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Abstract Defective renal excretion and increased production of uric acid engender hyperuricemia that predisposes to gout. However, molecular mechanisms underlying defective uric acid excretion remain largely unknown. Here, we report a rare genetic variant of gout-unprecedented NUMB gene within a hereditary human gout family, which was identified by an unbiased genome-wide sequencing approach. This dysfunctional missense variant within the conserved region of the NUMB gene (NUMBR630H) underwent intracellular redistribution and degradation through an autophagy-dependent mechanism. Mechanistically, we identified the uric acid transporter, ATP Binding Cassette Subfamily G Member 2 (ABCG2), as a novel NUMB-binding protein through its intracellular YxNxxF motif. In polarized renal tubular epithelial cells (RTECs), NUMB promoted ABCG2 trafficking towards the apical plasma membrane. Genetic loss-of-function of NUMB resulted in redistribution of ABCG2 in the basolateral domain and ultimately defective excretion of uric acid. To recapitulate the clinical situation in human gout patients, we generated a NUMBR630H knock-in mouse strain, which showed marked increases of serum urate and decreased uric acid excretion. The NUMBR630H knock-in mice exhibited clinically relevant hyperuricemia. In summary, we have uncovered a novel NUMB-mediated mechanism of uric acid excretion and a functional missense variant of NUMB in humans, which causes hyperuricemia and gout.

Abstract Preeclampsia is a multisystem progressive condition and is one of the most serious complications of pregnancy. Owing to its unclear pathogenesis, there are no precise and effective therapeutic targets for preeclampsia, and the only available treatment strategy is to terminate the pregnancy and eliminate the clinical symptoms. In recent years, non-coding RNAs have become a hotspot in preeclampsia research and have shown promise as effective biomarkers for the early diagnosis of preeclampsia over conventional biochemical markers. PIWI-interacting RNAs, novel small non-coding RNA that interact with PIWI proteins, are involved in the pathogenesis of various diseases at the transcriptional or post-transcriptional level. However, the mechanisms underlying the role of PIWI-interacting RNAs in the pathogenesis of preeclampsia remain unclear. In this review, we discuss the findings of existing studies on PIWI-interacting RNA biogenesis, functions, and their possible roles in preeclampsia, providing novel insights into the potential application of PIWI-interacting RNAs in the early diagnosis and clinical treatment of preeclampsia.

Barth syndrome (BTHS) is a rare X-linked recessive genetic disorder characterized by a broad spectrum of clinical features including cardiomyopathy, skeletal myopathy, neutropenia, growth delay, and 3-methylglutaconic aciduria. This disease is caused by loss-of-function mutations in the TAFAZZIN gene located on chromosome Xq28, resulting in cardiolipin deficiency. Most patients are diagnosed in childhood, and the mortality rate is highest in the early years. We report a case of acute, life-threatening metabolic decompensation occurring one day after birth. A novel TAFAZZIN splice site mutation was identified in the patient, marking the first reported case of such a mutation in BTHS identified in China. The report aims to expand our understanding of the spectrum of TAFAZZIN mutations in BTHS.

The complex pathogenesis of preeclampsia (PE), a significant contributor to maternal and neonatal mortality globally, is poorly understood despite substantial research. This review explores the involvement of exosomal microRNAs (exomiRs) in PE, focusing on their impact on the protein kinase B (AKT)/hypoxia-inducible factor 1-α (HIF1α)/vascular endothelial growth factor (VEGF) signaling pathway as well as endothelial cell proliferation and migration. Specifically, this article amalgamates existing evidence to reveal the pivotal role of exomiRs in regulating mesenchymal stem cell and trophoblast function, placental angiogenesis, the renin–angiotensin system, and nitric oxide production, which may contribute to PE etiology. This review emphasizes the limited knowledge regarding the role of exomiRs in PE while underscoring the potential of exomiRs as non-invasive biomarkers for PE diagnosis, prediction, and treatment. Further, it provides valuable insights into the mechanisms of PE, highlighting exomiRs as key players with clinical implications, warranting further exploration to enhance the current understanding and the development of novel therapeutic interventions.

Abstract Background Congenital central hypoventilation syndrome (CCHS) is a rare autosomal dominant disease that is mainly caused by PHOX2B mutations. The purpose of this study is to analyze and summarize the clinical and genetic characteristics of CCHS patients in the Chinese population from our study and previous literature. Methods The potential pathogenic gene mutations of CCHS were identified and verified by next generation sequencing combined with Sanger sequencing, fluorescent probe PCR and capillary electrophoresis. The clinical characteristics and gene mutations of CCHS cases in Chinese population were summarized from our study and previous literature to explore the genotype–phenotype correlations. Results We identified 48 CCHS cases including three new cases from our report in China. Overall, 77.1% of the patients had PHOX2B polyalanine repeat expansion mutations (PARMs), and the remaining 22.9% had 10 distinct PHOX2B non‐polyalanine repeat expansion mutations (NPARMs). Compared to those with PARMs, patients with NPARMs were more likely to have premature birth (54.5% vs. 2.8%, p

Abstract Background Patients with abnormally invasive placenta (AIP) are at high risk of massive postpartum hemorrhage. Resuscitative endovascular balloon occlusion of the aorta (REBOA), as an adjunct therapeutic strategy for hemostasis, offers the obstetrician an alternative for treating patients with AIP. This study aimed to evaluate the role of REBOA in hemorrhage control in patients with AIP. Methods This was a historical cohort study with prospectively collected data between January 2014 to July 2021 at a single tertiary center. According to delivery management, 364 singleton pregnant AIP patients desiring uterus preservation were separated into two groups. The study group (balloon group, n = 278) underwent REBOA during cesarean section, whereas the reference group (n = 86) did not undergo REBOA. Surgical details and maternal outcomes were collected. The primary outcome was estimated blood loss and the rate of uterine preservation. Results A total of 278 (76.4%) participants experienced REBOA during cesarean section. The patients in the balloon group had a smaller blood loss during cesarean Sect. (1370.5 [752.0] ml vs. 3536.8 [1383.2] ml; P

Holographic display has attracted widespread interest because of its ability to show the complete information of the object and bring people an unprecedented sense of presence. The absence of ideal recording materials has hampered the realization of their commercial applications. Here we report that the response time of a bismuth and magnesium co-doped lithium niobate (LN:Bi,Mg) crystal is shortened to 7.2 ms and a sensitivity as high as 646 cm/J. The crystal was used to demonstrate a real-time holographic display with a refresh rate of 60 Hz, as that of the popular high-definition television. Moreover, the first-principles calculations indicate that the electron mobility while Bi occupying Nb-site is significantly greater than that in Li-site, which directly induces the fast response of LN:Bi,Mg crystals when the concentration of Mg is above its doping threshold.

