Five years of change in adult twins: longitudinal changes of genetic and environmental influence on epigenetic clocks.

BACKGROUND: Epigenetic clocks were known as promising biomarkers of aging, including original clocks trained by individual CpG sites and principal component (PC) clocks trained by PCs of CpG sites. The effects of genetic and environmental factors on epigenetic clocks are still unclear, especially for PC clocks. METHODS: We constructed univariate twin models in 477 same-sex twin pairs from the Chinese National Twin Registry (CNTR) to estimate the heritability of five epigenetic clocks (GrimAge, PhenoAge, DunedinPACE, PCGrimAge, and PCPhenoAge). Besides, we investigated the longitudinal changes of genetic and environmental influences on epigenetic clocks across 5 years in 134 same-sex twin pairs. RESULTS: Heritability of epigenetic clocks ranged from 0.45 to 0.70, and those for PC clocks were higher than those for original clocks. For five epigenetic clocks, the longitudinal stability was moderate to high and was largely due to genetic effects. The genetic correlations between baseline and follow-up epigenetic clocks were moderate to high. Special unique environmental factors emerged both at baseline and at follow-up. PC clocks showed higher longitudinal stability and unique environmental correlations than original clocks. CONCLUSIONS: For five epigenetic clocks, they have the potential to identify aging interventions. High longitudinal stability is mainly due to genetic factors, and changes of epigenetic clocks over time are primarily due to changes in unique environmental factors. Given the disparities in genetic and environmental factors as well as longitudinal stability between PC and original clocks, the results of studies with original clocks need to be further verified with PC clocks.

Trehalose prevents the formation of aggregates of mutant ataxin-3 and reduces soluble ataxin-3 protein levels in an SCA3 cell model.

Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder caused by mutant ataxin-3 with an abnormally expanded polyQ tract and is the most common dominantly inherited ataxia worldwide. There are no suitable therapeutic options for this disease. Autophagy, a defense mechanism against the toxic effects of aggregation-prone misfolded proteins, has been shown to have beneficial effects on neurodegenerative diseases. Thus, trehalose, which is an autophagy inducer, may have beneficial effects on SCA3. In the present study, we examined the effects of trehalose on an SCA3 cell model. After trehalose treatment, aggregate formation, soluble ataxin-3 protein levels and cell viability were evaluated in HEK293T cells overexpressing ataxin-3-15Q or ataxin-3-77Q. We also explored the mechanism by which trehalose affects autophagy and stress pathways. A filter trap assay showed that trehalose decreased the number of aggregates formed by mutant ataxin-3 containing an expanded polyQ tract. Western blot and Cell Counting Kit-8 (CCK-8) results demonstrated that trehalose also reduced the ataxin-3 protein levels and was safe for ataxin-3-expressing cells, respectively. Western blot and total antioxidant capacity assays suggested that trehalose had great therapeutic potential for treating SCA3, likely through its antioxidant activity. Our data indicate that trehalose plays a neuroprotective role in SCA3 by inhibiting the aggregation and reducing the protein level of ataxin-3, which is also known to protect against oxidative stress. These findings provide a new insight into the possibility of treating SCA3 with trehalose and highlight the importance of inducing autophagy in SCA3.

Association between epigenetic age and type 2 diabetes mellitus or glycemic traits: A longitudinal twin study.

Epigenetic clocks based on DNA methylation have been known as biomarkers of aging, including principal component (PC) clocks representing the degree of aging and DunedinPACE representing the pace of aging. Prior studies have shown the associations between epigenetic aging and T2DM, but the results vary by epigenetic age metrics and people. This study explored the associations between epigenetic age metrics and T2DM or glycemic traits, based on 1070 twins (535 twin pairs) from the Chinese National Twin Registry. It also explored the temporal relationships of epigenetic age metrics and glycemic traits in 314 twins (157 twin pairs) who participated in baseline and follow-up visits after a mean of 4.6 years. DNA methylation data were used to calculate epigenetic age metrics, including PCGrimAge acceleration (PCGrimAA), PCPhenoAge acceleration (PCPhenoAA), DunedinPACE, and the longitudinal change rate of PCGrimAge/PCPhenoAge. Mixed-effects and cross-lagged modelling assessed the cross-sectional and temporal relationships between epigenetic age metrics and T2DM or glycemic traits, respectively. In the cross-sectional analysis, positive associations were identified between DunedinPACE and glycemic traits, as well as between PCPhenoAA and fasting plasma glucose, which may be not confounded by shared genetic factors. Cross-lagged models revealed that glycemic traits (fasting plasma glucose, HbA1c, and TyG index) preceded DunedinPACE increases, and TyG index preceded PCGrimAA increases. Glycemic traits are positively associated with epigenetic age metrics, especially DunedinPACE. Glycemic traits preceded the increases in DunedinPACE and PCGrimAA. Lowering the levels of glycemic traits may reduce DunedinPACE and PCGrimAA, thereby mitigating age-related comorbidities.

