Development of a coding SNP panel for tracking the origin of whole-exome sequencing samples.

Whole-exome sequencing (WES) is widely used to diagnose complex genetic diseases and rare conditions. The implementation of a robust and effective quality control system for sample identification and tracking throughout the WES process is essential. We established a multiplex panel that included 22 coding single-nucleotide polymorphism (cSNP) loci. The personal identification and paternity identification abilities of the panel were evaluated, and a preliminary validation of the practical feasibility of the panel was conducted in a clinical WES case. These results indicate that the cSNP panel could be a useful tool for sample tracking in WES.

Effects of vaginal microbiota on human papillomavirus infection and its related diseases.

With the knowledge of female reproductive tract microbiota gradually increasing, the connection between vaginal microbiota (VMB) and its related diseases is increasingly highlighted. Manifestation of VMB keeps changing with various dominated bacteria, which can affect the immune response of mucosal barrier and the entrance of pathogens. Human papillomavirus (HPV), as an oncogenic virus, is closely related to viral-associated cancer, such as cervical cancer. According to HPV infection status, VMB can transform into different types, and result in accelerating or restraining the progression of diseases, which have exposed the inner link between VMB and HPV. Therefore, probiotics therapy promises to be a new complementary therapy to rebuild a healthy VMB for patients, but there's still a long way to go before its ready for the clinic. This review focuses on composition, immune response, and application of VMB in HPV and its associated diseases and aims to provide the new ideas and directions for the research on VMB.

Characterization of posterior circulation blood perfusion in patients with different degrees of basilar artery tortuosity.

OBJECTIVE: The morphology of basilar artery (BA) may affect posterior circulation blood perfusion. We aimed to investigate whether different degrees of BA tortuosity could lead to the alterations of posterior circulation perfusion. METHODS: We collected 138 subjects with different BA tortuosity scores, including 32 cases of score 0, 45 cases of score 1, 43 cases of score 2, and 18 cases of score 3. A higher score represented a higher degree of BA tortuosity. Ordered logistic regression analysis was performed to investigate the risk factors for BA tortuosity. We quantitatively measured the cerebral blood flow (CBF) in eight posterior circulation brain regions using arterial spin labeling. SPSS 25.0 was used for statistical analysis. The correlation between the CBF and BA tortuosity was corrected by the Bonferroni method. The significance level was set at 0.006 (0.05/8). RESULTS: Hypertension (HR: 2.39; 95%CI: 1.23-4.71; P = 0.01) and vertebral artery dominance (HR: 2.38; 95%CI: 1.10-4.67; P = 0.03) were risk factors for BA tortuosity. CBF in occipital gray matter (R = -0.383, P < 0.001), occipital white matter (R = -0.377, P < 0.001), temporal gray matter (R = -0.292, P = 0.001), temporal white matter (R = -0.297, P < 0.001), and cerebellum (R = -0.328, P < 0.001) were negatively correlated with BA tortuosity degree. No significant correlation was found between the BA tortuosity degree and CBF in hippocampus (R = -0.208, P = 0.014), thalamus (R = -0.001, P = 0.988) and brainstem (R = -0.204, P = 0.016). CONCLUSIONS: BA tortuosity could affect posterior circulation blood perfusion. CBF was negatively correlated with BA tortuosity degree. The morphology of BA may serve as a biomarker for posterior circulation and the severity of posterior circulation ischemia.

Epidemiologic features and therapeutic strategies of kerion: A nationwide multicentre study.

BACKGROUND: Kerion is a severe type of tinea capitis that is difficult to treat and remains a public health problem. OBJECTIVES: To evaluate the epidemiologic features and efficacy of different treatment schemes from real-world experience. METHODS: From 2019 to 2021, 316 patients diagnosed with kerion at 32 tertiary Chinese hospitals were enrolled. We analysed the data of each patient, including clinical characteristics, causative pathogens, treatments and outcomes. RESULTS: Preschool children were predominantly affected and were more likely to have zoophilic infection. The most common pathogen in China was Microsporum canis. Atopic dermatitis (AD), animal contact, endothrix infection and geophilic pathogens were linked with kerion occurrence. In terms of treatment, itraconazole was the most applied antifungal agent and reduced the time to mycological cure. A total of 22.5% of patients received systemic glucocorticoids simultaneously, which reduced the time to complete symptom relief. Furthermore, glucocorticoids combined with itraconazole had better treatment efficacy, with a higher rate and shorter time to achieving mycological cure. CONCLUSIONS: Kerion often affects preschoolers and leads to serious sequelae, with AD, animal contact, and endothrix infection as potential risk factors. Glucocorticoids, especially those combined with itraconazole, had better treatment efficacy.