Abstract Background As a rare mitochondrial disease, combined oxidative phosphorylation deficiency 14 (COXPD14) is caused by biallelic variants in the phenylalanyl-tRNA synthetase 2, mitochondrial gene (FARS2) with clinical features of developmental delay, an elevated lactate level, early-onset encephalopathy, liver failure, and hypotonia. The objectives of this study were to analyze the clinical and molecular features of two Chinese siblings affected with COXPD14, and to review relevant literature. Methods Mutation screening was performed by whole exome sequencing (WES) in combination with Sanger sequencing validation to identify the disease-causing variants of the two patients. Results The two siblings presented with severe clinical features and both progressed aggressively and failed to survive after treatment abandonment. We identified two compound heterozygous FARS2 variants c.925G>A p.Gly309Ser and c.943G>C p.Gly315Arg in this proband, which were inherited from the unaffected father and mother, respectively. In addition, Sanger sequencing confirmed that the elder affected sister carried the same compound heterozygous variants. The c.925G>A p.Gly309Ser variant is known and commonly reported in COXPD14 patients, while c.943G>C p.Gly315Arg is a novel one. Neither of the variants was found in 100 Chinese healthy controls. Both variants were classified as “deleterious” and were located in the highly conserved regions of the protein. The above results suggested that the two variants were likely causative in this COXPD14-affected pedigree. Conclusions Our study expands the mutation spectrum of FARS2 and highlights the importance of genetic testing in the diagnosis of diseases with a wide variety of phenotypes, especially in the differential diagnosis of diseases.

Background: Placenta previa-accreta constitutes an increasing clinical problem, whose diagnosis remains challenging in obstetrics. The current work aimed to assess whether second-trimester serum alpha-fetoprotein (AFP) amounts are altered in pregnant women with placenta previa-accreta versus control values. Methods: A retrospective chart review was performed for 504 pregnant women treated between 1 January 2016 and 28 February 2021. This cohort included 105 placenta previa-accreta and 122 placenta previa control cases, as well as 277 body mass index (BMI)-matched individuals with healthy pregnancy. The multiple of the median (MoM) for AFP was obtained from clinical records. Results: Markedly elevated MoM for AFP was detected in the placenta previa-accreta group compared with the placenta previa control and healthy pregnant control groups (both p < 0.001). Serum AFP levels had a significant positive association with placenta accreta after adjustment for age, BMI, and gestational week at blood collection (β = 0.60; 95% confidence interval [95% CI]: 0.52, 0.68; p < 0.001). In addition, previous cesarean delivery history (β = 3.41; 95% CI: 2.18, 5.34; p < 0.001) also had a significant association with placenta accreta. Conclusions: Elevated second-trimester serum AFP had a positive association with placenta accreta. Such finding suggests a potential role for AFP in detecting pregnancies at high-risk of placenta accreta. This second-trimester biomarker of AFP may help classify women into the high- and low-risk groups for placenta accreta. In addition, we have validated a previous history of cesarean section as a risk factor for accreta in patients with placenta previa.

Abstract Preeclampsia (PE) is an idiopathic disease that occurs during pregnancy. It comprises multiple organ and system damage, and can seriously threaten the safety of the mother and infant throughout the perinatal period. As the pathogenesis of PE is unclear, there are few specific remedies. Currently, the only way to eliminate the clinical symptoms is to terminate the pregnancy. Although noncoding RNA (ncRNA) was once thought to be the “junk” of gene transcription, it is now known to be widely involved in pathological and physiological processes, including pregnancy-related disorders. Moreover, there is growing evidence that the unbalanced expression of specific ncRNA is involved in the pathogenesis of PE. In the present review, we summarize the expression patterns of ncRNAs, i.e., microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), and the functional mechanisms by which they affect the development of PE, and examine the clinical significance of ncRNAs as biomarkers for the diagnosis of PE. We also discuss the contributions made by genetic polymorphisms and epigenetic ncRNA regulation to PE. In the present review, we wish to explore and reinforce the clinical value of ncRNAs as noninvasive biomarkers of PE.

Lead-based halide perovskite semiconductors have demonstrated considerable potential in optoelectronic applications. However, the lack of high-quality crystals suitable for research has led to rare reports on CsPbF3 single crystals. Good quality CsPbF3 single crystals were successfully grown using the Bridgman method. The structure, luminescence, and electrical properties of crystals were investigated. At room temperature, the crystal structure was determined to be cubic perovskite, with a calculated bandgap of 3.68 eV. The measured emission spectrum showed one broad emission peak at approximately 400 nm. Three decay time constants were obtained from a sum of exponential functions fit to the fluorescence decay curve: 0.4 ns, 2.4 ns, and 15.0 ns for fast, middle, and slow decay times, respectively. The decay times excited by pulsed X-ray were measured to be 2.2 ns and 10.2 ns, indicating that CsPbF3 is an ultrafast scintillator. Furthermore, the electrical properties demonstrated that CsPbF3 exhibits high ion mobility, which is approximately 20 times that of electron mobility.

Abstract In less than 6 months, COVID-19 spread rapidly around the world and became a global health concern. Hypertension is the most common chronic disease in COVID-19 patients, but its impact on these patients has not been well described. In this retrospective study, 82 patients diagnosed with COVID-19 were enrolled, and epidemiological, demographic, clinical, laboratory, radiological and therapy-related data were analyzed and compared between COVID-19 patients with (29 cases) or without (53 cases) hypertension. The median age of the included patients was 60.5 years, and the cohort included 49 women (59.8%) and 33 (40.2%) men. Hypertension (31 [28.2%]) was the most common chronic illness, followed by diabetes (16 [19.5%]) and cardiovascular disease (15 [18.3%]). The most common symptoms were fatigue (55 [67.1%]), dry cough (46 [56.1%]) and fever ≥ 37.3 °C (46 [56.1%]). The median time from illness onset to positive RT-PCR test was 13.0 days (range 3–25 days). There were 6 deaths (20.7%) in the hypertension group and 5 deaths (9.4%) in the nonhypertension group, and more hypertensive patients with COVID-19 (8 [27.6%]) than nonhypertensive patients (2 [3.8%]) (P = 0.002) had at least one comorbid disease. Compared with nonhypertensive patients, hypertensive patients exhibited higher neutrophil counts, serum amyloid A, C-reactive protein, and NT-proBNP and lower lymphocyte counts and eGFR. Dynamic observations indicated more severe disease and poorer outcomes after hospital admission in the hypertension group. COVID-19 patients with hypertension have increased risks of severe inflammatory reactions, serious internal organ injury, and disease progression and deterioration.

