (HFMD) after enterovirus 71(EV71) infection, to preliminarily explore the possible mechanism preliminarily.@*Methods@#One hundred and thirty-two children with EV71 infection and HFMD combined with serum S100 protein and neuronspecific enolase (NSE) abnormalities who were admitted to Children′s Hospital Affiliated to Zhengzhou University from March 2015 to July 2016 were enrolled in the study.They were divided into the routine group and the Levocarnitine group by the random number grouping method.The routine group (66 cases, including 32 males and 34 females, median age of 2 years and 3 months) was given symptomatic treatment such as antiviral therapy while the Levo-carnitine group (66 cases, including 36 males and 30 females, median age of 2 years and 5 months) was treated with Levocarnitine for neuroprotection on the basis of routine group.Forty healthy children (23 males and 17 females, median age of 2 years and 6 months) who were examined at the Children′s Hospital Affiliated to Zhengzhou University during the same period were selected as the healthy control group.The levels of S100, NSE, soluble apoptosis-related factors (sFas), soluble apoptosis-related factor ligands (sFasL), malondialdehyde (MDA), superoxide dismutase (SOD) in serum were compared between the healthy control group and children with HFMD.The levels of above-mentioned indexes in cerebrospinal fluid and serum, efficacy-related indicators such as duration of fever, white blood cell count on the 3rd day of treatment, time to remission of nervous system symptoms, time of disease progression and critical conversion rate were compared between 2 groups of children with HFMD.The correlation between sFas, sFasL, MDA, SOD and S100, NSE was performed@*Results@#(1) The levels of S100 [(0.38±0.16) μg/L vs. (0.06±0.23) μg/L], NSE [(43.70±8.80) μg/L vs. 10.10±3.60) μg/L], sFas [(6.61±1.86) μg/L vs. (3.88±1.22) μg/L], sFasL[(101.40±20.7) μg/L vs. (54.4±13.3) μg/L] and MDA[(11.98±2.54) nmol/L vs. (4.08±1.45) nmol/L] in serum of HFMD group were significantly higher than those of the healthy control group (t=-12.245, -22.895, -8.273, -12.803, -17.960, all P<0.05), while the SOD level [(57.10±10.40) kU/L vs. (70.3±14.4) kU/L] was significantly lower (t=5.457, P<0.05). (2) With the extension of treatment time for HFMD children in the two groups, S100 and NSE in cerebrospinal fluid, S100, NSE, sFas, sFasL and MDA in serum decreased, while SOD level increased.On the 3rd and 7th day after treatment, S100 (t3=3.491, t7=14.434), NSE (t3=2.920, t7=23.490) in cerebrospinal fluid, S100 (t3=5.277, t7=3.614), NSE (t3=4.652, t7=10.525), sFas (t3=6.399, t7=7.514), sFasL (t3=11.155, t7=8.804) and MDA (t3=6.348, t7=7.499) in serum of Levocarnitine group were significantly lower than those of routine group (all P<0.05), while SOD (t3=3.162, t7=-3.529) was significantly higher than that of routine group (P<0.05). (3) The relief time of neurological symptom in levocarnitine group was significantly shorter than that in the routine group [(1.23±0.65) d vs. (1.84±0.47) d], and WBC on the 3rd day after treatment [(9.14±2.93)×109/L vs. (7.12±2.58)×109/L] and the progression time of the disease [(29.74±7.85) h vs. (17.36±8.73) h] were significantly better than the those in the routine group (t=-6.178, 4.204, 8.567, all P<0.05). The critical conversion rates of Levocarnitine group and the routine group were 7.58% and 18.18%, respectively, and the difference in critical conversion rate was not statistically significant (χ2=2.316, P>0.05). (4)There was a positive correlation between S100 and sFas, sFasL, MDA in children with HFMD (r=0.373, 0.735, 0.334, P<0.05). NSE was positively correlated with sFas and sFasL (r=0.479, 0.601, all P<0.05), while SOD and S100 were negatively correlated with NSE (r=-0.425, -0.460, all P<0.05).@*Conclusions@#Levocarnitine has good curative effect on severe HFMD in children infected by enterovirus EV71, which can effectively protect the cranial nerves.The mechanism may be related to scavenging oxygen free radicals and blocking nerve cell apoptosis.