A Video-based Automated Tracking and Analysis System of Plaque Burden in Carotid Artery Using Deep Learning: A Comparison with Senior Sonographers.

BACKGROUND AND OBJECTIVE: The incidence of stroke is rising, and it is the second major cause of mortality and the third leading cause of disability around the globe. The goal of this study was to rapidly and accurately identify carotid plaques and automatically quantify plaque burden using our automated tracking and segmentation US-video system. METHODS: We collected 88 common carotid artery transection videos (11048 frames) with a history of atherosclerosis or risk factors for atherosclerosis, which were randomly divided into training, test, and validation sets using a 6:3:1 ratio. We first trained different segmentation models to segment the carotid intima and adventitia, and calculate the maximum plaque burden automatically. Finally, we statistically analyzed the plaque burden calculated automatically by the best model and the results of manual labeling by senior sonographers. RESULTS: Of the three Artificial Intelligence (AI) models, the Robust Video Matting (RVM) segmentation model's carotid intima and adventitia Dice Coefficients (DC) were the highest, reaching 0.93 and 0.95, respectively. Moreover, the RVM model has shown the strongest correlation coefficient (0.61±0.28) with senior sonographers, and the diagnostic effectiveness between the RVM model and experts was comparable with paired-t test and Bland-Altman analysis [P= 0.632 and ICC 0.01 (95% CI: -0.24~0.27), respectively]. CONCLUSION: Our findings have indicated that the RVM model can be used in ultrasound carotid video. The RVM model can automatically segment and quantify atherosclerotic plaque burden at the same diagnostic level as senior sonographers. The application of AI to carotid videos offers more precise and effective methods to evaluate carotid atherosclerosis in clinical practice.

A deep learning-based calculation system for plaque stenosis severity on common carotid artery of ultrasound images.

OBJECTIVES: Assessment of plaque stenosis severity allows better management of carotid source of stroke. Our objective is to create a deep learning (DL) model to segment carotid intima-media thickness and plaque and further automatically calculate plaque stenosis severity on common carotid artery (CCA) transverse section ultrasound images. METHODS: Three hundred and ninety images from 376 individuals were used to train (235/390, 60%), validate (39/390, 10%), and test (116/390, 30%) on a newly proposed CANet model. We also evaluated the model on an external test set of 115 individuals with 122 images acquired from another hospital. Comparative studies were conducted between our CANet model with four state-of-the-art DL models and two experienced sonographers to re-evaluate the present model's performance. RESULTS: On the internal test set, our CANet model outperformed the four comparative models with Dice values of 95.22% versus 90.15%, 87.48%, 90.22%, and 91.56% on lumen-intima (LI) borders and 96.27% versus 91.40%, 88.94%, 91.19%, and 92.88% on media-adventitia (MA) borders. On the external test set, our model still produced excellent results with a Dice value of 92.41%. Good consistency of stenosis severity calculation was observed between CANet model and experienced sonographers, with Intraclass Correlation Coefficient (ICC) of 0.927 and 0.702, Pearson's Correlation Coefficient of 0.928 and 0.704 on internal and external test set, respectively. CONCLUSIONS: Our CANet model achieved excellent performance in the segmentation of carotid IMT and plaques as well as automated calculation of stenosis severity.

Preoperative Serum Thyroglobulin Levels Predict Radioiodine Therapy Outcome in Papillary Thyroid Microcarcinoma Patients.