Social poverty indicators with school bullying victimization: evidence from the global school-based student health survey (GSHS).

BACKGROUND: School bullying is prevalent in children and adolescents. Bullying victims are seen higher risk of negative psychological outcomes. Previously published studies suggested that social indicators may pose significant influence on bullying victimization. However, the association between social poverty and bullying victimization has not been exclusively discussed. METHODS: In this cross-sectional study, we analyzed the association between 6 commonly used social poverty indicators (Poverty Headcount Ratio, PHR; Poverty Gap, PG; Squared Poverty Gap, SPG; monthly household per capita income, PCI; Watts' Poverty Index, WPI; the Gini Index, Gini) and the prevalence of school bullying at country level by using the Global school-based Student Health Survey (GSHS) database. RESULTS: Altogether 16 countries were included into the final analysis, with school bullying victimization prevalence ranged from 12.9 to 47.5%. Bubble plots revealed statistically significant associations between the three indicators measuring absolute poverty level (PHR, PCI, WPI) and bullying victimization. Subsequently performed principal component regression indicated that, for all types of bullying victimization, the increase of absolute poverty level was related to elevated prevalence rates, and the association was particularly strong for verbal bullying victimization. CONCLUSIONS: Our study results may suggest that absolute social poverty is an important parameter for constructing and implementing school bullying victimization intervention strategies and measures.

Childhood maltreatment associated suicidal risk in Chinese children and adolescents: a mediation of resilience.

BACKGROUND: Existing evidence suggests that children and adolescents who had experienced childhood maltreatment (CM) are at higher suicidal risk. However, the mediation role of resilience in this association remains unclear. We aim to investigate the mediation via resilience in the associations between CM and three suicidal risk indicators (suicidal ideation, SI; suicidal plan, SP; suicidal attempt, SA) among a large sample of Chinese children and adolescents. METHODS: A population-based cross-sectional survey was conducted in southwestern China Yunnan province. A total of 9723 children and adolescents were included and analyzed by using a multi-stage stratified cluster sampling design. Univariate and multivariate logistic regression models were fitted to explore the associations between CM, resilience, and the three suicidal risk indicators, dose-response trends further elucidated by using the restricted cubic splines. Path models were adopted to estimate the mediation of resilience. RESULTS: The estimated prevalence rates for one-year SI, SP and SA were 32.86% (95% CI: 31.93-33.80%), 19.36% (95% CI: 18.57-20.16%) and 9.07% (95% CI: 8.51-9.66%). After adjustment, CM significantly associated with all 3 suicidal risk indicators, and the odds ratios (ORs) were 2.13 (95% CI: 1.91-2.37), 2.45 (95% CI: 2.13-2.81), and 3.61 (95% CI: 2.90-4.52) for one-year SI, SP, and SA, respectively. Path models revealed that resilience significantly mediated the associations between CM and the three suicidal risk indicators, and among all dimensions of resilience, family support presented the strongest mediation consistently. CONCLUSIONS: Our study results suggest that intervention measures which focusing on improving psychological resilience might be effective in reducing suicidal risk for children and adolescents who had experienced maltreatment. Prospective studies should be done to corroborate our findings.

Analysis of cantharidin-induced kidney injury and the protective mechanism of resveratrol in mice determined by liquid chromatography/mass spectrometry-based metabonomics.

Cantharidin (CTD) is the main active component in the traditional Chinese medicine Mylabris and an effective anti-tumor agent. However, it is relatively toxic and exhibits nephrotoxicity, which limits its clinical use. However, its toxic mechanism is not clear. The toxic effects of CTD exposure on the kidney and the protective effect of resveratrol (RES) were studied in a mouse model, by determination of serum biochemical and renal antioxidant indicators, histopathological and ultrastructural observation, and metabonomics. After CTD exposure, serum uric acid, creatinine, and tissue oxidative stress indicators increased, and the renal glomerular and tubular epithelial cells showed clear pathological damage. Ultrastructure observation revealed marked mitochondrial swelling, endoplasmic reticulum dilation, and the presence of autophagy lysosomes in glomerular epithelial cells. RES ameliorated the renal injury induced by CTD. Metabonomics analysis indicated that CTD can induce apoptosis and oxidative damage in kidney cells, mainly by disrupting sphingolipid and glutathione metabolism, increasing sphingosine and sphingomyelin levels, and decreasing glutathione levels. RES counteracts these effects by regulating renal cell proliferation, the inflammatory response, oxidative stress, and apoptosis, by improving the levels of phosphatidylcholine (PC), LysoPC, and lysophosphatidyl glycerol in the glycerophospholipid metabolism pathway, thereby reducing CTD-induced nephrotoxicity. The mechanisms of CTD-induced renal injury and the protective effect of RES were revealed by metabonomics, providing a basis for evaluating clinical treatment regimens to reduce CTD-induced nephrotoxicity.