Value of abnormal HLA-DR expression on CD14+ monocytes in estimating immune function status and clinical prognosis of patients with hand, foot and mouth disease / 中华微生物学和免疫学杂志

Objective@#To investigate the value of abnormal expression of HLA-DR on peripheral blood monocytes in evaluating the immune function status, clinical prognosis and severity of patients with hand, foot and mouth disease (HFMD).@*Methods@#From June 2017 to October 2018, 100 cases of mild HFMD, 80 cases of severe HFMD, 32 cases of critical HFMD and 40 healthy children (control group) were recruited in this study. The patients were divided into two groups, lower DR group (DR-L, HLA-DR expression<30%) and normal DR group (DR-N, HLA-DR expression>30%) according to the HLA-DR expression on monocytes. Flow cytometry was used to detect the CD14+ monocytes expressing HLA-DR and the absolute count of lymphocyte subsets. Immunoturbidimetry was used to detect the levels of IgG, IgM and IgA in plasma samples. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of IFN-γ and IL-10 in plasma samples. Pediatric critical illness score (PCIS) and the pediatric risk of mortality Ⅲ (PRISM Ⅲ) were used to estimate the severity of HFMD.@*Results@#① There were significant differences in HLA-DR expression on monocytes among children with mild, severe and critical HFMD (F=47.102, P<0.05). Patients with critical HFMD had the lowest HLA-DR expression (P<0.05). ② The numbers of CD14+ monocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells and NK cells in peripheral blood of the DR-L group were significantly lower than those of the DR-N group and the normal group, especially in patients with severe or critical HFMD (P<0.05). ③ There was no significant difference in the level of IgG, IgA or IgM among the DR-L, DR-N and control groups (P>0.05). ④ Compared with the DR-N group, the DR-L group showed decreased IFN-γ level and increased IL-10 level in plasma (P<0.05). The ratio of IFN-γ/IL-10 of the DR-L group was lower than that of the DR-N group and control group (P<0.05). HLA-DR expression was negatively correlated with the concentration of IL-10 in plasma (r=-0.704, P<0.05), and positively correlated with the IFN-γ/IL-10 ratio (r=0.773, P<0.05). ⑤ Compared with the DR-N group, the DR-L group showed lower PCIS and higher PRISM Ⅲ. HLA-DR expression was positively correlated with PCIS (r=0.715, P=0.00) and negatively correlated with PRISM Ⅲ (r=-0.610, P=0.00). ⑥ The incidence of pulmonary edema, pulmonary hemorrhage and cardiopulmonary failure and the mortality of HFMD patients in the DR-L group were significantly higher than those in the DR-N group (P<0.05).@*Conclusions@#Patients with severe or critical HFMD had cellular immune dysfunction and abnormal HLA-DR expression on CD14+ monocytes. Assessing the expression of HLA-DR on monocytes could be used to evaluate the cellular immunity of patients with severe or critical HFMD. Lower expression of HLA-DR on CD14+ monocytes might be associated with severe HFMD and poor prognosis.

Association of Serotonin Receptors with Attention Deficit Hyperactivity Disorder: A Systematic Review and Meta-analysis / 华中科技大学学报（医学）（英德文版）

