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Colorectal cancer (CRC) is an extremely malignant tumor with a high mortality rate. Little is known about the mechanism by which forkhead Box q1 (FOXQ1) causes CRC invasion and metastasis through the epidermal growth factor receptor (EGFR) pathway.To illuminate the mechanism by which FOXQ1 promotes the invasion and metastasis of CRC by activating the heparin binding epidermal growth factor (HB-EGF)/EGFR pathway.We investigated the differential expression and prognosis of FOXQ1 and HB-EGF in CRC using the Gene Expression Profiling Interactive Analysis (GEPIA) website (http://gepia.cancer-pku.cn/index.html). Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to detect the expression of FOXQ1 and HB-EGF in cell lines and tissues, and we constructed a stable low-expressing FOXQ1 cell line and verified it with the above method. The expression changes of membrane-bound HB-EGF (proHB-EGF) and soluble HB-EGF (sHB-EGF) in the low-expressing FOXQ1 cell line were detected by flow cytometry and ELISA. Western blotting was used to detect changes in the expression levels of HB-EGF and EGFR pathway-related downstream genes when exogenous recombinant human HB-EGF was added to FOXQ1 knockdown cells. Proliferation experiments, transwell migration experiments, and scratch experiments were carried out to determine the mechanism by which FOXQ1 activates the EGFR signaling pathway through HB-EGF, and then to evaluate the clinical relevance of FOXQ1 and HB-EGF.GEPIA showed that the expression of FOXQ1 in CRC tissues was relatively high and was related to a lower overall survival rate. PCR array results showed that FOXQ1 is related to the HB-EGF and EGFR pathways. Knockdown of FOXQ1 suppressed the expression of HB-EGF, and led to a decrease in EGFR and its downstream genesBased on these collective data, we propose that FOXQ1 promotes the invasion and metastasis of CRC

Nab-paclitaxel (Abraxane), which is a nanoparticle form of albumin-bound paclitaxel, is one of the standard chemotherapies for pancreatic ductal adenocarcinoma (PDAC). This study determined the effect of Abraxane in combination with a fusion protein, hIL15-ABD, on subcutaneous Panc02 and orthotopic KPC C57BL/6 murine PDAC models. Abraxane combined with hIL15-ABD best suppressed tumour growth and produced a 40%-60% reduction in the tumour size for Panc02 and KPC, compared to the vehicle group. In the combination group, the active form of interferon-γ (IFN-γ)-secreting CD8

Circular RNA is a newly discovered member of non‐coding RNA (ncRNA) and regulates the target gene by acting as a micro‐RNA sponge. It plays vital roles in various diseases. However, the functions of circular RNA in non‐small cell lung cancer (NSCLC) remain still unclear. Our data showed that circ‐WHSC1 was highly expressed in NSCLC cells and tissues. Both in vitro and in vivo experiments showed that circ‐WHSC1 promoted NSCLC proliferation. circ‐WHSC1 also promoted the migration and invasion of lung cancer cells. Through bioinformatic analysis and functional experiments, we showed that circ‐WHSC1 could act as a sponge for micro‐RNA‐7 (miR‐7) and regulate the expression of TAB2 (TGF‐beta activated kinase one binding protein two). Inhibition of the circ‐WHSC1/miR‐7/TAB2 pathway could effectively attenuate lung cancer progression. In summary, this study confirmed the existence and oncogenic function of circ‐WHSC1 in NSCLC. The research suggests that the circ‐WHSC1/miR‐7/TAB2 axis might be a potential target for NSCLC therapy.

ObjectivesDiabetic kidney disease (DKD) is one of the most common chronic complications in diabetic patients, and there are major limitations in its pathological diagnosis. This study’s objectives were to examine the changes in serum insulin-like growth factor-1 (IGF-1) and interleukin-6 (IL-6) levels in DKD patients with various urinary albumin/creatinine ratio (ACR) and to evaluate the utility of these two biological markers in the clinical diagnosis of the condition.MethodsWe chose 80 type 2 diabetic patients as the experimental group and 20 healthy normal participants as the control group. The experimental group was split into three groups based on the ACR range: diabetes without nephropathy group (ACR < 30 mg/g), microalbuminuric group (30 < ACR < 300 mg/g), and macroalbuminuric group (ACR > 300 mg/g). The levels of serum IL-6 and IGF-1 were assessed in each trial participant.ResultsSerum IGF-1 was higher in the experimental group than in the control group (P < 0.01), and serum IL-6 levels were also higher than in the control group (P < 0.001). In DKD patients, serum levels of IL-6 and IGF-1 tended to rise when ACR levels rose. By Pearson correlation analysis, serum IGF-1 and IL-6 were positively correlated with ACR (r = 0.765 and r = 0.651, all P < 0.001) and negatively correlated with eGFR (r = -0.389 and r = -0.364, all P < 0.01). Additionally, the receiver operating characteristic (ROC) characteristic curve showed that the area under the curve (AUC) values for serum IGF-1 and IL-6 were 0.9056 and 0.7850, respectively, while the AUR value for both combined was 0.9367.ConclusionSerum IGF-1 and IL-6 levels can be used to diagnose DKD, and the combined analysis of these two indicators can improve the sensitivity and specificity of the disease diagnosis.

This study investigated the effects of air temperature and ventilation on the sleep quality of elderly subjects and elucidated the mechanisms involved. Sixteen subjects aged over 65 years old were exposed to four conditions in a 2 × 2 design: air temperatures of 27°C and 30°C (with a ceiling fan in operation at 30°C) and two ventilation conditions (with and without mechanical ventilation) in experimental bedrooms. Their electroencephalogram, electrooculogram, chin electromyogram, electrocardiogram, respiration, oxygen saturation, and wrist skin temperature were measured continuously during sleep. Saliva samples were collected, and blood pressure was measured both before and after sleep. The results showed that at the temperature of 30°C, the total sleep time, sleep efficiency, and duration of REM sleep of the elderly decreased by 26.3 min, 5.5%, and 5.3 min, respectively, and time awake increased by 27.0 min, in comparison with 27°C, indicating that the sleep quality of the elderly is very vulnerable to heat exposure. Even a small heat load led to an overactive sympathetic nervous system and increased wrist skin temperature, which reduced sleep quality. Improving the ventilation increased the duration of deep sleep and REM sleep by 10.3 min and 3.7 min, respectively. Higher pollutant concentrations affected the respiration and autonomous nervous systems to reduce sleep quality. The benefits of improved thermal environment and ventilation on sleep quality were found to be additive. Good ventilation and the avoidance of raised temperatures in the bedroom are thus both important for the sleep quality of the elderly.

The Genome Sequence Archive (GSA) is a data repository for archiving raw sequence data, which provides data storage and sharing services for worldwide scientific communities. Considering explosive data growth with diverse data types, here we present the GSA family by expanding into a set of resources for raw data archive with different purposes, namely, GSA (https://ngdc.cncb.ac.cn/gsa/), GSA for Human (GSA-Human, https://ngdc.cncb.ac.cn/gsa-human/), and Open Archive for Miscellaneous Data (OMIX, https://ngdc.cncb.ac.cn/omix/). Compared with the 2017 version, GSA has been significantly updated in data model, online functionalities, and web interfaces. GSA-Human, as a new partner of GSA, is a data repository specialized in human genetics-related data with controlled access and security. OMIX, as a critical complement to the two resources mentioned above, is an open archive for miscellaneous data. Together, all these resources form a family of resources dedicated to archiving explosive data with diverse types, accepting data submissions from all over the world, and providing free open access to all publicly available data in support of worldwide research activities.