Abstract Background Gestational diabetes mellitus (GDM) is a pregnancy-specific carbohydrate intolerance Which can cause a large number of perinatal and postpartum complications. The members of Transforming growth factor-β (TGF-β) superfamily play key roles in the homeostasis of pancreatic β-cell and may involve in the development of GDM. This study aimed to explore the association between the polymorphisms of TGF-β1, TGF-β3 and the risk to GDM in Chinese women. Methods This study included 919 GDM patients (464 with preeclampsia and 455 without preeclampsia) and 1177 healthy pregnant women. TaqMan allelic discrimination real-Time PCR was used to genotype the TGF-β1 (rs4803455) and TGF-β3 (rs2284792 and rs3917201), The Hardy-Weinberg equilibrium (HWE) was evaluated by chi-square test. Results An increased frequency of TGF-β3 rs2284792 AA and AG genotype carriers was founded in GDM patients (AA vs. AG + GG: χ2 = 6.314, P = 0.012, OR = 1.270, 95%CI 1.054–1.530; AG vs. GG + AA: χ2 = 8.545, P = 0.003, OR = 0.773, 95%CI 0.650–0.919). But there were no significant differences in the distribution of TGF-β1 rs4803455 and TGF-β3 rs3917201 between GDM and healthy women. In addition, no significant differences were found in allele and genotype frequencies among GDM patients with preeclampsia (PE). Conclusions The AA and AG genotype of TGF-β3 rs2284792 polymorphism may be significantly associated with increased risk of GDM in Chinese population.

Abstract Objective Tourette syndrome (TS) is a childhood neurodevelopmental disorder caused by various genetic and environmental factors and presents with apparent genetic heterogeneity. As ASH1L potentially contributes to neurodevelopmental diseases, especially in TS, we aim to investigate the susceptibility of ASH1L on TS in the Chinese Han population. Methods Three tag single nucleotide polymorphisms (SNPs) (rs5005770, rs12734374, and rs35615695) in ASH1L were screened in 271 TS nuclear family trios and 337 healthy subjects by the TaqMan assays real time. A case–control study combined with family‐based analysis was applied to study the genetic susceptibility of common variants of ASH1L. Results The results revealed a significant over‐transmission of rs35615695 and rs5005770 (for rs35615695, transmission disequilibrium test, χ2 = 57.375, p = .000, HHRR, χ2 = 4.807, p = .028; for rs5005770, HRR, χ2 = 4.116, p = .042, HHRR, χ2 = 8.223, p = .004) in family‐based study. Furthermore, rs5005770 and rs35615695 still remained significant after Bonferroni correction (p

Abstract Background Several genome-wide association studies have identified single-nucleotide polymorphisms (SNPs), such as rs4409766, rs1004467, and rs3824755 in CYP17A1 and rs2021783 in CYP21A2, as new hypertension susceptibility genetic variants in the Chinese population. This study aimed to look into the relationship between preeclampsia (PE) and these SNPs in Chinese Han women. Methods Overall, 5021 unrelated pregnant women were recruited, including 2002 patients with PE and 3019 normal healthy controls. The real-time PCR (TaqMan) method was applied to genotype these four polymorphisms. Results A statistically obvious difference in the allelic frequencies was observed in CYP21A2 rs2021783 between cases and controls (χ 2 = 7.201, Pc = 0.028 by allele), and the T allele was associated with the occurrence and development of PE (OR = 1.151, 95% CI 1.039–1.275). We also found a significant association between rs2021783 and the development of early-onset PE (Pc = 0.008 by genotype, Pc = 0.004 by allele). For rs1004467 and rs3824755, the distribution of allelic frequencies differed markedly between mild PE and control groups (χ 2 = 6.843, Pc = 0.036; χ 2 = 6.869, Pc = 0.036), and patients with the TT genotype of rs1004467 were less easy to develop mild PE than were those carrying the CT or CC genotype (χ 2 = 7.002, Pc = 0.032, OR = 1.306, 95% CI 1.071–1.593). The GG genotype of rs3824755 appeared to a protective effect on the occurrence of mild PE (OR = 0.766, 95% CI 0.629–0.934). Conclusions CYP21A2 rs2021783 appears to be closely related to PE susceptibility, and CYP17A1 rs1004467 and rs3824755 seem to be closely associated with mild PE in Han women.

Abstract Background SMAD4 is frequently inactivated and associated with a poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Abnormal SMAD4 expression also plays an important role in the malignant progression of PDAC. Methods We investigated SMAD4 status in PDAC by immunohistochemical methods to explore the relationships between SMAD4 expression and clinicopathological features and then detected SMAD4 mutations by Sanger sequencing in 95 patients with PDAC to identify new mutation sites in PDAC. We further evaluated the effects of a missense mutation, Y353C, in the SMAD4 MH2 domain, on cell proliferation and migration in vitro. Results Immunohistochemistry showed that the expression of SMAD4 in PDAC carcinoma tissue was significantly lower than that in normal pancreatic tissue, and negative SMAD4 expression was closely related to tumour diameter, staging, lymph node metastasis and differentiation. Sanger sequencing analysis showed that the rate of SMAD4 mutation was 11.8% in 85 PDAC cases, and the novel SMAD4 Y353C missense mutation identified in this study promoted cell migration and invasion without affecting cell proliferation in vitro. Furthermore, SMAD4 Y353C resulted in reduced expression of E-cadherin and increased expression of Vimentin compared with wild-type SMAD4 overexpression. Conclusion This study supports the key role of SMAD4 as a tumour suppressor gene in PDAC and shows that SMAD4 Y353C is associated with poor progression of PDAC.

