IMD-Net: Interpretable multi-scale detection network for infrared dim and small objects.

This study proposed an interpretable multi-scale infrared small object detection network (IMD-Net) design method to improve the precision of infrared small object detection and contour segmentation in complex backgrounds. To this end, a multi-scale object enhancement module was constructed, which converted artificially designed features into network structures. The network structure was used to enhance actual objects and extract shallow detail and deep semantic features of images. Next, a global object response, channel attention, and multilayer feature fusion modules were introduced, combining context and channel information and aggregated information, selected data, and decoded objects. Finally, the multiple loss constraint module was constructed, which effectively constrained the network output using multiple losses and solved the problems of high false alarms and high missed detections. Experimental results showed that the proposed network model outperformed local energy factor (LEF), self-regularized weighted sparse model (SRWS), asymmetric contextual modulation (ACM), and other state of the art methods in the intersection-over-union (IoU) and Fmeasure values by 10.8% and 11.3%, respectively. The proposed method performed best on the currently available datasets, achieving accurate detection and effective segmentation of dim and small objects in various infrared complex background images.

Globus pallidus internus versus subthalamic nucleus deep brain stimulation for isolated dystonia: A 3-year follow-up.

BACKGROUND AND PURPOSE: Bilateral deep brain stimulation (DBS) surgery targeting the globus pallidus internus (GPi) or the subthalamic nucleus (STN) is widely used in medication-refractory dystonia. However, evidence regarding target selection considering various symptoms remains limited. This study aimed to compare the effectiveness of these two targets in patients with isolated dystonia. METHODS: This retrospective study evaluated 71 consecutive patients (GPi-DBS group, n = 32; STN-DBS group, n = 39) with isolated dystonia. Burke-Fahn-Marsden Dystonia Rating Scale scores and quality of life were evaluated preoperatively and at 1, 6, 12, and 36 months postoperatively. Cognition and mental status were assessed preoperatively and at 36 months postoperatively. RESULTS: Targeting the STN (STN-DBS) yielded effects within 1 month (65% vs. 44%; p = 0.0076) and was superior at 1 year (70% vs. 51%; p = 0.0112) and 3 years (74% vs. 59%; p = 0.0138). For individual symptoms, STN-DBS was preferable for eye involvement (81% vs. 56%; p = 0.0255), whereas targeting the GPi (GPi-DBS) was better for axis symptoms, especially for the trunk (82% vs. 94%; p = 0.015). STN-DBS was also favorable for generalized dystonia at 36-month follow-up (p = 0.04) and required less electrical energy (p < 0.0001). Disability, quality of life, and depression and anxiety measures were also improved. Neither target influenced cognition. CONCLUSIONS: We demonstrated that the GPi and STN are safe and effective targets for isolated dystonia. The STN has the benefits of fast action and low battery consumption, and is superior for ocular dystonia and generalized dystonia, while the GPi is better for trunk involvement. These findings may offer guidance for future DBS target selection for different types of dystonia.

Regulation of Hsa-miR-4639-5p expression and its potential role in the pathogenesis of Parkinson's disease.

Decreased DJ-1 protein impairs antioxidative activity of neurons and plays an important role in the occurrence of Parkinson's disease (PD). We have previously identified hsa-miR-4639-5p as the post-transcriptional regulator of DJ-1. Increased expression of hsa-miR-4639-5p reduced DJ-1 level and increased oxidative stress leading to neuronal death. Therefore, understanding the detailed mechanisms by which hsa-miR-4639-5p expression is regulated will not only facilitate diagnosis but also inform the pathogenesis of PD. We examined hsa-miR-4639-5 in either the plasma or exosomes derived from the central nervous system (CNS) neurons of PD patients and healthy controls. We showed that CNS-derived exosomes gave rise to the increased plasma hsa-miR-4639-5p in PD patients, pointing to hsa-miR-4639-5p dysregulation in the brain of PD patients. Using a dual-luciferase assay and a CRISPR-Cas9 system, we identified a core promoter of hsa-miR-4639 (-560 to -275 upstream the transcriptional starting site) of the gene for myosin regulatory light chain interacting protein. A polymorphism in the core promoter (rs760632 G>A) could enhance hsa-miR-4639-5p expression and increase PD risk. Furthermore, using MethylTarget™ assay, ChIP-qPCR, and specific inhibitors, we demonstrated that hsa-miR4639-5p expression was regulated by HDAC11-mediated histone acetylation but not DNA methylation/demethylation. Taken together, our study provides evidence that hsa-miR-4639-5p is a potential diagnostic marker and therapeutic target for PD. Interventions targeting hsa-miR-4639-5p might represent a novel therapy to promote healthy aging.