Diabetic retinopathy (DR) is a pathophysiologic vasculopathic process with obscure mechanisms and limited effective therapeutic strategies. Aryl hydrocarbon receptor (AhR) is an important regulator of xenobiotic metabolism and an environmental sensor. The aim of the present study was to investigate the role of AhR in the development of DR and elucidate the molecular mechanism of its downregulation. DR was evaluated in diabetes-induced retinal injury in wild type and AhR knockout (AhR-/-) mice. Retinal expression of AhR was determined in human donor and mice eyes by immunofluorescence since AhR activity was examined in diabetes. AhR knockout (AhRKO) mice were used to induce diabetes with streptozotocin, high-fat diet, or genetic double knockout with diabetes spontaneous mutation (Leprdb) (DKO; AhR-/-×Leprdb/db) for investigating structural, functional, and metabolic abnormalities in vascular and epithelial retina. Structural molecular docking simulation was used to survey the pharmacologic AhR agonists targeting phosphorylated AhR (Tyr245). Compared to diabetic control mice, diabetic AhRKO mice had aggravated alterations in retinal vasculature that amplified hallmark features of DR like vasopermeability, vascular leakage, inflammation, blood-retinal barrier breakdown, capillary degeneration, and neovascularization. AhR agonists effectively inhibited inflammasome formation and promoted AhR activity in human retinal microvascular endothelial cells and pigment epithelial cells. AhR activity and protein expression was downregulated, resulting in a decrease in DNA promoter binding site of pigment epithelium-derived factor (PEDF) by gene regulation in transcriptional cascade. This was reversed by AhR agonists. Our study identified a novel of DR model that target the protective AhR/PEDF axis can potentially maintain retinal vascular homeostasis, providing opportunities to delay the development of DR.

The CCL2-CCR2 axis is one of the major chemokine signaling pathways that has received special attention because of its function in the development and progression of cardiovascular disease. Numerous investigations have been performed over the past decades to explore the function of the CCL2-CCR2 signaling axis in cardiovascular disease. Laboratory data on the CCL2-CCR2 axis for cardiovascular disease have shown satisfactory outcomes, yet its clinical translation remains challenging. In this article, we describe the mechanisms of action of the CCL2-CCR2 axis in the development and evolution of cardiovascular diseases including heart failure, atherosclerosis and coronary atherosclerotic heart disease, hypertension and myocardial disease. Laboratory and clinical data on the use of the CCL2-CCR2 pathway as a targeted therapy for cardiovascular diseases are summarized. The potential of the CCL2-CCR2 axis in the treatment of cardiovascular diseases is explored.

Background To compare potential of ultrashort time-to-echo (UTE) T2* mapping and T2* values from T2*-weighted imaging for assessing lumbar intervertebral disc degeneration (IVDD),with Pfirrmann grading as a reference standard. Methods UTE-T2* and T2* values of 366 lumbar discs (L1/2-L5/S1) in 76 subjects were measured in 3 segmented regions: anterior annulus fibrosus, nucleus pulposus (NP), and posterior annulus fibrosus. Lumbar intervertebral discs were divided into 3 categories based on 5-level Pfirrmann grading: normal (Pfirrmann grade I),early disc degeneration (Pfirrmann grades II-III), and advanced disc degeneration (Pfirrmann grades IV-V). Regional differences between UTE-T2* and T2* relaxometry and correlation with degeneration were statistically analyzed. Results UTE-T2* and T2*value correlated negatively with Pfirrmann grades (P r = − 0.733; P r = -0.654; P P Conclusions UTE-T2* relaxometry provides another promising magnetic resonance imaging sequence for quantitatively evaluate lumbar IVDD and was more accurate than T2*mapping in the earlier stage degenerative process.

Homologous recombination (HR) repairs DNA double-strand breaks (DSBs) in the S and G2 phases of the cell cycle1–3. Several HR proteins are preferentially recruited to DSBs at transcriptionally active loci4–10, but how transcription promotes HR is poorly understood. Here we develop an assay to assess the effect of local transcription on HR. Using this assay, we find that transcription stimulates HR to a substantial extent. Tethering RNA transcripts to the vicinity of DSBs recapitulates the effects of local transcription, which suggests that transcription enhances HR through RNA transcripts. Tethered RNA transcripts stimulate HR in a sequence- and orientation-dependent manner, indicating that they function by forming DNA–RNA hybrids. In contrast to most HR proteins, RAD51-associated protein 1 (RAD51AP1) only promotes HR when local transcription is active. RAD51AP1 drives the formation of R-loops in vitro and is required for tethered RNAs to stimulate HR in cells. Notably, RAD51AP1 is necessary for the DSB-induced formation of DNA–RNA hybrids in donor DNA, linking R-loops to D-loops. In vitro, RAD51AP1-generated R-loops enhance the RAD51-mediated formation of D-loops locally and give rise to intermediates that we term ‘DR-loops’, which contain both DNA–DNA and DNA–RNA hybrids and favour RAD51 function. Thus, at DSBs in transcribed regions, RAD51AP1 promotes the invasion of RNA transcripts into donor DNA, and stimulates HR through the formation of DR-loops. RNA transcripts stimulate homologous recombination through the formation of DR-loops, intermediate structures that contain both DNA–DNA and DNA–RNA hybrids.

Objective: Ovarian cancer is one of the most common causes of death in gynecological tumors, and its most common type is epithelial ovarian cancer (EOC). This study aimed to establish a radiomics signature based on ultrasound images to predict the histopathological types of EOC. Methods: Overall, 265 patients with EOC who underwent preoperative ultrasonography and surgery were eligible. They were randomly sorted into two cohorts (training cohort: test cohort = 7:3). We outlined the region of interest of the tumor on the ultrasound images of the lesion. Then, the radiomics features were extracted. Clinical, Rad-score and combined models were constructed based on the least absolute shrinkage, selection operator, and logistic regression analysis. The performance of the models was evaluated using receiver operating characteristic curves and decision curve analysis (DCA). A nomogram was formulated based on the combined prediction model. Results: The combined model had good performance in predicting EOC histopathological types, with an AUC of 0.83 (95% CI: 0.77–0.90) and 0.82 (95% CI: 0.71–0.93) in the training and test cohorts, respectively. The calibration curves showed that the nomogram estimation was consistent with the actual observations. DCA also verified the clinical value of the combined model. Conclusions: The combined model containing clinical and ultrasound radiomics features showed an excellent performance in predicting type I and type II EOC. Advances in knowledge: This study presents the first application of ultrasound radiomics features to distinguish EOC histopathological types. The proposed clinical-radiomics nomogram could help gynecologists non-invasively identify EOC types before surgery.

There is a paucity of literature on the efficacy and safety of ultrafiltration in Chinese patients with heart failure (HF). Therefore, we aimed to compare the efficacy and safety of ultrafiltration with diuretics and provide information and evidence as to the best approach for patients with HF.In this single-center, non-randomized interventional study patients with HF either received diuretics or ultrafiltration. The efficacy outcomes included changes in the weight, dyspnea score, and 6-min walk distance from baseline to 48 h after treatment. Safety outcomes were evaluated in both the groups with respect to changes in systolic blood pressure, heart rate, serum creatinine, blood urea nitrogen, blood potassium ion concentration, and blood sodium ion concentration.A total of 149 patients with HF (diuretics, 73; ultrafiltration, 76) were included. At 48 h, patients in the ultrafiltration group showed significantly greater weight loss and better improvement in dyspnea score and 6-min walk distance compared to patients in the control group (P 0.05). However, the two groups showed no statistically significant difference in terms of safety outcomes such as systolic blood pressure, heart rate, serum creatinine, blood urea nitrogen, blood potassium ion concentration, and blood sodium ion concentration, suggesting similar safety profiles of both the groups.Ultrafiltration was associated with greater weight loss and better dyspnea score and 6-min walk distance with similar safety profiles as compared with diuretics. Ultrafiltration can be considered as an optimal option for Chinese patients with HF.

DNA repair and DNA damage signaling pathways are critical for the maintenance of genomic stability. Defects of DNA repair and damage signaling contribute to tumorigenesis, but also render cancer cells vulnerable to DNA damage and reliant on remaining repair and signaling activities. Here, we review the major classes of DNA repair and damage signaling defects in cancer, the genomic instability that they give rise to, and therapeutic strategies to exploit the resulting vulnerabilities. Furthermore, we discuss the impacts of DNA repair defects on both targeted therapy and immunotherapy, and highlight emerging principles for targeting DNA repair defects in cancer therapy.