Attention deficit hyperactivity disorder (ADHD) is one of the most common mental disorders in childhood,with a high heritability about 60％ to 90％.Serotonin is a monoamine neurotransmitter.Numerous studies have reported the association between the serotonin receptor family (5-HTR) gene polymorphisms and ADHD,but the results are still controversial.In this study,we conducted a meta-analysis of the association between 5-HTR1B,5-HTR2A,and 5-HTR2C genetic variants and ADHD.The results showed that the 861G allele of 5-HTR1B SNP rs6296 could significantly increase the risk of ADHD (OR=1.09,95％ CI:1.01-1.18);the 5-HTR2C gene rs518147 (OR=1.69,95％ CI:1.38-2.07) and rs3813929 (OR =1.57,95％ CI:1.25-1.97) were all associated with the risk of ADHD.In addition,we also carried on a casecontrol study to explore the relevance between potential candidate genes 5-HTR 1 A,5-HTR1E,5-HTR3A and ADHD.The results indicated that 5-HTR1A rs6295 genotype (CC+CG vs.GG OR=2.00,95％ CI:1.23-3.27) and allele (OR=1.77,95％ CI:1.16-2.72) models were statistically significantly different between case group and control group.This study is the first comprehensive exploration and summary of the association between serotonin receptor family genetic variations and ADHD,and it also provides more evidence for the etiology of ADHD.

Association of Bone Turnover Levels with MTHFR Gene Polymorphisms among Pregnant Women in Wuhan, China / 华中科技大学学报（医学）（英德文版）

Pregnancy is a critical stimulator of bone mineral resorption.We used to find the MTHFR gene polymorphisms are related with blood lead levels among pregnant women.Pregnancy-stimulated bone turnover may be associated with MTHFR gene polymorphisms too.In this article,we aimed to determine the relationship between MTHFR gene polymorphisms and bone turnover rates among the pregnant women.The participants including pregnant and non-pregnant women were selected and recruited during their routine prenatal or physical examination from July to October in 2012.A total of 1000 participants,including 250 pregnant women in the first,second,and third trimesters and 250 non-pregnant women,were enrolled in the study.Finally,after excluding 27 participants unable to provide blood samples,973 eligible participants (i.e.,234,249,and 248 pregnant women in the first,second,and third trimesters,respectively,and 242 non-pregnant women)were included in the research.The MTHFR gene 1298CC homozygote carriers were more susceptible to yield higher plasma homocysteine levels than the 1298AA/AC carriers,with standardized coefficients of 0.086 (P＜0.05) and 0.104 (P＜0.01) of all the participants and the pregnant women,respectively.The MTHFR gene 1793AA homozygote carriers more likely showed higher plasma osteocalcin levels (standardized β=0.091,P＜0.01) than the 1793GG/GA carriers among all the subjects.Plasma homocysteine levels were positively correlated with blood lead levels among the participants and the pregnant women with standardized coefficients of 0.320 (P＜0.01) and 0.179 (P＜0.01),respectively.Plasma osteocalcin levels were positively associated with blood lead levels among pregnant and non-pregnant women with standardized coefficients of 0.084 (P＜0.05) and 0.125 (P＜0.01),respectively.In conclusion,homocysteine and osteocalcin contents in plasma are associated with the MTHFR gene A1298C polymorphism and blood lead levels among pregnant women.The MTHFR gene A 1298C polymorphism-related homocysteine is a possible risk factor for increased blood lead levels among Chinese women.

Association of Serotonin Receptors with Attention Deficit Hyperactivity Disorder: A Systematic Review and Meta-analysis / 华中科技大学学报（医学）（英德文版）

Attention deficit hyperactivity disorder (ADHD) is one of the most common mental disorders in childhood,with a high heritability about 60％ to 90％.Serotonin is a monoamine neurotransmitter.Numerous studies have reported the association between the serotonin receptor family (5-HTR) gene polymorphisms and ADHD,but the results are still controversial.In this study,we conducted a meta-analysis of the association between 5-HTR1B,5-HTR2A,and 5-HTR2C genetic variants and ADHD.The results showed that the 861G allele of 5-HTR1B SNP rs6296 could significantly increase the risk of ADHD (OR=1.09,95％ CI:1.01-1.18);the 5-HTR2C gene rs518147 (OR=1.69,95％ CI:1.38-2.07) and rs3813929 (OR =1.57,95％ CI:1.25-1.97) were all associated with the risk of ADHD.In addition,we also carried on a casecontrol study to explore the relevance between potential candidate genes 5-HTR 1 A,5-HTR1E,5-HTR3A and ADHD.The results indicated that 5-HTR1A rs6295 genotype (CC+CG vs.GG OR=2.00,95％ CI:1.23-3.27) and allele (OR=1.77,95％ CI:1.16-2.72) models were statistically significantly different between case group and control group.This study is the first comprehensive exploration and summary of the association between serotonin receptor family genetic variations and ADHD,and it also provides more evidence for the etiology of ADHD.

