Population pharmacokinetic study of tacrolimus in pediatric patients with primary nephrotic syndrome / 药学学报

Tacrolimus is commonly used in the treatment for the refractory primary nephrotic syndrome (PNS) in the pediatric patients. Data were retrospectively obtained from 100 children with 357 tacrolimus trough concentrations in our center between May 2010 and March 2016. Information of age, sex, body weight, drug dose, co-therapy medications, laboratory tests and sampling time were collected. The population pharmacokinetic model was developed using nonlinear mixed effect modeling (NONMEM) software. A one-compartment model with first-order absorption and elimination best described the data. The population estimate of apparent clearance (CL/F) and apparent volume of distribution (V/F) was 6.54 L·h-1 and 86.2 L, respectively. Body weight (WT, kg), daily dose of tacrolimus (DD, mg·day-1) and co-therapy azole antifungal agent have a significant impact on the CL/F. The final PPK model of CL/F was:CL/F=6.54×((WT)/25)K×((DD)/1.5)0.293×0.657Azole,K=(WT-30.9)/(WT-30.9+10.4-30.9). When combined with azole antifungal agents, Azole was 1, whereas vice versa was 0. This is the first PPK study of tacrolimus conducted in pediatric patients with PNS, which may facilitate individualized drug therapy of tacrolimus.

[Value of serum miR-17-92 cluster in diagnosis of retinoblastoma].

OBJECTIVE: To investigate the value of serum miR-17-92 cluster in the diagnosis of retinoblastoma (RB). METHODS: Serum samples were collected from 20 children with RB and 20 healthy controls. Quantitative real-time PCR was used to measure the expression of miR-17-92 cluster. The expression of miR-17-92 cluster was compared between children with different stages of RB and the changes in the expression of miR-17-92 cluster after multimodality therapy were analyzed. The receiver operating characteristic (ROC) curve was used to investigate the value of serum miR-17-92 cluster in the diagnosis of RB. RESULTS: Compared with the healthy controls, the children with RB had significantly higher relative expression of miR-17-3P, miR-17-5P, miR-18a, and miR-20a in serum (P<0.05), and miR-18a showed the greatest increase. There were no significant differences in the relative expression of miR-19a, miR-19b-1, and miR-92a-1 between children with RB and healthy controls (P>0.05). There were no significant differences in the expression of miR-17-5P, miR-17-3P, miR-18a, and miR-20a between the children with early-to-moderate stage of RB and those with advanced stage of RB (P>0.05), but there were significant reductions after multimodality therapy (P<0.05). In the diagnosis of RB, the areas under the ROC curve (AUCs) for serum miR-17-3P, miR-17-5P, miR-18a, and miR-20a were 0.770, 0.755, 0.828, and 0.665 respectively, and miR-18a had the largest AUC, with a sensitivity of 90% and a specificity of 65%. CONCLUSIONS: miR-17-3P, miR-17-5P, miR-18a, and miR-20a are highly expressed in the serum of children with RB, and miR-18a may be used as a new marker for the diagnosis of RB.

[A preliminary study of retinoblastoma-related serum tumor markers].

OBJECTIVE: To screen out retinoblastoma (RB)-related serum tumor markers by measuring the levels of serum alpha fetoprotein (AFP), carcino-embryonic antigen (CEA), neuron-specific enolase (NSE), carbohydrate antigen 125 (CA125), carbohydrate antigen 153 (CA153), carbohydrate antigen 199 (CA199), and carbohydrate antigen 724 (CA724) in children with RB. METHODS: The levels of seven serum tumor markers (AFP, CEA, NSE, CA125, CA153, CA199, and CA724) were determined in 20 children with RB and 20 healthy children (control) using a chemiluminescent immunoassay. RESULTS: The serum levels and positive rates of NSE, CA153, and CA199 in the RB group were significantly higher than those in the control group (P<0.05). However, there were no significant differences in the levels of AFP, CEA, CA125, and CA724 between the two groups (P>0.05). NSE had the highest sensitivity, but a relatively low specificity for the diagnosis of RB. CA153 and CA199 had a relatively high specificity, but a relatively low sensitivity for the diagnosis of RB. CONCLUSIONS: The serum levels and positive rates of NSE, CA153, and CA199 are high in children with RB. Combined measurement of these three serum tumor markers may have an important diagnostic value for RB.

