Objective To discuss the effect of neonatal congenital hypothyroidism (CH)screening in preterm infants.Methods The result of 208 713 cases neonatal congenital hypothyroidism screening in Guangzhou neonatal screening center were analyzed,including 11589 cases preterm infant and 197 124 cases of full term.The difference of screening positive rate and incidence between preterm infants and full term infants group were compared and the efficiency of preterm infants congenital hypothyroidism screening were estimated.Results A total of 208 713 newborns were screened and the screening positive rate was 1.39%.123 cases were confirmed positive for CH and the incidence rate was 1 /1 697.124 cases were screening positive in preterm infants and the screening posi-tive rate was 1.06%.14 cases were confirmed positive for CH and the incidence rate was 1 /828 in preterm infants group.2 771 cases were screening positive in full term infants and the screening positive rate was 1.41%.109 cases were confirmed positive for CH and the incidence rate was 1 /1 809 in full term group.The screening positive rate was lower and the incidence rate of preterm infants group(χ2 =4.89,P <0.05)was higher than that of the full term infants group(χ2 =8.26,P <0.05).Conclusion The incidence rate of congenital hypothyroidism is higher in preterm infants.Neonatal screening is an effective measure for early diagnosis of preterm infants congenital hypothyroidism.

Objective To study the effect of IZL-2003Ⅱ Immune Therapy System on lymphocyte immuno-function induced by chemotherapy in advanced non-small-cell lung cancer(NSCLC)patients.Methods 112 cases of advanced NSCLC patients were randomly divided into the two groups .The treatment group ( n=56 ) was given IZL-2003ⅡImmune Therapy System after chemotherapy for 6d as a couse and the control group ( n=56) was given chem-otherapy only.The peripheral blood routine and T lymphocyte subgroup (CD3+,CD4+, CD8+and CD4+/CD8+)activity of patients in both group were measured by flow cytometry 1 day before chemotherapy and the 8th day after chemothera-py.ResultsThere was difference between the treatment group and control group on the increasing rate of Leucocyte (P<0.05)the 8th day after treatment;After the 8th day,the expression levels of CD8+T cells was lower,but has no significant(P<0.05);The expression levels of CD3+,CD4+and the ratio of CD4+/CD8+were higher in the treatment group(P<0.05).The expression levels of CD3+T cells was lower,but has no significant(P<0.05);The expression levels of CD4+T cells and the ratio of CD 4+/CD8+were significantly lower after treatment in control group ( P<0.05);the expression levels of CD8+T cell was higher significantly in the control group (P<0.05).Conclusion IZL-2003ⅡImmune Therapy System can antagonize myelosuppression and elevated the immunologyical function of advanced NSCLC patients significantly .

AIM:To direct embryonic stem cells(ESCs)into hematopoietic stem cells(HSCs)in vitro by simulating the hematogenic microenvironment in human early embryonic aorta-gonad-mesonephero(AGM)region.METHODS:Murine E14 embronic stem cell line was used for two-step differentiation.In the first step of primary differentiation,E14 ESCs were seeded into semisolid methylcellulose-based medium containing bone morphogenesis protein 4(BMP4)and vascular endothelial growth factor(VEGF)for embryoid body(EB)formation.On days 3,6,9,12 and 15,single EB cells were analyzed for Flk-1+ cells amount through flow cytometry.In the second step,single cell from EB containing most Flk-1+ cells was further co-cultured with human AGM stromal cells in non-contact system.On co-culture days of 3,6,9 and 12 days,cells were collected for cell count,flow cytometry for Sca-1+c-kit+ cells analysis,and colony forming cell assay.RESULTS:During the EB formation,BMP4+VEGF promoted Flk-1+ cell genesis on day 9 at peak pencentage value of 27.53%?2.84%,which was statistically higher than that in control group as 8.77?1.10(P

