BACKGROUND: Cephalocervical cancer is closely related with genetic factors, but do the first-degree relatives have a higher risk for cancers? Slenderstyle acanthopanax root-bark has an anti-mutation chromosome stabilizer, can it enhance the anticaner ability of the first-degree relatives? OBJECTIVE: To study the genetic factor of cephalocervical cancer and antimutagenic effect of slenderstyle acanthopanax root-bark.DESIGN:A controlled experiment with human peripheral blood as the sample.SETTING: The Department of Medical Genetics of the Basic Medical Science School, and the Department of Otolaryngology of the First Hospital of Jilin University; The University of Warwick, UK.PARTICIPANTS: The subjects were taken during the period of October 2001 to March 2002. The patients with cephalocervical tumor and their first-degree relatives were all from the Department of Otolaryngology,FirstHospital of Jilin University, and healthy group were well-being blood devoting volunteers from Changchun City Central Blood Bank. There were group( n = 50) included 25 males and 25 females who were healthy blood patients group( n =30) were composed of 22 males and 8 females who did first-degree relative group(n=30) consisted of 19 males and 11 females. They were the first-degree relatives of patients with carcinoma of larynx and carcinoma of nasopharynx. Except for the family history of cancer,they themselves were all healthy. Informed consents were obtained from all of them.METHODS: The peripheral blood was collected as the sample and the lymphocyte culturing was performed. The culture cycle was 72 hours and bleomycin(BLM) (15 mL) was added into it at the 67~ hour, also the slenderstyle acanthopanax root-bark(SARB) (800 mg/L) was added into the antimutagenesis experiment. The cells were collected after culturing for another 72 hours. The conventional method was used for slide preparation. The slides were stained with Giemsa solution without banding. Choosing the proper objective and observing the numbers of chromatid breaks. The numbers of chromatid breaks were converted into the numbers of chromatid breaks per cell (b/c value). Namely, b/c value equals to the quotient, the number of chromatid break divided by the number of the cell observed in the slide.MAIN OUTCOME MEASURES: The number of chromatid breaks per cell (b/c value).RESULTS: All the 110 cases in the 3 groups entered the stage of result It was lower in the control group than that in the patients group and first-degree relatives group(0.16 ± 0.06, 0.48 ± 0. 14, 0.42 ± 0. 12, P ＜0.01). There was no significant difference in b/c value between the paparison between b/c value induced by combined SARB with BLM and only BLM was performed: The b/c value of former is significantly lower than the latter (0.48±0.14,0.15 ±0.08,0.42±0.12, 0.17±0.11,P ＜ 0.01).CONCLUSION: The first-degree relatives of the patients with cephalocervical cancers should be classified as tumor high-risk group. SARB as a chromatid stabilizer has an obvious inhibitory effect on b/c value of the patients induced by BLM and that of the first-degree relatives.

Objective:To analyze the medication of one patient with ulcerative colitis to provide pharmaceutical care and support for rational drug use in patients with ulcerative colitis. Methods:During the treatment of the patient with severe ulcerative colitis, clin-ical pharmacists analyzed the drugs used by the patient and provided pharmaceutical care for doctors and the patient according to the ex-amination and diagnosis of the patient. Results:The compliance, therapeutic effect and medication safety of the patient were all im-proved by giving clinical drug rationalization suggestions and targeted medication monitoring and education, which fully embodied the necessity of work of clinical pharmacists in the medication of patients. Conclusion:Through case analysis, clinical thinking of clinical pharmacists can be developed to promote rational drug use, avoid adverse drug reactions and achieve optimal effect of drug treatment.

Objectives To report the ifrst Chinese case of early onset argininosuccinic aciduria. Methods A girl aged three days was admitted because of vomiting and lethargy from the second day of life. General laboratory examination, blood amino acids analysis, urine organic acids tests and gene studies were performed for the diagnosis. Results Severe hyperam-monemia, liver dysfunction, metabolic acidosis, hypokalemia and hypocalcemia were found. Bood citrulline was extremely elevated (1098.12μmol/L vs normal range 5 to 25μmol/L), while blood arginine was decreased. Urine orotic acid, uracil and argininosuccinic acid were signiifcantly elevated. Two known heterozygosis mutations on ASL gene, c.544C>T (p.R182X) and c.706C>T (p.R236W), conifrmed the diagnosis of argininosuccinic aciduria. Unfortunately, protein-restricted diet with L-arginine supplement showed no effect. The patient died at the 23th day of life. Conclusions Argininosuccinic aciduria is a severe inherit-ed metabolic disorder. Clinical diagnosis is dififcult. It is characterized biochemically by severe citrullinemia. Urine organic acids analysis and ASL gene analysis are important for the differential diagnosis. In this study, a case of neonate death due to early-on-set argininosuccinic aciduria was diagnosed by post-mortem investigation. ASL gene study is helpful for the genetic counseling and prenatal diagnosis of the disease.