Clinicopathological study of eight cases of atypical placental site nodule / 临床与实验病理学杂志

Purpose To investigate clinical and pathological features,diagnosis and differential diagnosis,treatment and prognosis of the atypical placental site nodules (APSN).Methods 8 cases of APSN were analyzed retrospectively.Their gross and microscopic features and immune phenotypes were observed,and the clinical histories and followed up were also reviewed.Results The patients were 26 to 42 years old (mean 32.8 years old).Clinical symptoms included occupation disease in uterine cavity,irregular vaginal bleeding,etc.Some patients were checked by hysteroscope and showed pale-yellow space-occupying lesions.Microscopically,the lesions consisted of single to multiple nodules or plaques of hyalinized extracelluar matrix,in which chorionic-type intermediate trophoblasts with mild atypia were haphasardly distributed.All the lesions were without myometrial invasion.Chorionic-type intermediate trophoblasts of the 3 cases expressed CK (AEI/AE3),p63,HLA-G,β-catenin,GATA-3 and the Ki-67 labelling index was 8％ ～ 15％.One of the 8 patients had a hysterectomy.Other seven patients were managed by lesionectomy under the hysteroscopy.8 patients were followed up with ultrasonography,curetting endometrium and endocervical mucosa and all of the patients were alive without the progress of the lesion.Conclusion APSN is easily misdiagnosed as squamous cell carcinoma,epithelioid leiomyosarcoma and other gestational trophoblastic diseases.It is important to understand the pathological features of APSN and we can avoid misdiagnosing for other benign or malignant tumours.Misdiagnosis will influence the clinical treatment.

[Changing trends and clinical characteristics of febrile seizures in children].

OBJECTIVE: To investigate the clinical characteristics and changing trends of febrile seizures (FS) in children. METHODS: The clinical data of 1 922 children with FS admitted from 2004 to 2013 were analyzed retrospectively. The clinical characteristics and changing trends of FS in the two five-year periods were analyzed. RESULTS: In 1 922 children with FS, the male/female ratio was 2.27:1. The mean age at onset was 3.0±1.8 years, while the peak age at onset was 1-3 years. There were 1 556 children (80.96%) with simple FS and 366 (19.04%) with complex FS. The number of children with FS in the second five-year period (1 202 cases) increased by 66.9% compared with that in the first five-year period (720 cases). The proportion of children with complex FS was significantly higher in the second five-year period than in the first five-year period (21.13% vs 15.56%; P<0.05). In children with simple FS, there were no significant differences in the age and body temperature at onset, convulsion duration, and the incidence of complications between the two five-year periods (P>0.05). However, children with complex FS had a significantly lower age at onset, a significantly lower body temperature at onset, a significantly longer convulsion duration, and a significantly higher incidence of complications including myocardial injury and hyponatremia in the second five-year period than in the first five-year period (P<0.05). CONCLUSIONS: In the last decade, the number of children with FS and incidence of complex FS increased, and the outcome became worse according to clinical characteristics, suggesting that more attention should be paid to timely diagnosis and treatment of complex FS.

[Preventive effect of behavioral therapy plus flunarizine in children with migraine].

OBJECTIVE: To investigate the preventive effect of behavioral therapy plus flunarizine in children with migraine. METHODS: Ninety pediatric patients with migraine between January 2011and January 2014 were randomly divided into treatment group (45 cases) and control group (45 cases). The treatment group received behavioral therapy in addition to oral flunarizine, while the control group received oral flunarizine alone. All patients were followed up for 3 months to evaluate the therapeutic effect by the Pediatric Migraine Disability Assessment Score (PedMIDAS) and improved Bussone headache index. RESULTS: There were no significant differences in PedMIDAS (P>0.05) and improved Bussone headache index (P>0.05) between the control and treatment groups before treatment. Significant differences were observed in PedMIDAS (16±8 vs 20±10; P<0.05) and improved Bussone headache index (25±18 vs 37±21; P<0.05) between the two groups after 3 months of treatment. CONCLUSIONS: Preventive treatment of behavioral therapy plus oral flunarizine shows a better clinical efficacy than oral flunarizine alone in children with migraine and holds promise for clinical application.