Anisodamine Hydrobromide ameliorates acute lung injury via inhibiting pyroptosis in murine sepsis model.

OBJECTIVE: Sepsis can have severe implications on lung function, leading to acute lung injury (ALI), a major contributor to sepsis-related mortality. Anisodamine hydrobromide (Ani HBr), a bioactive constituent derived from the root of Scopolia tangutica Maxim, a plant endemic to China, has demonstrated efficacy in treating septic shock. We aim to explore whether Ani HBr can alleviate sepsis-triggered acute lung injury (ALI) and elucidate the fundamental mechanisms involved. MATERIALS AND METHOD: The protective effects of Ani HBr were assessed in two models: in vitro, lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and in vivo, cecal ligation puncture (CLP)-induced sepsis. To measure the cell viability of RAW264.7 cells after Ani HBr treatment, we used the CCK-8 assay. We quantified the levels of pro-inflammatory cytokines expression using ELISA. We also measured the expression of pyrotosis indicators by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence. RESULTS: Our study demonstrates that Ani HBr can alleviate pulmonary edema, bleeding, and excessive inflammation induced by CLP. Additionally, it exhibits protective effects against cytotoxicity induced by LPS in RAW264.7 macrophage cells. Furthermore, Ani HBr downregulates the mRNA and protein levels of NLRP3, Caspase-1, GSDMD, IL-18, and IL-1ß in both animal models and cell cultures, thereby inhibiting pyroptosis in a similar mechanism to AC-YVAD-CMK (AYC)'s blockade of Caspase-1. Moreover, Ani HBr suppresses the production and release of proinflammatory cytokines. CONCLUSION: These findings suggest that Ani HBr could serve as a protective agent against sepsis-induced ALI by suppressing pyroptosis.

Prognostic value of tertiary lymphoid structures (TLS) in digestive system cancers: a systematic review and meta-analysis.

BACKGROUND: Existing literature suggests that tertiary lymphatic structure (TLS) is associated with the progression of cancer. However, the prognostic role of TLS in digestive system cancers remains controversial. This meta-analysis aims to synthesize currently available evidence in the association between TLS and the survival of digestive system cancers. METHODS: We systematically searched three digital databases (PubMed, Embase, Web of Science) for articles published from database inception to December 23, 2022. Study selection criteria are based on PECO framework: P (population: patients with digestive system cancers), E (exposure: presence of TLS), C (comparator: absence of TLS), O (outcome: overall survival, OS; recurrence-free survival, RFS; disease-free survival, DFS). The Quality in Prognostic Studies (QUIPS) tool was used to assess risk of bias for included studies. The study protocol was registered with PROSPERO (CRD42023416307). RESULTS: A total of 25 studies with 6910 patients were included into the final meta-analysis. Random-effects models revealed that the absence of TLS was associated with compromised OS, RFS, and DFS of digestive system cancers, with pooled hazard ratios (HRs) of 1.74 (95% CI: 1.50-2.03), 1.96 (95% CI: 1.58-2.44), and 1.81 (95% CI: 1.49-2.19), respectively. Subgroup analyses disclosed a stronger TLS-survival association for pancreatic cancer, compared with other digestive system cancers. CONCLUSION: TLS may be of prognostic significance for digestive system cancers. More original studies are needed to further corroborate this finding.

Automated Skeleton Network Generation for ReaxFF Molecular Dynamics Simulations of Hydrocarbon Fuel Pyrolysis and Oxidation via a Rate-Based Algorithm.

