Susceptibility of TSPAN5 polymorphisms to Kawasaki disease and immunoglobulin therapy resistance in southern Chinese children.

Kawasaki disease (KD) is a condition characterized by acute multi-system vasculitis and high fever in infants and children. Intravenous immunoglobulin (IVIG) is the established therapeutic approach of KD,foralleviating inflammation and mitigate the risk of arterial wall dilation and the development of coronary artery aneurysms (CAA). But almost 20% of the patients developed resistance to IVIG and displayed persistent fever after standard primary treatment. TSPAN5, belonging to the Tetraspanin family, has been demonstrated to modulate innate immunity in a range of human diseases. It accomplishes this by engaging with integrins and actively participating in the process of infection recognition. However, its relevance to susceptibility and IVIG therapy response of KD was unexposed. In the present study, our Integrative analysis of KD transcriptomic data and GTEx data revealed that the eQTL rs12504972 might modify the downregulation of TSPAN5 in KD patients. Moreover, our findings suggest a potential association between TSPAN5/rs12504972 and an elevated susceptibility as well as IVIG resistance among patients with Kawasaki disease in southern China. The results provided a new insight that TSPAN5 triggered KD susceptibility and resistance of IVIG therapy on the genomic level.

Ref-MEF: Reference-Guided Flexible Gated Image Reconstruction Network for Multi-Exposure Image Fusion.

Multi-exposure image fusion (MEF) is a computational approach that amalgamates multiple images, each captured at varying exposure levels, into a singular, high-quality image that faithfully encapsulates the visual information from all the contributing images. Deep learning-based MEF methodologies often confront obstacles due to the inherent inflexibilities of neural network structures, presenting difficulties in dynamically handling an unpredictable amount of exposure inputs. In response to this challenge, we introduce Ref-MEF, a method for color image multi-exposure fusion guided by a reference image designed to deal with an uncertain amount of inputs. We establish a reference-guided exposure correction (REC) module based on channel attention and spatial attention, which can correct input features and enhance pre-extraction features. The exposure-guided feature fusion (EGFF) module combines original image information and uses Gaussian filter weights for feature fusion while keeping the feature dimensions constant. The image reconstruction is completed through a gated context aggregation network (GCAN) and global residual learning GRL. Our refined loss function incorporates gradient fidelity, producing high dynamic range images that are rich in detail and demonstrate superior visual quality. In evaluation metrics focused on image features, our method exhibits significant superiority and leads in holistic assessments as well. It is worth emphasizing that as the number of input images increases, our algorithm exhibits notable computational efficiency.

LncRNA HCG11 enhances the chemosensitivity of non-small cell lung cancer cells to Gemcitabine via miR-17-5p/p21 axis.

BACKGROUND: This study investigated the inhibitory effects of lncRNA HLA Complex Group 11 (HCG11) on non-small cell lung cancer (NSCLC) and the molecular mechanisms. RESEARCH DESIGN AND METHODS: Bioinformatics analysis was conducted to determine the downstream targeted gene miR-17-5p/p21 and predict their binding sites. qRT-PCR and Western blot were used to detect expression levels, and dual luciferase and RIP assays were adopted to verify binding relationship. RESULTS: The lncRNA HCG11/miR-17-5p/p21 axis was found to regulate drug resistance, proliferation, apoptosis, and cell cycle of A549 and A549-Gemcitabine (GEM) cells. HCG11 acted as a ceRNA binding to miR-17-5p, which repressed p21 expression in turn. In vivo experiments demonstrated that HCG11 hindered tumor growth. Therefore, lncRNA HCG11, by targeting the miR-17-5p/p21 axis, suppressed GEM resistance and malignant progression of NSCLC cells. CONCLUSIONS: This study provides a reference for investigating the potential value of lncRNA HCG11 in the diagnosis of NSCLC and finding potential targets against clinical chemotherapeutic resistance in NSCLC.

Association between interpregnancy interval and risk of autism spectrum disorder: a systematic review and Bayesian network meta-analysis.

