The Evolution, Expression Patterns, and Domestication Selection Analysis of the Annexin Gene Family in the Barley Pan-Genome.

Plant annexins constitute a conserved protein family that plays crucial roles in regulating plant growth and development, as well as in responses to both biotic and abiotic stresses. In this study, a total of 144 annexin genes were identified in the barley pan-genome, comprising 12 reference genomes, including cultivated barley, landraces, and wild barley. Their chromosomal locations, physical-chemical characteristics, gene structures, conserved domains, and subcellular localizations were systematically analyzed to reveal the certain differences between wild and cultivated populations. Through a cis-acting element analysis, co-expression network, and large-scale transcriptome analysis, their involvement in growth, development, and responses to various stressors was highlighted. It is worth noting that HvMOREXann5 is only expressed in pistils and anthers, indicating its crucial role in reproductive development. Based on the resequencing data from 282 barley accessions worldwide, genetic variations in thefamily were investigated, and the results showed that 5 out of the 12 identified HvMOREXanns were affected by selection pressure. Genetic diversity and haplotype frequency showed notable reductions between wild and domesticated barley, suggesting that a genetic bottleneck occurred on the annexin family during the barley domestication process. Finally, qRT-PCR analysis confirmed the up-regulation of HvMOREXann7 under drought stress, along with significant differences between wild accessions and varieties. This study provides some insights into the genome organization and genetic characteristics of the annexin gene family in barley at the pan-genome level, which will contribute to better understanding its evolution and function in barley and other crops.

[Association between insomnia and type 2 diabetes: A two-sample Mendelian rando-mization study].

OBJECTIVE: To explore the robust relationship between insomnia and type 2 diabetes mellitus by two-sample Mendelian randomization analysis to overcome confounding factors and reverse causality in observational studies. METHODS: We identified strong, independent single nucleotide polymorphisms (SNPs) of insomnia from the most up to date genome wide association studies (GWAS) within European ancestors and applied them as instrumental variable to GWAS of type 2 diabetes mellitus. After excluding SNPs that were significantly associated with smoking, physical activity, alcohol consumption, educational attainment, obesity, or type 2 diabetes mellitus, we assessed the impact of insomnia on type 2 diabetes mellitus using inverse variance weighting (IVW) method. Weighted median and MR-Egger regression analysis were also conducted to test the robustness of the association. We calculated the F statistic of the selected SNPs to test the applicability of instrumental variable and F statistic over than ten indicated that there was little possibility of bias of weak instrumental variables. We further examined the existence of pleiotropy by testing whether the intercept term in MR-Egger regression was significantly different from zero. In addition, the leave-one-out method was used for sensitivity analysis to verify the stability and reliability of the results. RESULTS: We selected 248 SNPs independently associated with insomnia at the genome-wide level (P<5×10-8) as a preliminary candidate set of instrumental variables. After clumping based on the reference panel from 1000 Genome Project and removing the potential pleiotropic SNPs, a total of 167 SNPs associated with insomnia were included as final instrumental variables. The F statistic of this study was 39. 74, which was in line with the relevance assumption of Mendelian randomization. IVW method showed insomnia was associated with higher risk of type 2 diabetes mellitus that po-pulation with insomnia were 1. 14 times more likely to develop type 2 diabetes mellitus than those without insomnia (95% CI: 1.09-1.21, P<0.001). The weighted median estimator (WME) method and MR-Egger regression showed similar causal effect of insomnia on type 2 diabetes mellitus. And MR-Egger regression also showed that the effect was less likely to be triggered by pleiotropy. Sensitivity analyses produced directionally similar estimates. CONCLUSION: Insomnia is a risk factor of type 2 diabetes mellitus, which has positively effects on type 2 diabetes mellitus. Our study provides further rationale for indivi-duals at risk for diabetes to keep healthy lifestyle.

Safety and Effectiveness of a Novel Tips Access Set with Steerable Cannula in a Swine Model.