In this study, we present an automated approach of rate-based skeleton network generation for ReaxFF MD simulation (RxMD-SN) for deriving the reaction kinetic mechanism of large hydrocarbon fuels in pyrolysis and oxidation from large-scale ReaxFF MD simulations. The approach contains the statistical calculation of reaction rate constants and the generation of skeleton reaction networks using a rate-based algorithm. The RxMD-SN method takes advantage of reaction flux ranking at a small time interval in terms of temporal reaction rate to extract the core reaction networks, which allows for keeping the rare reaction events that may be dominant in a certain period of the reaction network. The kinetic models derived from ReaxFF MD simulation in CH4 oxidation can reproduce what was obtained in the ReaxFF MD simulation, which demonstrates the capability of RxMD-SN in capturing the global reaction kinetics. An evaluation of reaction rate constants indicates that close kinetic parameters are shared for n-octane oxidation of similar reaction classes, shared oxidation reactions of CH4 against n-heptane, and shared pyrolysis reactions of the RP-3 surrogate fuel against n-heptane. This capability of RxMD-SN is particularly beneficial in meeting the challenges in characterizing the oxidation reaction kinetics of large hydrocarbon molecules. RxMD-SN approach is potentially a general approach in chemical kinetics modeling on the basis of ReaxFF MD simulations.

Etanercept Combined with Glucocorticoid and Gamma Globulin for Treating Children with Toxic Epidermal Necrolysis: A Case Report.

Toxic epidermal necrolysis (TEN) is a type of drug eruption in dermatology emergencies that is rare in clinical practice but has a high mortality rate. The main causes are drug and viral infections. Unfortunately, no expert consensus on treating this disease exists, and a standard therapy is absent. Up to now, glucocorticoids combined with gamma globulin are commonly used in clinical practice, but their efficacy is highly controversial. This study reports on a 7-year-old girl with TEN who did not respond to traditional therapy, such as methylprednisolone combined with gamma globulin, but was finally cured with an additional low-dose etanercept. The results showed that etanercept therapy in paediatric TEN is safe, reliable and worth recommending.

Case report: Genetic diagnoses in a pediatric patient with retinoblastoma and comorbid global developmental delay: three distinct entities diagnosed by whole exome sequencing in a single patient.

Background: The objective of this study was to explore the genetic etiology and propose a genetic diagnosis and counseling strategy for children with retinoblastoma (RB) and global developmental delay (GDD). Case presentation: We report on a 2 years and 4 months old boy with binocular retinoblastoma and global developmental delay (included intellectual disability, language development delay, motor development delay, etc.). Genomic DNA was extracted from peripheral blood mononuclear cells isolated from the proband and his parents. Whole exome sequencing (WES) was carried out for the proband and his parents to identify genetic etiology, which was subsequently verified by quantitative polymerase chain reaction (qPCR).The WES revealed a gross heterozygous deletion in the RB transcriptional corepressor 1 (RB1, OMIM:614041) gene, including exon 7-8, in the affected proband but not in his parents. Additionally, two pathogenic copy number variations (CNVs) were identified: a duplication at 7q11.23 and a microdeletion at 16p11.2-p12.2, respectively. Furthermore, the genomic qPCR analysis demonstrated a 50% reduction in the copy numbers of exon 7 and exon 8 in the RB1 gene of the proband, as compared to those detected in his parents. Simultaneous variants in the RB1 gene and two pathogenic CNVs can precisely explain the genetic etiology of the proband. Conclusion: The present study firstly reports a novel gross deletion variant of the RB1 gene coexisting with two pathogenic CNVs in a pediatric patient with retinoblastoma and comorbid global developmental delay in China. Additionally, our findings strongly support the use of WES in pediatric patients with RB comorbid GDD, and WES is recommended as the first-tier test.

Development of multi-epitope mRNA vaccine against Clostridioides difficile using reverse vaccinology and immunoinformatics approaches.

Clostridioides difficile (C. difficile), as the major pathogen of diarrhea in healthcare settings, has become increasingly prevalent within community populations, resulting in significant morbidity and mortality. However, the therapeutic options for Clostridioides difficile infection (CDI) remain limited, and as of now, no authorized vaccine is available to combat this disease. Therefore, the development of a novel vaccine against C. difficile is of paramount importance. In our study, the complete proteome sequences of 118 strains of C. difficile were downloaded and analyzed. We found four antigenic proteins that were highly conserved and can be used for epitope identification. We designed two vaccines, WLcd1 and WLcd2, that contain the ideal T-cell and B-cell epitopes, adjuvants, and the pan HLA DR-binding epitope (PADRE) sequences. The biophysical and chemical assessments of these vaccine candidates indicated that they were suitable for immunogenic applications. Molecular docking analyses revealed that WLcd1 bonded with higher affinity to Toll-like receptors (TLRs) than WLcd2. Furthermore, molecular dynamics (MD) simulations, performed using Gmx_MMPBSA v1.56, confirmed the binding stability of WLcd1 with TLR2 and TLR4. The preliminary findings suggested that this multi-epitope vaccine could be a promising candidate for protection against CDI; however, experimental studies are necessary to confirm these predictions.