Objective: To analyze the association between alcohol consumption and hyperuricemia among residents in Chengdu City, so as to provide the evidence for prevention and control of hyperuricemia. Methods: Based on the Natural Cohort Study in Southwest Area, residents at ages of 30 to 79 years were recruited in Chengdu City in 2018. Information of demographics, smoking, alcohol consumption and diet were collected through a questionnaire survey. Blood uric acid was tested in the laboratory. Participants were divided into never, moderate and excessive drinking groups based on alcohol consumption. A multivariable logistic regression model was used to analyze the association between alcohol consumption and hyperuricemia, and subgroup analysis was conducted according to gender, current residence, physical activity and body mass index (BMI). Results: A total of 20 164 residents were investigated, including 8 776 males (43.52%) and 11 388 females (56.48%), with a mean age of (51.22±12.33) years. There were 9 769 never-drinkers (48.45%), 8 310 moderate-drinkers (41.21%), and 2 085 excessive-drinkers (10.34%). Hyperuricemia was detected in 4 101 patients, with a detection rate of 20.34%. Multivariable logistic regression analysis showed that moderate drinking (OR=1.122, 95%CI: 1.031-1.222) and excessive drinking (OR=1.529, 95%CI: 1.349-1.734) were associated with an increased risk of hyperuricemia. Moderate and excessive drinking were associated with an increased risk of hyperuricemia among men, urban residents, residents with a high level of physical activity, and those with BMI less than 24 kg/m2 (all P<0.05). Excessive drinking were associated with an increased risk of hyperuricemia among rural residents, residents with a low level of physical activity and with BMI of 24 kg/m2 and higher (all P<0.05). Conclusions Both moderate and excessive drinking are associated with an increased risk of hyperuricemia. Moderate drinking is not associated with a higher risk of hyperuricemia among rural residents, residents with a low level of physical activity and with BMI of 24 kg/m2 and higher.

Objective:To investigate the correlation between amide proton transfer-weighted (APTw) values and Ki-67 labeling index of cervical squamous cell carcinoma.Methods:From October 2017 to December 2018, 24 patients with cervical squamous cell carcinoma [International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ-Ⅲ] were prospectively enrolled in Peking Union Medical College Hospital and underwent pelvic morphological MRI on a 3.0 T MR scanner, including three-dimensional turbo-spin-echo APTw imaging and DWI. The maximum diameters of the lesions, APTw values and ADC values on the slice with the maximum diameter of the lesion were independently measured by two radiologists. The ICC was computed to evaluate the inter-observer consistency. Ki-67 immunohistochemical expression status was assessed by one pathologist. The Pearson correlation analysis was performed between the APTw values, maximum diameters, ADC values and Ki-67 labeling index.Results:The APTw values of cervical squamous cell carcinoma were (2.9±0.5)%. Inter-observer ICC was 0.972 (95%CI 0.937-0.988). The APTw values were positively moderately correlated with Ki-67 labeling index [(61.9±18.7)%, r=0.532, P=0.008]. The maximum diameters of the lesions were (28.7±10.6) mm. The mean ADC values were (0.998±0.217)×10 -3 mm 2/s. No correlations were found between maximum diameters, ADC values and Ki-67 labeling index ( r=0.038, P=0.859; r=0.238, P=0.263). Conclusion:APTw values can partially reveal the proliferation status of cervical squamous cell carcinoma.

Objective: To reveal the molecular epidemiologic characteristics of glucose-6-phosphate dehydrogenase (G6PD) gene and to evaluate based on the genetic analysis the newborn screening program performance and enzymatic diagnosis of G6PD deficiency in Guangzhou. Methods: G6PD enzyme activities were measured by quantitative fluorescence assay in dry blood spots of 16 319 newborns(8 725 males, 7 594 females) 3-7 days after birth in Guangzhou Newborn Center. They were born in Guangzhou form Oct. 1 to 20, 2016. The cutoff value of G6PD was less than 2.6 U/g Hb in dry blood spots. G6PD deficiency was diagnosed when G6PD<1 700 U/L or G6PD/6PGD<1 in red blood cells. Genetic analysis of G6PD gene was performed on the dry blood spot samples of 823 newborns (including positive 346, negative 477)with various levels of G6PD enzyme activities through fluorescence PCR melting curve analysis(FMCA) to detect 15 kinds of mutations reported to be common among Chinese.G6PD gene Sanger sequency was performed in seven highly suspicious patients with negative results by FMCA. Results: (1) Using the cutoff value of G6PD< 2.6 U/g Hb , a total of 687(4.2%) newborns showed positive screening results, including 560 (6.4%) males and 127(1.7%) females. (2) Among the newborns with positive screening results, 214 males and 122 females were randomly chosen for G6PD gene analysis. The results showed that 197 (92.1%) males were hemizygote and 108(88.6%) females were mutation carriers with one to four alleles. Among the newborns with negative screening results, 41 males with G6PD 2.6-2.8 U/g Hb and 436 females with G6PD 2.6-4.5 U/g Hb were chosen for genetic analysis.Mutations were detected in 5(12.2%)boys, and 226(51.8%) girls were carriers.G6PD gene Sanger sequency of seven highly suspicious patients showed that c.406C>T, c.551C>T, c.835A>T hemizygote were found in 3 male's samples, respectively. (3) The estimated prevalence of harboring mutation was 6.0% in males and 13.5% in females according to rates of mutation in samples with various levels of G6PD enzyme activities. Six common mutations were c.1388G>A、c.1376G>T, c.95A> G, c.871G>A, c.1024C>T, c.392G>T, accounting for 95.5% of detected alleles .(4) based on results of G6PD gene analysis, the newborn scereening of G6PD deficiency with cutoff value G6PD<2.6 U/g Hb yielded a positive predict value(PPV) of 93.5%, a false-positive rate of 0.5%, and a sensitivity of 99.0% for males. A PPV of 88.5%, a false-positive rate of 0.2% . The prevalence of severe type G6PD deficiency in females was about 1.5%. Compared with to genetic analysis, the sensitivity and PPV of G6PD activity assay in red blood cells were 95.5%, 97.2%, respectively. Conclusions The prevalence of G6PD deficiency in males was 6.0% in Guangzhou. Six mutations c.1388G>A, c.1376G>T, c.95A>G, c.871G>A, c.1024C>T, c.392G>T accounted for 95.5%. The cutoff value of G6PD<2.6 U/g Hb innewborn screening program and the criteria of biochemical diagnosis could accurately identify G6PD deficiency . Combined with biochemical and molecular analysis will improve the accuracy of diagnosis of G6PD deficiency and detect more heterozygous females.