Overexpression of alpha synuclein disrupts APP and Endolysosomal axonal trafficking in a mouse model of synucleinopathy.

Mutations or triplication of the alpha synuclein (ASYN) gene contribute to synucleinopathies including Parkinson's disease (PD), Dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Recent evidence suggests that ASYN also plays an important role in amyloid-induced neurotoxicity, although the mechanism(s) remains unknown. One hypothesis is that accumulation of ASYN alters endolysosomal pathways to impact axonal trafficking and processing of the amyloid precursor protein (APP). To define an axonal function for ASYN, we used a transgenic mouse model of synucleinopathy that expresses a GFP-human ASYN (GFP-hASYN) transgene and an ASYN knockout (ASYN-/-) mouse model. Our results demonstrate that expression of GFP-hASYN in primary neurons derived from a transgenic mouse impaired axonal trafficking and processing of APP. In addition, axonal transport of BACE1, Rab5, Rab7, lysosomes and mitochondria were also reduced in these neurons. Interestingly, axonal transport of these organelles was also affected in ASYN-/- neurons, suggesting that ASYN plays an important role in maintaining normal axonal transport function. Therefore, selective impairment of trafficking and processing of APP by ASYN may act as a potential mechanism to induce pathological features of Alzheimer's disease (AD) in PD patients.

The potential of soluble programmed death-ligand 1 (sPD-L1) as a diagnosis marker for colorectal cancer.

Colorectal cancer (CRC) is one of the most significant neoplasms with high morbidity and mortality. Activation of the programmed death protein 1/programmed death ligand 1 (PD-1/PD-L1) signaling pathway results in tumor immune evasion by suppressing the activity of T cells. The correlation of soluble PD-L1 (sPD-L1) in serum/plasma with clinicopathological features, lymph node metastasis, diagnosis and prognosis is less clear. The aim of this study was to investigate the relationship between sPD-L1 and clinicopathological features, and diagnosis potentialof CRC. Three hundred patients with CRC were included in this study. sPD-L1 was measured by ELISA. Pretreatment levels of sPD-L1 were significantly elevated in CRC patient sera compared to healthy control (HC) (P<0.001). The median value of sPD-L1 in HC, CRC with non-lymph node metastasis, and CRC with lymph node metastasis were 246.78±50.2pg/mL, 284.12±52.7pg/mL, and 321.31±55.3pg/mL, respectively. ROC analysis of sPD-L1 allowed significant differentiation between HC group and CRC group (lymph node metastasis and non lymph node metastasis (AUC=0.861, 95% CI 0.830-0.887, p<0.001). sPD-L1 is a potential biomarker for the diagnosis of CRC. Multivariate analysis showed that lymph node metastasis and tumor differentiation were independent prognostic factors (all P< 0.01), and sPD-L1 was not correlated with the CRC prognosis (p>0.05).

Rescue procedure for isolated dystonia after the secondary failure of globus pallidus internus deep brain stimulation.