Developmental validation of an mRNA kit: A 5-dye multiplex assay designed for body-fluid identification.

Identifying the sources of biosamples found at crime scenes is crucial for forensic investigations. Among the markers used for body fluid identification (BFI), mRNA has emerged as a well-studied marker because of its high specificity and remarkable stability. Despite this potential, commercially available mRNA kits specifically designed for BFI are lacking. Therefore, we developed an mRNA kit that includes 21 specific mRNA markers of body fluids, along with three housekeeping genes for BFI, to identify four forensic-relevant fluids (blood, semen, saliva, and vaginal fluids). In this study, we tested 451 single-body-fluid samples, validated the universality of the mRNA kit, and obtained a gene expression profile. We performed the validation studies in triplicates and determined the sensitivity, specificity, stability, precision, and repeatability of the mRNA kit. The sensitivity of the kit was found to be 0.1 ng. Our validation process involved the examination of 59 RNA mixtures, 60 body fluids mixtures, and 20 casework samples, which further established the reliability of the kit. Furthermore, we constructed five classifiers that can handle single-body fluids and mixtures using this kit. The classifiers output possibility values and identify the specific body fluids of interest. Our results showed the reliability and suitability of the BFI kit, and the Random Forest classifier performed the best, with 94% precision. In conclusion, we developed an mRNA kit for BFI which can be a promising tool for forensic practice.

Childhood maltreatment, parenting style and anxiety in Chinese youths: A case-control study.

BACKGROUND: Although evidence in supporting the associations between childhood maltreatment (CM), parenting style and anxiety in children and adolescents exists, few high-quality analytical epidemiological studies which focusing on clinically diagnosed anxiety disorders (AD) had been published. OBJECTIVE: The aim of this study was to further corroborate the associations between CM, parenting style, and AD in a large representative sample of Chinese children and adolescents. PARTICIPANTS AND SETTING: Study subjects were derived from the Mental Health Survey for Children and Adolescents in Yunnan (MHSCAY), a population-based cross-sectional program. METHODS: Individually matched case-control study design was adopted. Univariate and multivariate conditional binary logistic regression models were used to estimate the associations between CM, parenting style and AD. Dose-response trends were estimated using the Cochran-Armitage Chi-square test. A series of stratified analyses were conducted to explore effect modification on exposure-outcome association by some important features. RESULTS: Totally we screened out 202 cases and 404 matched controls, with an age mean of 14.43 years. Conditional logistic regression models revealed that EA and a higher level of parental over-protection were significantly associated with increased risk of AD, with adjusted ORs of 3.39 (95 % CI: 2.07-5.56) and 1.93 (95 % CI: 1.28-2.90). Stratified analysis identified noticeable effect modification by sex, age, and whether the only child in the family. CONCLUSIONS: Major findings of this study suggested that children and adolescents who had experienced EA or raised up by over-protective parents are at increased risk of AD. Targeted intervention measures should be developed and implemented for these high-risk youths.

Optimizing Analytical Thresholds for Low-Template DNA Analysis: Insights from Multi-Laboratory Negative Controls.

When analyzing challenging samples, such as low-template DNA, analysts aim to maximize information while minimizing noise, often by adjusting the analytical threshold (AT) for optimal results. A potential approach involves calculating the AT based on the baseline signal distribution in electrophoresis results. This study investigates the impact of reagent kits, testing quarters, environmental conditions, and amplification cycles on baseline signals using historical records and experimental data on low-template DNA. Variations in these aspects contribute to differences in baseline signal patterns. Analysts should remain vigilant regarding routine instrument maintenance and reagent replacement, as these may affect baseline signals. Prompt analysis of baseline status and tailored adjustments to ATs under specific laboratory conditions are advised. A comparative analysis of published methods for calculating the optimal AT from a negative signal distribution highlighted the efficiency of utilizing baseline signals to enhance forensic genetic analysis, with the exception of extremely low-template samples and high-amplification cycles. Moreover, a user-friendly program for real-time analysis was developed, enabling prompt adjustments to ATs based on negative control profiles. In conclusion, this study provides insights into baseline signals, aiming to enhance genetic analysis accuracy across diverse laboratories. Practical recommendations are offered for optimizing ATs in forensic DNA analysis.