Although the risk of autism spectrum disorder (ASD) has been reported to be associated with interpregnancy intervals (IPIs), their association remains debatable due to inconsistent findings in existing studies. Therefore, the present study aimed to explore their association. PubMed, Embase, Web of Science, and the Cochrane Library were systematically retrieved up to May 25, 2022. An updated search was performed on May 25, 2023, to encompass recent studies. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). Our primary outcome measures were expressed as adjusted odds ratios (ORs). Given various control measures for IPI and diverse IPI thresholds in the included studies, a Bayesian network meta-analysis was performed. Eight studies were included, involving 24,865 children with ASD and 2,890,289 children without ASD. Compared to an IPI of 24 to 35 months, various IPIs were significantly associated with a higher risk of ASD (IPIs < 6 months: OR = 1.63, 95% CI 1.53-1.74, n = 5; IPIs of 6-11 months: OR = 1.50, 95% CI 1.42-1.59, n = 4; IPIs of 12-23 months: OR = 1.19, 95% CI 1.12-1.23, n = 10; IPIs of 36-59 months: OR = 0.96, 95% CI 0.94-0.99, n = 2; IPIs of 60-119 months: OR = 1.15, 95% CI 1.10-1.20, n = 4; IPIs > 120 months: OR = 1.57, 95% CI 1.43-1.72, n = 4). After adjusting confounding variables, our analysis delineated a U-shaped restricted cubic spline curve, underscoring that both substantially short (< 24 months) and excessively long IPIs (> 72 months) are significantly correlated with an increased risk of ASD.  Conclusion: Our analysis indicates that both shorter and longer IPIs might predispose children to a higher risk of ASD. Optimal childbearing health and neurodevelopmental outcomes appear to be associated with a moderate IPI, specifically between 36 and 60 months. What is Known: • An association between autism spectrum disorder (ASD) and interpregnancy intervals (IPIs) has been speculated in some reports. • This association remains debatable due to inconsistent findings in available studies. What is New: • Our study delineated a U-shaped restricted cubic spline curve, suggesting that both shorter and longer IPIs predispose children to a higher risk of ASD. • Optimal childbearing health and neurodevelopmental outcomes appear to be associated with a moderate IPI, specifically between 36 and 60 months.

Hsa_circ_0022383 promote non-small cell lung cancer tumorigenesis through regulating the miR-495-3p/KPNA2 axis.

Hsa_circ_0022383 (circ_0022383) is a newly discovered circRNA. Its functions and relevant molecular mechanisms in tumorigenesis have not been reported. Here we aimed to explore how circ_0022383 regulates the tumorigenesis of non-small-cell lung cancer (NSCLC). We found thatcirc_0022383 expression was dramatically elevated in NSCLC tissues and cell lines. Upregulation of circ_0022383 was associated with poor prognosis in NSCLC patients. Silencing of circ_0022383 repressed cell proliferation and migration in vitro and inhibited oncogenesis and tumor metastasis in vivo. Moreover, our results discovered that circ_0022383 was mainly located in the cytoplasm of NSCLC cells. Mechanistically, circ_0022383 sponged miR-495-3p to modulate KPNA2 expression, thereby regulating NSCLC tumorigenesis and progression. In conclusion, our study demonstrates that circ_0022383 facilitates NSCLC tumorigenesis by regulating the miR-495-3p/KPNA2 axis, providing new insights into NSCLC development.

Association of living environmental and occupational factors with semen quality in chinese men: a cross-sectional study.