[Clinical features and risk factors of co-morbid tic disorder in children with attention deficit hyperactivity disorder].

OBJECTIVE: To study the clinical features and risk factors of co-morbid tic disorder (TD) in children with attention deficit hyperactivity disorder (ADHD). METHODS: A total of 312 children with ADHD were involved in this study. Subtypes of co-morbid TD, incidences of TD in different subtypes of ADHD (ADHD-I, ADHD-HI and ADHD-C) were observed. Thirteen potential factors influencing the comorbidity rate of TD in ADHD were evaluated by univariate analysis and multiple logistic regression analysis. RESULTS: Forty-two of 312 children with ADHD suffered from co-morbid TD (13.5%). Comorbidity rate of TD in children with ADHD-C (24.1%) was significantly higher than in those with ADHD-HI (10.9%) and ADHD-I (8.8%) (P<0.05). There were 21 cases (50.0%) of transient TD, 12 cases (28.6%) of chronic TD, and 9 cases (21.4%) of Tourette syndrome. The univariate analysis revealed 6 factors associated with comorbidity: addiction to mobile phone or computer games, poor eating habits, infection, improper family education, poor relationship between parents and poor relationship with schoolmates. Multiple logistic analysis revealed two independent risk factors for comorbidity: improper family education (OR=7.000, P<0.05) and infection (OR=2.564, P<0.05). CONCLUSIONS: The incidence of co-morbid TD in children with ADHD is influenced by many factors, and early interventions should be performed based on the main risk factors.

[An epidemiological survey of attention deficit hyperactivity disorder in school-age children in Shenzhen].

OBJECTIVE: To investigate the prevalence of attention deficit hyperactivity disorder (ADHD) and behavior problems among school-age children in Shenzhen City of Guangdong. METHODS: A total of 10553 students in Grades 1-6 from different primary schools in Shenzhen City were assessed by Conners Parent Symptom Questionnaire (PSQ) and Conners Teacher Rating Scale (TRS). Children showing abnormalities according to PSQ or TRS were further assessed according to the diagnostic standard for ADHD as laid out in the diagnostic and statistical manual for mental disorders- 4th edition (DSM-Ⅳ). RESULTS: A total of 8193 PSQ and TRS assessments were completed. The children were aged from 7 to 13 years. The total prevalence rate was 7.60% by PSQ and 5.59 % by TRS. Four hundred and forty-two children were diagnosed having ADHD by DSM-Ⅳ, with a prevalence rate of 5.39%. There were significant differences in the prevalence rate of ADHD among children aged 7 to 13 years (χ2=21.613, P<0.05). In children aged 7 to 9 years, the prevalence rate was higher (above 6%). The prevalence rate of ADHD in boys was significantly higher than in girls (6.65% vs 3.12%; P<0.05). Impulsion and hyperactivity (79.6%), learning (60.6%) and conduct disorders (52.0%) were the main behavioral problems in children with ADHD. The prevalence of learning disorders was higher in girls than in boys. Conclusions The prevalence rate of ADHD in children from primary schools in Shenzhen City is 5.39%, and it is higher in children aged 7 to 9 years. Boys have a higher prevalence rates of ADHD than girls. Impulsion and hyperactivity, learning and conduct disorders are common problems in children with ADHD.

[Clinical features of various subtypes of attention deficit hyperactivity disorders in children].