Abstract Background Although Mitochondrial DNA depletion syndrome (MDS) can be classified into three forms: myopathic, encephalomyopathic and hepatocerebral form, it is difficult to identify its form due to its clinical heterogeneity. Therefore, it is very important to conduct molecular genetic analysis on suspected patients. This study presented a male 38 weeks and 5 days infant with liver cytolysis and leukodystrophy. Case presentation A male infant proband was admitted to the department of NICU for feeding intolerance, irregular rhythm of respiration, hypoglycemia, lactic acidosis, liver cytolysis and neurological abnormalities. He was onset of mild jaundice with leukodystrophy and high lactate and phenylderivatives for urine organic acids on the 7th day. Whole exome sequencing (WES) and Sanger sequencing were performed to screen and confirm the suspicious pathogenic mutations. The results revealed this proband carried two compound heterozygous mutations in TWNK: c.1186 C > T / p.Pro396Ser and c.1844 G > C / p.Gly615Ala inherited by an autosomal recessive form from his parents, of which protein conservative analysis and structural modeling supported the pathogenicity of the two mutations. Unfortunately, the conditions described above were not improved until he was discharged from the hospital on the 23rd day and died at 4 months of age. Conclusions In this study, we investigated a Chinese family with the hepatocerebral form of MDS and conducted WES and Sanger sequencing to explore the causative mutations for this proband born from non-consanguineous and healthy parents. We identified two novel TWNK c.1186 C > T/ c.1844 G > C compound heterozygous mutations which were probably the disease-causing mutations of hepatocerebral form of MDS and described the clinical manifestations of the proband, which expanded the phenotypic spectrum of MDS caused by variants in TWNK. This study also emphasized WES technology can provide the genetic diagnosis of Mendelian genetic disease.

Background: Cohen syndrome (CS) is a clinically heterogeneous disorder characterized by extensive phenotypic variation with autosomal recessive inheritance. VPS13B was identified to be the disease-causing gene for CS. The objectives of the present study were to screen likely pathogenic mutations of the patient with developmental delay and mental retardation, and to determinate the effect of this splice-site mutation by reverse transcription analysis.Methods: Whole exome sequencing (WES) in combination with Sanger sequencing were performed to identify the causative mutations of this CS family. Subsequently, the impact of the intronic variant on splicing was analyzed by reverse transcription and the construction of expression vector.Results: A novel homozygous splice-site mutation (c.6940+1G>T) in the VPS13B gene was identified in this proband. Sanger sequencing analysis of the cDNA demonstrated that the c.6940+1G>T variant could cause the skipping of entire exon 38, resulting in the loss of 208 nucleotides and further give rise to the generation of a premature in-frame stop codon at code 2,247.Conclusions: The homozygous VPS13B splicing variant c.6940+1G>T was co-segregated with the CS phenotypes in this family and was identified to be the cause of CS after comprehensive consideration of the clinical manifestations, genetic analysis and cDNA sequencing result.

Abstract Background To assess the relationship between MOV10 rs2932538 polymorphism and susceptibility to preeclampsia (PE) in the Chinese Han population and to investigate whether the placental expression of MOV10 have association with PE. Methods We enrolled 1021 pregnant women with PE and 1594 normotensive pregnant women to analyze genotyping of MOV10 rs2932538. Clinical data and related test results of all subjects were collected and analyzed. For volunteers providing placentas, real‐time PCR, Western blot, and immunohistochemistry were applied to assess the expression level of MOV10. Results There was significant statistical difference between preeclamptic patients and healthy subjects in genotype distributions and alleles. The frequencies of genotypes TT+CT were significantly associated with the increased risk of preeclampsia. Besides, T alleles were found to be related to a higher risk of PE. Significant statistical difference was also observed on distributions of genotype in PE without/with severe features group compared or early onset/late onset versus controls. The placental expression of MOV10 was lower in preeclamptic women, however, no relationship was found between MOV10 expression level and MOV10 rs2932538 genotypes. Conclusion This study suggests that MOV10 rs2932538 polymorphism may be associated with PE susceptibility in the Chinese Han population. The placental expression of MOV10 decrease in PE but have no relationship with rs2932538 polymorphism.

Background: Thyroid dysgenesis (TD), which is caused by gland developmental abnormalities, is the most common cause of congenital hypothyroidism (CH). In addition, advances in diagnostic techniques have facilitated the identification of mild CH patients with a gland-in-situ (GIS) with normal thyroid morphology. Therefore, TD and GIS account for the vast majority of CH cases.Methods: Sixteen known genes to be related to CH were sequenced and screened for variations by next-generation sequencing (NGS) in a cohort of 377 CH cases, including 288 TD cases and 89 GIS cases.Results: In our CH cohort, we found that DUOX2 (21.22%) was the most commonly variant pathogenic gene, while DUOXA2 was prominent in TD (18.75%) and DUOX2 was prominent in GIS (34.83%). Both biallelic and triple variants of DUOX2 were found to be most common in children with TD and children with GIS. The most frequent combination was DUOX2 with DUOXA1 among the 61 patients who carried digenic variants. We also found for the first time that biallelic TG, DUOXA2, and DUOXA1 variants participate in the pathogenesis of TD. In addition, the variant p.Y246X in DUOXA2 was the most common variant hotspot, with 58 novel variants identified in our study.Conclusion: We meticulously described the types and characteristics of variants from sixteen known gene in children with TD and GIS in the Chinese population, suggesting that DUOXA2 and DUOX2 variants may confer susceptibility to TD and GIS via polygenic inheritance and multiple factors, which further expands the genotype-phenotype spectrum of CH in China.

Abstract Background Autosomal recessive congenital ichthyosis (ARCI) is a rare genetically heterogeneous cutaneous disease predominantly characterized by erythroderma, generalized abnormal scaling of the whole body and a collodion membrane at birth. Numerous causative genes have been demonstrated to be responsible for ARCI including PNPLA1 which can cause ARCI type 10. The objectives of this study are to describe clinical features of three ARCI patients from two Chinese unrelated families and to identify the underlying causative mutations. Methods Genomic DNA was extracted from peripheral venous blood obtained from the two Chinese ARCI families in Shandong province. Subsequently, targeted regions sequencing (TRS) followed by Sanger sequencing was conducted to identify and validate the likely pathogenic mutations of the ARCI families. Results Genetic analyses revealed four novel PNPLA1 variants that are predicted to be probably to lead to ARCI in three patients of two families. Patient 1 in one family was in compound heterozygous status for c.604delC/p.Arg202Glyfs*27 and c.820dupC/p.Arg274Profs*15, whereas c.738_742delinsCCCACAGATCCTGC/ p.Gly247_Tyr248delinsProGlnIleLeuHis, and c.816dupC/p.Arg274Profs*15 were found in patient 2 and 3 of the other family. In addition, these variants cosegregate in the two pedigrees and are all within highly conserved regions of the PNPLA1 protein, which indicate that the four mutations are likely pathogenic. Conclusion Our findings not only broaden the mutational spectrum of PNPLA1, but also contribute to establishing genotype–phenotype correlations for different forms of ARCI.