Sperm quality can be easily influenced by living environmental and occupational factors. This study aimed to discover potential semen quality related living environmental and occupational factors, expand knowledge of risk factors for semen quality, strengthen men's awareness of protecting their own fertility and assist the clinicians to judge the patient's fertility. 465 men without obese or underweight (18.5 < BMI < 28.5 kg/m2), long-term medical history and history of drug use, were recruited between June 2020 to July 2021, they are in reproductive age (25 < age < 45 years). We have collected their semen analysis results and clinical information. Logistic regression was applied to evaluate the association of semen quality with different factors. We found that living environment close to high voltage line (283.4 × 106/ml vs 219.8 × 106/ml, Cohen d = 0.116, P = 0.030) and substation (309.1 × 106/ml vs 222.4 × 106/ml, Cohen d = 0.085, P = 0.015) will influence sperm count. Experienced decoration in the past 6 months was a significant factor to sperm count (194.2 × 106/ml vs 261.0 × 106/ml, Cohen d = 0.120, P = 0.025). Living close to chemical plant will affect semen PH (7.5 vs 7.2, Cohen d = 0.181, P = 0.001). Domicile close to a power distribution room will affect progressive sperm motility (37.0% vs 34.0%, F = 4.773, Cohen d = 0.033, P = 0.030). Using computers will affect both progressive motility sperm (36.0% vs 28.1%, t = 2.762, Cohen d = 0.033, P = 0.006) and sperm total motility (57.0% vs 41.0%, Cohen d = 0.178, P = 0.009). After adjust for potential confounding factors (age and BMI), our regression model reveals that living close to high voltage line is a risk factor for sperm concentration (Adjusted OR 4.03, 95% CI 1.15-14.18, R2 = 0.048, P = 0.030), living close to Chemical plants is a protective factor for sperm concentration (Adjusted OR 0.15, 95% CI 0.05-0.46, R2 = 0.048, P = 0.001) and total sperm count (Adjusted OR 0.36, 95% CI 0.13-0.99, R2 = 0.026, P = 0.049). Time spends on computer will affect sperm total motility (Adjusted OR 2.29, 95% CI 1.11-4.73, R2 = 0.041, P = 0.025). Sum up, our results suggested that computer using, living and working surroundings (voltage line, substation and chemical plants, transformer room), and housing decoration may association with low semen quality. Suggesting that some easily ignored factors may affect male reproductive ability. Couples trying to become pregnant should try to avoid exposure to associated risk factors. The specific mechanism of risk factors affecting male reproductive ability remains to be elucidated.

Effect of postoperative radiotherapy on survival in patients with completely resected and pathologically confirmed stage N2 non-small-cell lung cancer: a systematic review and meta-analysis.

Background: The role of postoperative radiotherapy (PORT) for patients with completely resected stage N2 non-small-cell lung cancer (NSCLC) has been controversial. This study aimed to investigate the efficacy of PORT and prognosis in these patients. Objectives: An updated meta-analysis was conducted in this study to investigate the efficacy of PORT and prognosis in patients with completely resected and pathologically confirmed stage N2 NSCLC. Design: This study is a systematic review and meta-analysis. Data source and methods: Databases were searched up to 2 March 2022. All trials on patients with completely resected and pathologically confirmed stage N2 NSCLC undergoing PORT were screened, and data indicators in the PORT and non-PORT groups were extracted, respectively. The effect of PORT on overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) was estimated. Subgroup and sensitivity analyses were performed. Results: In all, 20 studies involving 6340 patients were finally included. The PORT significantly increased OS [hazard ratio (HR) = 0.77, 95% CI: 0.71-0.84, p < 0.001), LRFS (HR = 0.63, 95% CI: 0.52-0.76, p < 0.001), and DFS (HR = 0.72, 95% CI: 0.63-0.82, p < 0.001) while it showed no significant difference in improving DMFS (HR = 0.86, 95% CI: 0.71-1.05, p = 0.14). Conclusion: Our results suggest that in the postoperative treatment of patients with completely resected and pathologically confirmed stage N2 NSCLC, the addition of PORT provides better local recurrence control and survival benefit, but no benefit for distant metastases. The PORT may be incorporated into the postoperative treatment options for some patients with high-risk factors. However, it needs to be validated by more prospective studies in the future. Trail registration: CRD42022314095.

Whole-Exome Sequencing for Identification of Potential Sex-Biased Variants in Kawasaki Disease Patients.