Association of Bone Turnover Levels with MTHFR Gene Polymorphisms among Pregnant Women in Wuhan, China / 华中科技大学学报（医学）（英德文版）

Pregnancy is a critical stimulator of bone mineral resorption.We used to find the MTHFR gene polymorphisms are related with blood lead levels among pregnant women.Pregnancy-stimulated bone turnover may be associated with MTHFR gene polymorphisms too.In this article,we aimed to determine the relationship between MTHFR gene polymorphisms and bone turnover rates among the pregnant women.The participants including pregnant and non-pregnant women were selected and recruited during their routine prenatal or physical examination from July to October in 2012.A total of 1000 participants,including 250 pregnant women in the first,second,and third trimesters and 250 non-pregnant women,were enrolled in the study.Finally,after excluding 27 participants unable to provide blood samples,973 eligible participants (i.e.,234,249,and 248 pregnant women in the first,second,and third trimesters,respectively,and 242 non-pregnant women)were included in the research.The MTHFR gene 1298CC homozygote carriers were more susceptible to yield higher plasma homocysteine levels than the 1298AA/AC carriers,with standardized coefficients of 0.086 (P＜0.05) and 0.104 (P＜0.01) of all the participants and the pregnant women,respectively.The MTHFR gene 1793AA homozygote carriers more likely showed higher plasma osteocalcin levels (standardized β=0.091,P＜0.01) than the 1793GG/GA carriers among all the subjects.Plasma homocysteine levels were positively correlated with blood lead levels among the participants and the pregnant women with standardized coefficients of 0.320 (P＜0.01) and 0.179 (P＜0.01),respectively.Plasma osteocalcin levels were positively associated with blood lead levels among pregnant and non-pregnant women with standardized coefficients of 0.084 (P＜0.05) and 0.125 (P＜0.01),respectively.In conclusion,homocysteine and osteocalcin contents in plasma are associated with the MTHFR gene A1298C polymorphism and blood lead levels among pregnant women.The MTHFR gene A 1298C polymorphism-related homocysteine is a possible risk factor for increased blood lead levels among Chinese women.

Characteristics and risk factors for healthcare-associated infection in pa-tients with severe chronic hepatitis B / 中国感染控制杂志

Objective To investigate the clinical characteristics and risk factors for healthcare-associated infection (HAI)in patients with severe chronic hepatitis B (CHB),and provide theoretical basis for preventing and controlling HAI.Methods Retrospective survey was used to investigate the occurrence of HAI in hospitalized patients with severe CHB in a hospital between January 2012 and January 2015,risk factors for HAI were analyzed. Results A total of 126 patients with severe CHB were investigated,49 patients developed 106 times of HAI, incidence of HAI was 38.89%.The main HAI site was respiratory tract (n=47,44.34%),the next was abdominal cavity (n=34,32.08%).A total of 76 isolates of pathogens were detected,gram-negative bacteria,gram-positive bacteria,and fungi accounted for 53.95%(n =41 ),43.42%(n =33),and 2.63%(n =2)respectively.Risk factors for HAI in patients with severe CHB were patients ’ age ≥ 60 years, length of hospital stay ≥ 30 days, complications,invasive operation,serum albumin < 35 g/L,and white blood cell count (WBC)< 4 × 109/L. Conclusion Incidence of HAI in patients with severe CHB is high,the majority are respiratory tract and abdominal cavity infection,risk factors are old age,long length of hospital stay,invasive operation,hypoalbuminemia,and low WBC count.