RNA modifications regulate a variety of cellular processes including DNA repair.The RNA methyltransferase TRDMT1 generates methyl-5-cytosine (m5C) on messen-ger RNA (mRNA) at DNA double-strand breaks (DSBs) in transcribed regions, pro-moting transcription-coupled homologous recombination (HR). Here, we identifiedthat Fragile X mental retardation protein (FMRP) promotes transcription-coupled HRvia its interaction with both the m5C writer TRDMT1 and the m5C eraser ten-eleventranslocation protein 1 (TET1). TRDMT1, FMRP, and TET1 function in a temporalorder at the transcriptionally active sites of DSBs. FMRP displays a higher affinity forDNA:RNA hybrids containing m5C-modified RNA than for hybrids without modifica-tion and facilitates demethylation of m5C by TET1 in vitro. Loss of either the chroma-tin- or RNA-binding domain of FMRP compromises demethylation of damage-inducedm5C in cells. Importantly, FMRP is required for R-loop resolving in cells. Due to unre-solved R-loop and m5C preventing completion of DSB repair, FMRP depletion or lowexpression leads to delayed repair of DSBs at transcriptionally active sites and sensitizescancer cells to radiation in a BRCA-independent manner. Together, ourfindings presentan m5C reader, FMRP, which acts as a coordinator between the m5C writer and eraserto promote mRNA-dependent repair and cell survival in cancer.

RNA-DNA hybrids are generated during transcription, DNA replication and DNA repair and are crucial intermediates in these processes. When RNA-DNA hybrids are stably formed in double-stranded DNA, they displace one of the DNA strands and give rise to a three-stranded structure called an R-loop. R-loops are widespread in the genome and are enriched at active genes. R-loops have important roles in regulating gene expression and chromatin structure, but they also pose a threat to genomic stability, especially during DNA replication. To keep the genome stable, cells have evolved a slew of mechanisms to prevent aberrant R-loop accumulation. Although R-loops can cause DNA damage, they are also induced by DNA damage and act as key intermediates in DNA repair such as in transcription-coupled repair and RNA-templated DNA break repair. When the regulation of R-loops goes awry, pathological R-loops accumulate, which contributes to diseases such as neurodegeneration and cancer. In this Review, we discuss the current understanding of the sources of R-loops and RNA-DNA hybrids, mechanisms that suppress and resolve these structures, the impact of these structures on DNA repair and genome stability, and opportunities to therapeutically target pathological R-loops.

Background and aim This study aimed to clarify health-related quality of life (HRQoL) of patients with colorectal precancer and colorectal cancer (CRC) in China and to better understand related utility scores. Methods A hospital-based cross-sectional survey was conducted in precancer and CRC patients from 2012 to 2014, covering 12 provinces in China. HRQoL was assessed with EuroQol 5-Dimensions 3-Levels. Utility scores were derived using Chinese value set. A multivariate regression model was established to explore potential predictors of utility scores. Results A total of 376 precancer (mean age 58.7 years, 61.2% men) and 2470 CRC patients (mean age 58.6 years, 57.6% men) were included. In five dimensions, there was a certain percentage of problem reported among precancer (range: 12.0% to 36.7%) and CRC (range: 32.4% to 50.3%) patients, with pain/discomfort being the most serious dimension. Utility scores of precancer and CRC patients were 0.870 (95% confidence interval [CI], 0.855-0.886) and 0.751 (95% CI, 0.742-0.759), both of which were lower than those of general Chinese population (0.960 [95% CI, 0.960-0.960]). Utilities for patients at stage I to stage IV were 0.742 (95% CI, 0.715-0.769), 0.722 (95% CI, 0.705-0.740), 0.756 (95% CI, 0.741-0.772), and 0.745 (95% CI, 0.742-0.767), respectively. Multivariate analysis showed that therapeutic regimen, time point of the interview, education, occupation, annual household income, and geographic region were associated with utilities of CRC patients. Conclusion Health-related quality of life of both precancer and CRC patients in China declined considerably. Utility scores differed by sociodemographic and clinical characteristics, and findings of these utilities may facilitate implementation of further cost-utility evaluations.

Background Hyperplasia of mammary gland (HMG) has become a common disorder in women. A family history of breast cancer and female reproductive factors may work together to increase the risk of HMG. However, this specific relationship has not been fully characterized. Methods A total of 1881 newly diagnosed HMG cases and 1900 controls were recruited from 2012 to 2017. Demographic characteristics including female reproductive factors and a family history of breast cancer were collected. A multi-analytic strategy combining unconditional logistic regression, multifactor dimensionality reduction (MDR) and crossover approaches were applied to systematically identify the interaction effect of family history of breast cancer and reproductive factors on HMG susceptibility. Results In MDR analysis, high-order interactions among higher-level education, shorter breastfeeding duration and family history of breast cancer were identified (odds ratio [OR] 7.07 [95% confidence interval {CI} 6.08 to 8.22]). Similarly, in crossover analysis, HMG risk increased significantly for those with higher-level education (OR 36.39 [95% CI 11.47 to 115.45]), shorter duration of breastfeeding (OR 27.70 [95% CI 3.73 to 205.70]) and a family history of breast cancer. Conclusion Higher-level education, shorter breastfeeding duration and a family history of breast cancer may synergistically increase the risk of HMG.

PM2.5 is a class of airborne particles and droplets with sustained high levels in many developing countries. Epidemiological studies have indicated that PM2.5 is closely associated with the increased morbidity and mortality of lung cancer in the world. Unfortunately, the effects of PM2.5 on lung cancer are largely unknown. In the present study, we attempted to explore the role of PM2.5 in the etiology of NSCLC. Here, we found that long-term PM2.5 exposure led to significant pulmonary injury. Epithelial-mesenchymal transition (EMT) and cancer stem cells (CSC) properties were highly induced by PM2.5 exposure. EMT was evidenced by the significant up-regulation of MMP2, MMP9, TGF-β1, α-SMA, Fibronectin and Vimentin. Lung cancer progression was associated with the increased expression of Kras, c-Myc, breast cancer resistance protein BCRP (ABCG2), OCT4, SOX2 and Aldh1a1, but the decreased expression of p53 and PTEN. Importantly, mice with IL-17a knockout (IL-17a-/-) showed significantly alleviated lung injury and CSC properties following PM2.5 exposure. Also, IL-17a-/--attenuated tumor growth was recovered in PM2.5-exposed mice injected with recombinant mouse IL-17a, accompanied with significantly restored lung metastasis. Taken together, these data revealed that PM2.5 could promote the progression of lung cancer by enhancing the proliferation and metastasis through IL-17a signaling.

Background We aimed to obtain a set of health state utility scores of patients with esophageal cancer (EC) and precancerous lesions in China, and to explore the influencing factors of health-related quality of life (HRQoL). Methods A hospital-based multicenter cross-sectional study was conducted. From 2013 to 2014, patients with EC or precancerous lesions were enrolled. HRQoL was assessed using a European quality of life-5 dimension (EQ-5D-3L) instrument. Multivariable linear regression analysis was performed to explore the influencing factors of the EQ-5D utility scores. Results A total of 2090 EC patients and 156 precancer patients were included in the study. The dimension of pain/discomfort had the highest rate of self-reported problems, 60.5% in EC and 51.3% in precancer patients. The mean visual analog scale (VAS) score for EC and precancer patients were 68.4 ± 0.7 and 64.5 ± 3.1, respectively. The EQ-5D utility scores for EC and precancer patients were estimated as 0.748 ± 0.009 and 0.852 ± 0.022, and the scores of EC at stage I, stage II, stage III, and stage IV were 0.693 ± 0.031, 0.747 ± 0.014, 0.762 ± 0.015, and 0.750 ± 0.023, respectively. According to the multivariable analyses, the factors of region, occupation, household income in 2012, health care insurance type, pathological type, type of therapy, and time points of the survey were statistically associated with the EQ-5D utility scores of EC patients. Conclusions There were remarkable decrements of utility scores among esophageal cancer patients, compared with precancer patients. The specific utility scores of EC would support further cost-utility analysis in populations in China.