PURPOSE: This study aimed to assess the safety, effectiveness, and feasibility of the Liverty™ transjugular intrahepatic portosystemic shunt (TIPS) access set, which has an ergonomic handle that allows for in situ cannula tip deflection and a distal steerable cannula angle, versus the COOK® Rosch-Uchida Transjugular Liver Access Set (RUPS-100) in healthy pigs. METHODS: Twelve pigs randomly underwent TIPS with the Liverty™ set or the RUPS-100 set. Three interventionalists performed 4 TIPS procedures, 2 with each set. The primary outcome was procedural success, defined as successful establishment of the intrahepatic portosystemic shunt and stent placement. RESULTS: The shunt was successfully established in 11 pigs. The procedural success was achieved in all 6 pigs in the Liverty™ group and 5 out of 6 pigs for the RUPS-100 group (Fisher exact test, P > 0.999). The mean duration of puncture was shorter in the Liverty™ group versus the RUPS-100 group (12.3 ± 4.5 min vs. 16.2 ± 8.5 min), but without significant statistical difference (two sample t test, P = 0.359). The cannula angle was adjusted 69% of passes in the Liverty™ group, which was significantly higher than that in the RUPS-100 group (12%, P = 0.004). Overall, the TIPS procedural performance was comparable between the groups. Both sets were safe. No intraabdominal hemorrhage, vascular injuries, tissue or organ injuries, porto-biliary fistula, biliary peritonitis, and infection or abscess occurred in either group. CONCLUSION: The Liverty™ set is safe and has similar procedural metrics to the COOK® RUPS-100 set. It allows in situ adjustment of the angle of the stiffening cannula without increasing procedure time and lessens the occurrences of periprocedural complications.

Preparation of NH4Cl-Modified Carbon Materials via High-Temperature Calcination and Their Application in the Negative Electrode of Lead-Carbon Batteries.

The performance of lead-acid batteries could be significantly increased by incorporating carbon materials into the negative electrodes. In this study, a modified carbon material developed via a simple high-temperature calcination method was employed as a negative electrode additive, and we have named it as follows: N-doped chitosan-derived carbon (NCC). The performance of this material was compared with a control battery containing activated carbon (AC). X-ray diffraction (XRD), scanning electron microscopy (SEM) and Raman spectroscopy were engaged in analyzing the crystal structure and morphology of the material. Afterwards, the electrochemical and battery performance was examined through cyclic voltammetry (CV), linear voltammetry (LSV) and constant current charge-discharge testing. Markedly, the electrode plate containing 1 wt.% NCC indicates the highest specific capacity (106.48 F g-1) as compared to the control battery, which is 1.56 times higher than the AC electrode plate and 4.75 times higher than the blank electrode plate. The linear voltammetry shows that the hydrogen precipitation current density of the 1 wt.% NCC electrode plate is only -0.028 A cm-2, a much higher value than that of the AC electrode plate. In addition, the simulated battery containing 1 wt.% NCC has a cycle life of 4324 cycles, which is 2.36 times longer than that of the same amount of additive AC battery (1834 cycles) and 5.34 times longer than that of the blank battery (809 cycles). In summary, NCC carbon has the advantage of extending the life of lead-acid batteries, rendering it a promising candidate for lead-acid battery additives.

Primary Treatment for Clinically Early Cervical Cancer with Lymph Node Metastasis: Radical Surgery or Radiation?

OBJECTIVE: To compare survival outcomes between primary radical surgery and primary radiation in early cervical cancer. METHODS: Patient information was extracted from the Surveillance, Epidemiology, and Results database. Patients diagnosed with early cervical cancer of stage T1a, T1b, and T2a (American Joint Committee on Cancer, 7th edition) from 1998 to 2015 were included in this study after propensity score matching. Overall survival (OS) was analyzed using the Kaplan-Meier method. RESULTS: Among the 4964 patients included in the study, 1080 patients were identified as having positive lymph nodes (N1), and 3884 patients were identified as having negative lymph nodes (N0). Patients with primary surgery had significantly longer 5-year OS than those with primary radiotherapy in both the N1 group (P<0.001) and N0 group (P<0.001). In the subgroup analysis, similar results were found in patients with positive lymph nodes of stage T1a (100.0% vs. 61.1%), T1b (84.1% vs. 64.3%), and T2a (74.4% vs. 63.8%). In patients with T1b1 and T2a1, primary surgery resulted in longer OS than primary radiation, but not in patients with T1b2 and T2a2. In multivariate analysis, the primary treatment was identified as an independent prognostic factor in both N1 and N0 patients (HRN1=2.522, 95% CI=1.919-3.054, PN1<0.001; HRN0=1.895, 95% CI=1.689-2.126, PN0<0.001). CONCLUSION: In early cervical cancer stage T1a, T1b1, and T2a1, primary surgery may result in longer OS than primary radiation for patients with and without lymph node metastasis.