Introduction: Globus pallidus internus (GPi) deep brain stimulation (DBS) is widely used in patients with dystonia. However, 10-20% of patients receive insufficient benefits. The objectives of this study are to evaluate the effectiveness of bilateral subthalamic nucleus (STN) DBS along with unilateral posteroventral pallidotomy (PVP) in patients with dystonia who experienced unsatisfactory GPi-DBS and to address the reported rescue procedures after suboptimal DBS or lesion surgery in dystonia patients. Methods: Six patients with isolated dystonia who had previously undergone bilateral GPi-DBS with suboptimal improvement were included. Standardized assessments of dystonia using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and quality of life using SF-36 were evaluated before surgery and 1, 6 months, and last follow-up (LFU) after surgery. STN bilateral OFF (bi-OFF), unilateral ON (uni-ON), and bilateral ON (bi-ON) states were recorded at LFU. Specific items were used to find publications published before 10 April 2022 regarding rescue procedures after suboptimal DBS or lesion surgery in patients with dystonia for reference. Eleven original studies including case reports/series were identified for discussion. Results: Substantial clinical benefits were achieved in all six patients. Significant amelioration was achieved during the 1-month (6.5 ± 7.45; p = 0.0049), 6-month (5.67 ± 6.3; p = 0.0056) follow-ups, and at LFU (4.67 ± 4.72; p = 0.0094) when compared with the baseline (LFU of GPi DBS with on status) (17.33 ± 11.79) assessed by BFMDRS. The percentage of improvement reached 70.6, 74.67, and 77.05%, respectively. At LFU, significant differences were found between the stimulation bi-OFF and uni-ON (11.08 ± 8.38 vs. 9 ± 8.52, p = 0.0191), and between the stimulation bi-OFF and bi-ON (11.08 ± 8.38 vs. 4.67 ± 4.72, p = 0.0164). Trends depicting a better improvement in stimulation bi-ON compared with uni-ON (4.67 ± 4.72 vs. 9 ± 8.52, p = 0.0538) were observed. Conclusion: Our results suggest that bilateral STN-DBS plus unilateral PVP may be an effective rescue procedure for patients with isolated dystonia who experienced suboptimal movement improvement following GPi-DBS. However, given the heterogeneity of patients and the small sample size, these findings should be interpreted with caution.

[Analysis of two pedigrees affected with inherited dysfibrinogenemia due to a novel c.1115 T>A variant of the FGB gene].

OBJECTIVE: To analyze the phenotype and genotype of two Chinese family with inherited dysfibrinogenemia and the molecular pathogenic mechanism. METHODS: In the probands and their family members, coagulation routine, fibrinogen activity (Fg: A) and fibrinogen antigen (Fg: Ag) were detected. To find the mutation and exclude single nucleotide polymorphisms, all the exons and exons-intron boundaries of fibrinogen genes (FGA, FGB and FGG) were amplified by Ploymerase Chain Reaction (PCR), then sequenced. Bioinformatics prediction softwares were used to predict and score the change of function caused by the variant. PyMol were used to analyze the structure of protein caused by the variant. Clustal X software was used to analyze the conservation of the mutant amino acids. RESULTS: The thrombin time (TT) of the two was slightly prolonged and could not be corrected by protamine sulfate, and the fibrinogen activity was significantly reduced (1.25 g/L and 1.17 g/L), but the fibrinogen antigen content was normal, respectively (3.50 g /L and 3.81 g/L). Genetic analysis showed that both probands were heterozygous missense variants (FGB exon 7 c.1115T>A (p.Val372Glu)), both of which originated from the paternal line. The prediction results of the four bioinformatics softwares indicate that this variant could be disease causing. Clustal X software showed that Val372 is highly conserved among homologous species. Based on the guidelines of the American College of Medical Genetics and Genomics, c.1115T>A was predicted to be likely pathgenic (PM2+PP1+PP2+PP3+PP4). PyMol showed that the secondary structure and three-dimensional structure of fibrinogen protein were changed by p.Val372Glu variant. CONCLUSION: Inherited dysfibrinogenemia of the probands maybe caused by variant of FGB c.1115 T>A (p.Val372Glu), and the variant was firstly reported.

Expression of Serum Cytokines Profile in Neonatal Sepsis.