Clinical study ofHuangkui capsule combined with benzbromarone on the treatment of the patients with chronic uric acid nephropathy / 国际中医中药杂志

Objective To observe the clinical effect ofHuangkui capsule combined with benzbromarone on the treatment of the patients with chronic uric acid nephropathy (CUAN).Methods A total of 60 patients were recruited and divided into the treatment group and the control group by using the random number table method, each group 30 patients. Two groups were treated with conventional treatment, such as low purine, low protein diet, quit smoking and drinking extra water. The control group was added with oral benzbromarone, and the treatment group was added with oralHuangkui capsule. All the treatments last 8 weeks. Theblood uric acid (BUA), serum creatinine (SCr), blood urea nitrogen (BUN), cystatin C (Cys-C), SOD, 24-hour urinary protein quantity and Urinary sediment red blood cell count were detected by the automatic biochemical analyser.The clinical effect was evaluated by the Rheumatoid arthritis (RA) quality of life questionnaire.Results Compared with the control group, the total effective rate in the treatment group was 86.64% (26/30), which was significantly higher than that of 63.33% (19/30) in the control group (χ2=7.264, P=0.001). After treatment, the BUA (273.52 ± 110.37μmol/Lvs. 331.28 ± 126.54μmol/L,Z=-2.543), BUN (6.24 ± 1.23 mol/Lvs. 8.16 ± 2.35 mol/L,Z=-2.680), SCr (90.37 ± 20.16μmol/Lvs. 110.38 ± 16.72μmol/L,Z=-2.534), Cys C (0.86 ± 0.51 vs. 1.03 ± 0.10,Z=-2.372) in the treatment group were lower than those of the control group (P<0.01); SOD (156.37 ± 32.04μmol/Lvs. 43.36 ± 31.52μmol/L,Z=-2.041) in the treatment group was higher than that in the control group (P<0.01); the 24 hours urinary protein (439.86 ± 250.41 mg/24hvs.897.69 ± 213.37 mg/24h,Z=-2.853), urine sediment RBC counts (50.31 ± 14.06 points/μlvs.213.47 ± 38.46 points/μl, Z=-2.106) in the treatment group were lower than those in the control group (P<0.01); the physiological function(43.14 ± 2.06 pointsvs.36.48 ± 3.21 points,Z=10.362), the psychological function (40.76 ± 3.28 points vs. 16.54 ± 3.71 points,Z=9.547), social function (40.74 ± 3.58 points vs. 33.04 ± 5.48 points,Z=6.034), healthy self-awareness (24.57 ± 1.97 points vs. 22.63 ± 3.43 points,Z=4.236) and total score (127.38 ± 6.43 points vs. 107.69 ± 13.57 points,Z=6.754) in the treatment group were higher than those in the control group (P<0.01) . Conclusions TheHuangkui capsule combined with benzbromarone could reduce CUAN patient's blood uric acid levels, protect renal function, and improve the quality of life.

Preparation and evaluation of monodispersed, submicron, non-porous silica particles functionalized with ß-CD derivatives for chiral-pressurized capillary electrochromatography.

Submicron, non-porous, chiral silica stationary phase has been prepared by the immobilization of functionalized ß-CD derivatives to isocyanate-modified silica via chemical reaction and applied to the pressurized capillary electrochromatography (pCEC) enantio-separation of various chiral compounds. The submicron, non-porous, cyclodextrin-based chiral stationary phases (sub_µm-CSP2) exhibited excellent chiral recognition of a wide range of analytes including clenbuterol hydrochloride, mexiletine hydrochloride, chlorpheniramine maleate, esmolol hydrochloride, and metoprolol tartrate. The synthesized submicron particles were regularly spherical and uniformly non-porous with an average diameter of around 800 nm and a mean pore size of less than 2 nm. The synthesized chiral stationary phase was packed into 10 cm × 100 µm id capillary columns. The sub_µm-CSP2 column used in the pCEC system showed better separation of the racemates and at a higher rate compared to those used in the capillary liquid chromatography mode (cLC) system. The sub_µm-CSP2 possessed high mechanical strength, high stereoselectivity, and long lifespan, demonstrating rapid enantio-separation and good resolution of samples. The column provided an efficiency of up to 170,000 plates/m for n-propylbenzene.