Our previous study showed that elevated preoperative thyroglobulin (pre-Tg) level predicted the risk of developing radioiodine refractory in PTC patients. In the present study, we aimed to evaluate the prognostic value of pre-Tg in papillary thyroid microcarcinoma (PTMC). After a specific inclusion and exclusion criteria were applied, a total of 788 PTMCs were enrolled from Jiangyuan Hospital affiliated to Jiangsu Institute of Nuclear Medicine between Jan 2015 and Dec 2019. Among them, 107 PTMCs were treated with radioiodine therapy (RAIT) and the response to therapy was grouped as excellent response (ER), and non-excellent response (NER: indeterminate response, IDR and biochemical incomplete response, BIR). Multivariable logistic regression was used to identify predictors for the response of RAIT in PTMCs. Higher pre-Tg levels were detected in PTMCs with RAIT as compared with PTMCs without RAIT (p=0.0018). Higher levels of pre-Tg were also found in patients with repeated RAIT as compared with patients with single RAIT (p<0.0001). Furthermore, pre-Tg level was higher in PTMC with IDR (n=16) and much higher in BIR (n=9) as compared with patients with ER (n=82, p=0.0003) after RAIT. Multivariate analysis showed that pre-Tg level over 16.79 ng/ml [OR: 6.55 (2.10-20.39), p=0.001] was the only independent predictor for NER in PTMC with RAIT. We found that high level of pre-Tg predicted a poor RAIT outcome in PTMC. Our finding explores a prospective way in identifying high-risk PTMCs with poor response to RAIT.

Spatial patterns, factors, and ethnic differences: A study on ethnic minority villages in Yunnan, China.

This paper takes ethnic minority villages in Yunnan province of China, which have significant characteristics of multi-ethnic integration, as the research object. Through various spatial statistical analysis methods, we analyzed the overall distribution characteristics of ethnic villages in Yunnan, the distribution difference among various ethnic groups, and the influencing factors of the distribution pattern. It was found that: (1) The ethnic minority villages in Yunnan generally exhibit a kernel density characteristic of "three concentrated areas and multiple scattered points" and distribution characteristic of "hot spots in the west and cold spots in the east". Each ethnic group has a relatively concentrated region, presenting significant ethnic autocorrelation. (2) The differences in the relationship between villages and landscape among various ethnic groups have given rise to a unique three-dimensional distribution pattern, which is relate to ethnic origin and livelihood culture. Meanwhile, Han traditional villages tend to occupy areas with relatively better geographical conditions. (3) Natural factors, such as topographic relief, the distance between ethnic villages and rivers, and elevation, have a significant impact on the distribution of ethnic villages in Yunnan. Meanwhile, test results of social and human factors, including the distance from central cities, per capita GDP, and the gross annual output values of primary industry, indicate that the development of social economy and the promotion of urbanization pose challenges to the preservation of ethnic villages.

[Venetoclax Combined with CACAG Regimen in the Treatment of Patients with Refractory/Relapse Acute Myeloid Leukemia: A Prospective Clinical Study].

OBJECTIVE: To investigate the efficacy and safety of Venetoclax combined with CACAG regimen in treatment of patients with refractory/relapse acute myeloid leukemia(R/R AML). METHODS: The study was a singlecenter prospective clinical trial. The enrolled patients met the criteria for R/R AML. Treatment included Azacidine(75 mg/m2，d 1-7), Ara-C (75-100 mg/m2, q12h, d 1-5), Aclacinomycin(20 mg d1,d3,d5), Chidamide(30 mg d1,d4), Venetoclax(100 mg d1, 200 mg d2, 400 mg d3-d14, in combination with Triazole Drug, reduced to 100 mg/d), and granulocyte colony-stimulating factor (300 µg /d until neutrophil recovery). The primary endpoint of observation was overall response rate after 1 course of treatment. RESULTS: A total of 19 patients were enrolled from January 2022 to April 2023. After 1 course of treatmen, the overall response rate was 81.3%(13/16), the CR rate was 68.8%(11/16), and the PR was 12.5%(2/16). Among the 11 patients who got CR/CRi, 8 cases achieved CRm (minimal residual disease negative CR) and 3 cases did not. As of March 27, 2023, the median follow-up time was 111(19-406) days. The six-month overall survival and progression-free survival rates were both 55.7%, the 1-year overall survival and progression-free survival rates were 46.4% and 47.7%, respectively. In addition, compared with the non-CRm group, CRm patients had a better PFS (377 days vs 111 days, P =0.046). Treatment-related adverse events were mainly 3-4 degrees of bone marrow suppression, complicated by various degrees of infection(n=12), hypokalemia(n=12) and hypocalcemia (n=10) and elevated liver enzymes (n=8), of which 3/4 degrees accounted for 47.4%(9/19). CONCLUSION: The Venetoclax combined with CACAG regimen is an effective salvage therapy for patients with R/R AML, with high remission rate and safety profile.