Kawasaki disease (KD) is an autoimmune disease of unknown etiology and has become a main cause of childhood acquired heart disease. KD is more prevalent in males than in females. The reason for this sex bias is unknown. Here, we used whole-exome sequencing (WES) to identify significantly different variants between male and female KD patients. From WES result, a total of 19,500 shared genetic variants in 8421 genes were captured via a series of filters. Further comparisons based on sex were performed to obtain 34 potential sex-biased variants in 34 genes for GO and Reactome Gene Sets enrichment analyses. Moreover, we selected 6 variants associated with immune, cells adhesion, platelet function, homeostasis, and ion channel signaling and expanded the sample size (1247 KD patients containing 713 males and 534 females, 803 healthy population containing 481 males and 322 females) for genotyping validation. From the results, USH2A/rs148135241, LMO7/rs142687160, CEMIP/rs12441101, and EFCC1/rs142391828 presented significant differences of alleles/genotypes frequency distributions between male and female only in KD patients (which were consistent with the result of WES analysis) but not in healthy population. In addition, the result also found that only EFCC1/rs142391828 polymorphism was associated with KD susceptibility. This result suggested that those four variants might play critical roles in sex bias in KD. The study would be in favor of a sex-specific genome atlas establishing and novel sex-specific precision therapies development for KD.

Complete Chloroplast Genome Sequence of the Long Blooming Cultivar Camellia 'Xiari Qixin': Genome Features, Comparative and Phylogenetic Analysis.

The camellia flower is a famous woody plant with a long-cultivated history and high ornamental value. It is extensively planted and utilized around the world and owns a massive germplasm resource. Camellia 'Xiari Qixin' belongs to one of the typical cultivars in the four seasons camellia hybrids series. Due to its long flowering period, this kind of cultivar is identified as a precious resource of camellia flowers. In this study, the complete chloroplast genome sequence of C. 'Xiari Qixin' was first reported. Its whole chloroplast genome is 157,039 bp in length with an overall GC content of 37.30%, composed of a large single copy region (LSC, 86,674 bp), a small single copy region (SSC, 18,281 bp), and a pair of inverted repeat regions (IRs, 26,042 bp each). A total of 134 genes were predicted in this genome, including 8 ribosomal RNA genes, 37 transfer RNA genes, and 89 protein-coding genes. In addition, 50 simple sequence repeats (SSRs) and 36 long repeat sequences were detected. By comparing C. 'Xiari Qixin' and seven Camellia species on the chloroplast genome, seven mutation hotspot regions were identified, including psbK, trnS (GCU)-trnG(GCC), trnG(GCC), petN-psbM, trnF(GAA)-ndhJ, trnP(UGG)-psaJ, and ycf1. Phylogenetic analysis of 30 chloroplast genomes showed that the genetic relationship between C. 'Xiari Qixin' and Camellia azalea is quite close in evolution. These results could not only provide a valuable database for determining the maternal origin of Camellia cultivars, but also contribute to the exploration of the phylogenetic relationship and utilization of germplasm resources for Camellia.

The PTGS1 (rs1330344) CC Genotype Contributes to Susceptibility to Kawasaki Disease in Southern Chinese Children.

Kawasaki disease (KD) is an acute systemic vascular disease complicated by coronary artery injury. Although polymorphisms in prostaglandin-endoperoxide synthase 1 (PTGS1) are being increasingly explored in cardiovascular diseases, little is known regarding the connection between PTGS1 polymorphisms and KD risk. We evaluated 834 KD patients and 1474 healthy controls to explore the relationship between PTGS1 polymorphisms (rs1330344 and rs5788) and KD risk. Our results showed that the rs1330344 CC genotype was significantly associated with KD risk and coronary artery injury in children with KD. In combined analysis, individuals with 1-2 unfavorable genotypes had an increased risk of KD, compared with those with no risk genotype. Stratified analysis indicated that the rs1330344 CC genotype is strongly associated with increased risk of KD in children aged ≤60 months and females. Moreover, carrying 1-2 of these SNP genotypes had a higher risk of KD than those who harbored none of them in children ≤60 months of age and females; the risk of coronary artery dilatations/small aneurysms and medium/giant aneurysms was also significantly increased in KD patients. In summary, the PTGS1 rs1330344 CC genotype is associated with increased susceptibility to KD, which may contribute to KD pathogenesis and serve as a genetic biomarker.

Thymic stromal lymphopoietin induces platelet mitophagy and promotes thrombosis in Kawasaki disease.

