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Background: High sodium intake is an important risk factor for hypertension and cardiovascular disease. However, the association between gut microbiota composition and metabolomic profiles with dietary sodium intake and blood pressure (BP) is not well-understood. The metabolome, microbiome, and dietary salt intervention (MetaSalt) study aimed to investigate microbial and metabolomic profiles related to dietary sodium intake and BP regulation. Methods: This family-based intervention study was conducted in four communities across three provinces in rural northern China in 2019. Probands with untreated prehypertension or stage-1 hypertension were identified through community-based BP screening, and family members including siblings, offspring, spouses, and parents were subsequently included. All participants participated in a 3-day baseline examination with usual diet consumption, followed by a 10-day low-salt diet (3 g/d of salt or 51.3 mmol/d of sodium) and a 10-day high-salt diet (18 g/d of salt or 307.8 mmol/d of sodium). Differences in mean BP levels were compared according to the intervention phases using a paired Student's t-test. Results: A total of 528 participants were included in this study, with a mean age of 48.1 years, 36.7% of whom were male, 76.8% had a middle school (69.7%) or higher (7.1%) diploma, 23.4% had a history of smoking, and 24.4% were current drinkers. The mean arterial pressure at baseline was 97.2 ± 10.5 mm Hg for all participants, and significantly decreased during the low-salt intervention (93.8 ± 9.3, P

Carbon quantum dots (CQDs) as a rising class of carbon family have gained widespread attention in view of their multiple properties such as great photoluminescence (PL) properties, facile synthesis route, needing economical and cheap raw material, high physiochemical stability, and simple functionalization. This makes CQDs highly versatile and with potential for different applications. To date, CQDs-enabled photocatalysts are regarded as one of the most efficient technologies to degrade pollutants in water; however, poor activity under visible light and the recombination of photogenerated electron and hole pairs hinder getting an ideal performance that may be applied on a large scale. Conventional techniques have been modified via a new advanced method. In this review, we highlighted the strategies to improve the activity of conventional semiconductor photocatalysis via coupling with CQDs, and strategies to improve the photocatalytic activity such as functionalization, doping, and Z-scheme heterojunctions were discussed in detail. This review also covered the CQDs heterojunction application in pollutant degradation and discussed several examples with high-performance photocatalytic activity.

Background. Gastric cancer is the most common malignant tumor of the digestive system. It has a poor prognosis and is clinically challenging to treat. Ferroptosis is a newly defined mode of programmed cell death. The roles and prognostic value of ferroptosis-related long noncoding RNAs (lncRNAs) in gastric cancer remain unknown. Results. In the current study, 20 ferroptosis-related lncRNAs were identified via univariate Cox analysis, least absolute shrinkage, and selection operator Cox regression analysis and used to construct a prognostic signature and classify gastric cancer patients into high-risk and low-risk groups. The signature was validated using TCGA training and testing cohorts. The risk signature was an independent prognostic indicator of survival and accurately predicted the prognoses of patients with gastric cancer. It was also associated with immune cell infiltration. Gene set enrichment analysis was used to investigate underlying mechanisms that the 20 ferroptosis-related lncRNAs were involved in. Chemosensitivity and immune checkpoint inhibitor analyses indicated that high-risk patients were more sensitive to the immune checkpoint inhibitor programmed cell death protein 1. Conclusions. The important role of ferroptosis-related lncRNAs in immune infiltration identified in the current study may assist the determination of personalized prognoses and treatments in patients with gastric cancer. These 20 lncRNAs can be used as the diagnostic and prognostic markers for gastric cancer.

Chemoradiotherapy (CRT) has been widely applied in patients with advanced nasopharyngeal carcinoma (ANPC). However, limited imaging modality exists on the evaluation of early response to CRT. The purpose of this study was therefore to investigate whether 3D pseudo-continuous arterial spin labeling (3D pCASL) perfusion imaging could predict early response to CRT in ANPC patients.Seventy ANPC patients who received CRT underwent pre-treatment MRI including 3D pCASL perfusion measurements, and were categorized into response group (RG) and no-response group (NRG) according to RECIST 1.1. Pre-treatment 3D pCASL derived cerebral blood flow (CBF) values in tumors were compared between RG and NRG patients. Receiver-operating characteristic (ROC) analysis was performed to determine the optimal diagnostic cutoff value for CBF in predicting tumor response to CRT. Clinicopathological variables were also analyzed by using univariate and binary logistic regression. The corresponding obtained variables with statistical significance were further applied to create a nomogram in which the bootstrap resampling method was used for calibration.Forty-eight patients in RG had significantly higher pre-treatment CBF values in tumors compared with 22 patients in NRG (P 0.001). CBF showed the high area under the ROC curve (AUC = 0.843) in distinguishing RG from NRG patients. The corresponding cutoff value for CBF was 103.68 ml/100 g/min, with respective accuracy, sensitivity and specificity of 82.86%, 87.50% and 72.73%. The nomogram was generated by binary logistic regression results, incorporating three variables: CBF value, clinical stage and pathological type. The AUC, accuracy, sensitivity and specificity of the nomogram was respectively 0.893, 84.28%, 81.25% and 90.91% in predicting tumor response to CRT. Moreover, as shown in the calibration curve, a strong agreement was observed between nomogram prediction probability and actual clinical findings (P = 0.309).3D pCASL derived CBF in tumor could act as a noninvasive effective biomarker to predict tumor response to CRT in ANPC patients before clinical treatment. Furthermore, the nomogram combining CBF and clinicopathological variables could serve as a novel clinical analysis tool for treatment response prediction.