Unbalanced inflammatory reactions and oxidative stress are inseparably interconnected, and both may play crucial roles in the pathophysiological mechanisms of preeclampsia (PE). In the published previous studies, we have genotyped for SNPs that related to inflammation (rs2227485, rs153109, rs17855750, rs2027432, rs2275913, rs763780, rs4819554, and rs13015714) and oxidative stress (rs1695, rs4680, rs1800566, rs4807542, rs713041, rs7579, rs230813, rs1004467, rs3824755, and rs9932581) to investigate whether these polymorphisms were associated with susceptibility to PE in a Chinese Han population. In this present study, we collected these data of experimental and clinical from above studies for haplotype analysis of inflammation-related SNPs in 631 PE patients and 720 normal pregnancy and oxidative stress-related SNPs in 342 PE patients and 457 normal pregnancies for susceptibility to PE. The data of genotype distribution and allele frequency comparisons after correction for multiple comparisons (P/8 or P/10) showed 2 among the 8 candidate inflammation-related SNPs have significant differences (rs2027432 genotype χ2=407.377,p0.9), and the GT and GC haplotypes of rs4807542 and rs713041 in GPX4 showed significant differences between the PE and control groups (χ2=5.143,p=0.0233,p

The clinical manifestations of thyroid diseases in elderly patients are often atypical. This study aimed to establish reference intervals for thyroid function in the elderly in order to help diagnose thyroid diseases in this population. A total of 5345 healthy individuals were examined and divided into three groups according to their age: 4297 individuals aged < 65 years (19-64), 719 individuals aged between 65 and 79 years, and 329 individuals aged between 80 and 100 years. Levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody, and thyroglobulin antibody were measured in these subjects by using a fully automated analyzer. The following free triiodothyronine, free thyroxine, and thyroid-stimulating hormone reference intervals were obtained from each age group: For individuals aged < 65 years (19-64 years), FT3, FT4, and TSH were 3.40-6.44, 10.26-19.25 pmol/L and 0.50-4.81 μIU/mL, respectively. For individuals aged between 65 and 79 years, FT3, FT4 and TSH ranged between 3.01-5.91, 10.04-19.76 pmol/L, and 0.54-5.51 μIU/mL, respectively. For individuals aged between 80 and 100 years, FT3, FT4, and TSH varied between 2.82-5.57, 9.79-21.22 pmol/L, 0.31-6.28 μIU/mL respectively. FT3 concentration was lower and the concentrations of FT4 and TSH were higher in individuals aged ≥ 65 years than in those aged

Objective: We investigated whether the CXCL12-801G/A polymorphism was associated with preeclampsia (PE) susceptibility in a Chinese Han population. Methods: We examined 912 PE women and 1025 controls for the CXCL12-801G/A polymorphism by polymerase chain reaction (PCR) and correlations with clinical characteristics were examined. Results: No significant differences in genotypic and allelic frequencies of CXCL12-G801A were found between cases and controls (genotype: χ2 = 2.095, p = 0.351; allele: χ2 = 1.713, p = 0.191). There were also no significant differences between early/late-onset or mild/severe PE and control groups. Conclusion: The results indicate that 801G/A in CXCL12 may not play a major role in pathogenesis of PE in a Chinese Han population.

Context: The DUOX/DUOXA systems play a key role in H2O2 generation in thyroid cells, which is required for iodine organification and thyroid hormone synthesis. DUOX2/DUOXA2 defects can cause congenital hypothyroidism (CH), but it is unknown whether DUOX1/DUOXA1 mutations can also cause CH.Objective: We aimed to identify DUOX1/DUOXA1 mutations and explore their role in the development of CH by investigating their functional impacts on H2O2 generation.Patients and Methods: Forty-three children with CH with goiter were enrolled, in whom all exons and flanking intronic regions of DUOX1/DUOXA1 were directly sequenced. We characterized the functional effects of identified mutations on the expression of DUOX1 and DUOXA1 and H2O2 generation.Results: We identified a heterozygous DUOX1 missense mutation (G > A base substitution at nucleotide 3920 in exon 31) that changed a highly conserved arginine to glutamine at residual 1307 (p.R1307Q) in patient 1. A heterozygous-missense mutation (c.166 C>T; p.R56W) was identified in DUOXA1 in patient 2. Functional studies demonstrated that both p.R1307Q mutant or p.R56W mutant decreased the DUOX1 expression at mRNA and protein levels, with a corresponding impairment in H2O2 generation (P < 0.01). The results also showed that intact DUOXA1 was required for full activity of DUOX1 and H2O2 generation.Conclusions: We have identified two heterozygous missense mutations in DUOX1 and DUOXA1 in two patients that can cause CH through disrupting the coordination of DUOX1 and DUOXA1 in the generation of H2O2. This study for the first time demonstrates that the DUOX1/DUOXA1 system, if genetically defective, can cause CH.

Background/Aims: Increasing evidence shows that oxidative stress plays an important part in the pathophysiological mechanisms of preeclampsia (PE). Polymorphic variants of oxidative stress-related candidate genes GST1 and GPX1 can affect the antioxidant activities of their encoded enzymes. Therefore, this study aimed to explore the associational analysis between GSTP1 and GPX1 single nucleotide polymorphisms (SNPs) and susceptibility to PE in Chinese Han women. Methods: DNA from 1130 PE patients and 1226 healthy individuals was genotyped for SNPs rs1695 in GSTP1 and rs1050450 in GPX1 using a predesigned TaqMan SNP genotyping assay. The χ2 test compared differences in genetic distributions between the two groups in a case-control study. Results: No significant differences in allelic or genotypic frequencies of GSTP1 rs1695 or GPX1 rs1050450 were detected between cases and controls (GSTP1 rs1695: χ2=1.122, p=0.571 by genotype, χ2=0.138, p=0.710, odds ratio=1.027, 95% confidence interval 0.892-1.183 by allele; GPX1 rs1050450: χ2=0.036, p=0.982 by genotype, χ2=0.002, p=0.960, odds ratio=1.005, 95% confidence interval 0.822-1.229 by allele). Moreover, no significant differences in genetic distribution were found between early/late-onset PE or mild/severe PE and control subgroups. Conclusion: Our results suggest that GSTP1 rs1695 and GPX1 rs1050450 SNPs have no effects on the risk of PE in the Chinese Han population. However, these results should be confirmed by replication in different populations.