Evaluation of Turbulence Index and Flow Pattern for Atherosclerotic Carotid Stenosis: A High-Frame-Rate Vector Flow Imaging Study.

OBJECTIVE: The emerging high-frame-rate vector flow imaging provides a new way of hemodynamic evaluation for complex blood flow. This study was aimed at exploring quantitatively the characteristics of complex flow with turbulence (Tur) index and analyzing flow patterns in atherosclerotic internal carotid artery stenosis (ICAS) using high-frame-rate vector flow imaging. METHODS: This study prospectively included 60 patients with ICAS. Tur values in different segments of stenosis and cardiac phases were compared. Spearman correlation analysis was performed between clinical plaque characteristics with turbulence grading by ln(Tur). Three complex flow patterns were qualitatively drawn on vector flow mode, and the rates of detection of flow patterns in different stenosis groups and ulceration groups were compared. RESULTS: Highly disordered blood flow was observed in the stenotic (Tur [M, QR] = 12.5%, 21.5%) and distal segment (15.4%, 27.2%), particularly during systole (21.0%, 30.7%, 33.3%, 38.7%, p < 0.05). Spearman correlation analysis revealed that stenosis rate was correlated with turbulence grading in the stenotic (ρ = 0.65, p < 0.05) and distal segment (ρ = 0.79, p < 0.05), and ulcer formation was correlated with turbulence grading in the stenotic segment (ρ = 0.58, p < 0.05). The overall rate of detection of three flow patterns was higher in the severe stenosis group (22/22) versus the mild to moderate stenosis group (21/38) (p < 0.001) and in the ulcer group (21/23) versus the non-ulcer group (23/37) (p < 0.001). CONCLUSION: High-frame-rate vector flow imaging was helpful in assessing the severity and characteristics of flow turbulence. Lumen geometric factors could affect flow turbulence and blood flow patterns around the plaque. This would provide important hemodynamic information for the detection of high-risk plaque.

Computation-Aided Phylogeny-Oriented Engineering of ß-Xylosidase: Modification of "Blades" to Enhance Stability and Activity for the Bioconversion of Hemicellulose to Produce Xylose.

Hemicellulose is a highly abundant, ubiquitous, and renewable natural polysaccharide, widely present in agricultural and forestry residues. The enzymatic hydrolysis of hemicellulose has generally been accomplished using ß-xylosidases, but concomitantly increasing the stability and activity of these enzymes remains challenging. Here, we rationally engineered a ß-xylosidase from Bacillus clausii to enhance its stability by computation-aided design combining ancestral sequence reconstruction and structural analysis. The resulting combinatorial mutant rXYLOM25I/S51L/S79E exhibited highly improved robustness, with a 6.9-fold increase of the half-life at 60 °C, while also exhibiting improved pH stability, catalytic efficiency, and hydrolytic activity. Structural analysis demonstrated that additional interactions among the propeller blades in the catalytic module resulted in a much more compact protein structure and induced the rearrangement of the opposing catalytic pocket to mediate the observed improvement of activity. Our work provides a robust biocatalyst for the hydrolysis of agricultural waste to produce various high-value-added chemicals and biofuels.

Characteristics and Correlations of Wall Shear Stress and Flow Turbulence in the Carotid Bifurcation Evaluated Using an Ultrasound Vector Flow Imaging.