Cross-sectional studies have reported that high sodium sensitivity is more common among individuals with hypertension. Experimental studies have also reported various animal models with sodium-resistant hypertension. It is unknown, however, whether sodium sensitivity and resistance precede the development of hypertension. We conducted a feeding study, including a 7-day low-sodium diet (1180 mg/day) followed by a 7-day high-sodium diet (7081 mg/day), among 1718 Chinese adults with blood pressure (BP) P P =0.006 for nonlinear trend). Furthermore, a J-shaped association between systolic BP responses to sodium intake and incident hypertension was identified ( P

ObjectiveTo construct a polygenic risk score (PRS) for stroke and evaluate its utility in risk stratification and primary prevention for stroke.MethodsUsing a meta-analytic approach and large genome-wide association results for stroke and stroke-related traits in East Asians, we generated a combined PRS (metaPRS) by incorporating 534 genetic variants in a training set of 2,872 patients with stroke and 2,494 controls. We then validated its association with incident stroke using Cox regression models in large Chinese population-based prospective cohorts comprising 41,006 individuals.ResultsDuring a total of 367,750 person-years (mean follow-up 9.0 years), 1,227 participants developed stroke before age 80 years. Individuals with high polygenic risk had an about 2-fold higher risk of incident stroke compared with those with low polygenic risk (hazard ratio [HR] 1.99, 95% confidence interval [CI] 1.66–2.38), with the lifetime risk of stroke being 25.2% (95% CI 22.5%–27.7%) and 13.6% (95% CI 11.6%–15.5%), respectively. Individuals with both high polygenic risk and family history displayed lifetime risk as high as 41.1% (95% CI 31.4%–49.5%). Individuals with high polygenic risk achieved greater benefits in terms of absolute risk reductions from adherence to ideal fasting blood glucose and total cholesterol than those with low polygenic risk. Maintaining favorable cardiovascular health (CVH) profile could substantially mitigate the increased risk conferred by high polygenic risk to the level of low polygenic risk (from 34.6% to 13.2%).ConclusionsOur metaPRS has great potential for risk stratification of stroke and identification of individuals who may benefit more from maintaining ideal CVH.Classification of EvidenceThis study provides Class I evidence that metaPRS is predictive of stroke risk.

Developing advanced negative and positive electrode materials for asymmetric supercapacitors (ASCs) as electrochemical energy storage devices can enable the device to reach high energy/power densities resulting from the cooperative effect of the two electrodes. In this work, a nanochain-like hybrid nanostructured composite of MoO3 with rich oxygen vacancies (MoO3−x) in situ grown on N-doped graphene nanotubes (N-GNTs) is synthesized as the negative electrode for an ASC. It can deliver a large specific capacitance (591 F g−1 at 2 A g−1), as well as an outstanding rate capability. Simultaneously, N-GNTs@Na+-preinserted MnO2 (NaxMnO2) nanosheet arrays are fabricated as the positive electrode of the ASC, which can exhibit an enhanced specific capacitance of 429 F g−1 with a wide potential window of 0–1.2 V. When these two different electrodes are assembled in an ASC, a maximum energy density of 105 W h kg−1 at 2.2 kW kg−1, and an ultralong lifespan with 95.4% capacitance retention after 10 000 cycles are achieved, which are superior to those of the reported ASC devices to date. Density functional theory (DFT) calculations show that benefitting from the designed vacancy defects and unique N-GNT skeleton, the electronic structure and adsorption energy can be adjusted to greatly boost the electrical conductivity and ion adsorption efficiency and subsequently enhance the capacitive properties of the electrodes in the ASC.

The recent applications of fully convolutional networks (FCNs) have shown to improve the semantic segmentation of very high resolution (VHR) remote-sensing images because of the excellent feature representation and end-to-end pixel labeling capabilities. While many FCN-based methods concatenate features from multilevel encoding stages to refine the coarse labeling results, the semantic gap between features of different levels and the selection of representative features are often overlooked, leading to the generation of redundant information and unexpected classification results. In this article, we propose an attention-guided label refinement network (ALRNet) for improved semantic labeling of VHR images. ALRNet follows the paradigm of the encoder-decoder architecture, which progressively refines the coarse labeling maps of different scales by using the channelwise attention mechanism. A novel attention-guided feature fusion module based on the squeeze-and-excitation module is designed to fuse higher level and lower level features. In this way, the semantic gaps among features of different levels are declined, and the category discrimination of each pixel in the lower level features is strengthened, which is helpful for subsequent label refinement. ALRNet is tested on three public datasets, including two ISRPS 2-D labeling datasets and the Wuhan University aerial building dataset. Results demonstrated that ALRNet had shown promising segmentation performance in comparison with state-of-the-art deep learning networks. The source code of ALRNet is made publicly available for further studies.