Risk factors for death in children with severe hand, foot and mouth disease / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the death risk factors in children with severe hand, foot and mouth disease (HFMD).</p><p><b>METHODS</b>A total of 164 children with severe HFMD between May 2010 and September 2012 were recruited and classified into death and survival groups according to their prognosis. The differences in general information, clinical signs and symptoms and laboratory examinations were compared between the two groups. The multivariate logistic regression analysis was used to identify death risk factors in children with severe HFMD.</p><p><b>RESULTS</b>There were significant differences in the incidences of atypical rash, persistent fever, dyspnea, pulmonary hemorrhage, heart rate increase, blood pressure abnormalities, cold sweat, capillary refill time>3 seconds and frequent seizures, and blood glucose, serum creatine kinase and serum lactate levels between the death and the survival groups (P<0.05). The multivariate logistic regression analysis showed three independent death risk factors for children with severe HFMD: pulmonary hemorrhage (OR=9.466, 95%CI: 1.786-21.256), abnormal blood pressure (OR=5.224, 95%CI: 1.012-28.985) and elevated serum lactate level (OR=2.154, 95%CI: 1.020-8.253).</p><p><b>CONCLUSIONS</b>Pulmonary hemorrhage, abnormal blood pressure and elevated serum lactate are major death risk factors for children with severe HFMD.</p>

Metabonomics Study on Luteolin Intervention of Breast Cancer MCF-7 Cells / 分析化学

The metabolic profiles of control and MCF-7 cells treated with luteolin were analyzed separately using gas chromatography/mass spectrometry ( GC/MS ) to study the mechanism of the luteolin treatment on MCF-7 cells. Cell viability assays showed that luteolin had inhibition effect on MCF-7 cells. Partial least square discriminant analysis ( OPLS-DA) was used to process the metabolic data. Since cells in phase of S were increased significantly, we speculated that luteolin had a blocking effect on pentose phosphate pathway of MCF-7 cells, which contributed to its inhibition effect on proliferation of MCF-7 cells.

miR-216b suppresses cell proliferation and invasion by targeting PKCα in nasopharyngeal carcinoma cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To elucidate whether miR-216b suppresses cell proliferation and invasion by targeting PKCα, thus to reveal the molecular mechanism that miR-216b functions as a tumor suppressor in nasopharyngeal carcinoma (NPC).</p><p><b>METHODS</b>PKCα 3'UTR-luciferase vector was constructed and dual-luciferase reporter gene assay was employed to examine the effect of miR-216b on luciferase activity. Nasopharyngeal cancer CNE2 cells were transfected with miR-216b mimics, and then qRT-PCR and Western blotting were performed to detect the expressions of PKCa mRNA and protein. The effects of PKCα downregulation on cell proliferation and invasion were assessed after PKCα siRNA were transfected into CNE2 cells. CNE2 cells were cotransfected with miR-216b mimics and PKCα plasmid, and the proliferation of CNE2 cells was assayed using a MTS cell proliferation assay kit.</p><p><b>RESULTS</b>The results of dual-luciferase reporter gene assay demonstrated that miR-216b could bind to the 3'-untranslated region (UTR) of PKCα and inhibited the luciferase activity to 62.4% of that of the mimics control cells. The expressions of PKCα mRNA and protein were significantly down-regulated by 49.1% and 55.7%, respectively, in comparison with that of the control cells. siRNA-mediated downregulation of PKCα suppressed the proliferation and invasion ability of CNE2 cells, and could partially mimic the tumor-inhibiting effect of miR-216b. Moreover, the overexpressed PKCα may partially reverse the inhibitory effect of miR-216b on proliferation of CNE2 cells.</p><p><b>CONCLUSION</b>miR-216b suppresses cell proliferation and invasion by targeting PKCα in NPC cells.</p>

Comparison of the retinal modulation transfer function between amblyopes successfully corrected and normal subjects.

