Weihai's urban development model is representative of coastal cities in China. Landsat MSS/ TM/OLI images were used to extract the land use types of Weihai from 1985-2015 using the object-oriented support vector machine (SVM) classification method. The landscape pattern indexes were calculated based on the classification results of land use. The temporal and spatial characteristics of land use and landscape pattern were analyzed by considering Weihai's economic development. The overall kappa (OK) coefficients were greater than 83% and the overall accuracy (OA) values were greater than 85%. Over 80% of both producer's accuracy (PA) and user's accuracy (UA) values of different land use types were greater than 85%. Changes in land use and landscape patterns were closely related to the local economic development. The areas of cultivated land and woodland continued to decrease. The expansion of construction land came mainly from the cultivated land and woodland as with as very little from waters. Under the combined effect of economic development and human activities, the landscape pattern of Weihai as a whole has been decentralized. The internal structure is relatively complex and the fragmentation of land use is increasing. The development model of Weihai is the expansion-aggregation-expansion.

ObjectiveTo develop and internally validate a prediction model for 6-year risk of stroke and its primary subtypes in middle-aged and elderly Chinese population.DesignThis is a retrospective cohort study from a prospectively collected database.ParticipantsWe included a total 3124 adults aged 45–80 years, free of stroke or myocardial infarction at baseline in the 2009–2015 cohort of China Health and Nutrition Survey.Primary and secondary outcome measuresThe outcome of the prediction model was stroke. Investigated predictors were: age, gender, body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), hypertension (HBP), drinking status, smoking status, diabetes and site. Stepwise multiple Cox regression was applied to identify independent predictors. A nomogram was constructed to predict 6-year risk of stroke based on the multiple analysis results. Bootstraps with 1000 resamples were applied to both C-index and calibration curve.ResultThe overall incidence of overall stroke was 2.98%. Age, gender, HBP and TC were found as significant risk predictors for overall stroke; age, gender, HBP and LDL-C were found as significant risk predictors for ischaemic stroke; age, gender, HBP, BMI and HDL-C were found as significant risk predictors for haemorrhagic stroke. The nomogram was constructed using significant variables included in the model, with a C-index of 0.74 (95% CI: 0.72 to 0.76), 0.74 (95% CI: 0.71 to 0.77), and 0.81 (95% CI: 0.78 to 0.84) for overall stroke, ischaemic stroke, and haemorrhagic stroke model, respectively. The calibration curves demonstrated the good agreements between predicted and observed 6-year risk probability.ConclusionOur nomogram could be convenient, easy to use and effective prognoses for predicting 6-year risk of stroke in middle-aged and elderly Chinese population.

Background Phenylalanine hydroxylase deficiency (PAHD) is the most prevalent inherited disorder of amino acid metabolism in China. Its complex phenotype includes many variants and genotypes among different populations. Methods and results In this study, we analyzed the phenylalanine hydroxylase gene (PAH) variants in a cohort of 93 PAHD patients from Fujian Province. We also assessed genotype and phenotype correlation in patients with PAHD. A total of 44 different pathogenic variants were identified, including five novel variants. The three most prevalent variants among all patents were c.158G > A, p.(Arg53His) (18.03%), c.721C > T, p.(Arg241Cys) (14.75%), and c.728G > A, p.(Arg243Gln) (7.65%). The frequency of the c.158G > A, p.(Arg53His) variant was highest in patients with mild hyperphenylalaninemia, whereas the frequency of the c.1197A > T, p.(Val399 =) and c.331C > T, p.(Arg111Ter) variants was highest in patients with classic phenylketonuria. The most abundant genotypes observed in PAHD patients were c.[158G > A];[728G > A], c.[158G > A];[442-1G > A], and c.[158G > A];[721C > T]. Comparing allelic phenotype to genotypic phenotype values yielded fairly accurate predictions of phenotype, with an overall consistency rate was 85.71% for PAHD patients. Conclusions Our study identified a PAH variant spectrum in PAHD patients from Fujian Province, Southeastern China. Quantitative correlation analysis between genotype and phenotype severity is helpful for genetic counseling and management.