Kawasaki disease (KD) is an acute systemic vasculitis primarily affecting infants and children. Activated platelets predispose patients to coronary artery structural lesions that may lead to thrombotic cardiovascular events. To discover potential proteins underlying platelet activation in KD, we conducted a protein chip assay of 34 cytokines and discovered thymic stromal lymphopoietin (TSLP) was aberrantly expressed, which remained elevated after intravenous immunoglobulin G (IVIG) treatment and during convalescence in KD patients in comparison to healthy controls. Enzyme-linked immunosorbent assay (ELISA) corroborated the upregulation of TSLP in KD patients, which was exacerbated in convalescent patients complicated with thrombosis. TSLP receptors on platelets were also significantly upregulated in KD patients complicated with thrombosis. Platelet activation, apoptosis, and mitochondrial autophagy (mitophagy) were increased in convalescence KD patients complicated with thrombosis. In vitro, TSLP induced platelet activation and platelet mitophagy in healthy blood donors, as observed in KD patients. TSLP, similar to mitophagy agonist carbonyl cyanide 3-chlorophenyl hydrazone (CCCP), promoted thrombosis, which was attenuated by the mitophagy inhibitor Mdivi-1. Co-immunoprecipitation in TSLP-treated platelets revealed TSLP receptor (TSLPR) bound to mitophagy regulators, Parkin and Voltage Dependent Anion Channel Protein 1 (VDAC1).Thus, our results demonstrated that TSLP induced platelet mitophagy via a novel TSLPR/Parkin/VDAC1 pathway that promoted thrombosis in KD. These results suggest TSLP as a novel therapeutic target against KD-associated thrombosis.

Association between Rab31/rs9965664 polymorphism and immunoglobulin therapy resistance in patients with Kawasaki disease.

Background: Kawasaki disease (KD) is an acute febrile systemic vasculitis affecting infants and young children. A high dose of intravenous immunoglobulin (IVIG) is the first-line strategy for patients with KD to reduce persistent inflammation and the risk of coronary artery aneurysm (CAA) formation. Unfortunately, 10-20% of the patients showed no response to the treatment and were defined as resistant to IVIG. Rab31 has been reported to regulate innate immunity in several human diseases. However, whether single nucleotide polymorphism (SNP) in Rab31 gene could predispose to IVIG therapy response in KD was uncovered. Methods: Rab31/rs9965664 polymorphism was genotyped in 1,024 Chinese patients with KD through TaqMan assay. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of association between Rab31/rs9965664 polymorphism and IVIG therapeutic effects. Results: Our results showed that Rab31/rs9965664 AA/GA genotype was significantly associated with an increased risk of IVIG resistance compared to GG genotype (GA vs. GG: p = 0.0249; AA vs. GG: p = 0.0016; AA/GA vs. GG: p = 0.0039; and AA vs. GG/GA: p = 0.0072). Moreover, the KD individuals carrying the rs9965664 A allele displayed lower Rab31 protein levels, and the expression level of Rab31 in the IVIG-resistant group was decreased significantly when compared to that observed in the response group. A mechanical study demonstrated that Rab31 modulated IVIG response through NLRP3 and p38 pathways. Conclusion: These results suggested that Rab31/rs9965664 polymorphism might be associated with an increased risk of IVIG resistance in southern Chinese patients with KD. The possible mechanism is that Rab31 regulates the NLRP3 pathway negatively to inhibit IVIG response.

LNC-ZNF33B-2:1 gene rs579501 polymorphism is associated with organ dysfunction and death risk in pediatric sepsis.