We explored the importance of inhaled air temperature on thermal comfort, perceived air quality, acute non-clinical health symptoms, and physiological responses. Sixteen subjects stayed in a stainless-steel chamber for 90 min. They experienced four conditions with two inhaled air temperatures of 22 and 30 °C and two ambient temperatures of 22 and 30 °C in a 2 x 2 design. They wore breathing masks covering their mouth and nose to control the inhaled air temperature; the air was provided from an adjacent twin stainless-steel chamber. The subjects evaluated thermal conditions and health symptoms on visual-analogue scales. Skin temperature and electrocardiography were recorded. Whole-body thermal sensation and skin temperature did not change when the temperature of inhaled air was changed. Perceived air quality was significantly improved when subjects sat in the chamber at 30 °C and inhaled air with a temperature of 22 °C; under these conditions lip and throat dryness were significantly reduced. The lower inhaled air temperature increased time-domain heart rate variability indicators and decreased heart rate and the LF/HF ratio, suggesting that the parasympathetic nervous system was activated and the sympathetic nervous system was suppressed.

Objectives: To investigate the prognostic role of magnetic resonance imaging (MRI)-based radiomics signature and clinical characteristics for overall survival (OS) and disease-free survival (DFS) in the early-stage cervical cancer. Methods: A total of 207 cervical cancer patients (training cohort: n = 144; validation cohort: n = 63) were enrolled. 792 radiomics features were extracted from T2W and diffusion-weighted imaging (DWI). 19 clinicopathological parameters were collected from the electronic medical record system. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to select significant features to construct prognostic model for OS and DFS. Kaplan-Meier (KM) analysis and log-rank test were applied to identify the association between the radiomics score (Rad-score) and survival time. Nomogram discrimination and calibration were evaluated as well. Associations between radiomics features and clinical parameters were investigated by heatmaps. Results: A radiomics signature derived from joint T2W and DWI images showed better prognostic performance than that from either T2W or DWI image alone. Higher Rad-score was associated with worse OS (p < 0.05) and DFS (p < 0.05) in the training and validation set. The joint models outperformed both radiomics model and clinicopathological model alone for 3-year OS and DFS estimation. The calibration curves reached an agreement. Heatmap analysis demonstrated significant associations between radiomics features and clinical characteristics. Conclusions: The MRI-based radiomics nomogram showed a good performance on survival prediction for the OS and DFS in the early-stage cervical cancer. The prediction of the prognostic models could be improved by combining with clinical characteristics, suggesting its potential for clinical application. Advances in knowledge: This is the first study to build the radiomics-derived models based on T2W and DWI images for the prediction of survival outcomes on the early-stage cervical cancer patients, and further construct a combined risk scoring system incorporating the clinical features.

The clinical application of music therapy and research into its use and effectiveness are common in Western countries. The physiological role of this type of therapy is to stimulate the central nervous system through music, which may have a sedative, analgesic effect, and reduce negative emotions. Previous studies have confirmed that music can be effective for a range of psychological disorders, including post-stroke depression (PSD). There is, however, a lack of systematic evaluation of its effectiveness, and variability in sample size and in the quality of research has detracted from the persuasiveness of findings.Based on PRISMA 2020, articles on music therapy intervention in post-stroke depression were identified through the Web of Science, PubMed, EMBASE, CNKI, Weipu, and Wanfang databases. The retrieval time was taken from the establishment of the database to October 18, 2022. Two researchers conducted a stringent evaluation of the quality of the articles and extracted the data. They then used RevMan5.3 software for meta-analysis.Twenty articles were listed, involving 1625 patients. Meta-analysis results showed that music therapy could lower scores on the Hamilton Depression Rating Scale (HDRS/Ham-D), the National Institutes of Health stroke scale and self-rated depression scale for patients with PSD. Music therapy was also shown to improve the Barthel Index for Activities of Daily Living and treatment efficacy of PSD patients. However, music therapy did not reduce the incidence of adverse reactions in PSD patients.Music therapy has benefits in improving HDRS/Ham-D score and symptoms of PSD patients, and could be more widely applied.

Background With the global spread of the coronavirus disease pandemic, governments have become more interested in applying telehealth technology in 2020. Objective This study integrates the technology acceptance model and information system success model to explore the influence of satisfaction, attitudes, and continued use of telehealth systems among middle-aged and older people in remote areas. Methods The study participants were patients over 40 years (inclusive) who lived in remote townships in eastern Taiwan, were diagnosed with diabetes or hypertension, and used the telehealth care system. In total, 545 questionnaires were returned, resulting in a recovery rate of 99%. Results Accepting the hypothesized structural equation model, this study found that information, system, and service quality were influenced by the mediating effect of perceived ease of use and the perceived usefulness of the technology acceptance model. The use of telehealth care systems among chronic patients increased significantly.

Overexpression of HER2 is associated with cancer phenotypes, such as proliferation, survival, metastasis and angiogenesis, and has been validated as a therapeutic target. However, only a portion of patients benefited from anti-HER2 treatments, and many would develop resistance. A more effective HER2 targeted therapeutics is needed. Here, we adopted a prodrug system that uses 5-fluorocytosine (5-FC) and a HER2-targeting scaffold protein, ZHER2:2891, fused with yeast cytosine deaminase (Fcy) to target HER2-overexpressing cancer cells and to convert 5-FC to a significantly more toxic chemotherapeutic, 5-fluorouracil (5-FU). We cloned the coding gene of ZHER2:2891 and fused with those of ABD (albumin-binding domain) and Fcy. The purified ZHER2:2891-ABD-Fcy fusion protein specifically binds to HER2 with a Kd value of 1.6 nM ZHER2:2891-ABD-Fcy binds to MDA-MB-468, SKOV-3, BT474, and MC38-HER2 cells, which overexpress HER2, whereas with a lower affinity to HER2 non-expresser, MC38. Correspondingly, the viability of HER2-expressing cells was suppressed by relative low concentrations of ZHER2:2891-ABD-Fcy in the presence of 5-FC, and the IC50 values of ZHER2:2891-ABD-Fcy for HER2 high-expresser cells were approximately 10–1000 fold lower than those of non-HER2-targeting Fcy, and ABD-Fcy. This novel prodrug system, ZHER2:2891-ABD-Fcy/5-FC, might become a promising addition to the existing class of therapeutics specifically target HER2-expressing cancers.

To study the serological characteristics and molecular biological basis of 8 individuals with Para-Bombay phenotypes in Guangxi area.Serological tests were used to identify the blood groups of red cells. Molecular biological methods, including PCR-SSP for ABO genotyping and DNA sequencing for FUT1, were used to detect the genotypes of ABO and FUT1 which determined the expression of H antigen.Eight individuals in the study were all the Para-Bombay phenotypes, including 4 cases of BThere are varieties of molecular genetic mechanisms for Para-Bombay phenotypes. In this study, the FUT1 mutations that cause Para-Bombay phenotypes in Guangxi area are mainly h3, h广西地区8例类孟买血型个体的血清学鉴定及FUT1基因突变分析.对广西地区8例类孟买血型个体进行血清学及分子生物学背景分析。.采用血型血清学方法对研究标本进行血型鉴定，用分子生物学方法进行基因型分析，包括以PCR-SSP方法进行ABO基因分型和测序，对决定H抗原表达的FUT1基因进行分析。.8例类孟买血型中，4例为B类孟买血型存在多种分子遗传机制，在本研究中，广西地区类孟买血型个体中发现导致类孟买血型的FUT1基因突变主要包括h3、h

The second branchial cleft cyst lacks typical symptoms, and its clinical manifestations are complex and varied. Among them, the second branchial cleft cyst manifested by sleep snoring is relatively rare, and it can easily lead to missed diagnosis or misdiagnosis. This paper reports a case of a second branchial cleft abscess with snoring as the main manifestation. The branchial cleft cyst was removed using an endoscopic branchial cleft.