MHBase: A comprehensive database of short microhaplotypes for advancing forensic genetic analysis.

Microhaplotypes (MHs) were first recommended by Prof. Kidd for use in forensics because they can improve human identification, kinship analysis, mixture deconvolution, and ancestry prediction. Since their introduction, extensive research has demonstrated the advantages of MHs in forensic applications and provided useful data for different populations. Currently, two databases, ALFRED (ALlele FREquency Database) and MicroHapDB (MicroHaplotype DataBase), house the published MH information and population data. We previously constructed a single nucleotide polymorphism SNP-SNP MH database (D-SNPsDB) of MHs within 50 bp on the whole human genome for 26 populations integrating basic data such as physical genome positions, mapping of variant identifiers (rsIDs), allele frequencies, and basic variant information. Building upon the previous research, we further selected MHs containing at least two variants (SNPs and/or insertions/deletions [InDels]) within a short DNA fragment (≤ 50 bp) in 26 populations based on the 1000 Genomes Project dataset (Phase 3) to construct a more comprehensive database. Subsequently, we established a user-friendly website that allows users to search the MH database (MHBase) based on their research objectives and study population to find suitable loci and provides other functions such as querying reported loci, performing online calculations using the PHASE software, and calculating ancestral-related parameters. The loci in the database are classified as SNP-based MHs, which include only SNPs, and InDel-including MHs, which contain at least one InDel. Here, we provide a detailed overview of the MHBase and an analysis of shared loci at the global and continental levels, ancestral markers, the genetic distance within loci, and mapping with the genome annotation file. The website is an accessible and useful tool for researchers engaged in marker discovery, population studies, assay development, and panel design.

GLP1R rs3765467 Polymorphism Is Associated with the Risk of Early Onset Type 2 Diabetes.

Objective: To investigate the relationship between glucagon-like peptide-1 receptor gene polymorphisms and susceptibility to early onset type 2 diabetes. Methods: Samples from 316 type 2 diabetes patients with early onset type 2 diabetes (n = 137) and late-onset type 2 diabetes (n = 179) and 145 nondiabetic individuals were analyzed. Multiplex PCR combined with resequencing Hi-Reseq technology was used to detect single nucleotide polymorphisms of the glucagon-like peptide-1 receptor gene, and the allele frequency, genotype distribution, and clinical parameters were analyzed between each diabetes subgroup and the control group. Results: Sixteen single nucleotide polymorphisms were identified in the exonic region of the glucagon-like peptide-1 receptor gene according to the minor allele frequency (MAF > 0.05) in the participants. Among these, the glucagon-like peptide-1 receptor rs3765467 (G⟶A) mutation was statistically associated with early onset type 2 diabetes. Compared with that of the GG carriers, carriers of genotype AA at rs3765467 had a decreased risk of early onset type 2 diabetes after adjusting for sex and body mass index. In the dominant model, the frequencies of the rs3765467 AA + GA genotype were significantly decreased in the early onset type 2 diabetes group, and carriers of genotype AA + GA at rs3765467 had a decreased risk of early onset type 2 diabetes after adjusting for sex and body mass index. Moreover, fasting C peptide levels were significantly higher in GA + AA genotype carriers than those in GG genotype carriers. Conclusion: The glucagon-like peptide 1 receptor rs3765467 polymorphism was significantly associated with age at type 2 diabetes diagnosis and thus may be used as a marker to screen and detect individuals at risk of developing early onset type 2 diabetes.

de Winter syndrome, an easily ignored but life-threatening disease: a case report / 浙江大学学报·医学版

de Winter syndrome is a special equivalent of anterior ST-segment elevation myocardial infarction (STEMI) characterized by the absence of overt ST-elevation with upsloping ST-segment depression followed by tall symmetrical T-waves in the precordial leads, often associated with total occlusion of the proximal left anterior descending coronary artery. Herein we present a case of de Winter syndrome in a 63-year-old man, whose initial ECG showed no ST-segment elevation, but subsequent coronary angiography confirmed total occlusion of the proximal LAD coronary artery. The patient was successfully treated via mechanical reperfusion therapy and stenting through percutaneous coronary intervention (PCI). de Winter syndrome is associated with a high mortality often due to insufficient awareness of this condition by clinicians. Immediate reperfusion therapy by PCI is the life-saving treatment for the patients diagnosed with this syndrome, and prompt recognition of the ECG pattern is critical to ensure the timely administration of the therapy.