Efficacy and safety of a phenylalanine-free amino acid-based enteral formula (AA-PKU2) in 1-8 year-old children with phenylketonuria: a prospective, open, self-controlled and multi-center study in China / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of a phenylalanine-free amino acid-based enteral formula (AA-PKU2) in the treatment of children with phenylketonuria (PKU) aged 1-8 years.</p><p><b>METHODS</b>A prospective, open, self-controlled, multi-center trial was performed, enrolling 121 PKU children (1-8 years in age) consecutively between July, 2009 and May, 2011. Enteral nutrition therapy was administered for 32 weeks. The data on blood phenylalanine (PHE) levels, metal development, weight, height, head circumference, serum nutritional biomarkers (total protein, pre-albumin, albumin, total cholesterol, total triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol), and measurements from routine blood and urine examinations and from renal and hepatic function tests were collected before the therapy and at 8 weeks and 32 weeks after the therapy and were comparatively analyzed.</p><p><b>RESULTS</b>The mean blood PHE level at 8 and 32 weeks of AA-PKU2 treatment was 353±253 and 361±280 µmol/L respectively, significantly lower than that before the treatment (487±327 µmol/L; P<0.01). The difference in intelligence quotient scores before and after AA-PKU2 treatment was not significant (P>0.05) when assessed by the Gesell tests in children aged 1-4 years but significant (P<0.01) when assessed by WPPSI or WISR-R tests in children over 4 years. The average height, weight and head circumference at 8 and 32 weeks after treatment were significantly increased as compared to these measurements before treatment (P<0.01) with absolute levels similar to those in the control children. In contrast, the mean values of total protein, pre-albumin, albumin, total cholesterol, total triglyceride, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol at both time points were not different either from those prior to the treatment or from those in the control children. Mild diarrhea was the adverse events associated with AA-PKU2 treatment, which occurred in 3 (2.5%) cases. All these 3 patients fully recovered without treatment.</p><p><b>CONCLUSIONS</b>The phenylalanine-free amino acid-based formula, AA-PKU2, is effective and safe in controlling blood PHE levels and improving mental development with adequate nutritional support in PKU.</p>

Analysis on direct economic burden of stroke in the rural population of Hanzhong, Shaanxi Province / 中华流行病学杂志

<p><b>OBJECTIVE</b>To analyze the direct economic burden of stroke in rural areas of Hanzhong.</p><p><b>METHODS</b>Plan on primary interview was made after the purpose of the study had been informed to the managers of the 'surveillance field base', heads and members of the monitor assistants and detailed information was collected in the fields. Every single patient of stroke was then interviewed by the above said interviewers,using a self-designed questionnaire. 164 patients with stroke were interviewed in 53 villages with 75,000 persons lived there. The main items involved in the questionnaire would include: costs for inpatient or outpatient, reaching-out fees, fee for accommodation during treatment as outpatient, costs for treatment at home, long term medicine, caregivers and funerals as well as average income.</p><p><b>RESULTS</b>The median of annual direct economic burden was 3100 Yuan for each patient in Hanzhong rural area. There were no significant differences seen between males and females or among age groups (P > 0.05). The proportion of patients with medians of annual direct economic burden of: 1000 Yuan and below, 1001-5000 Yuan, 5001-10,000 Yuan, 10,001-20,000 Yuan and over 20,001 Yuan, were 29.2%, 36.0%, 18.3%, 9.8% and 6.0% respectively. The median of annual direct economic burden of first episode stroke was 5500 Yuan for each patient, and that of stroke was 1700 Yuan for each chronic patient. The direct economic burden of first episode was significantly higher than that of stroke (P < 0.01). The costs of hospitalization, accommodation of hospitalization and treatment at home of middle-aged patients were significant higher than that of old age patients (P < 0.05).</p><p><b>CONCLUSION</b>In this study, the direct economic burden of stroke was 2.9 times of the annual personal average income, which was contrary to the reports from other countries. However, the State Health Bureau bore 87.1% of the direct economic burden for urban patients, but patients in the rural areas had to pay from their own pockets. The direct economic burden of stroke was heavy in Hanzhong rural region, which called for measures to be made to decrease the direct economic burden of stroke in the region.</p>

Oral immunization of mice with vaccine of attenuated Salmonella typhimurium expressing Helicobacter pylori urease B subunit / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To prepare the live recombinant vaccine of attenuated Salmonella typhimurium SL3261 expressing Helicobacter pylori (H. pylori) B subunit (UreB) and to determine whether it could be used as an oral vaccine against H. pylori infection.</p><p><b>METHODS</b>Using genomic DNA of H. pylori Sydney strain (SSI) as template, the H. pylori UreB gene fragment was amplified by PCR and subcloned into the expression vector pTC01. The recombinant plasmid pTC01-UreB was then transferred into LB5000 to obtain modified forms, and further conversed into the attenuated Salmonella typhimurium SL3261 to obtain recombinant SL3261/pCT01-UreB as an oral immunization reagent, which was then used to orally immunize Balb/c mice twice at a three-week interval. Twelve weeks later, anti-UreB IgA antibodies in intestinal fluid and IgG antibodies in sera were determined by ELISA. The relating data in control groups (including body weight, gastric inflammation, etc.) were also collected.</p><p><b>RESULTS</b>The sequencing analysis showed that the UreB gene fragment amplified by PCR was consistent with the sequence of the H. pylori UreB gene. The restriction enzyme digestion revealed that the correct pTC01-UreB was obtained. SDS-PAGE and Western blot showed that a 61KD protein was expressed in SL3261/pTC01-UreB, which could be recognized by anti-H. pylori UreB antiserum and was absent in the control containing only Salmonella typhimurium SL3261 strain. The multiple oral immunization with SL3261/pTC01-UreB could significantly induce H. pylori specific mucosal IgA response as well as serum IgG responses. IFN-gamma and IL-10 levels were significantly increased in SL3261/pTC01-UreB group, and no obvious side effect and change in gastric inflammation were observed.</p><p><b>CONCLUSION</b>The attenuated vaccine of Salmonella typhimurium expressing H. pylori UreB can be used as an oral vaccine against H. pylori infection.</p>

Six novel mutations in PAH gene detected by sequencing / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore new mutation in phenylalanine hydroxylase (PAH) gene.</p><p><b>METHODS</b>The PAH genes from 40 phenylketonuria (PKU) patients and 30 normal controls were screened by PCR-single strand conformation polymorphism (SSCP) and further sequencing.</p><p><b>RESULTS</b>Eleven mutations and 3 polymorphisms in PAH gene were found. No abnormalities in the PAH gene from 30 controls were detected.</p><p><b>CONCLUSION</b>M276K, M276R, 280insT, IVS10nt+32T-->A, IVS4nt+47C-->T were demonstrated as novel mutations in comparison with the PAH mutation database. One mission mutation (H290R) was first documented in Chinese PKU gene.</p>