OBJECTIVE: To study the features of various subtypes of attention deficit hyperactivity disorders (ADHD) in children. METHODS: Sex composition, risk factors, comorbidities, intelligence quotient and behavioral problems were investigated in 175 children with ADHD who met the Diagnostic Statistical Manual of Mental Disorder Criteria (DSM-IV). The children were classified into three groups: ADHD predominantly inattentive (ADHD-I, n=82), ADHD predominantly hyperactive-impulsive (ADHD-HI, n=24) and ADHD combined type (ADHD-C, n=69). RESULTS: There were no significant differences in the sex composition among the three groups. The rates of birth abnormality in the ADHD-I and the ADHD-C groups were higher than those in the ADHD-HI group. Negative parenting practices were noted more frequently in the ADHD-HI and the ADHD-C groups than the ADHD-I group. There were no significant differences in the performance intelligence quotient (PIQ), verbal intelligence quotient (VIQ) and full intelligence quotient (FIQ) among the three groups. However, the incidence of imbalance between VIQ and PIQ in the ADHD-I group was higher than the other two groups. The rate of comorbidities with oppositional defiant disorder (ODD) and tic disorder (TD) in the ADHD-C and the ADHD-HI groups was higher than that in the ADHD-I group. Both the ADHD-I and the ADHD-C groups had a higher rate of comorbidities with learning disorder (LD) than the ADHD-HI group. The impulsive/hyperactive and conduct problems were more severe and the hyperactivity index was higher in the ADHD-C and the ADHD-HI groups than those in the ADHD-I group, while the learning difficulties in the ADHD-I group were the most severe. CONCLUSIONS: The children with ADHD-C or ADHD-HI have higher incidences of comorbidities with ODD and TD than those with ADHD-I who the learning difficulties and the imbalance between VIQ and PIQ are more severe.

Analysis of the changing trends of frequency and localization of gastric cancers arising from different sites of the stomach in population of the high incidence area of esophageal and gastric cancers in Hebei province / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the changing trends of frequency and localization of gastric cancers arising from the gastric cardia, corpus and antrum during the past 14 years in population of the high incidence area of esophageal and gastric carcinoma in Hebei province, China.</p><p><b>METHODS</b>The clinicopathological data of 4334 cases of gastric carcinomas among the local residents of Cixian and Zanhuang counties, initially diagnosed in our department from 1993 to 2006, were retrospectively analyzed. The proportion of gastric carcinomas arising from the gastric cardia, corpus and antrum in different years and in patients with different sex and ages were analyzed and compared, and the changing trends of the frequency of gastric carcinoma arising from different sites of the stomach were statistically analyzed.</p><p><b>RESULTS</b>Among all the 4334 gastric carcinomas, gastric cardia carcinoma accounted for 68.0%, significantly higher than that of corpus (24.2%) and antrum (7.9%; chi(2) = 124.396, P < 0.0001). An increasing tendency in the proportion of gastric cardia carcinoma from 1993 to 2006 was seen. The percentage of cardiac carcinoma in the high incidence area of esophageal carcinoma (Cixian county) was higher than that in the high incidence area of gastric cancer (Zanhuang county) (71.2% vs. 51.2%; chi(2) = 109.648, P < 0.0001). The increase in the incidence of cardiac carcinoma in Cixian county was mainly due to the increase of cardiac carcinoma from 1993 to 2006, while the contributing factor for the increase in the proportion of cardiac carcinomas was resulted from the decrease of incidence of antrum carcinoma in Zanhuang county during the same period. The occurring site of gastric carcinoma was related with age of patients (chi(2) = 58.380, P < 0.0001). The percentage of carcinoma of the gastric body was highest in < 50 year age group, while that in the gastric cardia was highest in 61 - 70 year age group (71.6%).</p><p><b>CONCLUSION</b>The major occurring site of gastric carcinoma is the gastric cardia among the local residents in population of the high incidence areas of esophageal and gastric carcinomas during the past 14 years in Hebei province, China. The increasing trend of cardiac carcinoma and decreasing trend of corpus carcinoma in Cixian county and antrum carcinoma in Zanhuang county will be maintained in the coming years if the epidemiological conditions will not be changed.</p>

Comparison of the reliability of two ELISA kits for detecting IgM antibody against hepatitis E virus / 中华预防医学杂志