Factors associated with compassion fatigue and compassion satisfaction in obstetrics and gynaecology nurses: A cross-sectional study.

AIMS: To examine the factors influencing compassion fatigue and compassion satisfaction in obstetrics and gynaecology nurses and to explore the combined results of multiple factors. DESIGN: An online cross-sectional study was conducted. REVIEW METHODS: Data were collected from 311 nurses using a convenience sampling method from January to February 2022. Stepwise multiple linear regression analysis and mediation tests were performed. RESULTS: Compassion fatigue in obstetrics and gynaecology nurses was in the moderate to high levels. Physical status, number of children, emotional labour, lack of professional efficacy, emotional exhaustion and the none-only-child can influence compassion fatigue; lack of professional efficacy, cynicism, social support, work experience, employment status and night shift were predictive of compassion satisfaction. Social support partially mediated between lack of professional efficacy and compassion fatigue/compassion satisfaction; emotional labour moderated in the mediated analysis model. CONCLUSION: Moderate to high levels of compassion fatigue was present in 75.88% of obstetrics and gynaecology nurses. Some factors affect compassion fatigue and compassion satisfaction. Thus, nursing managers should consider factors and construct a monitoring system to reduce compassion fatigue and improve compassion satisfaction. IMPLICATIONS FOR THE PROFESSION: The results will provide a theoretical basis for improving job satisfaction and the quality of care in obstetrics and gynaecology nurses. And this may raise concerns about the occupational health of obstetrics and gynaecology nurses in China. REPORTING METHOD: The study was reported according to the STROBE. PATIENT OR PUBLIC CONTRIBUTION: The nurses spent time filling out the questionnaires during the data collection phase and answered the questions sincerely. WHAT DOES THIS ARTICLE CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY?: Obstetrics and gynaecology nurses with 4-16 years of experience are prone to experience compassion fatigue. The effect of lack of professional efficacy on compassion fatigue and compassion satisfaction can be improved by social support. RELEVANCE TO CLINICAL PRACTICE: Reducing nurse compassion fatigue and improving compassion satisfaction are important for providing quality nursing care to obstetrics and gynaecology patients. In addition, clarifying the influencing factors of compassion fatigue and compassion satisfaction can improve nurses' work efficiency and job satisfaction, and provide theoretical guidance for managers to implement interventions.

Amifostine-Loaded Nanocarrier Traverses the Blood-Brain Barrier and Prevents Radiation-Induced Brain Injury.

Radiation-induced brain injury (RIBI) is a severe, irreversible, or even life-threatening cerebral complication of radiotherapy in patients with head and neck tumors, and there is no satisfying prevention and effective treatment available for these patients. Amifostine (AMF) is a well-known free radical scavenger with demonstrated effectiveness in preventing radiation-induced toxicity. However, the limited permeability of AMF across the blood-brain barrier (BBB) when administered intravenously reduces the effectiveness of AMF in preventing RIBI. Herein, we construct a nanoparticle (NP) platform for BBB delivery of AMF. AMF is conjugated with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-n-[poly(ethylene glycol)]-hydroxy succinamide [DSPE-PEG-NHS, PEG M 2000], and the product is DSPE-PEG-AMF. Then, the nanoparticles (DAPP NPs) were formed by self-assembly of poly(lactic-co-glycolic acid) (PLGA), DSPE-PEG-AMF, and polysorbate 80 (PS 80). PEG shields the nanoparticles from blood clearance by the reticuloendothelial system and lengthens the drug circulation time. PS 80 is used to encapsulate nanoparticles for medication delivery to the brain. The results of our study showed that DAPP NPs were able to effectively penetrate the blood-brain barrier (BBB) in healthy C57BL/6 mice. Furthermore, in a well-established mouse model of X-knife-induced brain injury, treatment with DAPP NPs (corresponding to 250 mg/kg AMF) was found to significantly reduce the volume of brain necrosis compared to mice treated with AMF (250 mg/kg). Importantly, the use of DAPP NPs was also shown to significantly mitigate the effects of radiation-induced neuronal damage and glial activation. This work presents a convenient brain-targeted AMF delivery system to achieve effective radioprotection for the brain, providing a promising strategy with tremendous clinical translation potential.