Background: Sepsis is a severe systemic reaction disease induced by bacteria and virus invading the bloodstream and subsequently causing multiple systemic organ dysfunctions. For example, the kidney may stop producing urine, or the lungs may stop taking in oxygen. Recent studies have shown that long non-coding RNAs (lncRNAs) are related to the dysfunction of organs in sepsis. This study aims to screen and validate the sepsis-associated lncRNAs and their functional single nucleotide polymorphisms (SNPs). Result: Unconditional multiple logistic regression based on the recessive model (adjusted odds ratio = 2.026, 95% CI = 1.156-3.551, p = 0.0136) showed that patients with the CC genotype of rs579501 had increased risk of sepsis. Stratification analysis by age and gender indicated that patients with the rs579501 CC genotype had higher risk of sepsis among children aged <12 months (adjusted odds ratio = 2.638, 95% CI = 1.167-5.960, p = 0.0197) and in male patients (adjusted odds ratio = 2.232, 95% CI = 1.127-4.421, p = 0.0213). We also found a significant relationship between rs579501 and severe sepsis risk (CC versus AA/AC: adjusted odds ratio = 2.466, 95% CI = 1.346-4.517, p = 0.0035). Stratification analysis for prognosis and number of organ dysfunctions demonstrated that the rs579501 CC genotype increased non-survivors' risk (adjusted odds ratio = 2.827, 95% CI = 1.159-6.898, p = 0.0224) and one to two organs with dysfunction risk (adjusted odds ratio = 2.253, 95% CI = 1.011-5.926, p = 0.0472). Conclusion: Our findings showed that the lnc-ZNF33B-2:1 rs579501 CC genotype increases the susceptibility to sepsis. From the medical perspective, the lnc-ZNF33B-2:1 rs579501 CC genotype could be serving as a biochemical marker for sepsis.

Transformer-Based Model with Dynamic Attention Pyramid Head for Semantic Segmentation of VHR Remote Sensing Imagery.

Convolutional neural networks have long dominated semantic segmentation of very-high-resolution (VHR) remote sensing (RS) images. However, restricted by the fixed receptive field of convolution operation, convolution-based models cannot directly obtain contextual information. Meanwhile, Swin Transformer possesses great potential in modeling long-range dependencies. Nevertheless, Swin Transformer breaks images into patches that are single-dimension sequences without considering the position loss problem inside patches. Therefore, Inspired by Swin Transformer and Unet, we propose SUD-Net (Swin transformer-based Unet-like with Dynamic attention pyramid head Network), a new U-shaped architecture composed of Swin Transformer blocks and convolution layers simultaneously through a dual encoder and an upsampling decoder with a Dynamic Attention Pyramid Head (DAPH) attached to the backbone. First, we propose a dual encoder structure combining Swin Transformer blocks and reslayers in reverse order to complement global semantics with detailed representations. Second, aiming at the spatial loss problem inside each patch, we design a Multi-Path Fusion Model (MPFM) with specially devised Patch Attention (PA) to encode position information of patches and adaptively fuse features of different scales through attention mechanisms. Third, a Dynamic Attention Pyramid Head is constructed with deformable convolution to dynamically aggregate effective and important semantic information. SUD-Net achieves exceptional results on ISPRS Potsdam and Vaihingen datasets with 92.51%mF1, 86.4%mIoU, 92.98%OA, 89.49%mF1, 81.26%mIoU, and 90.95%OA, respectively.

The swallowing threshold and starch hydrolysis of cooked rice with different moisture contents for human mastication.

Swallowing threshold is a critical parameter that marks the condition of food after mastication in the human mouth being ready to be swallowed. In the current study, a new aspect was investigated in which the food boluses from cooked rice with three moisture contents (52%, 63% and 73% on a wet basis) were masticated and collected just before swallowing by a group of twelve voluntary participants. Both mechanical/textural properties and physicochemical characteristics of the cooked rice and their boluses were investigated. The results show that the oral duration of the cooked rice was positively associated with rice hardness, but negatively correlated with the moisture content of rice boluses. After chewing, the textural properties except cohesiveness and adhesiveness varied little among the rice bolus samples. A significant decrease in the textural parameters was shown for the cooked rice with a low (52%) and middle (63%) moisture content after mastication. In contrast, the decrease was insignificant for the cooked rice having the highest moisture content (73%). Consistently, a negative correlation between the hardness of cooked rice and the amount of soluble reducing sugar in the rice boluses was presented. The salivary impregnation and the particle size distribution of the rice boluses at the swallowing threshold were independent on rice physics (i.e., initial moisture content, texture) and oral physiology. In addition, due to the high efficiency of salivary α-amylase, the starch in cooked rice could be hydrolyzed as much as one-third during oral digestion. The present study suggests that the initial moisture content of cooked rice and mastication conditions such as the presence of α-amylase and salivary impregnation could influence the physicochemical properties of rice boluses at the swallowing threshold. These factors should be carefully considered in future in vitro digestion studies of carbohydrate-based food products.