Objective: Sepsis remains a major cause of neonatal death. To better characterize the inflammatory response during neonatal sepsis, we compared the differences in serum cytokines and chemokines between full-term neonates with sepsis and without infection. Methods: We enrolled 40 full-term neonates with sepsis and 26 full-term neonates without infection as controls between October 2016 and June 2018. Forty cytokines /chemokines in serum were analyzed using the Luminex Bead Immunoassay System. Results: Our results showed that serum IL-6, IL-8, TNF-α, IL-1ß, MIF, CXCL13, CXCL1, CXCL2, CXCL5, CXCL6, CXCL16, CCL27, CCL2, CCL8, CCL3, CCL20, CCL23, and CX3CL1 levels were significantly increased in neonates with sepsis compared to those in the control group (all p<0.05). The levels of serum CCL20, and IL-17 were higher in late-onset sepsis (LOS) than those in early-onset sepsis (EOS) (all p<0.05). Conversely, serum CXCL16 was lower in LOS than that in EOS (p<0.05). Conclusion: Our findings revealed that excessive pro-inflammatory cytokines might be involved in neonatal sepsis. In addition, chemokines significantly increased the recruitment of immune cells after infection to participate in the anti-infection defense of neonates, but this could lead to damage.

Optimizing multicontrast MRI reconstruction with shareable feature aggregation and selection.

This paper proposes a new method for optimizing feature sharing in deep neural network-based, rapid, multicontrast magnetic resonance imaging (MC-MRI). Using the shareable information of MC images for accelerated MC-MRI reconstruction, current algorithms stack the MC images or features without optimizing the sharing protocols, leading to suboptimal reconstruction results. In this paper, we propose a novel feature aggregation and selection scheme in a deep neural network to better leverage the MC features and improve the reconstruction results. First, we propose to extract and use the shareable information by mapping the MC images into multiresolution feature maps with multilevel layers of the neural network. In this way, the extracted features capture complementary image properties, including local patterns from the shallow layers and semantic information from the deep layers. Then, an explicit selection module is designed to compile the extracted features optimally. That is, larger weights are learned to incorporate the constructive, shareable features; and smaller weights are assigned to the unshareable information. We conduct comparative studies on publicly available T2-weighted and T2-weighted fluid attenuated inversion recovery brain images, and the results show that the proposed network consistently outperforms existing algorithms. In addition, the proposed method can recover the images with high fidelity under 16 times acceleration. The ablation studies are conducted to evaluate the effectiveness of the proposed feature aggregation and selection mechanism. The results and the visualization of the weighted features show that the proposed method does effectively improve the usage of the useful features and suppress useless information, leading to overall enhanced reconstruction results. Additionally, the selection module can zero-out repeated and redundant features and improve network efficiency.

Economical and easily detectable markers of digestive tumors: platelet parameters.

Aim: This study aimed to evaluate the clinical values of platelet parameters in patients with digestive tumors. Patients & methods: A total of 974 people were classified into three groups: malignant group, patients with digestive malignant tumors; benign group, patients with benign tumors; and normal group: healthy individuals. Results: Compared with the benign and normal groups, the malignant group showed significantly increased platelet count (PLT) and plateletcrit (PCT) and significantly reduced mean platelet volume (MPV) and platelet-large cell rate (P-LCR, p < 0.001). Elevated PLT and PCT and reduced MPV and P-LCR indicated poor overall survival in patients with digestive tumors. Conclusion: PLT, PCT, MPV and P-LCR were proven to be predictive biomarkers for patients with digestive malignant tumors. Elevated PLT and PCT or decreased MPV and P-LCR indicated poor overall survival.

High Frequency Deep Brain Stimulation of Superior Cerebellar Peduncles in a Patient with Cerebral Palsy.

Background: Globus pallidus internus (GPi) deep brain stimulation (DBS) is widely used in patients with isolated dystonia; however, its use remains controversial in patients with acquired dystonia and cerebral palsy. Case presentation: We report the first case of a cerebral palsy patient, who failed to recover 2 years after GPi DBS; DBS was administered on both superior cerebellar peduncles (SCPs) and dentate nuclei (DNs). The monopolar stimulation results suggested that DBS was better administered via the SCPs than via the DNs. At six months follow-up, the patient exhibited a significant improvement of dystonia and spasticity, as well as in her quality of life. Discussion: SCP DBS may be a potential treatment for cerebral palsy patients with dystonia and spasticity who do not respond well to GPi DBS.

Upregulation of RIN3 induces endosomal dysfunction in Alzheimer's disease.