What is already known about this topic? Short-term PM2.5 exposure has been associated with hourly, 24-hour, daytime, and nighttime blood pressure (BP) levels, and further studies focusing whether and how the associations with other ambulatory BP monitoring indicators are warranted. What is added by this report? This study observed that short-term PM2.5 exposure was associated with BP elevations and was the first to report the associations of short-term PM2.5 exposure with BP variability. Circadian rhythm of BP and BP load among hypertensive patients were found to be modified by controlled BP status or taking angiotensin receptor blockers (ARBs). What are the implications for public health practice? This study suggested that antihypertensive therapy, especially with well-controlled BP status may be potential measurements to attenuate adverse impacts of PM2.5 for hypertensive patients with intermediate-to-high risk of cardiovascular disease (CVD).

BACKGROUND Differentiating nasopharyngeal carcinoma (NPC) from nasopharyngeal lymphoma (NPL) is useful for deciding the appropriate treatment. However, the diagnostic accuracy of current imaging methods is low. PURPOSE To explore the feasibility of arterial spin labeling (ASL) perfusion imaging in the qualitative and quantitative differentiation between NPC and NPL to improve the diagnosis of malignancies in the nasopharynx. STUDY TYPE Retrospective. POPULATION Ninety seven patients: NPC (65 cases) and NPL (32 cases), histologically confirmed. FIELD STRENGTH/SEQUENCE 3T/3D fast spin echo pseudo-continuous ASL imaging with spiral readout scheme, 3D inverse recovery- fast spoiled gradient recalled echo brain volume (BRAVO) imaging. ASSESSMENT Cerebral blood flow (CBF) images from ASL perfusion imaging were assessed by three radiologists. Each tumor was visually scored based on CBF images. Intratumoral CBF and intramuscular CBF values were obtained from intratumoral and lateral pterygoid muscle areas, respectively. Through dividing intratumoral CBF by intramuscular CBF, normalized CBF (nCBF) was further calculated. STATISTICAL TESTS Fleiss's kappa and intraclass correlation coefficients (ICCs) were used to assess interobserver agreement among the three readers. The Mann-Whitney U-test was used to compare visual scoring, and an unpaired t-test was performed to compare CBF value between the NPC and NPL groups. The area under the curve (AUC) value was used to quantify the diagnostic ability of each parameter. RESULTS Good interobserver agreements were validated by high Fleiss's kappa and ICC values (all >0.80). NPCs showed significantly higher visual scores than NPLs (P

Although emerging studies from high-income countries investigated the relationship between sedentary behavior (SB) and cardiovascular risk, little evidence came from developing countries. Moreover, the benefits of reallocating time from SB to physical activity (PA) on incident cardiovascular disease (CVD) are unknown. Using three cohorts from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project, we included 93 110 adults who were free from CVD at baseline. Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD, including stroke, coronary heart disease, and CVD death. Isotemporal substitution models were applied to estimate the per-hour effects of replacing SB with PA. After 5.8 years follow-up, 3799 CVD cases were identified. A gradient positive association between sedentary time and incident CVD was observed. Relative to those with

Background:. The association of milk intake with cardiovascular disease (CVD) and cause-specific mortality remained controversial and evidence among the Chinese population was limited. We aimed to study the relationship between milk intake and CVDs among general Chinese adults. Methods:. A total of 104,957 participants received questionnaire survey. Results of physical examination such as anthropometric measurements and biochemical tests during 2007 to 2008, demographic data and their information on milk intake were collected through standardized questionnaires. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) of CVD incidence, cause-specific mortality and all-cause mortality related to milk intake. Restricted cubic splines (RCSs) were applied to examine dose-response associations. Results:. Among the 91,757 participants with a median follow-up period of 5.8 years, we documented 3877 CVD cases and 4091 all-cause deaths. Compared with participants who never consumed milk, the multivariate-adjusted HRs (95% CIs) of CVD incidence for 1 to 150 g/day, 151 to 299 g/day, and ≥300 g/day were 0.94 (0.86–1.03) (P > 0.05), 0.77 (0.66–0.89) (P

Real-time assessment of therapeutic response in patients with advanced lung cancer presents a major challenge throughout the treatment process. Currently, computed tomography imaging is often used; however, it is radiation-based and hysteretic and is not suitable for repeated use as a real-time assessment. Blood biomarkers represent a novel solution for assessing therapeutic response in patients with advanced lung cancer. In the present study, the efficacy of a methylation marker [methylated prostaglandin E receptor 4 (mPTGER4)] and four protein markers [carcinoma antigen 125 (CA125), carcinoembryonic antigen (CEA), cytokeratin 19-fragments (cyfra21-1) and neuron-specific enolase (NSE)] were simultaneously evaluated to determine their potential in facilitating therapeutic response monitoring as well as their prognostic values in patients with stage IV lung cancer. The results indicated that, following treatment, the blood levels of methylated PTGER4 and NSE had significantly decreased, and mPRGER4, CA125, CEA and NSE exhibited a significant decrease in percentage level. Since mPTGER4 exhibited a higher rate of positive detection prior to therapy, and a greater response of sensitivity to therapy compared to the protein markers, it may represent an improved marker for the monitoring of therapeutic response. The efficacy of the markers in predicting the overall survival (OS) rate of patients with stage IV lung cancer was also assessed. Results from the follow-up of patients (up to 891 days) revealed that the blood levels of mPTGER4, CA125 and NSE before treatment were able to predict overall survival (OS) rate. Additionally, the percentage change in expression levels of CA125, CEA and NSE was also able to predict the OS rate. In conclusion, the present results indicate that mPTGER4 represents an improved biomarker for monitoring therapeutic efficacy compared with CA125, CEA, Cyfra21-1 and NSE. In predicting the long-term survival of patients with stage IV lung cancer; however, the pre-treatment levels of mPTGER4, CA125 and NSE and the percentage changes of CA125, CEA and NSE may be used as the markers.