Development and validation of a prognostic nomogram for early stage non-small cell lung cancer: a study based on the SEER database and a Chinese cohort.

OBJECTIVE: This study aimed to construct a nomogram to effectively predict the overall survival (OS) of patients with early-stage non-small-cell lung cancer (NSCLC). METHODS: For the training and internal validation cohorts, a total of 26,941 patients with stage I and II NSCLC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. A nomogram was constructed based on the risk factors affecting prognosis using a Cox proportional hazards regression model. And 505 patients were recruited from Jiaxing First Hospital for external validation. The discrimination and calibration of the nomogram were evaluated by C-index and calibration curves. RESULTS: A Nomogram was created after identifying independent prognostic factors using univariate and multifactorial factor analysis. The C-index of this nomogram was 0.726 (95% CI, 0.718-0.735) and 0.721 (95% CI, 0.709-0.734) in the training cohort and the internal validation cohort, respectively, and 0.758 (95% CI, 0.691-0.825) in the external validation cohort, which indicates that the model has good discrimination. Calibration curves for 1-, 3-, and 5-year OS probabilities showed good agreement between predicted and actual survival. In addition, DCA analysis showed that the net benefit of the new model was significantly higher than that of the TNM staging system. CONCLUSION: We developed and validated a survival prediction model for patients with non-small cell lung cancer in the early stages. This new nomogram is superior to the traditional TNM staging system and can guide clinicians to make the best clinical decisions.

The Associated of the Risk of IVIG Resistance in Kawasaki Disease with ZNF112 Gene and ZNF180 Gene in a Southern Chinese Population.

Background: Kawasaki disease (KD) was one of the most common primary vasculitis. IVIG resistance was associated with an increased risk of coronary artery aneurysm. Accumulating evidences demonstrated that inflammatory gene polymorphisms might play important roles in IVIG resistance, and zinc finger proteins were closely related to immune inflammation regulation, but the effect of ZNF112/rs8113807 and ZNF180/rs2571051 on IVIG resistance in KD patients has not been reported. Methods: A total of 996 KD patients were recruited, and the assay of TaqMan-real-time polymerase chain reaction was used for ZNF112/rs8113807 and ZNF180/rs2571051 genotyping. Odds ratio (OR) and 95% confidence interval (CI) were calculated for estimating the relationship between the polymorphisms of the both SNPs (ZNF112/rs8113807 and ZNF180/rs2571051) and the risk of IVIG resistance. Results: Both of the ZNF112/rs8113807 CC/TC genotype and the ZNF180/rs2571051 TT/CT genotype increased the risk of IVIG resistance in KD (rs8113807: CC vs TT: adjusted OR = 1.83, 95% CI = 1.06-3.16, p = 0.0293; CC/TC vs TT adjusted: OR = 1.49, 95% CI = 1.10-2.02, p = 0.0094. rs2571051: TT vs CC adjusted: OR = 2.64, 95% CI = 1.62-4.29, p < 0.0001; TT/CT vs CC adjusted: OR = 2.14, 95% CI = 1.37-3.37, p = 0.0009; TT vs CC/CT adjusted: OR = 1.66, 95% CI = 1.22-2.27, p = 0.0014). Furthermore, the combinative analysis of risk genotypes in ZNF112/rs8113807 and ZNF180/rs2571051 showed that patients with two unfavorable genotypes were more likely to increase risk of IVIG resistance than those who carried with zero or one unfavorable genotypes (adjusted: OR = 1.68, 95% CI = 1.24-2.27, p = 0.0008). Conclusion: Our findings enriched the genetic background of IVIG resistance risk in the KD development and suggested that the ZNF112/rs8113807 C-carrier and the ZNF180/rs2571051 T-carrier were associated with increased risk of IVIG resistance in KD patients in Chinese southern population.

The rs8506 TT Genotype in lincRNA-NR_024015 Contributes to the Risk of Sepsis in a Southern Chinese Child Population.