<p><b>OBJECTIVE</b>To study the reliability of two ELISA kits for detecting IgM antibody against hepatitis E virus (HEV).</p><p><b>METHODS</b>Serum samples from 92 healthy subjects, 71 cases suspected of hepatitis E, 55 patients with confirmed diagnosis of acute hepatitis E, 50 individuals with rheumatoid factor (RF) positive and 54 persons with anti-HAV IgM positive were detected with three hepatitis E diagnostic kits. MP-IgM (MP, Singapore), Wantai-IgM and anti-HEV IgG (Wantai, China). HEV RNA was analyzed with RT-PCR in 52 of 71 cases suspected of hepatitis E.</p><p><b>RESULTS</b>In healthy subjects,cases suspected of hepatitis E and confirmed acute hepatitis E, the concordance between the two anti-HEV IgM reagents was 73.39% (160/218) and the significant differences in the positive rates of two assays were not observed [46.79% (102/218) vs 44.04% (96/218), chi2 = 0.62, P > 0.05]. Of 71 patients suspected of hepatitis E, the sensitivity for diagnosing acute hepatitis E of Wantai-IgM and MP-IgM were 83.08% (54/65) and 78.46% (51/65) (chi2 = 0.16, P > 0.05), respectively. Among those suspected of hepatitis E with HEV RNA positive, the sensitivity of Wantai-IgM was obviously higher than that of MP-IgM [(97.14%, 34/35) vs (74.29%, 26/35), chi2 = 4.9, P < 0.05]. 48 of 55 patients (87.27%) with confirmed diagnosis of hepatitis E were Wantai-IgM positive while 37 (67.27%) was MP-IgM positive (chi2 = 4.0, P < 0.05). The specificity of Wantai-IgM was higher than MP-IgM [100.00% (202/202) vs 89. 11% (180/202), chi2 = 20.05, P < 0.005]. RF and anti-HAV IgM might cause MP-IgM false positive without interference on Wantai-IgM.</p><p><b>CONCLUSION</b>Wantai-IgM should be a good ELISA kit for the diagnosis of acute hepatitis E.</p>

The preliminary analysis on immunogenicity of DNA vaccines against human papillomavirus 58 / 病毒学报

In order to evaluate the immunogenicity of HPV 58 L1 DNA vaccines, five DNA vaccines had been constructed with pcDNA3.1 vector containing different L1 genes of HPV 58, which were designated as L1h, L1hDeltac, L1S, L1SM and L1wt. The protein expression of DNA vaccines in vitro was tested by Western blot. The ability of forming pseudovirus was evaluated by transfecting DNA vaccine together with pcDNA3.1-h58L2 and pcDNA3.1-GFP into 293FT cells. The neutralizing antibodies and cellular immune response produced in BALB/c mice immunized with the DNA vaccines were detected by using pseudovirus-based neutralization assay and ELISPOT respectively. The results showed that the five DNA vaccines had been successfully constructed; the level of protein expression of L1hDeltac was the highest and those for L1S and L1SM were of medium, while no expressed target protein of L1wt was detected. Only L1S could form the pseudovirus while the other four vaccines could not. L1S and L1h could induce neutralizing antibody. However, the average titer of neutralizing antibody for L1S (1:6,400) was much higher than that for L1h (1:48) and the other three vaccines could not induce neutralizing antibody. No cellular immune response for all five DNA vaccines was detectable by ELISPOT. The results indicated that DNA vaccine against HPV 58 can form pseudovirus in vitro, also can induce high level of neutralizing antibodies. This provides reference for screening HPV vaccine in future.

Epidemiological survey on the infection of hepatitis E virus among pigs in Henan province / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate hepatitis E virus (HEV) infection among pigs in Henan province.</p><p><b>METHODS</b>A total of 623 swine sera, collected from 5 districts, were divided into two groups, under 3-month of age and over 3-month of age. They were tested for HEV antigen and antibody by using ELISAs, respectively. The sera positive for HEV antigen were tested for HEV RNA with RT-PCR. The positive products of RT-PCR were cloned and sequenced.</p><p><b>RESULTS</b>The positive rates of anti-HEV antibody of the groups under 3-month and over 3-month of age were 90.27% and 92.55%, respectively, without statistical difference, while those of HEV antigen were 15.93% and 5.69%, respectively, with significant difference. The positive rates of anti-HEV antibody and HEV antigen were significantly different among different districts. HEV RNA was detectable in 5 of 47 HEV antigen positive samples. The sequence analysis showed that in 4 of 5 specimens the sequence belonged to genotype 4 while in the remaining one the sequence was genotype 1.</p><p><b>CONCLUSION</b>The prevalence rate of HEV infection in pigs was high in Henan province and the rate differed in different districts.</p>