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 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.

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

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.

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

Objective: To investigate the incidence and constituent ratio of odontogenic tumors or odontogenic cysts in School and Hospital of Stomatology, Jilin University and to provide the reference for the clinical treatment. Methods: According to the WHO 2017 histological classification criteria, the pathological data of 4181 patients diagnosed as odontogenic tumors or odontogenic cysts in the Department of Pathology, Jilin University Stomatological Hospital from January 1961 to December 2017 were collected. Statistical analysis of the pathological types, gender, age and location of various tumors and cysts was conducted. Results: Of 4 181 cases, 1 055 were tumors and 3 126 were cysts. Among odontogenic tumors, benign tumors accounted for 96.11% (1 014/1 055), and malignant tumors accounted for 3.89% (41/1 055). The most common pathological type of odontogenic tumors was ameloblastoma [53.27% (562/1 055)], followed by cemento-ossifying fibroma [21.23% (224/1 055)] and odontoma [12.99% (137/1 055)]. The male-female ratio was 1∶1.04. The high-risk ages were 10-39. Maxilla-mandible ratio was 1∶2.85.As for cysts, radicular cysts [50.45% (1 577/3 126)] was the most common pathological type, followed by odontogenic keratocyst [25.59% (800/3 126)] and dentigerous cysts [21.56% (674/3 126)]. The male-female ratio was 1.37∶1. The high-risk ages were 20-49. Maxilla-mandible ratio was 1.37∶1. Conclusions There was no gender preference for odontogenic tumors in Jilin Province area in the 57 years. The majority tumors occurred in the radicular. The most common pathological type was ameloblastoma. As for odontogenic cysts, males showed a higher incidence and the majority cysts occurred in the maxilla. The most common pathological type was radicular cysts.

Objective: To analyz the current situation of the diagnosis, treatment and prevention of methylmalonic acidemia, the phenotypes, biochemical features and genotypes of the patients in the mainland of China, were investigated. Methods: Tottally 1 003 patients of methylmalonic acidemia from 26 provinces and municipalities of the mainland of China were enrolled. The clinical data, biochemical features and gene mutations were studied. Blood aminoacids and acylcarnitines, urine organic acids, and plasma total homocysteine were determined for the biochemical diagnosis. Gene analyses were performed for the genetic study of 661 patients. The patients were treated with individual intervention and long-term follow up. Prenatal diagnoses were carried out for 165 fetuses of the families. Results: Among 1 003 patients (580 boys and 423 girls), 296 cases (29.5%) had isolated methylmalonic acidemia; 707 cases (70.5%) had combined homocysteinemia; 59 patients (5.9%) were detected by newborn screening; 944 patients (94.1%) had the onset at the ages from several minutes after birth to 25 years and diagnosed at 3 days to 25 years of age. The main clinical presentations were psychomotor retardation and metabolic crisis. Multi-organ damage, including hematological abnormalities, pulmonary hypertension, kidney damage, were found. MMACHC, MUT, MMAA, MMAB, HCFC1, SUCLG1, SUCLA2 mutations were found in 631 patients (96.6%) out of 661 patients who accepted gene analysis. MMACHC mutations were detected in 460 patients (94.7%) out of 486 cases of methylmalonic acidemia combined with homocysteinemia. MUT mutations were found in 158 (90.3%) out of 169 cases of isolated methylmalonic acidemia. The development of 59 patients detected by newborn screening were normal; 918 cases (97.2%) were diagnosed after onset accepted the treatment. Forty-five of them completely recovered with normal development. Twenty-six patients (2.7%) died; 873 (92.5%) patients had mild to severe psychomotor retardation. Methylmalonic acidemia were found in 35 out of 165 fetuses by metabolites assay of amniotic fluid and amniocytes gene analysis. Conclusion Combined methylmalonic acidemia and homocysteinemia is the common type of methylmalonic acidemia in the mainland of China. CblC defect due to MMACHC mutations is the most common type of methylmalonic acidemia combined with homocysteinemia. MUT gene mutations are frequent in the patients with isolated methylmalonic acidemia. Newborn screening is key for the early diagnosis and the better outcome. Combined diagnosis of biochemical assays and gene analysis are reliable for the prenatal diagnosis of methylmalonic acidemia.