BACKGROUND: In Alzheimer's Disease (AD), about one-third of the risk genes identified by GWAS encode proteins that function predominantly in the endocytic pathways. Among them, the Ras and Rab Interactor 3(RIN3) is a guanine nucleotide exchange factor (GEF) for the Rab5 small GTPase family and has been implicated to be a risk factor for both late onset AD (LOAD) and sporadic early onset AD (sEOAD). However, how RIN3 is linked to AD pathogenesis is currently undefined. METHODS: Quantitative PCR and immunoblotting were used to measure the RIN3 expression level in mouse brain tissues and cultured basal forebrain cholinergic neuron (BFCNs). Immunostaining was used to define subcellular localization of RIN3 and to visualize endosomal changes in cultured primary BFCNs and PC12 cells. Recombinant flag-tagged RIN3 protein was purified from HEK293T cells and was used to define RIN3-interactomes by mass spectrometry. RIN3-interacting partners were validated by co-immunoprecipitation, immunofluorescence and yeast two hybrid assays. Live imaging of primary neurons was used to examine axonal transport of amyloid precursor protein (APP) and ß-secretase 1 (BACE1). Immunoblotting was used to detect protein expression, processing of APP and phosphorylated forms of Tau. RESULTS: We have shown that RIN3 mRNA level was significantly increased in the hippocampus and cortex of APP/PS1 mouse brain. Basal forebrain cholinergic neurons (BFCNs) cultured from E18 APP/PS1 mouse embryos also showed increased RIN3 expression accompanied by early endosome enlargement. In addition, via its proline rich domain, RIN3 recruited BIN1(bridging integrator 1) and CD2AP (CD2 associated protein), two other AD risk factors, to early endosomes. Interestingly, overexpression of RIN3 or CD2AP promoted APP cleavage to increase its carboxyl terminal fragments (CTFs) in PC12 cells. Upregulation of RIN3 or the neuronal isoform of BIN1 increased phosphorylated Tau level. Therefore, upregulation of RIN3 expression promoted accumulation of APP CTFs and increased phosphorylated Tau. These effects by RIN3 was rescued by the expression of a dominant negative Rab5 (Rab5S34N) construct. Our study has thus pointed to that RIN3 acts through Rab5 to impact endosomal trafficking and signaling. CONCLUSION: RIN3 is significantly upregulated and correlated with endosomal dysfunction in APP/PS1 mouse. Through interacting with BIN1 and CD2AP, increased RIN3 expression alters axonal trafficking and procession of APP. Together with our previous studies, our current work has thus provided important insights into the role of RIN3 in regulating endosomal signaling and trafficking.

Association between long-term occupational manganese exposure and bone quality among retired workers.

Despite well documents for manganese-induced neurological deficits, limited researches are available for effects of manganese (Mn) exposure on the bone. Here we aimed to explore the associations between long-term occupational Mn exposure and bone quality among retired workers. We conducted a cross-sectional study of 304 exposed subjects (n, male = 161 and female = 143) and 277 control retired workers (n, male = 65 and female = 212) recruited from a ferromanganese refinery. Self-reported occupation types were used as exposure classification confirmed by expert consultation. Bone quality was measured by quantitative ultrasound (QUS). In sex-stratified analyses throughout, stiffness index (SI) and T-score levels of the participants in the highest exposed group [tertile 3 of Mn cumulative exposure index (Mn-CEI)] were significantly lower as compared with the control group among female workers (SI, mean, 61.60 vs. 68.17; T-score, mean, -3.01 vs. -2.34, both P < 0.05). In addition, SI and T-score were found to be negatively associated with Mn-CEI only in the highest exposure group as compared with the female controls (both P = 0.01). However, we did not find the significant difference for SI or T-score among the male subjects in exposure models and the male controls (P > 0.05). Our results suggest that female retired workers in the highest Mn-exposed model (tertile 3 of Mn-CEI) potentially experience a higher risk of developing osteoporosis compared with the female controls. Further investigations on possible mechanisms on bone quality alteration are needed in the future.

Corrigendum: Association of Two Polymorphisms in CCL2 With Parkinson's Disease: A Case-Control Study.

[This corrects the article DOI: 10.3389/fneur.2019.00035.].

Deep brain stimulation of the globus pallidus internus versus the subthalamic nucleus in isolated dystonia.