Background Evidence of the effects of long-term fine particulate matter (PM2.5) exposure on cardiovascular diseases (CVDs) is rare for populations exposed to high levels of PM2.5 in China and in other countries with similarly high levels. Objectives The aim of this study was to assess the CVD risks associated with long-term exposure to PM2.5 in China. Methods A nationwide cohort study, China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China), was used, with 116,972 adults without CVD in 2000 being included. Participants were followed until 2015. Satellite-based PM2.5 concentrations at 1-km spatial resolution during the study period were used for exposure assessment. A Cox proportional hazards model with time-varying exposures was used to estimate the CVD risks associated with PM2.5 exposure, adjusting for individual risk factors. Results Annual mean concentrations of PM2.5 at the China-PAR sites ranged from 25.5 to 114.0 μg/m3. For each 10 μg/m3 increase in PM2.5 exposures, the multivariate-adjusted hazard ratio was 1.251 (95% confidence interval: 1.220 to 1.283) for CVD incidence and 1.164 (95% confidence interval: 1.117 to 1.213) for CVD mortality. The slopes of concentration-response functions of PM2.5 exposure and CVD risks were steeper at high PM2.5 levels. In addition, older residents, rural residents, and never smokers were more prone to adverse effects of PM2.5 exposure. Conclusions This study provides evidence that elevated long-term PM2.5 exposures lead to increased CVD risk in China. The effects are more pronounced at higher PM2.5 levels. These findings expand the current knowledge on adverse health effects of severe air pollution and highlight the potential cardiovascular benefits of air quality improvement in China and other low- and middle-income countries.

This meta-analysis was performed to quantitatively evaluate the dose-response association between obstructive sleep apnea (OSA) and risk of type 2 diabetes mellitus (T2DM).PubMed, Embase, and Web of Science were searched up to 12 December 2018 for articles that assessed the OSA-T2DM association. Random effects models were used to analyze the quantitative association between OSA and risk of T2DM. Restricted cubic splines were used to model the dose-response association between apnea-hypopnea index (AHI), used to assess the severity of OSA according to events/h, and risk of T2DM.We included 16 cohort studies in our meta-analysis. During a median follow-up of 10.5 years (range: 3.0-22.0), 19 355 T2DM cases were reported among 338 912 study participants. The pooled relative risk of T2DM was 1.40 (95% CI, 1.32-1.48) for OSA in the binary meta-analysis and 1.08 (1.01-1.14) for each 5-event/h increase in AHI value. We found a positive linear association between OSA and T2DM risk.Our dose-response meta-analysis revealed a linear association between OSA and T2DM.背景: 该研究对阻塞性睡眠呼吸暂停综合征(obstructive sleep apnea, OSA)和2型糖尿病发病风险的关系进行定量评价, 并探索其潜在的剂量-反应关系。 方法: 检索PubMed、Embase和 Web of Science数据库中2018年12月12日前发表的关于OSA和2型糖尿病的相关性研究。采用随机效应模型定量分析OSA和2型糖尿病发病风险的关系。通过限制性立方样条模型评估呼吸暂停低通气指数(基于次数/小时评价OSA严重程度的指标)和2型糖尿病发病风险的剂量-反应关系。 结果: 本研究共纳入16个队列研究, 包括研究对象 338,912人, 随访时间为中位数10.5年(范围为3.0-22.0年), 随访期间19,355名研究对象确诊2型糖尿病。二元meta分析显示OSA使2型糖尿病的发病相对风险度为1.40 ( 95%CI:1.32-1.48), 呼吸暂停低通气指数每增加5次/小时, 2型糖尿病的发病相对风险度为1.08(95%CI:1.01-1.14)。OSA与2型糖尿病的发病风险成线性正相关。 结论: OSA的严重程度和2型糖尿病的发病风险有关, 且存在线性剂量-反应关系。.

Background The association of psychological factors with postoperative pain has been well documented. The incorporation of psychoeducational intervention into a standard analgesia protocol seems to be an attractive approach for the management of acute postoperative pain. Our study aimed to evaluate the impact of psychoeducational intervention on acute postoperative pain in pulmonary nodule (PN) patients treated with thoracoscopic surgery. Methods In this study, 76 PN patients treated with thoracoscopic surgery and intravenous patient-controlled analgesia (IV-PCA) plus psychoeducational evaluation and intervention were selected as the psychoeducational intervention group (PG). Another 76 PN patients receiving IV-PCA without psychoeducational intervention after thoracoscopic surgery, treated as the control group (CG), were identified from the hospital database and matched pairwise with PG patients according to age, sex, preoperative body mass index (BMI), opioid medications used for IV-PCA and the educational attainment of patients. Results The most common psychological disorders were anxiety and interpersonal sensitivity, which were recorded from 82.9% (63/76) and 63.2% (48/76) of PG patients. The numerical rating scale (NRS) pain scores of the PG patients were significantly lower than those of the CG patients at 2 and 24 h after surgery (P P = 0.038). PG patients had a significantly lower incidence of rescue analgesia than CG patients (28.9% vs. 44.7%, P = 0.044). Nausea/vomiting was the most common side effect of opioid medications, recorded for 3 (3.9%) PG patients and 10 (13.2%) CG patients (P = 0.042). In addition, no significant difference was observed between PG and CG patients in terms of grade 2 or higher postoperative complications (10.5% vs. 17.1%, P = 0.240). Conclusions Psychoeducational intervention for PN patients treated with thoracoscopic surgery resulted in reduced acute postoperative pain, less opioid consumption and fewer opioid-related side effects.