An ammonium-tolerant mutant of Actinobacillus succinogenes, YZ25, was obtained in the medium containing 61-242 mmol/L NH4+ after DES mutagenesis. Succinic acid produced by the mutant YZ25 reached 32.68 g/L when the medium contains 50 g/L glucose and 121 mmol/L ammonium, which was increased by 180.5% compared with that of the parent strain. The effects of different ammonium salts on the growth of the mutant and its metabolic response to high ammonium concentrations were investigated. The results showed that low ammonium concentration could improve the specific growth rates of the mutants, while high ammonium concentration inhibited cell growth. The ammonia-nitrogen half-inhibition constants (Ki) for different ammonium salts were as follows: 215 mmol/L for (NH4)2SO4, 265 mmol/L for NH4HCO3, 235 mmol/L for NH4Cl, and 210 mmol/L for NH4NO3. The process of ammonium inhibition on the mutant YZ25 was investigated in 3.0 L stirred fermenter. When NH4OH was used to buffer the pH, cell growth was not inhibited. However, production of succinic acid and consumption of glucose gradually decreased when cells entered the stationary phase, and the glucose could not be utilized completely at the end of fermentation. The possible ammonium inhibition mechanism was discussed based on the metabolic pathway of A. succinogenes.
Actinobacillus ; genetics ; growth & development ; metabolism ; Bioreactors ; Drug Tolerance ; Fermentation ; Industrial Microbiology ; Mutation ; Quaternary Ammonium Compounds ; metabolism ; pharmacology ; Succinic Acid ; metabolism

OBJECTIVE3β- hydroxysteroid dehydrogenase deficiency (3βHSD), a rare form of congenital adrenal hyperplasia (CAH) resulted from mutations in the HSD3B2 gene that impair steroidogenesis in both adrenals and gonads. We report clinical features and the results of HSD3B2 gene analysis of a Chinese pubertal girl with salt wasting 3βHSD deficiency.

METHODWe retrospectively reviewed clinical presentations and steroid profiles of the patient diagnosed in Guangzhou Women and Children's Medical Center in 2013. PCR and direct sequencing were used to identify any mutation in the HSD3B2 gene.

RESULTA 13-year-old girl was diagnosed as CAH after birth because of salt-wasting with mild clitorimegaly and then was treated with glucocorticoid replacement. Breast and pubic hair development were normal, and menarche occurred at 12 yr, followed by menstrual bleeding about every 45 days. In the last one year laparoscopic operation and ovariocentesis were performed one after another for recurrent ovary cysts. Under corticoid acetate therapy, ACTH 17.10 pmol/L (normal 0-10.12), testosterone 1.31 nmol/L (normal <0.7), dehydroepiandrosterone sulfate 13.30 µmol/L (normal 0.95 - 11.67), cortisol 720 nmol/L (normal 130-772.8), androstenedione, 17-hydroxyprogesterone and progesterone were normal. Estradiol 461 pmol/L, follicle-stimulating hormone 3.04 IU/L, luteinizing hormone 8.52 IU/L in follicular phase. A pelvic ultrasound showed lateral ovaries cysts (58 mm × 50 mm × 35 mm) and a midcycle-type endometrium. A novel nonsense mutation c.73G >T (p.E25X) was identified in HSD3B2 gene. The girl was homozygous and her mother was heterozygous, while her father was not identified with this mutation.