This study managed to create thermal comfort conditions at three temperatures (24°C-T24, 26°C-T26, and 28°C-T28) by adjusting clothing and air velocity. Thirty-six subjects (18 males and 18 females) were exposed to each of the three conditions for 4.5 h in a design balanced for order of presentation of conditions. During each exposure, they rated the physical environment, their comfort, the intensity of acute subclinical health symptoms, and their mental load, and they performed a number of cognitive tasks. Their physiological reactions were monitored. The subjects rated T24 to be comfortably cool, T26 to be comfortably neutral, and T28 to be comfortably warm. Their self-estimated performance did not differ between conditions but 12 of 14 objective metrics of cognitive performance decreased significantly at the elevated temperatures: compared with T24, their average cognitive performance decreased by 10% at T26 and by 6% at T28. At the elevated temperatures, their parasympathetic nervous system activity (as indicated by PNN50) and their arterial blood oxygen saturation level (SpO2) were both lower, which would be expected to result in reduced cognitive performance. The subjects also rated their acute subclinical health symptoms as more intense and their workload as higher at the elevated temperatures. These results suggest that where cognitive performance is the priority, it is wise to ensure a comfortably cool environment. The present study also supports the use of fans or natural ventilation to reduce the need for mechanical cooling.

Amino acids have been implicated with virus infection and replication. Here, we demonstrate the effects of two basic amino acids, arginine and lysine, and their ester derivatives on infection of two enveloped viruses, SARS-CoV-2, and influenza A virus. We found that lysine and its ester derivative can efficiently block infection of both viruses in vitro. Furthermore, the arginine ester derivative caused a significant boost in virus infection. Studies on their mechanism of action revealed that the compounds potentially disturb virus uncoating rather than virus attachment and endosomal acidification. Our findings suggest that lysine supplementation and the reduction of arginine-rich food intake can be considered as prophylactic and therapeutic regimens against these viruses while also providing a paradigm for the development of broad-spectrum antivirals.

Humans emit carbon dioxide (CO2 ) as a product of their metabolism. Its concentration in buildings is used as a marker of ventilation rate (VR) and degree of mixing of supply air, and indoor air quality (IAQ). The CO2 emission rate (CER) may be used to estimate the ventilation rate. Many studies have measured CERs from subjects who were awake but little data are available from sleeping subjects and the present publication was intended to reduce this gap in knowledge. Seven females (29 ± 5 years old; BMI: 22.2 ± 0.8 kg/m2 ) and four males (27 ± 1 years old; BMI: 20.5 ± 1.5 kg/m2 ) slept for four consecutive nights in a specially constructed capsule at two temperatures (24 and 28°C) and two VRs that maintained CO2 levels at ca. 800 ppm and 1700 ppm simulating sleeping conditions reported in the literature. The order of exposure was balanced, and the first night was for adaptation. Their physiological responses, including heart rate, pNN50, core body temperature, and skin temperature, were measured as well as sleep quality, and subjective responses were collected each evening and morning. Measured steady-state CO2 concentrations during sleep were used to estimate CERs with a mass-balance equation. The average CER was 11.0 ± 1.4 L/h per person and was 8% higher for males than for females (P

Reactive oxygen species (ROS) inflict multiple types of lesions in DNA, threatening genomic integrity. How cells respond to ROS-induced DNA damage at telomeres is still largely unknown. Here, we show that ROS-induced DNA damage at telomeres triggers R-loop accumulation in a TERRA- and TRF2-dependent manner. Both ROS-induced single- and double-strand DNA breaks (SSBs and DSBs) contribute to R-loop induction, promoting the localization of CSB and RAD52 to damaged telomeres. RAD52 is recruited to telomeric R-loops through its interactions with both CSB and DNA:RNA hybrids. Both CSB and RAD52 are required for the efficient repair of ROS-induced telomeric DSBs. The function of RAD52 in telomere repair is dependent on its ability to bind and recruit POLD3, a protein critical for break-induced DNA replication (BIR). Thus, ROS-induced telomeric R-loops promote repair of telomeric DSBs through CSB–RAD52–POLD3-mediated BIR, a previously unknown pathway protecting telomeres from ROS. ROS-induced telomeric SSBs may not only give rise to DSBs indirectly, but also promote DSB repair by inducing R-loops, revealing an unexpected interplay between distinct ROS-induced DNA lesions.

Background Spontaneous intracerebral hemorrhage (ICH) is a devastating disease with high mortality rate. This study aimed to predict hematoma expansion in spontaneous ICH from routinely available variables by using support vector machine (SVM) method. Methods We retrospectively reviewed 1157 patients with spontaneous ICH who underwent initial computed tomography (CT) scan within 6 h and follow-up CT scan within 72 h from symptom onset in our hospital between September 2013 and August 2018. Hematoma region was manually segmented at each slice to guarantee the measurement accuracy of hematoma volume. Hematoma expansion was defined as a proportional increase of hematoma volume > 33% or an absolute growth of hematoma volume > 6 mL from initial CT scan to follow-up CT scan. Univariate and multivariate analyses were performed to assess the association between clinical variables and hematoma expansion. SVM machine learning model was developed to predict hematoma expansion. Findings 246 of 1157 (21.3%) patients experienced hematoma expansion. Multivariate analyses revealed the following 6 independent factors associated with hematoma expansion: male patient (odds ratio [OR] = 1.82), time to initial CT scan (OR = 0.73), Glasgow Coma Scale (OR = 0.86), fibrinogen level (OR = 0.72), black hole sign (OR = 2.52), and blend sign (OR = 4.03). The SVM model achieved a mean sensitivity of 81.3%, specificity of 84.8%, overall accuracy of 83.3%, and area under receiver operating characteristic curve (AUC) of 0.89 in prediction of hematoma expansion. Interpretation The designed SVM model presented good performance in predicting hematoma expansion from routinely available variables. Fund This work was supported by Health Foundation for Creative Talents in Zhejiang Province , China, Natural Science Foundation of Zhejiang Province , China ( LQ15H180002 ), the Science and Technology Planning Projects of Wenzhou , China ( Y20180112 ), Scientific Research Staring Foundation for the Returned Overseas Chinese Scholars of Ministry of Education of China , and Project Foundation for the College Young and Middle-aged Academic Leader of Zhejiang Province , China. The funders had no role in study design, data collection, data analysis, interpretation, writing of the report.

BACKGROUND: Previous studies have suggested that breast parenchymal texture features may reflect the biologic risk factors associated with breast cancer development. Therefore, combining the characteristics of normal parenchyma from the contralateral breast with radiomic features of breast tumors may improve the accuracy of digital mammography in the diagnosis of breast cancer. PURPOSE: To determine whether the addition of radiomic analysis of contralateral breast parenchyma to the characterization of breast lesions with digital mammography improves lesion classification over that with radiomic tumor features alone. MATERIALS AND METHODS: This HIPAA-compliant, retrospective study included 182 patients (age range, 25–90 years; mean age, 55.9 years ± 14.9) who underwent mammography between June 2002 and July 2009. There were 106 malignant and 76 benign lesions. Automatic lesion segmentation and radiomic analysis were performed for each breast lesion. Radiomic texture analysis was applied in the normal regions of interest in the contralateral breast parenchyma to assess the mammographic parenchymal patterns. The classification performance of both individual features and the output from a Bayesian artificial neural network classifier was evaluated with the leave-one-patient-out method by using the area under the receiver operating characteristic curve (AUC) as the figure of merit in the task of differentiating between malignant and benign lesions. RESULTS: The performance of the combined lesion and parenchyma classifier in the differentiation between malignant and benign mammographic lesions was better than that with the lesion features alone (AUC = 0.84 ± 0.03 vs 0.79 ± 0.03, respectively; P = .047). Overall, six radiomic features—spiculation, margin sharpness, size, circularity from the tumor feature set, and skewness and power law beta from the parenchymal feature set—were selected more than 50% of the time during the feature selection process on the combined feature set. CONCLUSION: Combining quantitative radiomic data from tumors with contralateral parenchyma characterizations may improve diagnostic accuracy for breast cancer. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Shaffer in this issue.