AIM: To analyze the retinal modulation transfer function between amblyopes whose visual acuity was corrected to 5.0 and normal subjects at the same age. METHODS: RM-800 used to detect contrast sensitivity was adopted to measure MTF of 96 amblyopes (96 eyes) whose visual acuity was corrected to 5.0 and 80 normal controls (80 eyes) at the same age under six interference fringes (IVA=0.06, 0.1, 0.2, 0.4, 0.6, 0.8). RESULTS: The functional values of amblyopes were significantly lower than those of normal subjects in every fringe (P<0.01), especially in medium and high frequency. CONCLUSION: For amblyopes, MTF was still abnormal after stopping the treatments.

Spatial analysis of neural tube defects in a rural coal mining area.

Shanxi province in northern China has one of the highest reported prevalence rates of neural tube defects (NTDs) in the world. The current study selected Heshun, the county with the highest rate of NTDs in Shanxi, as a study area and tested whether residence in a coal mining area was a contributing factor. A NTD cluster was detected in an area within 6 km of the coal mines for almost every year during 1998-2005. Poisson regression analysis revealed that there may be an association between production in coal mines and prevalence of NTDs in coal mine areas. Future work identifying factors independently correlated with NTDs in coal mining regions may provide further insights into the health effects of coal mines on NTDs.

[Substance P and its receptors are involved in the effect of histamine H3 receptor agonist, IMETIT on nasal allergic symptoms in guinea pigs].

OBJECTIVE: To explore the influence of histamine H3 receptor agonist, IMETIT and simultaneous use of IMETIT and H1-receptor antagonist, Loratadine, on the symptoms of allergic rhinitis (AR) and substance P(SP) secretion and expression of SP receptor (SP-R) mRNA in AR model in guinea pigs. METHODS: Guinea pigs were divided randomly into 4 groups: AR group (group A), IMETIT group (group B), Loratadine group (group C) and IMETIT+Loratadine group (group D). The severity of AR was assessed by determining the extent of three markers of allergic symptoms (sneezing, nasal rubbing and nose blocking). The changes in the nasal mucosa were studied by pathological methods. The expression of positive cell of SP was detected by immunohistochemistry. SP-R mRNA expression in nasal mucosa was used to do reverse transcriptive-polymerase chain reaction (RT-PCR). Statistical analysis was performed using a SPSS 13.0 software. RESULTS: In Group B, the mean (x ± s) number of sneeze [(15.0 ± 1.3) times], scratching nose [(16.5 ± 2.3) times] and respiratory frequency [(76.3 ± 4.1) times/min] were significantly improved than those in group A [(23.5 ± 2.6) times, (26.1 ± 4.1) times and (66.5 ± 5.8) times/min, respectively), P value were 0.000, 0.000 and 0.001, respectively]. The numbers of SP-positive cells [(11.6 ± 3.6)/HP] and SP-R mRNA expression (0.64 ± 0.04) in group B were reduced significantly compared to group A [(27.1 ± 9.7)/HP, (0.83 ± 0.03), P value were 0.000, 0.000, respectively]. Sneeze [(10.0 ± 2.3) times], scratching nose [(11.8 ± 1.7) times] and respiration [(90.0 ± 5.0) times/min] in Group D were improved significantly than those in group B (P value were 0.000, 0.002 and 0.000, respectively). SP-positive cells [(2.0 ± 1.7)/HP] and SP-R mRNA expression (0.52 ± 0.06) in Group D compared with group B were also significantly reduced (P value were 0.012 and 0.000, respectively). Pathological changes in guinea pig nasal mucosa in group B, group D were alleviated than those in group A. The combination of IMETIT and Loratadine had a synergistic effect on these effects (F value were 11.59, 8.28, 5.61, 5.48, 6.50, respectively, P value were 0.002, 0.008, 0.025, 0.027, 0.017). CONCLUSIONS: IMETIT and the combination of IMETIT with Loratadine can effectively relieve the symptoms of AR in guinea pigs, its mechanism may be relevant to reduce SP secretion and the expression of SP-R mRNA, and the two has a synergistic effect. It may be useful as a novel therapeutic approach in nasal allergy.