Jianfeng Huang,* Wenzheng Chen,* Changyu Chen,* Zhigang Jie, Tao Xiao Department of Gastrointestinal Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhigang Jie; Tao Xiao, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Nanchang University, No. 1519 Dongyue Road, Nanchang, 330006, Jiangxi, People’s Republic of China, Email Jiezg123@126.com; xiaotao@ncu.edu.cnPurpose: N6-methyladenosine (m6A) RNA modification plays an important role in regulating tumor microenvironment (TME) infiltration. However, the relationship between the expression pattern of m6A-related long non-coding RNAs (lncRNAs) and the immune microenvironment of gastric cancer (GC) is unclear.Methods: In this study, 23 m6A-related lncRNAs were identified by Pearson’s correlation analysis and univariate Cox regression analysis. According to the expression of these lncRNAs, we identified two distinct molecular clusters by consensus clustering and compared the differences of the TME and enriched pathways between the two clusters. We further constructed a prognostic risk signature and verified it using The Cancer Genome Atlas training and testing cohorts.Results: The results showed that cluster 1 was associated with tumor-related and immune activation-related pathways. In addition, cluster 1 was also associated with higher ImmuneScore, StromalScore, and ESTIMATEScore. The results of the stratified survival analysis and independent prognosis analysis indicated that the risk signature is an independent prognostic indicator for patients with GC. In addition, it can effectively predict survival status in patients with different clinical characteristics. Furthermore, we found that the risk signature was associated with a variety of tumor-infiltrating immune cells, and that low risk scores were significantly correlated with high expression of programmed death-1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4), as well as sensitivity to chemotherapeutic drugs (eg, fluorouracil and oxaliplatin).Conclusion: This evidence contributes to our understanding of the regulation of TME infiltration by m6A-related lncRNAs and may lead to more effective immunotherapy and chemotherapy for patients with GC.Keywords: N6-methyladenosine, gastric cancer, tumor microenvironment, lncRNA risk signature, prognostic

Simple Summary There is strong evidence that locally advanced human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) carries a significantly better prognosis than HPV negative OPSCC, suggesting the possibility of treatment de-escalation and, therefore, toxicity reduction in this patient population. The lack of success in clinical trials towards this end presses the need to risk stratify locally advanced HPV+ OPSCC patients who can safely have treatment de-escalated. The present study had recourse to radiomics for this purpose and showed that radiomics has the ability to discriminate patients with locally advanced HPV+ OPSCC who went on to develop distant metastasis after completion of definitive chemoradiation or radiation alone. The implications of this study aid in demonstrating the potential pivotal role of radiomics in predictive risk assessment and personalizing therapy for this patient population. Abstract (1) Background and purpose: clinical trials have unsuccessfully tried to de-escalate treatment in locally advanced human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) with the goal of reducing treatment toxicity. The aim of this study was to explore the role of radiomics for risk stratification in this patient population to guide treatment. (2) Methods: the study population consisted of 225 patients with locally advanced HPV+ OPSCC treated with curative-intent radiation or chemoradiation therapy. Appearance of distant metastasis was used as the endpoint event. Radiomics data were extracted from the gross tumor volumes (GTVs) identified on the planning CT, with gray level being discretized using three different bin widths (8, 16, and 32). The data extracted for the groups with and without distant metastasis were subsequently balanced using three different algorithms including synthetic minority over-sampling technique (SMOTE), adaptive synthetic sampling (ADASYN), and borderline SMOTE. From these different combinations, a total of nine radiomics datasets were derived. Top features that minimized redundancy while maximizing relevance to the endpoint were selected individually and collectively for the nine radiomics datasets to build support vector machine (SVM) based predictive classifiers. Performance of the developed classifiers was evaluated by receiver operating characteristic (ROC) curve analysis. (3) Results: of the 225 locally advanced HPV+ OPSCC patients being studied, 9.3% had developed distant metastases at last follow-up. SVM classifiers built for the nine radiomics dataset using either their own respective top features or the top consensus ones were all able to differentiate the two cohorts at a level of excellence or beyond, with ROC area under curve (AUC) ranging from 0.84 to 0.95 (median = 0.90). ROC comparisons further revealed that the majority of the built classifiers did not distinguish the two cohorts significantly better than each other. (4) Conclusions: radiomics demonstrated discriminative ability in distinguishing patients with locally advanced HPV+ OPSCC who went on to develop distant metastasis after completion of definitive chemoradiation or radiation alone and may serve to risk stratify this patient population with the purpose of guiding the appropriate therapy.