INTRODUCTION: The aim of the study was to evaluate characteristics and provide the normal values of wall shear stress (WSS) and flow turbulence (Tur), and the relationship between them in the carotid bifurcation based on an ultrasound vector flow imaging (V Flow) in healthy adults. METHODS: Max and mean WSS and Tur values at three segments (initial segments of internal and external carotid arteries [IICA and IECA]; distal segment of common carotid artery [DCCA]), both in anterior and posterior walls, were successfully obtained in 56 healthy adults, using ultrasound V Flow function. Relationship between mean WSS and Tur was further explored. RESULTS: The mean WSS value was 0.71 Pa, 0.86 Pa, and 0.96 Pa at IICA, IECA, and DCCA, respectively (IICA < IECA < DCCA, p < 0.05). The mean Tur value was 13.85%, 5.46%, and 4.17% at IICA, IECA, and DCCA, respectively (IICA > IECA > DCCA, p < 0.05). A cutoff value (WSS = 0.4 Pa) was selected and Tur values were significantly higher in group with WSS cutoff value <0.4 Pa than group with WSS cutoff value ≥0.4 Pa (p < 0.01). CONCLUSION: WSS and Tur are moderately negatively correlated, which can be used in the quantitative evaluation of carotid bifurcation and could be a potential dual-parameter tool in the clinical research for early detection of carotid atherosclerosis.

Association of psychological distress and DNA methylation: A 5-year longitudinal population-based twin study.

AIM: To identify the psychological distress (PD)-associated 5'-cytosine-phosphate-guanine-3' sites (CpGs), and investigate the temporal relationship between dynamic changes in DNA methylation (DNAm) and PD. METHODS: This study included 1084 twins from the Chinese National Twin Register (CNTR). The CNTR conducted epidemiological investigations and blood withdrawal twice in 2013 and 2018. These included twins were used to perform epigenome-wide association studies (EWASs) and to validate the previously reported PD-associated CpGs selected from previous EWASs in PubMed, Embase, and the EWAS catalog. Next, a cross-lagged study was performed to examine the temporality between changes in DNAm and PD in 308 twins who completed both 2013 and 2018 surveys. RESULTS: The EWAS analysis of our study identified 25 CpGs. In the validation analysis, 741 CpGs from 29 previous EWASs on PD were selected for validation, and 101 CpGs were validated to be significant at a false discovery rate <0.05. The cross-lagged analysis found a unidirectional path from PD to DNAm at 14 CpGs, while no sites showed significance from DNAm to PD. CONCLUSIONS: This study identified and validated PD-related CpGs in a Chinese twin population, and suggested that PD may be the cause of changes in DNAm over time. The findings provide new insights into the molecular mechanisms underlying PD pathophysiology.

Constructing an Ultra-Rapid Nanoconfinement-Enhanced Fluorescence Clinical Detection Platform by Using Machine Learning and Tunable DNA Xerogel "Probe".

Low mass transfer efficiency and unavoidable matrix effects seriously limit the development of rapid and accurate determination of biosensing systems. Herein, we have successfully constructed an ultra-rapid nanoconfinement-enhanced fluorescence clinical detection platform based on machine learning (ML) and DNA xerogel "probe", which was performed by detecting neutrophil gelatinase-associated lipocalin (NGAL, protein biomarker of acute kidney injury). By regulating pore sizes of the xerogels, the transfer of NGAL in xerogels can approximate that in homogeneous solution. Due to electrostatic attraction of the pore entrances, NGAL rapidly enriches on the surface and inside the xerogels. The reaction rate of NGAL and aptamer cross-linked in xerogels is also accelerated because of the nanoconfinement effect-induced increasing reactant concentration and the enhanced affinity constant KD between reactants, which can be promoted by ∼667-fold than that in bulk solution, thus achieving ultra-rapid detection (ca. 5 min) of human urine. The platform could realize one-step detection without sample pretreatments due to the antiligand exchange effect on the surface of N-doped carbon quantum dots (N-CQDs) in xerogels, in which ligand exchange between -COOH and underlying interfering ions in urine will be inhibited due to higher adsorption energy of -COOH on the N-CQD surface relative to the interfering ions. Based on the ML-extended program, the real-time analysis of the urine fluorescence spectra can be completed within 2 s. Interestingly, by changing DNA, aptamer sequences, or xerogel fluorescence intensities, the detection platform can be customized for targeted diseases.

Fusion data from FT-IR and MALDI-TOF MS result in more accurate classification of specific microbiota.