Background/Aims: Several lines of evidence have been reported that oxidative stress plays an important role in the pathogenesis of Preeclampsia (PE). Therefore, this research is aimed to investigate whether polymorphisms of CYBA are related to susceptibility to PE in Chinese Han women. Methods: We studied the genetic frequency of the rs9932581 and 1049255 polymorphisms in CYBA in 1029 PE patients and 1400 controls of later pregnant women by the TaqMan allelic discrimination real-time PCR and a case-control model. Results: Our research indicated that no significant differences were found for the genotypic or allelic frequencies at the two polymorphic sites in CYBA between PE patients and controls. To further study the relationship between the polymorphic sites and PE, we also found that there is no significant difference in the genetic distributions identified between the mild or severe PE and early or the late-onset PE and controls. Conclusion: The study demonstrated that the genetic variants of rs9932581 and rs1049255 in CYBA might not be associated with PE. However, investigations of genetic variability that influence on the disease outcome are needed in other large prospective populations or regions, so the complicated interconnection of genetic and environmental elements can be emulated for better understanding.

Background/Aims: Preeclampsia (PE) is a systemic inflammatory response syndrome involving varieties of cytokines, and previous studies have shown that IL-33 and its receptor IL-1RL1 play pivotal roles in the development of it. As a polygenetic hereditary disease, it is necessary to study the gene analysis for PE. Therefore, the present study was to determine whether IL-33 rs3939286 and IL-1RL1 rs13015714 associated with susceptibility to PE in Chinese Han women. Methods: 1,031 PE patients and 1,298 controls were enrolled and the genotyping for rs3939286 in IL-33 and rs13015714 in IL-1RL1 was performed by TaqMan allelic discrimination real-time PCR. Hardy-Weinberg equilibrium (HWE) was examined to ensure the group representativeness and Pearson's chi-square test was used to compare the differences in genetic distributions between the two groups. Results: No significant differences in genotypic and allelic frequencies of the two polymorphisms loci were observed between cases and controls. There were also no significant differences in genetic distributions between mild/severe and early/late-onset PE and control groups. Conclusion: Although our data suggested that the polymorphisms of IL-33 rs3939286 and IL-1RL1 rs13015714 might not be critical risk factors for PE in Chinese Han women, the results need to be validated in different nations.

We grew a set of indium and molybdenum co-doped lithium niobate crystals with various indium doping concentrations and investigated their photorefractive properties at different wavelengths (442, 488 and 532 nm). It was found that the diffraction efficiency of 1.0 mol% indium and 0.5 mol% molybdenum co-doped lithium niobate crystal could reach 61.57% at 488 nm. Moreover for 3.0 mol% indium and 0.5 mol% molybdenum co-doped lithium niobate crystal, the response time was greatly shortened to 0.61, 0.76, and 0.74 s at 442, 488, and 532 nm, respectively, while the photorefractive sensitivity reached as high as 7.35 cm/J at 442 nm. These results indicate that co-doping of indium is an efficient way to further enhance the photorefractive properties of molybdenum-doped lithium niobate crystal.

Background/Aims: Accumulating evidence suggests that an excessive maternal systemic inflammatory response to pregnancy with exaggerated activation of the innate immune system plays a critical role in the development of preeclampsia (PE). In this study, we investigated whether polymorphisms in the Toll-like receptor 3 (TLR3) gene are associated with susceptibility to PE in the Chinese Han population. Methods: We recruited 987 PE patients and 1227 healthy pregnant women. Two polymorphisms (rs3775291 and rs3775296) located in TLR3 were genotyped by TaqMan allelic discrimination real-time PCR. The association between the genotype or allele frequencies and PE was examined using chi-square tests. Clinical data were compared between cases and controls using Student's t test. Results: No significant difference was determined in the genetic distribution of rs3775291 and rs3775296 between cases and controls. There were also no significant differences in the genotype and allele frequencies of either SNP between healthy pregnant women and patients with late or early onset PE, or with mild or severe PE. Conclusion: Although this is the first study of the association between TLR3 polymorphisms and preeclampsia, we found that TLR3 polymorphisms are unlikely to play a significant role in the development of preeclampsia in the Chinese Han population.

We mainly investigated the effect of the valence state of photorefractive resistant elements on the photorefractive properties of codoped crystals, taking the Zn and Mo codoped LiNbO3 (LN:Mo,Zn) crystal as an example. Especially, the response time and photorefractive sensitivity of 7.2 mol% Zn and 0.5 mol% Mo codoped with LiNbO3 (LN:Mo,Zn7.2) crystal are 0.65 s and 4.35 cm/J at 442 nm, respectively. The photorefractive properties of the LN:Mo,Zn crystal are similar to the Mg and Mo codoped LiNbO3 crystal, which are better than the Zr and Mo codoped LiNbO3 crystal. The results show that the valence state of photorefractive resistant ions is an important factor for the photorefractive properties of codoped crystals and that the LN:Mo,Zn7.2 crystal is another potential material with fast response to holographic storage.

Tourette syndrome (TS) is a polygenic neuropsychiatric disease. Previous studies have indicated that dysregulation in the histaminergic system may play a crucial role in disease onset. In this study, we investigated the role of the histidine decarboxylase gene (HDC) in TS susceptibility in the Chinese Han population. After genotyping 241 TS nuclear families trios, we analyzed three tag HDC single nucleotide polymorphisms (rs854150, rs854151, and rs854157) in a family-based study using the transmission disequilibrium test (TDT) and haplotype relative risk (HRR). TDT showed no over-transmission in these SNPs across the HDC region (for rs854150: χ2 = 0.472, P = 0.537, OR = 1.097, 95%CI = 0.738-1.630; for rs854151: χ2 = 0.043, P = 0.889, OR = 1.145, 95%CI = 0.767-1.709; for rs854157:χ2 = 0.984, P = 0.367, OR = 1.020, 95%CI = 0.508-2.049). HRR also showed the same tendency (for rs854150: χ2 = 0.211, P = 0.646, OR = 1.088, 95%CI = 0.759-1.559; for rs854151: χ2 = 0.134, P = 0.714, OR = 0.935, 95%CI = 0.653-1.339; for rs854157:χ2 = 0.841, P = 0.359, OR = 1.206, 95%CI = 0.808-1.799). Additionally, the haplotype-based haplotype relative risk showed a negative association. Although these findings indicate an unlikely association between HDC and TS in the Chinese Han population, a potential role for HDC cannot be ruled out in TS etiology. Future research should investigate this more thoroughly using different populations and larger samples.