Worldwide, the incidence rate of gastric cancer ranks fifth, and the mortality rate of gastric cancer ranks third among all malignant tumors. However, the pathogenesis of gastric cancer remains poorly understood. In this study, we demonstrated that the expression level of NELFE is higher in human gastric cancer tissues than in adjacent nontumor tissues. A high level of NELFE is associated with worse postoperative overall survival (OS) and relapse-free survival (RFS) rates in patients with gastric cancer. Moreover, the expression of NELFE is correlated with high tumor grade and lymph node metastasis in gastric cancer patients. Knockdown of NELFE dramatically inhibits the cell proliferation and metastasis of gastric cancer xenografts in vivo. Furthermore, we found that NELFE binding to the 3’UTR of E2F2 affects the mRNA stability of E2F2 to regulate the expression level of E2F2. In gastric cancer, E2F2 also acts as an oncogene to inhibit the proliferation and migration of gastric cancer cells by knocking down the expression level of E2F2. However, overexpressing E2F2 in cells with NELFE knockdown significantly reverses the inhibition of cell proliferation and migration induced by NELFE knockdown. Therefore, NELFE at least partially functions as an oncogene through E2F2. Moreover, CIBERSORTx analysis of the proportion of tumor-infiltrating immune cells (TICs) revealed that immune cells are correlated with NELFE and E2F2 expression, suggesting that NELFE and E2F2 might be responsible for the preservation of the immunodominant status for gastric cancer. In conclusion, NELFE acts as an oncogene in gastric cancer and can be used as a potential therapeutic target.

Although emerging researches have linked ambient fine particulate matter (PM(2.5)) to obesity, evidence from high-polluted regions is still lacking. We thus assessed the long-term impacts of PM(2.5) on body mass index (BMI) and the risk of the prevalence of overweight/obesity (BMI≥25 kg/m(2)), by incorporating the well-established Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project comprising 77,609 participants with satellite-based PM(2.5) estimates at 1-km spatial resolution. The average of long-term PM(2.5) level was 70.4 μg/m(3), with the range of 32.1–94.2 μg/m(3). Each 10 μg/m(3) increment of PM(2.5) was associated with 0.421 kg/m(2) (95% confidence interval [CI]: 0.402, 0.439) and 13.5% (95% CI: 12.8%, 14.3%) increased BMI and overweight/obesity risk, respectively. Moreover, compared with the lowest quartile of PM(2.5) (≤57.5 μg/m(3)), the relative risk of the prevalence of overweight/obesity from the highest quartile (>85.9 μg/m(3)) was 1.611 (95% CI: 1.566, 1.657). The exposure-response curve suggested a non-linear relationship between PM(2.5) exposure and overweight/obesity. Besides, the association was modified by age, diabetes mellitus, hypertension and dyslipidemia status. Our study provides the evidence for the adverse impacts of long-term PM(2.5) on BMI and overweight/obesity in China, and the findings are important for policy development on air quality, especially in severely polluted areas.

Objective We aimed to evaluate whether hypertriglyceridemic waist-to-height ratio (HWHtR) and its dynamic status was associated with hypertension (HTN). Methods We examined data for 10 312 nonhypertensive participants aged at least 18 years from the Rural Chinese Cohort Study at the baseline examination who were followed until 2014 with a median follow-up of 6 years. HWHtR was defined by combined triglyceride level and waist-to-height ratio (WHtR). Multiple logistic regression models were used to examine the probability of incident HTN according to HWHtR and its transformation, estimating odds ratios (ORs) and 95% confidence intervals (CIs). Results A total of 127 men and 225 women with high triglyceride level and high WHtR (HTHWH) had incident HTN during follow-up. After adjusting for potential confounders, the probability of HTN was increased with HTHWH for men [OR 1.49 (95% CI 1.01-2.20)] but this association was not significant for women [1.21 (0.88-1.66)]. The results of the sensitivity analyses were robust for men and women. The ORs were generally consistent on subgroup analysis by age,BMI, SBP and DBP for men. As compared with persistent normal triglyceride level and normal WHtR (NTNWH), the transformation from baseline NTNWH to follow-up HTHWH was associated with increased probability of HTN for men [OR 4.16 (95% CI 2.21-7.84)]. However, for women, the association of changed HWHtR from baseline to follow-up with probability of HTN was not significant for almost all transformation groups. Conclusion HWHtR and its dynamic status was associated with incident HTN for rural Chinese men. From this cohort study, HWHtR may be an indicator for interventions aiming to reduce HTN among these men.

Background and Purpose— Previous results on the association between lipids and stroke were controversial. We investigated the association of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C ), high-density lipoprotein cholesterol (HDL-C), and triglyceride with stroke. Methods— Six cohort studies in China with 267 500 participants were included. Cox proportional hazards regression models and restricted cubic spline analyses were used to estimate hazard ratios and 95% CIs and explore linear and nonlinear relationships of lipids and stroke, respectively. Results— The median follow-up duration ranged from 6 to 19 years. During 2 295 881 person-years, 8072 people developed stroke. Multivariable adjusted hazard ratios (95% CIs) per 1 mmol/L increase in TC, LDL-C, triglyceride were 1.08 (1.05–1.11), 1.08 (1.04–1.11), 1.07 (1.05-1.09) for ischemic stroke, respectively. Compared with participants with TC 160-199.9 mg/dL, hazard ratios (95% CIs) were 1.43 (1.11–1.85) for hemorrhagic stroke in those with TC P P =0.029 and P >0.05). Conclusions— TC, LDL-C, and triglyceride showed positive associations with ischemic stroke. The risk of hemorrhagic stroke was higher when TC was lower than 120 mg/dL. LDL-C and triglyceride showed no association with hemorrhagic stroke. The risks of ischemic and hemorrhagic stroke might be higher when HDL-C was lower than 50 mg/dL.