[Objective] The purpose of this paper is to explore and summarize the experience of Professor ZHOU Xiaohong's treatment of non-erosive reflux disease(NERD),and promote the application in clinic.[Method] By following the professor ZHOU Xiaohong clinical copy and collecting related medical record,the autor summed up the viewpoints and medication experience of Professor ZHOU Xiaohong in the treatment of NERD,and referred to traditional Chinese medicine and western medicine literature as the theoretical basis,and attached to the corresponding test case,in order to verify.[Results] Professor ZHOU Xiaohong believes that the pathogenesis of NERD is closely related to the liver,and modern research has confirmed that it is affected by mental and psychological factors.Stagnated heat in liver and stomach is the basic pathogenesis,and to soothe the liver and relieve depression is basic treatment,and according to the severity of the disease stage,treatment is different.Clearing heat and normalizing the stomach at acute episode and relieving qi stagnancy in liver in relieving period.At the same time with relieving sore throat and resolving phlegm and eliminating stagnation medicine and symptomatic treatment,the qi regulating,and the disease can be cured.[Conclusion] Professor ZHOU Xiaohong has rich clinical experience and unique clinical effect,it is worth further study.

Objective To investigate the clinical,biochemical and genetic findings in patients with isolated methylmalonic aciduria. Methods From January 2001 to December 2014,a total of 126 patients with isolated methyl-malonic aciduria from Peking University First Hospital were enrolled in this study. In 60 patients,gene analysis was per-formed. The clinical characteristics,laboratory findings,treatment and outcomes were retrospectively analyzed. Results Among the 126 patients,only 3 cases(2. 4% )were detected through newborn screening and treated with dietary in-tervention,cobalamin and L - camitine. The age at onset of 123 cases(97. 6% )varied from a few hours after birth to 7 years and 11 months old. The common presentations were recurrent vomiting,mental retardation,poor feeding,lethargy, respiratory distress,coma,seizures,cutaneous lesion and jaundice with 11 patients(8. 73% )dead. Abnormal family his-tory was found in 27(21. 4% )patients. Metabolic acidosis and anemia were frequent laboratory findings. Basal ganglia damage and white matter changes were observed in most patients. Sixty patients got genetic analysis,and 58 cases of them had MUT gene mutations. One case had MMAA defect. One case had MMAB defect. In MUT gene,12 novel muta-tions were identified. After treatment,mild to severe psychomotor retardation was observed in 112 patients with isolated methylmalonic aciduria. Conclusions The clinical manifestation of patients with isolated methylmalonic aciduria is complex,and prone to appear metabolic crisis. MUT defect is the main cause. Early metabolic investigation is very im-portant to reach diagnosis. Newborn screening,early diagnosis and adequate therapy are key points to reduce the morta-lity and handicap.

Objective To introduce a case of ethylmalonic encephalopathy which is an autosomal recessive metabolic disorder caused by mutations in the ETHE1 gene. Methods The clinical course and gene mutation in a case of ethylmalonic encephalopathy was retrospectively analysed. Results A previously healthy girl presented with intractable diarrhea from the age of 7 months. Since then, progressive psychomotor regression has been observed. When she was 23 months, her blood butyr-ylcarnitine was signiifcantly increased (4.48μmol/L vs. normal range 0.0~1.0μmol/L), and isovalerylcarnitine (0.70μmol/L vs. normal range 0.0~0.65μmol/L) was also elevated. Her urine levels of ethylmalonic acid and methylsuccinate acid were markedly increased. Cranial MRI revealed bilateral basal ganglia lesions supporting the diagnosis of ethylmalonic encephalopathy. On her ETHE1 gene, a reported mutation (c.488G>A, p.R163Q) and a novel mutation (c.203T>C, p.L68P) were identiifed. After lactose-free dietary treatment and the supplements of L-carnitine, coenzyme Q10, vitamins B1, B2 and C, gradual improvement in general condition, intelligence and motor development has been observed. Conclusions Ethylmalonic aciduria is common in the patients with inborn errors of mitochondrial fatty acid beta-oxidation. In ethylmalonic encephalopathy, elevated blood levels of butyrylcarnitine and isovalerylcarnitine are common and ETHE1 sequencing is helpful in its diagnosis.