Interleukin (IL)-17 is a proinflammatory cytokine mainly secreted by activated T helper 17 cells and involved in inflammatory immune responses. This study aimed to investigate the association between IL-17 variants as well as serum IL-17 levels with gout in male Chinese Han individuals. A total of 1,101 male gout patients and 1,239 ethic-matched controls were enrolled. Genetic distributions of three variants (rs2275913 in IL-17A, rs763780 in IL-17F, and rs4819554 in IL-17RA) were detected by real-time polymerase chain reaction using the Taqman probe method. The plasma concentrations of IL-17A and IL-17F were measured in 228 gout patients and 198 controls that came from above samples by an enzyme-linked immunosorbent assay. No significant differences were observed in the genetic distribution of these polymorphisms between cases and controls (rs2275913: χ2 = 0.15, p = 0.928 by genotype, χ2 = 0.14, p = 0.711 by allele; rs763780: χ2 = 2.24, p = 0.326 by genotype, χ2 = 0.26, p = 0.609 by allele; rs4819554: χ2 = 1.79, p = 0.409 by genotype, χ2 = 1.46, p = 0.227 by allele). Levels of serum IL-17A and IL-17F were significantly decreased in gout patients (both p0.05). Although the genetic variants in IL-17 we studied in this research do not appear to be involved in the development of gout in male Chinese Han individuals, the IL-17 cytokine family may participate in gouty inflammation in an undefined way, which requires further validation.

A series of LiNbO3: Mo, Hf crystals with 0.5 mol % fixed MoO3 and various HfO2 concentrations (0.0, 2.0, and 3.5 mol %) were grown by the Czochralski technique. The photorefractive properties of the LiNbO3: Mo, Hf crystals were investigated by two-wave coupling measurements and the beam distortion method was employed to obtain the optical damage resistance ability. The UV-visible and OH− absorption spectra were also studied. The experimental results imply that the photorefractive properties of LiNbO3: Mo crystals at laser wavelengths of 532, 488, and 442 nm can be greatly enhanced by doping HfO2 over the threshold concentration. At 442 nm especially, the response time of LN: Mo, Hf3.5 can be shortened to 0.9 s with a diffraction efficiency of 46.07% and a photorefractive sensitivity reaching 6.28 cm/J. Besides this, the optical damage resistance at 532 nm is 3 orders of magnitude higher than that of the mono-doped LiNbO3: Mo crystal, which is beneficial for applying it in the field of high-intensity lasers.

A series of pure congruent lithium niobate (LiNbO3, CLN) crystals were grown and directly polarized under different electric currents in the growth furnace. Their holographic properties were investigated from the ultraviolet to the visible range. The response time shortened, whereas the diffraction efficiency increased incrementally with the electric current. In particular, the response time of CLN polarized under 100 mA can be reduced by a factor of 10 with a still high saturation diffraction efficiency of about 40.8% at 351 nm. Moreover, its response speed improved by 60 times and 10 times for 473 and 532 nm laser, respectively. The light erasing behavior implies that at least two kinds of photorefractive centers exist in the crystals. Increasing the polarization current induces two pronounced UV absorption peaks and a wide visible absorption peak in CLN crystals. The diffusion effect dominates the photorefractive process and electrons are the dominant carriers. The possible mechanism for the fast photorefractive response is discussed. Increasing the polarization electric current is an effective method to improve the photorefractive response of LN crystal.

Previous studies have suggested an important role for IL-17, mainly secreted by Th17 cells, in the development of systemic inflammation in preeclampsia (PE). This study therefore investigated the association between genetic variants in IL-17A, IL-17F, and IL-17RA and susceptibility to PE in Chinese Han women. We recruited 1,031 PE patients and 1,298 controls of later pregnant women, and used TaqMan allelic discrimination real-time PCR to genotype the polymorphisms of IL17A rs2275913, IL-17F rs763780, and IL-17RA rs4819554. No significant differences in genotypic or allelic frequencies were found at all three polymorphic sites between PE patients and controls (rs2275913: genotype χ2 = 0.218, p = 0.897 and allele χ2 = 0.157, p = 0.692, OR = 1.024, 95%CI 0.911-1.152; rs763780: genotype χ2 = 1.948, p = 0.377 and allele χ2 = 1.242, p = 0.265, OR = 0.897, 95%CI 0.741-1.086; rs4819554: genotype χ2 = 0.633, p = 0.729 and allele χ2 = 0.115, p = 0.735, OR = 1.020, 95%CI 0.908-1.146). There were also no significant differences in genetic distributions between mild/severe PE or early/late-onset PE and control subgroups. Our data indicate that the genetic variants of rs2275913 in IL-17A, rs763780 in IL-17F, and rs4819554 in IL-17RA may not play a role in the pathogenesis of PE in Chinese Han women. However, these findings should be confirmed in other ethnic populations.

Bismuth-doped lithium niobate (LN:Bi) crystals were grown by Czochralski method and their optical damage resistance, photorefraction, absorption spectra, and defect energy levels were investigated. The experimental results indicate that the photorefractive properties of LN:Bi were enhanced as compared with congruent one, the photorefractive response time was greatly shortened, the photorefractive sensitivity was increased, and the diffraction efficiency of near-stoichiometric LN:Bi (SLN:Bi) reached 31.72% and 49.08% at 532 nm and 488 nm laser, respectively (light intensity of 400 mW/cm2). An absorption peak at about 350 nm was observed in the absorption spectrum of LN:Bi. And the defect energy levels simulation indicates new defect levels appear in the forbidden gap of LN:Bi crystals. Therefore bismuth can act as photorefractive centers in LN crystals.