Classification of species at the individual tree level would be beneficial to many applications including forest landscape visualization, forest management, and biodiversity monitoring. This article develops a patch-based classification algorithm of individual tree species based on convolutional neural network. The individual trees are first detected using the local maximum method from the canopy height model, as derived from light detection and ranging (LiDAR) data. The detected individual trees are then cropped into patches for classification based on the tree apexes, and three spatial scale image patches are chosen for analysis and discussion. A modified ResNet50 deep network is further employed for the cropped individual tree patches classification. The patch-based method accounts for the contexture information of a tree and does not require the feature selection or the feature reduction processes. About 1388 training samples including Ficus microcarpa Linn. f., Delonix regia , Chorisia speciosa A.St.-Hil., Dimocarpus longan Lour., Musa nana Lour., Carica papaya , and Others (the other tree species except the above six) were collected from both field work and visual interpretation. Aerial images, LiDAR data, and Worldview images were used for the tree species classification. For 362 test tree samples, the results of patch size 64 achieve the best accuracies, and the proposed method outperforms the traditional machine learning method with the overall accuracy of 89.06% + 0.58% using aerial images only. Transferability Study to the Luhu Park also indicated the feasibility of our method. While challenges in individual tree detection and multisource data fusion remain, the solution shows the potential in characterizing tree species at the individual tree level using remote sensing data.

Objective To evaluate the impact of systematic nutrition management (SNM) on nutritional status, treatment-related toxicity, quality of life (QoL), response rates, and survival in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) treated by radiotherapy (RT). Methods In this retrospective study, 56 patients with LA-NPC were selected as nutrition management group (NG) for SNM during RT till 1 month later. Another 56 patients with LA-NPC receiving RT without SNM as control group (CG) were identified from the hospital database and matched pairs with NG patients according to age, gender, stage, and body mass index (BMI) prior to RT. Results At 1 month after RT, the percentage of malnourished patients with BMI 0.05) for the 2-year progression-free survival and overall survival (84.2% versus 79.5% and 94.7% versus 92.3%, respectively.). Conclusion SNM for LA-NPC patients treated by RT resulted in better nutritional status, reduced treatment-related toxicity and improved QoL.

Primary ciliary dyskinesia (PCD) is a rare phenotypically and genetically heterogeneous disorder resulting from abnormal cilia ultrastructure and function. Few studies have reported the phenotype and genetic characteristics of PCD caused by mutations in DNAAF3. In this study, four PCD patients with DNAAF3 mutations underwent extensive clinical assessments, cilia ultrastructural and motion evaluations. All patients presented with situs inversus totalis, neonatal respiratory distress, and sinusitis; however, they did not have recurrent infections of the lower airways. The nasal nitric oxide level of these patients was markedly reduced. The respiratory cilia were found to be uniformly immotile, with their dynein arms defects. A total of 7 (5 novel) variants in DNAAF3 were identified and cosegregated in their families by Trio-based whole-exome sequencing. As the first report on DNAAF3 mutations in PCD patients in China, our study not only contributes to a deeper appreciation of the phenotypic characteristics of patients with DNAAF3 mutations but also expands the spectrum of DNAAF3 mutations and may contribute to the genetic diagnosis of and counseling for PCD.

Vertically aligned nanocrystalline films with heterojunctions have attracted much attention as gas sensors because they provide high efficient transport pathways for carriers and large surface area with high activity for adsorption. In this work, a heterogeneous CoTiO3/TiO2 film is prepared by radio frequency sputtering TiO2 on prefabricated CoTiO3 film with a post annealing process. The vertically aligned nanocrystalline surface is achieved by atom inter diffusion and growth competition of the two phases. The obtained CoTiO3/TiO2 film shows nano-columnar arrays structure with dominant (104) orientation. As a humidity sensor, the film shows ultra-high response with fast response/recovery and good stability. The response value reaches 157.23 to 95% relative humidity, which is 38 times that of the pristine CoTiO3 film. Such excellent sensing performance is attributed to the corporation of vertically aligned nanocrystalline surface, advanced hydrophilicity and uniformly distributed heterojunctions.

Automated extraction of buildings from remotely sensed data is important for a wide range of applications but challenging due to difficulties in extracting semantic features from complex scenes like urban areas. The recently developed fully convolutional neural networks (FCNs) have shown to perform well on urban object extraction because of the outstanding feature learning and end-to-end pixel labeling abilities. The commonly used feature fusion or skip-connection refine modules of FCNs often overlook the problem of feature selection and could reduce the learning efficiency of the networks. In this paper, we develop an end-to-end trainable gated residual refinement network (GRRNet) that fuses high-resolution aerial images and LiDAR point clouds for building extraction. The modified residual learning network is applied as the encoder part of GRRNet to learn multi-level features from the fusion data and a gated feature labeling (GFL) unit is introduced to reduce unnecessary feature transmission and refine classification results. The proposed model - GRRNet is tested in a publicly available dataset with urban and suburban scenes. Comparison results illustrated that GRRNet has competitive building extraction performance in comparison with other approaches. The source code of the developed GRRNet is made publicly available for studies.