Association between periodontitis and COVID-19 infection: a two-sample Mendelian randomization study.

Background and Objective: Epidemiological studies report associations between coronavirus disease 2019 (COVID-19) and periodontitis; however, causality has not been proven. The aim of this study is to assess the associations between COVID-19 susceptibility and periodontitis with two-sample Mendelian randomization (MR) analyses. Methods: A two-sample summary MR analysis was performed using data for outcome and exposure from the OpenGWAS database on people of European descent. Periodontal complex traits (PCTs) were chosen as a proxy for the periodontitis phenotype. The causal association between PCT3 (Aggregatibacter actinomycetemcomitans), PCT5 (Porphyromonas gingivalis), and gingival crevicular fluid (GCF) interleukin-1ß (IL-1ß) and COVID-19 were considered. Genome-wide association study (GWAS) data with the two largest sample sizes were selected as COVID-19 outcomes (datasets ebi-a-GCST010776 and ebi-a-GCST010777). Single-nucleotide polymorphisms (SNPs) associated with PCT3, PCT5, and GCF IL-1ß at statistical significance at genome-wide level (P < 5 × 10-8) were identified as genetic instruments. We used two-sample summary MR methods and tested the existence of a pleiotropic effect with MR-Egger. Results: Inverse-variance weighted (IVW) estimates showed that there was a positive association between COVID-19 risk and periodontitis (ebi-a-GCST010776: odds ratio [OR] = 1.02 (95% confidence interval (CI), 1.00-1.05), P = 0.0171; ebi-a-GCST010777: OR = 1.03 (95% CI, 1.00-1.05), P = 0.0397). The weighted median also showed directionally similar estimates. Exploration of the causal associations between other PCTs and COVID-19 identified a slight effect of local inflammatory response (GCF IL-1ß) on COVID-19 risk across the two datasets (ebi-a-GCST010776: IVW OR = 1.02 (95% CI, [1.01-1.03]), P < 0.001; ebi-a-GCST010777: IVW OR = 1.03 (95% CI, [1.02-1.04]), P < 0.001). The intercepts of MR-Egger yielded no proof for significant directional pleiotropy for either dataset (ebi-a-GCST010776: P = 0.7660; ebi-a-GCST010777: P = 0.6017). Conclusions: The findings suggests that periodontitis and the higher GCF IL-1ß levels is causally related to increase susceptibility of COVID-19. However, given the limitations of our study, the well-designed randomized controlled trials are needed to confirm its findings, which may represent a new non-pharmaceutical intervention for preventing COVID-19.

Loss of CBX2 causes genomic instability and Wnt activation in high grade serous ovarian carcinoma cells.

High grade serous ovarian carcinoma (HGSOC) is lethal with insidious onset, rapid progression, poor prognosis, and limited treatment options. Polycomb repressor complexes (PRC) 1 and 2 are intimately involved in progression of many types of cancer including HGSOC. Unlike the consistent constitution of PRC2, PRC1 consists of diverse components whose clinical significance in HGSOC are not entirely clear. Here, prognosis-associated PRC1 components were identified through data-mining. CBX2 promoted proliferation and reduced apoptosis of HGSOC cell lines OVCAR4, OVCAR3, and CAOV3. Complete loss of CBX2 by CRISPR-cas9 editing (CBX2KO ) destabilized genome stability with increased spontaneous chromosomal breaks and tendency to polyploidy accompanied by disrupted cell cycle especially stalled G2/M transition and caused severe cell death. Wnt/ß-catenin/LEF1/TCF7L1 was activated in surviving OVCAR4-CBX2KO clones to bypass the crisis caused by loss of CBX2. The relieve of TCF7L1 core-promoter region occupied by CBX2 might be one of the possible explanations to TCF7L1 increase in OVCAR4-CBX2KO clones. Subcutaneous tumor model further validated that depletion of CBX2 repressed HGSOC cell line derived tumor growth. High immunohistochemistry score of CBX2 in primary ovarian cancer tissue associated with advanced clinical stage (p = 0.033), poor overall survival (HR = 3.056, 95% CI: 1.024-9.123), and progression free survival (HR = 4.455, 95% CI: 1.513-13.118) in HGSOC. Overall, our results suggested that CBX2 was a promising prognostic factor and therapeutic target in HGSOC.