Objective To explore the clinical, therapeutic and genetic features of IVD gene in late-onset non-classical isovaleric aciduria. Methods One boy and two girls presented with intractable vomiting were admitted. Urine organic acids and blood acylcarnitines proifles were analyzed. Isovaleric aciduria was diagnosed and conifrmed by IVD gene analysis. The patients were treated with leucine-restricted diet and the supplements of L-carnitine and glycine. Results Three patients had recurrent vomiting, drowsiness, odor of sweaty feet and metabolic acidosis from the age of 1 to 2 years. All of them had normal intelligence and leukopenia. One had oligocythemia. The blood isovalerylcarnitines (4.6 to 8.2μmol/L) and urine isovalerylglycines (36.1 to 1783.56 mmol/mmol creatinine) were elevated. Six mutations were found in their IVD gene. Four mutations (c.157C>T, c.214G>A, c.1183C>G and c.1208A>G) were reported. Two (c.1039G>A and c.1076A>G) were novel. The patients completely recovered after treatment with protein-restricted diet and the supplements of L-carnitine and glycine. Currently, they were aged 19 months to 14 years with normal physical and psychomotor development. Conclusions The clinical features of late-onset non-classical isovaleric aciduria are complex. It is onset in infants and young children and characteristic of recurrent vomiting and metabolic acidosis, which can be diagnosed by the blood acylcarnitine spectrum, urine organic acid analysis, and conifrmed by genetic analysis. L-carnitine supplement and diet intervention has signiifcant effects.

OBJECTIVETo investigate the phenotype and genotype of a Chinese boy and his family affected by infantile Sandhoff disease.

METHODSThe proband, a boy, was the first child born to a non-consanguineous couple. He showed startle reaction after birth and progressive psychomotor regression from the age of 8 months. From the age of 16 months, he presented seizures. When he was admitted at 17 months old, severe mental retardation and weakness were observed. Fundus examination revealed bilateral cherry-red spots in the macula and optic atrophy. Cranial MRI revealed abnormal signals in the thalamus, basal ganglia and white matter. Enzymatic assay and genetic testing were performed for the diagnosis. His mother visited us at 18 weeks of pregnancy seeking for prenatal diagnosis. HEXB gene diagnosis to the fetus was performed by direct sequencing.

RESULTSSignificant deficient total β-hexosaminidase (A and B) activity in peripheral leucocytes of the patient (0.0 nmol/h/mg compared with normal control, 41.9 to 135.1 nmol/h/mg) supported the diagnosis of Sandhoff disease. On his HEXB gene, two mutations were found. c.1645G-A (p.G549R) was novel. c.IVS7-48T was a reported mutation. Now, the patient was 2 years and 3 months old, with progressive general failure, severe epilepsy, blindness and hypermyotonia. Subsequently, the mother visited us at 18 weeks of pregnancy seeking for prenatal diagnosis. HEXB gene analysis of the amniocytes was performed by direct sequencing. Both of the two mutations were not detected from cultured amniocytes. The result revealed that the fetus was not affected by Sandhoff disease. A healthy girl, the sibling of the proband, was born in term. Postnatal enzyme analysis and genetic analysis of the cord blood cells confirmed the prenatal diagnosis.

CONCLUSIONOne novel mutation on HEXB gene was identified. Prenatal diagnosis to the fetus of this family was performed by amniocytes gene analysis.

Adult ; Amniotic Fluid ; cytology ; Child, Preschool ; DNA Mutational Analysis ; Female ; Genetic Testing ; Humans ; Male ; Mutation ; Pregnancy ; Prenatal Diagnosis ; Sandhoff Disease ; diagnosis ; genetics ; beta-Hexosaminidase beta Chain ; genetics

OBJECTIVEArgininemia is a rare disorder of urea cycle defect. The clinical manifestations of this disorder are similar to those of cerebral palsy so that the diagnosis is usually much delayed. This study aimed to investigate the phenotypes and genotypes of seven Chinese patients suffering from argininemia.

METHODThree boys and four girls with spastic tetraplegia were diagnosed as argininemia by blood aminoacids analysis and ARG1 gene study. Patients were given a protein-restricted diet, citrulline, sodium benzoate, and other treatment intervention. The mother of Patient 5 and 6 accepted genetic counseling and underwent prenatal diagnosis by amniocentesis.