OBJECTIVE: Surgical procedures involving deep brain stimulation (DBS) of the globus pallidus internus (GPi) or subthalamic nucleus (STN) are well-established treatments for isolated dystonia. However, selection of the best stimulation target remains a matter of debate. The authors' objective was to compare the effectiveness of DBS of the GPi and the STN in patients with isolated dystonia. METHODS: In this matched retrospective cohort study, the authors searched an institutional database for data on all patients with isolated dystonia who had undergone bilateral implantation of DBS electrodes in either the GPi or STN in the period from January 30, 2014, to June 30, 2017. Standardized assessments of dystonia and health-related quality of life using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and SF-36 were conducted before and at 1, 6, and 12 months after surgery. No patients were lost to the 6-month follow-up; 5 patients were lost to the 12-month follow-up. RESULTS: Both GPi (14 patients) and STN (16 patients) stimulation produced significant improvement in dystonia and quality of life in all 30 patients found in the database search. At the 1-month follow-up, however, the percentage improvement in the BFMDRS total movement score was significantly (p = 0.01) larger after STN DBS (64%) than after GPi DBS (48%). At the 12-month follow-up, the percentage improvement in the axis subscore was significantly (p = 0.03) larger after GPi DBS (93%) than after STN DBS (83%). Also, the total amount of electrical energy delivered was significantly (p = 0.008) lower with STN DBS than with GPi DBS (124 ± 52 vs 192 ± 65 µJ, respectively). CONCLUSIONS: The GPi and STN are both effective targets in alleviating dystonia and improving quality of life. However, GPi stimulation may be better for patients with axial symptoms. Moreover, STN stimulation may produce a larger clinical response within 1 month after surgery and may have a potential economic advantage in terms of lower battery consumption.

Lack of Association Between DJ-1 Gene Promoter Polymorphism and the Risk of Parkinson's Disease.

Low DJ-1 protein level caused by DJ-1 gene mutation leads to autosomal recessive Parkinson's disease (PD) due to impaired antioxidative activity. In sporadic PD patients, although mutations were rarely found, lower DJ-1 protein level was also reported. Dysregulation of DJ-1 gene expression might contribute to low DJ-1 protein level. Since the promoter is the most important element to initiate gene expression, whether polymorphisms in the DJ-1 promoter result in the dysregulation of gene expression, thus leading to low protein level and causing PD, is worth exploring. The DJ-1 promoter region was sequenced in a Chinese cohort to evaluate possible links between DJ-1 promoter polymorphisms, PD risk and clinical phenotypes. Dual-luciferase reporter assay was conducted to evaluate the influence of promoter polymorphisms on DJ-1 transcriptional activity. Related information in an existing genome-wide association studies (GWAS) database were looked up, meta-analysis of the present study and other previous reports was conducted, and expression quantitative trait loci (eQTL) analysis was performed to further explore the association. Three single nucleotide polymorphisms (SNPs) (rs17523802, rs226249, and rs35675666) and one 18 bp deletion (rs200968609) were observed in our cohort. However, there was no significant association between the four detected genetic variations and the risk of PD either in allelic or genotype model, in single-point analysis or haplotype analysis. This was supported by the meta-analysis of this study and previous reports as well as that of GWAS database PDGene. Dual luciferase reporter assay suggested these promoter polymorphisms had no influence on DJ-1 transcriptive activity, which is consistent with the eQTL analysis results using the data from GTEx database. Thus, DJ-1 promoter polymorphisms may play little role in the dysregulation of DJ-1 expression and PD susceptibility in sporadic PD.

[Clinical and genotypic analysis of two Chinese pedigrees affected with hereditary coagulable factor VII deficiency].