PURPOSE Radiomic texture analysis is typically performed on images acquired under specific, homogeneous imaging conditions. These controlled conditions may not be representative of the range of imaging conditions implemented clinically. We aim to develop a two-stage method of radiomic texture analysis that incorporates the reproducibility of individual texture features across imaging conditions to guide the development of texture signatures which are robust across mammography unit vendors. METHODS Full-field digital mammograms were retrospectively collected for women who underwent screening mammography on both a Hologic Lorad Selenia and GE Senographe 2000D system. Radiomic features were calculated on manually placed regions of interest in each image. In stage one (robustness assessment), we identified a set of nonredundant features that were reproducible across the two different vendors. This was achieved through hierarchical clustering and application of robustness metrics. In stage two (classification evaluation), we performed stepwise feature selection and leave-one-out quadratic discriminant analysis (QDA) to construct radiomic signatures. We refer to this two-state method as robustness assessment, classification evaluation (RACE). These radiomic signatures were used to classify the risk of breast cancer through receiver operator characteristic (ROC) analysis, using the area under the ROC curve as a figure of merit in the task of distinguishing between women with and without high-risk factors present. Generalizability was investigated by comparing the classification performance of a feature set on the images from which they were selected (intravendor) to the classification performance on images from the vendor on which it was not selected (intervendor). Intervendor and intravendor performances were also compared to the performance obtained by implementing ComBat, a feature-level harmonization method and to the performance by implementing ComBat followed by RACE. RESULTS Generalizability, defined as the difference between intervendor and intravendor classification performance, was shown to monotonically decrease as the number of clusters used in stage one increased (Mann-Kendall P

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower motor neurons with no effective cure. Electrophysiological studies have found decremental responses during low-frequency repetitive nerve stimulation (RNS) except for diffused neurogenic activities. However, the difference between ALS and generalized myasthenia gravis (GMG) in terms of waveform features is unclear. In the current study, we explored the variation trend of the amplitudes curve between ALS and GMG with low-frequency, positive RNS, and the possible mechanism is discussed preliminarily. Methods: A total of 85 ALS patients and 41 GMG patients were recruited. All patients were from Peking Union Medical College Hospital (PUMCH) between July 1, 2012 and February 28, 2015. RNS study included ulnar nerve, accessory nerve and facial nerve at 3 Hz and 5 Hz stimulation. The percentage reduction in the amplitude of the fourth or fifth wave from the first wave was calculated and compared with the normal values of our hospital. A 15% decrease in amplitude is defined as a decrease in amplitude. Results: The decremental response at low-frequency RNS showed the abnormal rate of RNS decline was 54.1% (46/85) in the ALS group, and the results of different nerves were 54.1% (46/85) of the accessory nerve, 8.2% (7/85) of the ulnar nerve and 0% (0/85) of the facial nerve stimulation, respectively. In the GMG group, the abnormal rate of RNS decline was 100% (41/41) at low-frequency RNS of accessory nerves. However, there was a significant difference between the 2 groups in the amplitude after the sixth wave. Conclusions: Both groups of patients are able to show a decreasing amplitude of low-frequency stimulation RNS, but the recovery trend after the sixth wave has significant variation. It implies the different pathogenesis of NMJ dysfunction of these 2 diseases. Key words: Amyotrophic lateral sclerosis; Generalized myasthenia gravis; Neuromuscular junction; Repetitive nerve stimulation

To examine temporal trends in stillbirth and its associated risk factors in Taiwan. This was a population-based cohort study. Data were extracted from the Birth Certificate Application database. Singleton births at 28 or more gestational weeks were included. A total of 1,536,796 births, including 3741 stillbirths, were analyzed from January 2006 to December 2013. The stillbirth rate was 2.4 per 1000 births and there was no change in the stillbirth rate during the study period. The adjusted odds ratio (aOR) for stillbirth was 1.28 for maternal age between 35 and 40 years and 1.79 for maternal age ≥ 41 years, with 21–34 years as the reference. The risk for stillbirth increased in single women (aOR, 2.4), female baby (aOR, 1.08), small for gestational age (aOR, 6.34) and large for gestational age (aOR, 1.52) infants, and women with hypertension (aOR, 3.78), diabetes mellitus (aOR, 2.04), anemia (aOR, 1.65), and oligohydramnios or polyhydramnios (aOR, 2.46).Women with heart disease and maternal age ≤ 20 years had no significant association with stillbirth after adjusting for various risk factors. Although the rate of stillbirth was stable during the study period, the incidence of risk factors associated with stillbirth, such as advanced maternal age, hypertension, diabetes mellitus, and anemia, had increased over time. Understanding about the risk factors might change protocols and allow for earlier detection of problems and prevention of stillbirths. Prevention or management of risk factors should be undertaken to reduce stillbirth rate.

DNA double-strand breaks pose a direct threat to genomic stability. Studies of DNA damage and chromatin dynamics have yielded opposing results that support either increased or decreased chromatin motion after damage. In this study, we independently measure the dynamics of transcriptionally active or repressed chromatin regions using particle tracking microrheology. We find that the baseline motion of transcriptionally repressed regions of chromatin are significantly less mobile than transcriptionally active chromatin, which is statistically similar to the bulk motion of chromatin within the nucleus. Site specific DNA damage using KillerRed tags induced in loci within repressed chromatin causes an increased motion, while loci within transcriptionally active regions remains unchanged at similar time scales. We also observe a time-dependent response associated with a further increase in chromatin decondensation. Global induction of damage with bleocin displays similar trends of chromatin decondensation and increased mobility only at 53BP1-labeled damage sites but not at non-damaged sites, indicating that chromatin dynamics are tightly regulated locally after damage. These results shed light on the evolution of the local and global DNA damage response associated with chromatin remodeling and dynamics, with direct implications for their role in repair.

Background Two-dimensional (2D) specimen radiography (SR) and tomosynthesis (DBT) for breast cancer yield data that lack high-depth resolution. A volumetric specimen imager (VSI) was developed to provide full-3D and thin-slice cross-sectional visualization at a 360° view angle. The purpose of this prospective trial was to compare VSI, 2D SR, and DBT interpretation of lumpectomy margin status with the final pathologic margin status of breast lumpectomy specimens. Methods The study enrolled 200 cases from two institutions. After standard imaging and interpretation was performed, the main lumpectomy specimen was imaged with the VSI device. Image interpretation was performed by three radiologists after surgery based on VSI, 2D SR, and DBT. A receiver operating characteristic (ROC) curve was created for each method. The area under the curve (AUC) was computed to characterize the performance of the imaging method interpreted by each user. Results From 200 lesions, 1200 margins were interpreted. The AUC values of VSI for the three radiologists were respectively 0.91, 0.90, and 0.94, showing relative improvement over the AUCs of 2D SR by 54%, 13%, and 40% and DBT by 32% and 11%, respectively. The VSI has sensitivity ranging from 91 to 94%, specificity ranging from 81 to 85%, a positive predictive value ranging from 25 to 30%, and a negative predicative value of 99%. Conclusions The ROC curves of the VSI were higher than those of the other specimen imaging methods. Full-3D specimen imaging can improve the correlation between the main lumpectomy specimen margin status and surgical pathology. The findings from this study suggest that using the VSI device for intraoperative margin assessment could further reduce the re-excision rates for women with malignant disease.