RESULTSeven patients presented with progressive spastic tetraplegia and poor physical growth from the age of 1 month to 4 years. Argininemia was found at the age of 1 year and 10 months to 12 years. Five patients had mental retardations. Three had seizures. Their blood arginine elevated (86.66 to 349.83 µmol/L, normal controls 5 to 25 µmol/L). Liver dysfunction was found in six patients. Five patients had elevated blood ammonia levels. In four patients, cerebral atrophy was observed by cranial magnetic resonance imaging. Nine mutations in the ARG1 gene were identified from 7 patients. Only two mutations, c.703G > A in exon 7 and c.32T > C in exon 1 had been reported. c.34G > T, c.53G > A, c.67delG, c.232dupG, c.374C > T, c.539G > C and c.646-649delCTCA, were novel mutations of ARG1. A homozygous mutation c.703G > A was found in the amniocytes of Patient 5's mother, indicating that the fetus was affected by argininemia. Induced abortion was performed. c.53G > A from Patient 6 was not found in the amniocytes of her mother, indicating that the fetus was not affected by hepatocyte arginase deficiency. The result was confirmed by postnatal mutation analysis of cord blood and the normal blood arginine of the newborn.

CONCLUSIONArgininemia is one of the few treatable causes of pediatric spastic paralysis. In this study, seven Chinese patients with spastic tetraplegia were detected by blood aminoacids analysis and confirmed by molecular analysis. Seven novel mutations on ARG1 gene were identified. Prenatal diagnosis of the fetus of a family was performed by amniocytes ARG1 gene analysis.

Abortion, Induced ; Amniocentesis ; Arginase ; Arginine ; blood ; Asian Continental Ancestry Group ; Child ; Child, Preschool ; DNA Mutational Analysis ; Diet, Protein-Restricted ; Exons ; Female ; Fetus ; Genotype ; Homozygote ; Humans ; Hyperammonemia ; diagnosis ; Hyperargininemia ; diagnosis ; physiopathology ; Infant ; Infant, Newborn ; Male ; Mutation ; Phenotype ; Pregnancy ; Prenatal Diagnosis ; Quadriplegia ; diagnosis ; physiopathology ; Seizures

OBJECTIVEWe report the first case of acute encephalopathy induced by vaccination in an infant with methylmalonic aciduria cblA in China.

METHODThe clinical presentation, blood acylcarnitines analysis, urine organic acids analysis and gene studies of the patient were summarized.

RESULTThe proband, a boy, was admitted at the age of 15 months because of recurrent vomiting, acidosis and development delay for 8 months. The previously healthy boy presented vomiting and coma just one hour after hepatitis B vaccination at the age of seven months. Moderate dehydration, electrolyte disturbance and metabolic acidosis had been found. Although his acute metabolic crisis had been corrected soon after intravenous transfusion, psychomotor retardation and recurrent vomiting had been observed. When he was 15 months old, vomiting and lethargy occurred again 3 hours after DTaP vaccination. He was weakened as the illness became worse and got coma with dyspnea 7 days later. He was hospitalized with the suspected diagnosis of viral encephalitis. Blood acylcarnitines analysis, urine organic acids analysis and gene study had been performed for the etiologic investigation.His blood propionylcarnitine (16.3 µmol/L vs. normal range 1.0-5.0 µmol/L) and propionylcarnitine/free carnitine ratio (0.27 vs. normal range 0.03 to 0.25) increased. Markedly elevated urinary methylmalonic acid (388.21 mmol/mol creatinine vs. normal range 0.2 to 3.6 mmol/mol creatinine) and normal plasma total homocysteine supported the diagnosis of isolated methylmalonic aciduria. Two mutations, c.650 T>A (p.L217X) and c.742 C>T (p.Q248X), were identified in his MMAA gene, confirmed the diagnosis of cblA. Each parent carried one of the two mutations. Progressive clinical and biochemical improvement has been observed after hydroxylcobalamin injection, protein-restricted diet with the supplements of special formula and L-carnitine. He is currently 2 years and 7 months old with normal development and general condition.

CONCLUSIONA boy with cblA was firstly detected after the acute encephalopathy induced by vaccination in China. It is important to pay more attention to the patients with metabolic crisis or organ damage after vaccination. Metabolic studies are keys to the diagnosis of potential diseases and improve the outcome.

Amino Acid Metabolism, Inborn Errors ; complications ; Brain Diseases ; chemically induced ; Carnitine ; analogs & derivatives ; Diet, Protein-Restricted ; Hepatitis B Vaccines ; adverse effects ; Humans ; Infant ; Male ; Methylmalonic Acid ; urine ; Mutation ; Vaccination ; adverse effects ; Vitamin B Complex ; Vomiting