Background: Sepsis is a highly life-threatening heterogeneous syndrome and a global health burden. Studies have shown that many genetic variants could influence the risk of sepsis. Long non-coding RNA lincRNA-NR_024015 may participate in functional alteration of endothelial cell via vascular endothelial growth factor (VEGF) signaling, whereas its relevance between the lincRNA-NR_024015 polymorphism and sepsis susceptibility is still unclear. Methods: 474 sepsis patients and 678 healthy controls were enrolled from a southern Chinese child population in the present study. The polymorphism of rs8506 in lincRNA-NR_024015 was determined using Taqman methodology. Results: Overall, a significant association was found between rs8506 polymorphism and the risk of sepsis disease (TT vs. CC/CT: adjusted OR = 1.751, 95%CI = 1.024-2.993, P = 0.0406). In the stratified analysis, the results suggested that the carriers of TT genotypes had a significantly increased sepsis risk among the children aged 12-60 months, females, early-stage sepsis and survivors (TT vs. CC/CT: ORage = 2.413; ORfemale = 2.868; ORsepsis = 2.533; ORsurvivor = 1.822; adjusted for age and gender, P < 0.05, respectively). Conclusion: Our study indicated that lincRNA-NR_024015 rs8506 TT genotype might contribute to the risk of sepsis in a southern Chinese child population. Future research is required to elucidate the possible immunoregulatory mechanisms of this association and advance the development of novel biomarkers in sepsis.

TRIM66 Promotes Malignant Progression of Non-Small-Cell Lung Cancer Cells via Targeting MMP9.

Lung cancer has a higher incidence and mortality rate than other cancers, and over 80% of lung cancer cases were classified as non-small-cell lung cancer (NSCLC). TRIM66 is one of the crucial members of TRIM, which has a deep connection with the behavior of various malignant tumors. But it remains uncertain regarding its exact function and underlying mechanism in NSCLC. In our study, qRT-PCR and Western blot were employed to validate that TRIM66 was overexpressed in NSCLC. The migration, invasion, and epithelial-mesenchymal transformation (EMT) progression of NSCLC cells were determined by Western blotting and Transwell experiments after knocking down TRIM66, and it was found that knockdown TRIM66 inhibited the migration, invasion, and EMT processes of NSCLC cells. Next, the binding relationship between TRIM66 and MMP9 was verified by Co-IP assay. After determining the interaction between them, rescue assays showed that overexpression of MMP9 was capable to promote the migration, invasion, and EMT of NSCLC cells. However, the transfection of si-TRIM66 could reverse this facilitating effectiveness. To sum up, we concluded that by targeting MMP9, TRIM66 could exert a cancer-promoting role in the progression of NSCLC cells.

A comprehensive pan-cancer analysis of the expression characteristics, prognostic value, and immune characteristics of TOP1MT.

Background: Mitochondria are at the heart of a number of metabolic pathways providing enormous energy for normal cell growth and regulating tumor cell growth as well as survival. Mitochondrial topoisomerase I (TOP1MT) is a type IB topoisomerase found in the mitochondria of vertebrates. However, no pan-cancer analysis of TOP1MT has been reported. This study aims to explore TOP1MT expression in pan-cancer tissues and identify whether it can be a target for mitochondrial anticancer therapy. Methods and results: The original TOP1MT expression data in 33 different types of cancer patients were downloaded from the TCGA and GTEx databases. TOP1MT was highly expressed in cancer tissues, including BLCA, BRCA, CHOL, COAD, DLBC, ESCA, GBM, HNSC, KIRC, KIRP, LGG, LIHC, LUAD, LUSC, PAAD, PCPG, PRAD, READ, SKCM, STAD, THYM, UCEC, and UCS. According to Kaplan-Meier survival curve analysis, high TOP1MT expression in BLCA, HNSC, KIRP, PAAD, UCEC, and LIHC cancer tissues was linked to poor prognosis of cancer patients, i.e., poor OS, disease-specific survival, and PFI. Linkedomics analysis identified a positive correlation of TOP1MT expression with CNA, but a negative correlation with methylation. TOP1MT expression significantly correlated with immune cells and immune checkpoints in the TIMER database. Functional analysis showed a close relationship between TOP1MT expression and ribosomes. Conclusion: In summary, TOP1MT is a potential biomarker for mitochondrial anticancer therapy and cancer immunotherapy.