CONCLUSIONA classic 3βHSD deficiency is characterized by salt wasting and mild virilization in female. Ovary cysts may be the one of features of gonad phenotype indicating ovary 3βHSD deficiency. A novel homozygous mutation c.73G >T(p.E25X) was related to the classical phenotype.

17-alpha-Hydroxyprogesterone ; Adolescent ; Adrenal Hyperplasia, Congenital ; diagnosis ; genetics ; Androstenedione ; China ; Codon, Nonsense ; Delayed Diagnosis ; Female ; Follicle Stimulating Hormone ; Homozygote ; Humans ; Hydrocortisone ; Luteinizing Hormone ; Mutation ; genetics ; Ovarian Cysts ; genetics ; Progesterone Reductase ; genetics ; Recurrence ; Retrospective Studies

Objective: To explore the TPO, DUOX2 and DUOXA2 genotypes and phenotypes of children with permanent congenital hypothyroidism(PCH) suspected dyshormonogenesis in Guangzhou, identified and treated at Guangzhou Newborn Screening Center. Six of them were born between 2011 and 2012. Method: Retrospectively analyzed the clinical data of 9 children with PCH suspected dyshormonogenesis. Genetic analysis of TPO, DUOX2 and DUOXA2 genes were performed with Sanger sequencing. Result: Of the 9 patients, four were identified variants in TPO gene including three cases with biallelic variants and one case with monoallelic variant. Novel c. 1784G>C( p. R595T) variant in TPO was predicted to be damaging by SIFT and PolyPhen-2. Four patients harbored monoallelic known variants in DUOX2 gene and the other one harbored heterozygous known mutation c. 738C>G(p.Y246X) in DUOXA2 gene.Two adolescent patients with biallelic variants in TPO gene showed classical PCH phenotypes with thyroid goiter or nodules. The six patients with monoallelic variant in TPO, DUOX2 or DUOXA2 presented variable phenotypes. Among the 433 578 newborns in the 2011-2012 cohort, there were 156 cases of CH. Six of these cases were PCH suspected dyshormonogenesis, among which 1 case was confirmed TPO biallelic variants and 5 cases were monoallelic variants of TPO, DUOX2, or DUOXA2 genes. Conclusion TPO and DUOX2 variants are the common molecular pathogenesis in children with PCH suspected dyshormonogenesis. Monoallelic variants in TPO, DUOX2 or DUOXA2 are associated with PCH and showed wide variability in their phenotypes. The novel variant p. R595T in TPO is probably a pathologic variant. The prevalence of PCH caused by TPO gene defects is rare in Guangzhou.

Objective To study the influence of postnatal age and season of sample collection on congenital hypothyroidism (CH) screening and to determine the appropriate cut-off value. Method From January 2015 to December 2017, neonatal thyroid stimulating hormone (TSH) screening data in Guangzhou were retrospectively analysed. The infants were assigned into four groups according to sampling postnatal age:24～＜48 h, 48～＜72 h, 3～＜7＜d and≥7 d, and assigned into another four groups according to their birth seasons. Based on the data of 2015 and 2016, the cut-off value of TSH for hypothyroidism were adjusted. The data of 2017 were used to verify the accuracy of the adjusted cut-off value. The cut-off value was determined based on the receiver operating characteristic (ROC) curve and percentile method. Specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of the cut-off value were also calculated. Result A total of 459854 newborns were screened from 2015 to 2016. 7329 were positive in preliminary screening, 371 were still positive after recall for re-examination, and 318 were confirmed with CH eventually. The optimal TSH cut-off value calculated using ROC curve was 9 mIU/L, with a percentage of 98.7. The cut-off value with sampling time≥48 h was set to 9 mIU/L in spring, summer and autumn, and 10 mIU/L in winter. The cut-off of sampling time 24～＜48 h was set to 10 mIU/L in all seasons. The data of 264993 newborns screened in 2017 were verified using the adjusted cut-off value. The overall positive rate was reduced from 1.27％to 1.02％, and the PPV was increased from 6.07％to 7.58％without adding false negative cases. Conclusion Adjusting cut-off values of TSH for CH screening according to postnatal age and season can effectively reduce false positive rates.