OBJECTIVE: To explore molecular etiology and clinical characteristics of two pedigrees affected with hereditary factor VII(FVII) deficiency. METHODS: The nine exons and flanking sequences of the F7 gene of the probands were amplified by PCR. The amplicons were analyzed by direct sequencing. Suspected mutations were subjected to SWISS-MODEL modeling and analysis of protein structure change by Pymol software and conservation of amino acids across various species. RESULTS: For proband of pedigree 1, the prothrombin time (PT), FVII activity (FVII:C) and FVII antigen (FVII:Ag) were 36.3 s, 3%, 53.56%, respectively. Sequencing revealed a compound heterozygous variants of c.80_81delCT and c.1371G>T(p.Arg439Ser). His son carried a heterozygous c.1371G>T (p.Arg439Ser) variant. For proband of pedigree 2, the PT, FVII:C and FVII:Ag were 22.3 s, 4%, 1.58%, respectively. Sequencing has revealed a compound heterozygous c.278G>T(p.Arg75Met) missense variant in exon 3 and c.1278T>G (p.His408Gln) in exon 9 of the F7 gene. His mother and son both carried a heterozygous c.278G>T(p.Arg75Met) variant. Three-dimensional simulation and homology analysis revealed that the p.Arg439Ser and p.Arg75Met can respectively alter part of hydrogen bonds and two highly conserved amino acids. CONCLUSION: Two novel heterozygous missense variants of the F7 gene [c.1371G>T(p.Arg439Ser) and c.278G>T(p.Arg75Met)] probably account for the decrease of factor VII in the two pedigrees.

Association of Two Polymorphisms in CCL2 With Parkinson's Disease: A Case-Control Study.

Background: Parkinson's disease (PD) is the most common neurodegenerative movement disorder that is known to be related to neuro-inflammation. Chemokines participate in this process usually through upregulation of expression levels, which are closely related to the polymorphisms in their genes. Recent studies have further revealed the association between these polymorphisms and the risk of PD in multiple populations, but not the Chinese Han population. Methods:The promoter region of CCL2 was sequenced in 411 PD patients and 422 gender-age matched control from a Chinese Han population using PCR-RFLP method. Their genotype frequencies were analyzed statistically. Dual-luciferase reporter assays were conducted in neuroblastoma cells to assess the promoter transcriptional activity of the rs1024611 variants (T>C) and the GRCh38.p12chr17:34252593 G>C alleles in CCL2. Results:We found that the frequency of the CCL2 genotype of rs1024611 was significantly different between the PD and control groups (p = 0.021), while the C allele was associated with a significantly increased risk in the PD group (p = 0.004). Moreover, C allele of this newly identified alteration in CCL2 (GRCh38.p12chr17:34252593 G>C) was also found to be associated with an increased risk of PD (P genotype = 0.006, P allele = 0.006). Dual-luciferase reporter assay results indicated that rs1024611 C allele and GRCh38.p12chr17:.34252593 C allele increased the transcriptional activity of the CCL2 promoter. Conclusions: We, for the first time, report a risk polymorphism (rs1024611) and a new locus (GRCh38.p12chr17:.34252593 G>C) on CCL2, both of which are suggested as risk factors for PD in a Chinese Han population.

Follow-up of the manganese-exposed workers healthy cohort (MEWHC) and biobank management from 2011 to 2017 in China.

BACKGROUND: Long-term excess exposure to environmental manganese (Mn) can lead to multi-system damage, especially in occupational populations. Therefore, we established a manganese-exposed workers healthy cohort (MEWHC), focusing on the systemic health effects related to Mn exposure. Here, we aimed to describe the follow-up activity for the MEWHC study and establish a standardized biological sample bank for the scientific management of high-quality biospecimens and the attached data from 2011 to 2017. METHODS: Baseline examinations for onsite workers were conducted, and the biobank for the MEWHC was first established in 2011; follow-up examinations occurred four times between July 2012 and November 2017. All questionnaires, clinical data and biological samples were routinely collected during each follow-up activity. Additional workers were recruited in 2016, which further enriched the resources of the biobank. RESULTS: A total of 2359 onsite workers and 612 retired workers at a ferromanganese refinery were enrolled in the prospective cohort, and their biological samples were obtained in the preliminary baseline survey and the follow-up investigation, including 2971 blood and urine samples from the cohort. In addition, 1524 hair samples, 1404 nail (toe and finger nails) and 1226 fecal samples were also collected. All specimens were preserved in the biobank, and the data were scientifically managed using a computer system. CONCLUSIONS: The MEWHC study in China provides an effective way to obtain biological samples such as plasma, DNA, hair and urine for storage in a biobank for further study. The standardized management of various samples is crucial for accessing high-quality biospecimens.