Three conditions were established to investigate the effects of ventilation and related ventilation noise on sleep quality: No mechanical ventilation/low noise (A); Mechanical ventilation /low noise (B); Mechanical ventilation/high noise (C). The interventions were achieved by idling a mechanical ventilation system or operating it in two different modes. Nine young people and nine older people were all exposed to each of the three conditions for a whole night's sleep, but data from only 15 subjects were analyzed as three young subjects apparently slept with open windows in condition A. Sleep quality was measured objectively with polysomnography (PSG), which monitored signals of electroencephalogram (EEG), bilateral electrooculogram (EOG), and chin electromyogram (EMG) continuously during the sleeping period. Saliva samples were collected before sleep at night and after waking in the morning, and the concentrations of cortisol and lysozyme in them were determined. Without mechanical ventilation, the indoor CO2 level averaged about 1400 ppm during the night. Operating the mechanical ventilation decreased the indoor CO2 to below 1000 ppm, which improved objectively measured sleep quality: wake time after sleep onset (WASO) decreased on average by 15 min (p < 0.05) and sleep efficiency (SE) increased on average by about 4% (p < 0.05). Increased ventilation noise level (50.8dB(A) vs. 34.7dB(A); 54.9dB(C) vs. 48dB(C)) did not significantly change SE or WASO but did change the duration of sleep stages: It decreased the duration of deep sleep by 11min (p < 0.05) and REM sleep by 17 min (p < 0.01) and increased the duration of light sleep by 17 min (p < 0.05). The ventilation noise significantly increased the concentration of lysozyme in the elderly (p < 0.05) although no significant effects on cortisol could be shown. These results confirm that a low ventilation rate has negative effects on sleep quality and that ventilation noise at or above 50dB(A) may disrupt sleep.

A higher ratio of M1/M2 macrophages and an elevated chemerin level are both related to increased risk of preeclampsia. However, the crosstalk between these two events and their collective contribution to preeclampsia are not well understood. In this study, we assessed the impacts of chemerin chemokine-like receptor 1 (CMKLR1)/p-Akt/CEBPα axis in regulating macrophage polarization and mediating the pathogenic effects of chemerin on preeclampsia. We showed that chemerin, in a dose- and time-dependent manner, stimulated M1 macrophage polarization, inhibited macrophage-induced trophoblast invasion and migration, and suppressed macrophage-mediated angiogenesis. All these chemerin-induced phenotypes are essentially mediated by sequentially CMKLR1, Akt activation, and CEBPα. Mechanistically, CEBPα acted as a transcriptional activator for both IRF8 and chemerin. In vivo, chemerin aggravated preeclampsia, while α-NETA, an inhibitor for CMKLR1, significantly suppressed M1 macrophage polarization and alleviated preeclampsia. In summary, chemerin, by activating CMKLR1/Akt/CEBPα axis, forms a positive feedback loop, promotes M1 macrophage polarization, suppresses trophoblast migration/invasion and angiogenesis, and contributes to preeclampsia. Therefore, targeting chemerin signaling may benefit the prevention and/or treatment of preeclampsia.

Population genetic analysis based on genetic markers harbors valuable forensic applications. In this regard, it is informative and imperative to explore Han groups as they are the largest population of China. In particular, there is a largely underrepresented amount of information from recent decades regarding the southeast costal Han Chinese. Therefore, the aim of this study is to investigate the available genetic characteristics of the Han population living in the Jinjiang, Fujian Province, Southeastern China.We sampled 858 saliva samples and used the commercially available Microreader™ Y Prime Plus ID System to identify population data of Y-short tandem repeat (STR) loci of this region.A total of 822 different haplotypes were observed. The overall haplotype diversity, discriminatory power and haplotype match probability were 0.9999, 0.9999 and 0.0012, respectively.Our results showed that the Jinjiang Han population was closely genetically related to Han groups of China. Overall, we identified a set of 37 Y-STRs that are highly polymorphic, and that can provide meaningful information in forensic practice and human genetic research.

The excessive M1 polarization of macrophages drives the occurrence and development of inflammatory diseases. The reprogramming of macrophages from M1 to M2 can be achieved by targeting metabolic events. Taurine promotes for the balance of energy metabolism and the repair of inflammatory injury, preventing chronic diseases and complications. However, little is known about the mechanisms underlying the action of taurine modulating the macrophage polarization phenotype. In this study, we constructed a low-dose LPS/IFN-γ-induced M1 polarization model to simulate a low-grade pro-inflammatory process. Our results indicate that the taurine transporter TauT/SlC6A6 is upregulated at the transcriptional level during M1 macrophage polarization. The nutrient uptake signal on the membrane supports the high abundance of taurine in macrophages after taurine supplementation, which weakens the status of methionine metabolism, resulting in insufficient S-adenosylmethionine (SAM). The low availability of SAM is directly sensed by LCMT-1 and PME-1, hindering PP2Ac methylation. PP2Ac methylation was found to be necessary for M1 polarization, including the positive regulation of VDAC1 and PINK1. Furthermore, its activation was found to promote the elimination of mitochondria by macrophages via the mitophagy pathway for metabolic adaptation. Mechanistically, taurine inhibits SAM-dependent PP2Ac methylation to block PINK1-mediated mitophagy flux, thereby maintaining a high mitochondrial density, which ultimately hinders the conversion of energy metabolism to glycolysis required for M1. This reprogramming of energy metabolism strongly opposes the conditions required for M1 polarization and tilts M2. Our findings reveal a novel mechanism of taurine-coupled M1 macrophage energy metabolism, providing novel insights into the occurrence and prevention of low-grade inflammation, and propose that the sensing of taurine and SAM availability may allow communication to inflammatory response in macrophages.

Although the environment can greatly influence an individual's sleep quality, China is yet to conduct comprehensive research on the topic. This study investigated the bedroom environment and sleep quality of 41 households during summer in Shanghai. Bedroom environments were comprehensively evaluated through environmental perception questionnaires filled by participants after waking up every morning. Parameters, such as air temperature, relative humidity, CO2 concentration, and noise level were continuously monitored. Furthermore, participants' sleep quality was observed using both subjective questionnaires and physiological measures. Environmental measurements showed that the most comfortable air temperature and relative humidity was 24.8 °C and 64%, respectively. Physiological measurements showed that the average duration of slow wave sleep (SWS) and sleep efficiency (SE) was 73.8 min and 86.7%, respectively. Additionally, SWS was negatively correlated with air temperature (r = −0.377, p = 0.015) and CO2 concentration (r = −0.362, p = 0.02), and SE was negatively correlated with noise level (r = −0.32, p = 0.042). The subjective and objective results consistently indicated that higher air temperature, CO2 concentration, and noise level leads to poor sleep quality in summer. In addition, air temperature and CO2 concentration had a greater impact on the sleep quality of males, while noise level had a greater impact on the sleep quality of females.

More than 80% of patients with ovarian epithelial cancer (OEC) show complete remission after initial treatment but eventually experience recurrence of the disease. This study aimed to develop a radiomics signature to identify a new prognostic indicator based on preoperative ultrasound imaging. A total of 111 patients with OEC who underwent transvaginal ultrasound before surgery were included. Of these, 76 were divided into the training cohort and 35 into the test cohort. We defined the region of interest (ROI) of the tumor by manually drawing the tumor contour on the ultrasound image of the lesion. The radiomics features were extracted from ultrasound images. The radiomics score (Rad-Score) was constructed using the least absolute shrinkage and selection operator (LASSO) analysis and Cox regression. Combined with the ultrasound radiomics features, significant clinical variables were also used to establish predictive models for 5-year progression-free survival (PFS) prediction. The efficiency of the model was evaluated using the area under the curve (AUC). Kaplan–Meier analysis was used to evaluate the association between the Rad-Score and PFS. The combined model was superior to the clinical and Rad-Score models in estimating 5-year PFS and achieved an AUC of 0.868 (95%CI 0.766–0.971) in the training cohort. The Rad-Score was negatively correlated with prognosis in the training and test cohorts. The combined model that incorporated both clinical parameters and ultrasound radiomics features achieved a good prognosis in patients with OEC, which might aid clinical decision-making.