Linear and nonlinear analyses of the association between low-density lipoprotein cholesterol and diabetes: The spurious U-curve in observational study.

Objective: Hyperlipidemia is traditionally considered a risk factor for diabetes. The effect of low-density lipoprotein cholesterol (LDL-C) is counterintuitive to diabetes. We sought to investigate the relationship between LDL-C and diabetes for better lipid management. Methods: We tested the shape of association between LDL-C and diabetes and created polygenic risk scores of LDL-C and generated linear Mendelian randomization (MR) estimates for the effect of LDL-C and diabetes. We evaluated for nonlinearity in the observational and genetic relationship between LDL-C and diabetes. Results: Traditional observational analysis suggested a complex non-linear association between LDL-C and diabetes while nonlinear MR analyses found no evidence for a non-linear association. Under the assumption of linear association, we found a consistently protective effect of LDL-C against diabetes among the females without lipid-lowering drugs use. The ORs were 0.84 (95% CI, 0.72-0.97, P=0.0168) in an observational analysis which was more prominent in MR analysis and suggested increasing the overall distribution of LDL-C in females led to an overall decrease in the risk of diabetes (P=0.0258). Conclusions: We verified the liner protective effect of LDL-C against diabetes among the females without lipid-lowering drug use. Non-linear associations between LDL-C against diabetes in observational analysis are not causal.

Identification of Novel Metabolic Subtypes Using Multi-Trait Limited Mixed Regression in the Chinese Population.

The aggregation and interaction of metabolic risk factors leads to highly heterogeneous pathogeneses, manifestations, and outcomes, hindering risk stratification and targeted management. To deconstruct the heterogeneity, we used baseline data from phase II of the Fangshan Family-Based Ischemic Stroke Study (FISSIC), and a total of 4632 participants were included. A total of 732 individuals who did not have any component of metabolic syndrome (MetS) were set as a reference group, while 3900 individuals with metabolic abnormalities were clustered into subtypes using multi-trait limited mixed regression (MFMR). Four metabolic subtypes were identified with the dominant characteristics of abdominal obesity, hypertension, hyperglycemia, and dyslipidemia. Multivariate logistic regression showed that the hyperglycemia-dominant subtype had the highest coronary heart disease (CHD) risk (OR: 6.440, 95% CI: 3.177-13.977) and that the dyslipidemia-dominant subtype had the highest stroke risk (OR: 2.450, 95% CI: 1.250-5.265). Exome-wide association studies (EWASs) identified eight SNPs related to the dyslipidemia-dominant subtype with genome-wide significance, which were located in the genes APOA5, BUD13, ZNF259, and WNT4. Functional analysis revealed an enrichment of top genes in metabolism-related biological pathways and expression in the heart, brain, arteries, and kidneys. Our findings provide directions for future attempts at risk stratification and evidence-based management in populations with metabolic abnormalities from a systematic perspective.

Disease patterns of coronary heart disease and type 2 diabetes harbored distinct and shared genetic architecture.