Microbes are usually present as a specific microbiota, and their classification remains a challenge. MALDI-TOF MS is particularly successful in library-based microbial identification at the species level as it analyzes the molecular weight of peptides and ribosomal proteins. FT-IR allows more accurate classification of bacteria at the subspecies level due to the high sensitivity, specificity and repeatability of FT-IR signals from bacteria, which is not achievable with MALDI-TOF MS. Previous studies have shown that more accurate identification results can be obtained by the fusion of FT-IR and MALDI-TOF MS spectral data. Here, we constructed 20 groups of model microbiota samples and used FT-IR, MALDI-TOF MS, and their fusion data to classify them. Hierarchical clustering analysis (HCA) showed that the classification accuracy of FT-IR, MALDI-TOF MS, and the fusion data was 85%, 90%, and 100%, respectively. These results indicate that both FT-IR and MALDI-TOF MS can effectively classify specific microbiota, and the fusion of their spectral data could improve the classification accuracy. The FT-IR and MALDI-TOF MS data fusion strategy may be a promising technology for specific microbiota classification.

A filter-electrochemical microfluidic chip for multiple surface protein analysis of exosomes to detect and classify breast cancer.

Breast cancer (BC) is a complex disease with high variability and no specific tumor markers available for diagnosis. Exosomes contain rich maternal tumor information and are a novel non-invasive biomarker with the potential for cancer diagnosis and prognosis. However, analysis of exosomal protein markers in blood samples is challenging due to lengthy sample workups and insufficient sensitivity. To address this difficulty, we developed a novel filter-electrochemical microfluidic chip (FEMC) to detect and classify BC directly in whole blood without requiring heavy purification methods. In our system, exosome enrichment was performed using a dual filtration system. The target was directed through a curved channel onto four screen-printed electrodes (SPEs), where it was captured by the previously modified antibodies. Simultaneously, Zr-MOFs encapsulated with a large number of methylene blue molecules (MB@UiO-66) were absorbed on the surface of exosomes due to the high affinity for phosphate groups. This process leads to the amplification of electrical signals. The approach demonstrated that the utilization of BC exosome-associated tumor biomarkers (i.e., PMSA, EGFR, CD81, and CEA), enabled the classification of various BC mouse models samples and clinical BC samples. The entire FEMC assay was completed in 1 h with a limit of detection of 1 × 104 particles/mL. Thus, the FEMC assay can provide real-time detection information, allowing timely and better-informed opportunities for clinical BC diagnosis and typing.

Curcumin induces mitophagy by promoting mitochondrial succinate dehydrogenase activity and sensitizes human papillary thyroid carcinoma BCPAP cells to radioiodine treatment.

Thyroid cancer is one of the most common endocrine malignancies. Differentiated thyroid cancer (DTC) treatment is based on the ability of thyroid follicular cells to accumulate radioactive iodide (RAI). DTC generally has a good prognosis. However, tumor dedifferentiation or defect in certain cell death mechanism occurs in a subset of DTC patients, leading to RAI resistance. Therefore, developing novel therapeutic approaches that enhance RAI sensitivity are still warranted. We found that curcumin, an active ingredient in turmeric with anti-cancer properties, rapidly accumulated in the mitochondria of thyroid cancer cells but not normal epithelial cells. Curcumin treatment triggered mitochondrial membrane depolarization, engulfment of mitochondria within autophagosomes and a robust decrease in mitochondrial mass and proteins, indicating that curcumin selectively induced mitophagy in thyroid cancer cells. In addition, curcumin-induced mitophagic cell death and its synergistic cytotoxic effect with radioiodine could be attenuated by autophagy inhibitor, 3-methyladenine (3-MA). Interestingly, the mechanism of mitophagy-inducing potential of curcumin was its unique mitochondria-targeting property, which induced a burst of SDH activity and excessive ROS production. Our data suggest that curcumin induces mitochondrial dysfunction and triggers lethal mitophagy, which synergizes with radioiodine to kill thyroid cancer cells.

Genetic and Environmental Influences on Blood Pressure and Serum Lipids Across Age-Groups.