It is required that the clinical screening of metabolic disorders in newborns meet International Organization for Standardization 15189-2012 approval. The new tandem mass spectrometry (MS/MS) based screening system and its companion reagent should be independently authenticated before their implementation in clinical diagnosis laboratories. Linearity, stability, accuracy, and precision evaluations were carried out to verify the performance of the Waters ACQUITY TQD MS/MS system with the NeoBase non-derivatized MS/MS PerkinElmer kit for detecting amino acids and acylcarnitine in newborns with metabolic disorders. Statistically, the correlation coefficient ( R 2 ) of 0.9982 to 0.9999 indicates good linearity. The measurements at the beginning and end of the reagent storage procedure were taken for stability verification. No significant difference was detected between the 2 periods. The amino acid exhibited a degree of bias in the range of 0% to 14.17%, with acylcarnitine's being was in the range of 0% to 14.84%; they consequently passed the quality assessment requirements for clinical laboratories of the China National Centre. The amino acids’ within-run, between-run, and day-to-day run precision were 1.19% to 7.68%, 1.63% to 5.01%, and 4.77% to 12.48%, respectively, while the total imprecision was 5.55% to 13.33%. Acylcarnitine's within-run, between-run, and day-to-day run precision was 1.2% to 8.43%, 0.19% to 9.60%, and 2.33% to 10.74%, respectively, while it's total imprecision was 6.57% to 13.99%. The manufacturer declared that the total imprecision of the tests, using Multiple Reaction Monitoring, should be less than or equal to 25% of the coefficient of variation for the kit's high and low-quality control levels. The performance of the non-derivatized MS/MS screening system in detecting the amino acids and acylcarnitines passed the test's requirements. It was maintained in accordance with the routine clinical chemical detection system.

Propionic acidemia is associated with pathogenic variants in PCCA or PCCB gene. We investigated the potential pathogenic variants in PCCA or PCCB genes in Fujian Han population. Two probands and their families of Han ethnicity containing two generations were subject to newborn screening using tandem mass spectrometry, followed by diagnosis using urine gas chromatography mass spectrometry. Sanger sequencing was used to identify potential mutations in PCCA and PCCB genes. Compound heterozygous variants were identified in PCCB gene in two siblings of the first family, the youngest girl showed a novel missense variant c.1381G>C (p.Ala461Pro) in exon 13 and a heterozygous missense variant c.1301C>T (p.Ala434Val) in exon 13, which were inherited respectively from their parents. The oldest boy is a carrier with a novel missense variant c.1381G>C (p.Ala461Pro) in exon 13 which were inherited from his father. In the second family, c.1535G>A homozygous mutations were identified in the baby girl, which were inherited respectively from their parents. In silico analysis, several different types of bioinformatic software were utilized, which predicted that the novel variant c.1381G>C in PCCB gene was damaged. According to ACMG principle, the missense variant c.1381G>C (p.Ala461Pro) in exon 13 was a Variant of Undetermined Significance (VUS). One novel missense variant and two missense variants in PCCB gene were identified in the study. The novel variant of PCCB gene identified VUS was identified for the first time in the Chinese population, which enriched the mutational spectrum of PCCB gene.