OBJECTIVE: To investigate the association between Obsessive-Compulsive Disorder (OCD) and a functional polymorphism of MCP-1 in the Chinese Han population. METHOD: We genotyped and performed a case-control association analysis of the MCP-1 -2518G/A polymorphism in 200 OCD patients and 294 healthy control subjects. RESULTS: There was no significant difference in MCP-1 -2518G/A genotypic and allelic frequencies between OCD cases and controls (x² = 1.123, df = 2, P = 0.57 by genotype; x² = 0.802, df = 1, P = 0.37 by allele). CONCLUSIONS: Our results indicated that MCP-1 -2518G/A may not play a major role in the genetic predisposition of the Chinese Han population to OCD. However, further studies using a larger number of subjects are required to obtain a clear conclusion.OBJETIVO: Investigar a relação entre Transtorno Obsessivo-Compusilvo (TOC) e um polimorfismo funcional de MCP-1 na população chinesa de etnia Han. MÉTODOS: Determinamos os genótipos e realizamos uma análise de associações de casos-controle de polimorfismo MCP-1 -2518G/A em 200 indivíduos com TOC e 294 indivíduos saudáveis (controle). RESULTADOS: Não houve diferença significativa no genótipo MCP-1 -2518G/A e nas frequências alélicas entre casos de TOC e controles (x² = 1,123, df = 2, P = 0,57 por genotipo; x² = 0,802, df = 1, P = 0,37 por alelo). CONCLUSÕES: Nossos resultados indicaram que MCP-1 -2518G/A pode não ter grande participação na predisposição genética da etnia Han no que diz respeito ao TOC. Contudo, novos estudos com um maior número de indivíduos são necessários para uma conclusão mais clara.

BACKGROUND: Mutations in PKHD1 cause autosomal recessive Caroli disease, which is a rare congenital disorder involving cystic dilatation of the intrahepatic bile ducts. However, the mutational spectrum of PKHD1 and the phenotype-genotype correlations have not yet been fully established. METHODS: Whole exome sequencing (WES) was performed on one twin sample with Caroli disease from a Chinese family from Shandong province. Routine Sanger sequencing was used to validate the WES and to carry out segregation studies. We also described the PKHD1 mutation associated with the genotype-phenotype of this twin. RESULTS: A combination of WES and Sanger sequencing revealed the genetic defect to be a novel compound heterozygous genotype in PKHD1, including the missense mutation c.2507 T>C, predicted to cause a valine to alanine substitution at codon 836 (c.2507T>C, p.Val836Ala), and the nonsense mutation c.2341C>T, which is predicted to result in an arginine to stop codon at codon 781 (c.2341C>T, p.Arg781*). This compound heterozygous genotype co-segregates with the Caroli disease-affected pedigree members, but is absent in 200 normal chromosomes. CONCLUSIONS: Our findings indicate exome sequencing can be useful in the diagnosis of Caroli disease patients and associate a compound heterozygous genotype in PKHD1 with Caroli disease, which further increases our understanding of the mutation spectrum of PKHD1 in association with Caroli disease.

OBJECTIVE: The purpose of our study is to investigate the relationship between IL-1β -31C/T (rs1143627) and -511T/C (rs16944) polymorphisms and the preeclampsia (PE), and analyze the Linkage disequilibrium (LD) and haplotype frequency of the two polymorphism loci. METHODS: Polymorphisms at -31C/T and -511T/C of IL-1β were genotyped with the method of polymerase chain reaction-restriction fragment length polymorphism (PCR- RFLP) in 232 PE and 447 control subjects. Genotype and allele frequencies between case-control groups were compared by chi-square(X2) tests. Two-point LD and haplotype frequency analyses were done with the software Haploview4.2. RESULTS: Significant statistical differences were found between PE and control groups regarding genotype and allele frequencies of the two polymorphisms of IL-1β (For IL-1β -31C/T: X2 = 11.478, P = 0.003; For IL-1β-511T/C: X2 = 9.687, P = 0.008). LD analysis revealed that the IL-1β -31C/T SNP was in high LD with the IL-1β-511C/T SNP(D' = 0.92, r2 = 0.79). Both CT and TC haplotypes showed significant differences between case and control groups. Only the plasma level of Prothrombin Time had a significantly statistical difference among TT, CT and CC groups of the preeclamptic two polymorphisms of IL-1β-31C/T and -511T/C (for IL-1β-31C/T, F = 1.644, P = 0.01; F = 1.587, P = 0.016). CONCLUSION: Our results revealed IL-1β was associated with the PE in Chinese Han population. The CT haplotype may increase the risk of PE, while haplotype TC could be considered as a protective haplotype of PE.

BACKGROUND: Glucose transporter 9 (GLUT9) is a high-capacity/low-affinity urate transporter. To date, several recent genome-wide association studies (GWAS) and follow-up studies have identified genetic variants of SLC2A9 associated with urate concentrations and susceptibility to gout. We therefore investigated associations between gout and polymorphisms and haplotypes in the presumptive promoter region of GLUT9 in Chinese males. METHODOLOGY/PRINCIPAL FINDINGS: The approximately 2000 bp presumptive promoter region upstream of the start site of exon 1 of GLUT9 was sequenced and subjected to genetic analysis. A genotype-phenotype correlation was performed and polymorphisms-induced changes in transcription factor binding sites were predicted. Of 21 SNPs identified in GLUT9, five had not been previously reported. Two of the SNPs (rs13124007 and rs6850166) were associated with susceptibility to gout (p = 0.009 and p = 0.042, respectively). The C allele of rs13124007 appeared to be the risk allele for predisposition to gout (p = 0.006, OR 1.709 [95% CI 1.162-2.514]). For rs6850166, an increased risk of gout was associated with the A allele (p = 0.029, OR 1.645 [95% CI 1.050-2.577]). After Bonferroni correction, there was statistically difference in rs13124007 allele frequencies between gout cases and controls (P = 0.042). Haplotype analyses showed that haplotype GG was a protective haplotype (p = 0.0053) and haplotype CA was associated with increased risk of gout (p = 0.0326). Genotype-phenotype analysis among gout patients revealed an association of rs13124007 with serum triglycerides levels (P = 0.001). The C to G substitution in polymorphism rs13124007 resulted in a loss of a binding site for transcription factor interferon regulatory factor 1 (IRF-1). CONCLUSIONS/SIGNIFICANCE: Polymorphisms rs13124007 and rs6850166 are associated with susceptibility to gout in Chinese males.

Till now it is difficult to obtain a p-type lithium niobate crystal. Here the carrier types in various doped and oxidized LiNbO3 crystals have been investigated by holographic technique. The experimental results show tetravalent ions (Zr4+ and Hf4+) with doping concentrations just above optical damage resistant thresholds is helpful to increase the concentration of holes. And 3.0 mol% ZrO2 doped LiNbO3 can be used as a p-type crystal. The dominant carrier of iron doped LiNbO3 crystal can be changed to holes when treated by thermo-electric oxidization. Then the possible mechanism on how to obtain a p-type LiNbO3 was discussed.