Aging plays a crucial role in the mechanisms of the impacts of genetic and environmental factors on blood pressure and serum lipids. However, to our knowledge, how the influence of genetic and environmental factors on the correlation between blood pressure and serum lipids changes with age remains to be determined. In this study, data from the Chinese National Twin Registry (CNTR) were used. Resting blood pressure, including systolic and diastolic blood pressure (SBP and DBP), and fasting serum lipids, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TGs) were measured in 2378 participants (1189 twin pairs). Univariate and bivariate structural equation models examined the genetic and environmental influences on blood pressure and serum lipids among three age groups. All phenotypes showed moderate to high heritability (0.37-0.59) and moderate unique environmental variance (0.30-0.44). The heritability of all phenotypes showed a decreasing trend with age. Among all phenotypes, SBP and DBP showed a significant monotonic decreasing trend. For phenotype-phenotype pairs, the phenotypic correlation (Rph) of each pair ranged from -0.04 to 0.23, and the additive genetic correlation (Ra) ranged from 0.00 to 0.36. For TC&SBP, TC&DBP, TG&SBP and TGs&DBP, both the Rph and Ra declined with age, and the Ra difference between the young group and the older adult group is statistically significant (p < .05). The unique environmental correlation (Re) of each pair did not follow any pattern with age and remained relatively stable with age. In summary, we observed that the heritability of blood pressure was affected by age. Moreover, blood pressure and serum lipids shared common genetic backgrounds, and age had an impact on the phenotypic correlation and genetic correlations.

Optimal choice of stapler and digestive tract reconstruction method after distal gastrectomy for gastric cancer: A prospective case-control study.

BACKGROUND: Gastric cancer is the most common cause of cancer-related deaths, and is classified according to its location in the proximal, middle, or distal stomach. Surgical resection is the primary approach for treating gastric cancer. This prospective study aimed to determine the best reconstruction method after distal gastrectomy for gastric cancer. AIM: To explore the efficacy of different staplers and digestive tract reconstruction (DTR) methods after radical gastrectomy and their influence on prognosis. METHODS: Eighty-seven patients who underwent radical gastrectomy for distal gastric cancer at our institution between April 2017 and April 2020 were included in this study, with a follow-up period of 12-26 mo. The patients were assigned to four groups based on the stapler and DTR plan as follows: Billroth Ⅰ (B-I) reconstruction + linear stapler group (group A, 22 cases), B-I reconstruction + circular stapler group (group B, 22 cases), Billroth II (B-II) reconstruction + linear stapler group (group C, 22 cases), and B-II reconstruction + circular stapler group (group D, 21 cases). The pathological parameters, postoperative gastrointestinal function recovery, postoperative complications, and quality of life (QOL) were compared among the four groups. RESULTS: No significant differences in the maximum diameter of the gastric tumors, total number of lymph nodes dissected, drainage tube removal time, QLQ (QOL questionnaire)-C30 and QLQ-STO22 scores at 1 year postoperatively, and incidence of complications were observed among the four groups (P > 0.05). However, groups A and C (linear stapler) had significantly lower intraoperative blood loss and significantly shorter anastomosis time, operation time, first fluid diet intake time, first exhaust time, and length of postoperative hospital stay (P < 0.05) than groups B and D (circular stapler). CONCLUSION: Linear staplers offer several advantages for postoperative recovery. B-I and B-II reconstruction methods had similar effects on QOL. The optimal solution can be selected according to individual conditions and postoperative convenience.

ETCM v2.0: An update with comprehensive resource and rich annotations for traditional Chinese medicine.

Existing traditional Chinese medicine (TCM)-related databases are still insufficient in data standardization, integrity and precision, and need to be updated urgently. Herein, an Encyclopedia of Traditional Chinese Medicine version 2.0 (ETCM v2.0, http://www.tcmip.cn/ETCM2/front/#/) was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient Chinese medical books, 9872 Chinese patent drugs, 2079 Chinese medicinal materials and 38,298 ingredients. To facilitate the mechanistic research and new drug discovery, we improved the target identification method based on a two-dimensional ligand similarity search module, which provides the confirmed and/or potential targets of each ingredient, as well as their binding activities. Importantly, five TCM formulas/Chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0, which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy, to summarize the rules of prescription use, and to find alternative drugs for endangered Chinese medicinal materials. Moreover, ETCM v2.0 provides an enhanced JavaScript-based network visualization tool for creating, modifying and exploring multi-scale biological networks. ETCM v2.0 may be a major data warehouse for the quality marker identification of TCMs, the TCM-derived drug discovery and repurposing, and the pharmacological mechanism investigation of TCMs against various human diseases.