Liupao tea, a drink homologous to medicine and food. It can treat dysentery, relieve heat, remove dampness, and regulate the intestines and stomach. The objective of this study is to explore the material basis and mechanism of Liupao tea intervention in COVID-19 and to provide a new prevention and treatment programme for COVID-19. We used high performance liquid chromatography to analyze the extract of Liupao tea and establish its fingerprint. The main index components of the fingerprint were determined using SARS-COV-2 3-chymotrypsin-like protease (3CL

This study investigated associations between total isoflavones and their categories (daidzein, genistein, glycitein) intake and the risks for metabolic disorders. We used the data of 6786 Chinese adults from the Nutrition Health Atlas Project. We performed multiple logistic regression and restricted cubic spline models assessing the risks for metabolic disorders (non-alcoholic fatty liver disease (NAFLD), hyperlipidaemia, hypertension, diabetes and overweight/obesity) in each category of isoflavones. Higher total isoflavones, daidzein and genistein intake were inversely associated with NAFLD (p p p

Levosimendan is a calcium sensitizer used for managing heart failure (HF) because of its inotropic and vasodilatory effects. As many patients do not respond to levosimendan as a monotherapy, it may be necessary to combine it with other diuretic agents such as recombinant human brain natriuretic peptide (rhBNc P). The aim of this study was to investigate efficacy of levosimendan when combined with rhBNP in patients with diuretic resistance and low ejection fraction (EF) rate. The study included HF patients with diuretic resistance and low EF. Before grouping, patients with a 24-hour urine volume of

Epidermal growth factor receptor (EGFR) specific therapeutics is of great importance in cancer treatment. Fcy-hEGF fusion protein, composed of yeast cytosine deaminase (Fcy) and human EGF (hEGF), is capable of binding to EGFR and enzymatically convert 5-fluorocytosine (5-FC) to 1000-fold toxic 5-fluorocuracil (5-FU), thereby inhibiting the growth of EGFR-expressing tumor cells. To develop EGFR-specific therapy, 188Re-liposome-Fcy-hEGF was constructed by insertion of Fcy-hEGF fusion protein onto the surface of liposomes encapsulating of 188Re. Western blotting, MALDI-TOF, column size exclusion and flow cytometry were used to confirm the conjugation and bio-activity of 188Re-liposome-Fcy-hEGF. Cell lines with EGFR expression were subjected to treat with 188Re-liposome-Fcy-hEGF/5-FC in the presence of 5-FC. The 188Re-liposome-Fcy-hEGF/5-FC revealed a better cytotoxic effect for cancer cells than the treatment of liposome-Fcy-hEGF/5-FC or 188Re-liposome-Fcy-hEGF alone. The therapeutics has radio- and chemo-toxicity simultaneously and specifically target to EGFR-expression tumor cells, thereby achieving synergistic anticancer activity.

To study two novel CD36 gene mutations at the CD36 splicing sites found in Guangxi population, as well as the molecular basis and population incidence of them.DNA sequencing and cDNA clonal sequencing were used to detect CD36 exon sequence and the protein coding region sequence of CD36 mRNA for 2 CD36 deficient individuals (HHC and WGM) found in Guangxi population. Eukaryotic expression cell lines were established for the discovery of CD36 mRNA abnormal transcripts and Western blot assay was used to verify the effect of abnormal CD36 mRNA transcripts on CD36 expression. A DNA PCR-SSP genotyping method was established for the two CD36 novel mutations, and the population distribution was investigated among 110 CD36 deficient individuals in Guangxi region and 296 random individuals in Guangxi population.Novel mutation of c.430 -1GC was found at the CD36 splicing site in HHC and WGM individuals, and novel mutation of c.1006 +2TG at the CD36 splicing site was also found in the WGM individual. CD36 cDNA clonal sequencing showed that CD36 c.430 -1GC could lead to the production of the two CD36 mRNA transcript variants: c.429_430ins［430-17_430-2;C］(p.Ala144fsTer1) and c.430_609del(p.Ala144_Pro203del)(GenBank:HM 217023.1); and CD36 c.1006 +2TG could lead to the production of CD36 mRNA transcript variant of c.819_1006 del (p.Ser274GlufsTer16) (GenBank: HM217025.1). It was verified that all the three transcript variants could lead to CD36 deficiency by establishment of eukaryotic expression cell lines and Western blot assay. A study of the population incidence of two novel CD36 splicing site mutations found showed that in 110 CD36 deficient individuals and in 296 random individuals in Guangxi region, the mutation rate of CD36 c.430 -1GC was 10.91% (12/110) and 1.35% (4/296), respectively, while CD36 c.1006 +2TG was 2.73% (3/110) and 0 (0/296), respectively.This study identifies two novel CD36 mutations at CD36 splicing site, and preliminary clarified their molecular basis for the CD36 deficiency and the distribution characteristics in Guangxi population as well. It provides an experimental and theoretical basis for studying the molecular mechanism and characteristics of CD36 deficiency in Chinese population.位于CD36基因剪切位点的2个新突变及其导致CD36缺失的分子基础.对在广西人群中发现的2个位于CD36剪切位点的新基因突变，以及它们导致CD36缺失的分子基础和在人群中的发生率进行研究.对在广西人群中发现的2例CD36缺失个体（HHC和WGM）使用DNA测序和cDNA克隆测序，检测他们的CD36外显子序列及mRNA蛋白编码区序列，对所发现的CD36 mRNA异常转录本建立真核表达细胞株并用Western blot实验验证异常转录本对CD36表达的影响。对所发现的新突变基因建立DNA PCR-SSP基因分型方法，在广西地区的110名CD36缺失个体群和广西地区随机的296名人群间展开人群分布调查.在HHC和WGM个体中，发现了CD36剪切位点新突变CD36 c.430 -1GC，且在WGM个体中还发现了CD36 c.1006 +2TG的剪切位点新突变。cDNA克隆测序显示，CD36 c.430 -1GC可导致c.429_430ins［430-17_430-2;C］（p.Ala144fsTer1）和c.430_609del(p.Ala144_Pro203del，GenBank注册号:HM217023.1）2种CD36 mRNA异常转录本的产生，而CD36 c.1006 +2TG可导致c.819_1006del（p.Ser274GlufsTer16）(GenBank注册号:HM217025.1）CD36 mRNA异常转录本的产生。通过建立的真核表达细胞株及Western blot实验验证了以上3种异常转录本均可导致CD36表达缺失。对所发现的2个剪切位点突变基因展开的人群发生率的研究显示，在110名CD36缺失个体群和随机的296名人群中，CD36 c.430 -1GC突变发生率分别为10.91%（12/110）和1.35%（4/296），而CD36 c.1006 +2TG突变的发生率分别为2.73%（3/110）和0（0/296）.本研究发现了2个位于CD36基因剪切位点的新突变，初步阐明了它们导致CD36缺失的分子基础及在广西人群中的分布特征，为中国人群CD36缺失的分子机制及特征研究提供了实验和理论依据.

Intracranial germinoma (IG) rarely occurs in adults. Its optimal treatment strategy is unclear. We evaluated the outcomes of radiotherapy in adults with intracranial germinoma. Data of 29 adult patients (age, 18–52 years; median age, 24.3 years) with IG treated with radiotherapy at Taipei Veterans General Hospital were retrospectively reviewed. They were followed up for a median time of 5.9 years (range, 1.0–12.8 years). We used the Kaplan–Meier method to estimate the progression-free survival (PFS) and overall survival (OS), and univariate and multivariate Cox proportional hazards regression models to identify the factors affecting PFS. PFS and OS were compared between adult and pediatric patients with IG. The 1-, 3-, and 5-year PFS rates were 96.6%, 85.8%, and 77.8%, respectively, in the adult patients, and the OS rate were all 100%. Seven patients (24.1%) experienced recurrence, and in six of them, salvage therapy successfully controlled the disease. Two patients (6.9%) died after 5 years of follow-up due to disease progression and central pontine myelinolysis. In the univariate and multivariate Cox analysis, bifocal lesions had a significantly lower PFS than those with single lesions (p = 0.008). Kaplan–Meier survival analysis showed that adult patients had a poorer PFS (p = 0.06) and OS (p = 0.025) than pediatric patients. Our study showed bifocal lesions were associated with lower PFS than a single lesion among adult IG patients, and adult IG patients tended to have poorer PFS and OS compared to pediatric IG patients. For adult patients with bifocal IG, we recommend treatment with craniospinal irradiation, whole ventricle irradiation (WVI) with chemotherapy, or frequent spine images follow-up for patients who received only WVI.