BACKGROUND: Coronary heart disease (CHD) and type 2 diabetes (T2D) are two complex diseases with complex interrelationships. However, the genetic architecture of the two diseases is often studied independently by the individual single-nucleotide polymorphism (SNP) approach. Here, we presented a genotypic-phenotypic framework for deciphering the genetic architecture underlying the disease patterns of CHD and T2D. METHOD: A data-driven SNP-set approach was performed in a genome-wide association study consisting of subpopulations with different disease patterns of CHD and T2D (comorbidity, CHD without T2D, T2D without CHD and all none). We applied nonsmooth nonnegative matrix factorization (nsNMF) clustering to generate SNP sets interacting the information of SNP and subject. Relationships between SNP sets and phenotype sets harboring different disease patterns were then assessed, and we further co-clustered the SNP sets into a genetic network to topologically elucidate the genetic architecture composed of SNP sets. RESULTS: We identified 23 non-identical SNP sets with significant association with CHD or T2D (SNP-set based association test, P < 3.70 × [Formula: see text]). Among them, disease patterns involving CHD and T2D were related to distinct SNP sets (Hypergeometric test, P < 2.17 × [Formula: see text]). Accordingly, numerous genes (e.g., KLKs, GRM8, SHANK2) and pathways (e.g., fatty acid metabolism) were diversely implicated in different subtypes and related pathophysiological processes. Finally, we showed that the genetic architecture for disease patterns of CHD and T2D was composed of disjoint genetic networks (heterogeneity), with common genes contributing to it (pleiotropy). CONCLUSION: The SNP-set approach deciphered the complexity of both genotype and phenotype as well as their complex relationships. Different disease patterns of CHD and T2D share distinct genetic architectures, for which lipid metabolism related to fibrosis may be an atherogenic pathway that is specifically activated by diabetes. Our findings provide new insights for exploring new biological pathways.

Genetic predisposition to adverse events in Chinese children aged 3-24 months after diphtheria, tetanus, acellular pertussis and haemophilus influenzae type b combined vaccination.

BACKGROUND: Post-vaccination safety is a major public health concern. The genetic predisposition on immune response has not been clearly identified. Clarifying whether individual genetic predisposition plays a role on adverse events (AEs) is critical for the prevention of AEs. METHODS: From July 2019 to June 2020, we performed a case-control study among children aged 3-24 months in seven Chinese provinces. Each child received a combination vaccination against diphtheria, tetanus, acellular pertussis, and Haemophilus influenzae type b (DTaP-Hib). Through daily telephone follow-up, we collected AEs within seven days. Oral swab samples were collected to investigate the effects of single nucleotide polymorphisms (SNPs) on the risk of AEs. RESULTS: 304 participants were included in the study. In univariate analysis, we discovered three protective SNPs (rs452204, OR = 0.67, P = 0.0352; rs9282763 and rs839, OR = 0.64, P = 0.0256) and one risk SNP (rs9610, OR = 2.20, P = 0.0397). In multivariate analysis, the effects of rs452204 and rs839 were found to be stable. The interaction between rs452204 and rs9610 was observed (OR = 7.25, 95% CI: 1.44-36.58, P = 0.0165). CONCLUSION: Genetic predisposition was associated with the risk of AEs after DTaP-Hib vaccination, emphasizing the potential application in the prevention of AEs.

Identifying novel genetic loci associated with polycystic ovary syndrome based on its shared genetic architecture with type 2 diabetes.

Genome-wide association studies (GWAS) have identified several common variants associated with polycystic ovary syndrome (PCOS). However, the etiology behind PCOS remains incomplete. Available evidence suggests a potential genetic correlation between PCOS and type 2 diabetes (T2D). The publicly available data may provide an opportunity to enhance the understanding of the PCOS etiology. Here, we quantified the polygenic overlap between PCOS and T2D using summary statistics of PCOS and T2D and then identified the novel genetic variants associated with PCOS behind this phenotypic association. A bivariate causal mixture model (MiXeR model) found a moderate genetic overlap between PCOS and T2D (Dice coefficient = 44.1% and after adjusting for body mass index, 32.1%). The conditional/conjunctional false discovery rate method identified 11 potential risk variants of PCOS conditional on associations with T2D, 9 of which were novel and 6 of which were jointly associated with two phenotypes. The functional annotation of these genetic variants supports a significant role for genes involved in lipid metabolism, immune response, and the insulin signaling pathway. An expression quantitative trait locus functionality analysis successfully repeated that 5 loci were significantly associated with the expression of candidate genes in many tissues, including the whole blood, subcutaneous adipose, adrenal gland, and cerebellum. We found that SCN2A gene is co-localized with PCOS in subcutaneous adipose using GWAS-eQTL co-localization analyses. A total of 11 candidate genes were differentially expressed in multiple tissues of the PCOS samples. These findings provide a new understanding of the shared genetic architecture between PCOS and T2D and the underlying molecular genetic mechanism of PCOS.