Background Rare studies focused on the tandem mass spectrometry (MS/MS) findings for the primary carnitine deficiency (PCD) in the neonates in China mainland. In this study, we aim to analyze the gene mutation spectrum of PCD in Fujian Province in China mainland. Methods Primary carnitine deficiency (PCD) samples used in this study were selected from 95,453 cases underwent neonatal screening between May 2015 and February 2020. SLC22A5 gene sequencing was performed on the neonates and their parents with C0 level of less than 8.8 μmol/L. Results Ten patients (male: 7; female: 3) were finally included in this study. Among these patients, nine were neonates, and one was maternal decline of C0 of less than 8.8 μmol/L. The maternal case showed two types of mutations of SLC22A5 including c.760C>T(p.R254*) and c.1400C>G(p.S467C). The other nine neonates showed compound mutations involving nine types in 18 sites, among which two mutations [i.e., c.37G>T(p.E13*) and c.694A>G(p.T232A)] were novel that had never been reported before. Bioinformatic analysis indicated that c.37G>T(p.E13*) was a pathogenic mutation, while the c.694A>G (p.T232A) was considered to be likely pathogenic. Conclusion MS/MS screening on PCD contributed to the early diagnosis and screening. In addition, SLC22A5 gene mutation analysis contributed to the PCD screening.

Background: We aim to explore the realization of 16 quality control indices of neonatal disease screening in neonatal disease management information system, and to establish the multi-center management evaluation model under the framework of the whole province. Methods: Based on the network management system for neonatal screening originally used in our province, the quality management module of neonatal disease was developed and applied according to the quality control index. A quantitative evaluation method was established for the quality of all maternal and child health care institutions involved in neonatal disease screening related to neonatal disease screening, specimen collection and recall of suspected cases. Results: The quality management information was shared by all neonatal screening agencies. Comprehensive evaluation was given to the multi-center quality management measurements. Comprehensive evaluation was performed to quality among different medical institutions. Evaluation of applicability and timeliness of quality in practical work was conducted accordingly. Conclusions: The timeliness of self-improvement in centers and medical institutions were improved. The application of neonatal disease screening quality management index improved the requirements for neonatal screening management. The quality management module was adopted to conduct dynamic management of the whole management process, which greatly improved the overall management level of neonatal screening.

Background:To eliminate the harm induced by iodine deficiency, a strategy of universal salt iodization (USI) is adopted. During this period, it shows a significant increasing trend in the prevalence of thyroid nodules, resulting in shining a spotlight on whether thyroid nodules are related to the level of iodine nutrition. In this study, a 1:1 matched case-control study is conducted to investigate whether thyroid nodules are related to the level of iodine nutrition and whether there are differences in thyroid function indicators. And other influencing factors of thyroid nodules are further explored. Methods:Villages with median urinary iodine (MUI) <100μg/L, 100-199μg/L, and 200-299μg/L in general population were selected as the survey sites. The residents who have lived there for more than 5 years with thyroid nodules tested by B-ultrasound were the case group, while those without nodules found by B-ultrasound examination were the control group that matched 1:1 with the case group by age (±3 years), gender and region. All subjects completed questionnaires, collected blood and urine samples to detect the thyroid function indicators and urinary iodine concentration. Results: There was no statistically significant difference in the MUI between the case group and the control group in the areas with adequate iodine intake, the areas with mild iodine deficiency(P>0.05); The MUI of the case group in the areas where iodine intake was more than adequate was lower than that of the control group(P<0.05); The case group’s levels of Tg and FT4 in both areas with mild iodine deficiency and more than adequate iodine intake were higher than those of the control group, whereas only the level of Tg of the case group was higher than that of the control group in the areas with adequate iodine intake, meaning that the difference was statistically significant (P<0.05); Other indicators had no statistical significance. The conditional Logistic regression model fitted by Enter method resulted that there were statistically significant correlations between history of thyroid disorders, Tg, TgAb and thyroid nodules. Conclusions: On the one hand, there was no statistical correlation between the iodine nutrition and thyroid nodules in the areas with adequate iodine intake and areas with mild iodine deficiency. On the other hand, in the areas with more than adequate iodine intake, the urine iodine concentration in the nodule group was lower than that in the non-nodule group, which indicates that when the urine iodine concentration is 200-299 μg/L, a slight increase in urinary iodine may help inhibit the occurrence of nodules. History of thyroid disorders and increased Tg and TgAb levels were risk factors for thyroid nodules. Tg can serve as a functional biomarker for thyroid nodules.