The spatial and temporal differentiation characteristics of cultural heritage in the Yellow River Basin.

Understanding the temporal and spatial distribution characteristics of the cultural heritage of the Yellow River Basin can effectively improve the scientific understanding of the historical changes, environmental evolution, and cultural and economic development of the Yellow River Basin and thus provide a scientific and reasonable decision-making basis for the protection and development of its cultural heritage. The research object of this paper are the national cultural relic protection units. These are examined using the GIS spatial analysis method to explore the spatial and temporal distribution characteristics and spatial structure of 2,102 national material cultural heritage sites in the Yellow River basin. The results show that the spatial distribution of cultural heritage has a significant spatial agglomeration effect. The whole basin is concentrated in stable high- and low-value areas, and the difference between the high- and low-value areas is clear. Some aspects of the spatial structure heterogeneity are strong, showing a low value dispersion distribution trend. In different periods, the distribution direction and scope of cultural heritage have low ranges of rotation, a clear direction, and a high degree of centripetal distribution. The spatial and temporal distribution of cultural heritage is the result of the combined action of natural geographical environment such as climate change, topography, river hydrology, and human environment such as administrative institutional changes, ideological evolution, and social and economic development.

Integrative Identification of Genetic Loci Jointly Influencing Diabetes-Related Traits and Sleep Traits of Insomnia, Sleep Duration, and Chronotypes.

Accumulating evidence suggests a relationship between type 2 diabetes mellitus and sleep problems. A comprehensive study is needed to decipher whether shared polygenic risk variants exist between diabetic traits and sleep traits. METHODS: We integrated summary statistics from different genome-wide association studies and investigated overlap in single-nucleotide polymorphisms (SNPs) associated with diabetes-related traits (type 2 diabetes, fasting glucose, fasting insulin, and glycated hemoglobin) and sleep traits (insomnia symptoms, sleep duration, and chronotype) using a conditional/conjunctional false discovery rate approach. Pleiotropic genes were further evaluated for differential expression analysis, and we assessed their expression pattern effects on type 2 diabetes by Mendelian randomization (MR) analysis. RESULTS: We observed extensive polygenic pleiotropy between diabetic traits and sleep traits. Fifty-eight independent genetic loci jointly influenced the risk of type 2 diabetes and the sleep traits of insomnia, sleep duration, and chronotype. The strongest shared locus between type 2 diabetes and sleep straits was FTO (lead SNP rs8047587). Type 2 diabetes (z score, 16.19; P = 6.29 × 10-59) and two sleep traits, sleep duration (z score, -6.66; P = 2.66 × 10-11) and chronotype (z score, 7.42; P = 1.19 × 10-13), were shared. Two of the pleiotropic genes, ENSA and PMPCA, were validated to be differentially expressed in type 2 diabetes, and PMPCA showed a slight protective effect on type 2 diabetes in MR analysis. CONCLUSIONS: Our study provided evidence for the polygenic overlap between diabetic traits and sleep traits, of which the expression of PMPCA may play a crucial role and provide support of the hazardous effect of being an "evening" person on diabetes risk.

Synchronous bilateral breast carcinoma irradiation: A comparative investigation between flattened and unflattened beams.

Synchronous bilateral breast carcinoma (SBBC) radiotherapy is a very complicated and time-consuming process. Considering the advantages of unflattened (FFF) beams at a high dose rate, this work investigated the feasibility of FFF beam application in SBBC radiotherapy and compared the advantages between FFF and flattened (FF) beams. CT images of 13 patients with SBBC were retrospectively collected to design intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans using FF and FFF beams. Dosimetric verification was applied for each plan. The target volume metrics, dose received by organs at risk (OARs), and delivery parameter of the plans were documented. All plans met the universal tolerance limits in dosimetric verification. FFF decreased the volume to receive 5 Gy (V5Gy), V7Gy, and mean dose of the left lung but slightly increased the V30Gy of the liver for VMAT and decreased the V17Gy and V20Gy of the right lung for IMRT. No remarkable differences between FF and FFF were found in the other investigated OARs and all the investigated target volume metrics. The mean treatment times of FFF were 66 and 45 s shorter than those of FF for IMRT and VMAT, respectively. FFF beams were feasible and had advantages in reducing treatment time and protecting the lung while maintaining the target volume metrics in SBBC irradiation.

Indirect Genetic Effects of ADIPOQ Variants on Lipid Levels in a Sibling Study of a Rural Chinese Population.

Variations in lipid levels are the result of combinations of genetic and environmental factors. We aim to investigate the indirect effect between siblings of the three polymorphisms of ADIPOQ on serum lipid levels in rural Chinese populations. A total of 2571 sibling pairs were enrolled as study participants. A generalized estimating equation was used to accommodate a family-based design. We used stratified analysis to detect sex combination differences in the indirect genetic effect. We found a significant association between the number of altered risk alleles of rs182052 and ego lipid levels of TG (ß = 0.177, P = 0.003), TC (ß = 0.140, P = 0.004) and LDL-C (ß = 0.098, P = 0.014). Ego and altered genotypes of rs182052 demonstrated a joint effect on ego lipid levels of TC (ß = 0.212, P = 0.019), HDL-C (ß = 0.099, P = 0.002) and LDL-C (ß = 0.177, P = 0.013) in recessive inheritance mode. In opposite-sex siblings, the altered GG genotype of rs182052 increased the ego lipid levels. Thus, our findings demonstrate that ADIPOQ has an indirect genetic effect on lipid levels in sibling pairs, and there are sex-combination differences in the indirect genetic effect in siblings.

Clinical utility of 3D magnetic resonance elastography in patients with biliary obstruction.

OBJECTIVES: Three-dimensional magnetic resonance elastography (3D-MRE) allows for multiparametric modeling of both elastic and viscous tissue characteristics. Our aim was to compare 3D-MRE with conventional liver shear stiffness assessment in gauging obstructive jaundice (OJ), predicting the adequacy of biliary decompression after drainage, and discriminating OJ from liver fibrosis. METHODS: Patients with no histories of liver disease (n = 201) were studied in retrospect, grouped by bilirubin levels as no jaundice (NJ ≤ 2 mg/dL; n = 75), mild OJ (>2 mg/dL and ≤ 4 mg/dL; n = 56), and severe OJ (> 4 mg/dL; n = 70). For comparison, another 75 patients with chronic hepatitis B and C infections and histologically proven liver fibrosis were similarly analyzed. Each patient underwent spin-echo echo-planar-imaging MRE at 60 Hz with 3D wave postprocessing. Logistic regression and ordinary regression models were used to compare the 3D-MRE model with liver shear stiffness. RESULTS: Liver shear stiffness, loss modulus, and damping ratio were incorporated into a 3D-MRE model, which significantly outperformed shear stiffness in predicting OJ severity (accuracy: 0.801 vs 0.672; p < 0.001). Both the 3D-MRE model and liver shear stiffness performed equally well in predicting the outcome of biliary drainage procedure (C-statistics: 0.852 vs 0.847; p = 0.48). The 3D-MRE model also demonstrated significantly better C-statistics than that of liver shear stiffness in discriminating mild OJ from F1-F2 liver fibrosis (0.765 vs 0.641; p = 0.005) and severe OJ from F3-F4 liver fibrosis (0.750 vs 0.635; p = 0.031). CONCLUSIONS: 3D-MRE is an innovative imaging method for gauging OJ severity, predicting the outcome of biliary drainage procedure, and discriminating OJ from liver fibrosis. KEY POINTS: • 3D-MR elastography achieved promising results for predicting the severity of obstructive jaundice. • Advanced parameters of 3D-MR elastography demonstrated significantly better performance than that of shear stiffness of 2D-MR elastography in discriminating obstructive jaundice from liver fibrosis caused by chronic hepatitis B/C. • Both 3D-MR elastography and 2D-MR elastography were equivalent in predicting the outcome of biliary drainage procedure.