Purpose: Lung adenocarcinoma (LUAD) is a main subtype of lung cancer, which is the leading cause of cancer-related deaths. The five-year survival rates of lung cancer patients are still comparatively low. Therefore, potential therapeutic targets are urgently needed to improve the survival of lung cancer patients. In this study, we identified FAM111B as an oncogene and potential therapeutic target for LUAD. Methods: The TCGA database and tissue microarray analysis were used to compare the expression of FAM111B in tumor tissue and normal tissues and evaluate the relationship between FAM111B expression and clinical survival. FAM111B was knocked down and overexpressed to observe whether FAM111B could affect the proliferation, migration, cell cycle, and apoptosis of LUAD cells in vivo and in vitro. Results: FAM111B was highly expressed in tumor tissues compared with normal tissues (P

Elevated resting heart rate (RHR) is associated with risk of type 2 diabetes mellitus (T2DM). However, the association of change in RHR (ΔRHR) and incident T2DM is not fully elucidated. We aimed to assess the dose-response association between 6-year ΔRHR and T2DM.A total of 12155 non-T2DM participants ≥18 years old were enrolled during 2007-2008 and followed up during 2013-2014. ΔRHR was calculated by subtracting the baseline RHR from the RHR value at 6-year follow-up. Age-, sex-, and RHR-specific relative risks (RRs) and 95% confidence intervals (CIs) for the effect of ΔRHR on incident T2DM were calculated by using modified Poisson regression models. As compared with ΔRHR of 0 beats/min, the adjusted risk of T2DM was significantly increased with RHR increment and reduced with RHR reduction. ΔRHR was positively associated with future risk of T2DM [RR per unit increase: 1.03 (1.03-1.04)]. As compared with stable change in RHR group (-5ΔRHR5 beats/min), for ΔRHR ≤ -10 beats/min, -10ΔRHR ≤ -5 beats/min, 5≤ΔRHR10 beats/min, and ΔRHR ≥10 beats/min groups, the pooled adjusted RR (95% CI) of T2DM was 0.69 (0.55-0.86), 0.90 (0.73-1.11), 1.31 (1.07-1.61), and 1.90 (1.59-2.26), respectively. This significant association still existed on subgroup analyses based on age, sex, and baseline RHR and sensitivity analyses.Dynamic RHR change was significantly associated with incident T2DM. Our study suggests that RHR may be a non-invasive clinical indicator for interventions aiming to reduce incident T2DM in the general population.

Background Although cancer has become one of the leading health burdens, to the authors' knowledge, evidence regarding its relationship with a healthy lifestyle in the Chinese population remains limited. Methods The authors evaluated the association between clustering of healthy lifestyle factors and cancer risk using 3 prospective cohort studies with 101,208 Chinese adults from the general population. Hazard ratios (HRs) and corresponding 95% confidential intervals (95% CIs) related to healthy lifestyle factors were calculated using Cox proportional hazard models, and population-attributable risk percentages were estimated further. Results The results demonstrated that each additional healthy lifestyle factor was associated with a 6% (range, 3%-9%) lower risk of overall cancer. Compared with having none to 3 healthy lifestyle factors, HRs related to adherence to all 6 healthy lifestyle factors were 0.78 (95% CI, 0.60-1.02) and 0.82 (95% CI, 0.67-1.00), respectively, for men and women. It was estimated that approximately 18.4% and 2.3%, respectively, of overall cancer cases for men and women were attributable to nonadherence to all 6 healthy lifestyle factors. Conclusions The results of the current study indicate that adherence to clustering of healthy lifestyle factors was associated with a reduced risk of cancer incidence among Chinese adults. Greater efforts urgently are needed to promote the adoption of multiple healthy lifestyle behaviors to reduce the increasing burden of cancer.

Background: \ud Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene.\ud \ud Objectives: \ud This study sought to test the association between the rs9349379 genotype and SCAD.\ud \ud Methods: \ud Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD.\ud \ud Results: \ud The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence.\ud \ud Conclusions: \ud The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD.

Previous studies revealed that fine particulate matter (PM 2.5 ) exposure adversely affected blood pressure (BP), but factors that might attenuate this association were still unclear. Using a multicenter panel study among 277 hypertensive participants with intermediate-to-high risk of cardiovascular disease from 4 cities in China, we aimed to explore whether BP control status and antihypertensive medications were potential modifying factors. Each participant carried personal-portable monitors to record individual real-time PM 2.5 levels and 24-hour ambulatory BP up to 3× within 1 year. Generalized linear mixed model with individual-specific random intercept was used to assess effect sizes. We identified adverse impacts of short-term PM 2.5 exposure on BP. However, these impacts were attenuated among patients with controlled BP. For example, per interquartile range (43.78 µg/m 3 ) increment in the prior 10-hour moving average of PM 2.5 , systolic BP increased −0.20 (95% CI, −0.57 to 0.18) mm Hg and 0.85 (95% CI, 0.36–1.35) mm Hg among those with controlled and uncontrolled BP, respectively ( P interaction , 0.0009). Furthermore, among those with uncontrolled BP, treatment with angiotensin receptor blocker would potentially lower BP in responses to PM 2.5 , with systolic BP associated with per interquartile range increment in 10-hour moving average PM 2.5 of 0.32 (95% CI, −0.37 to 1.00) mm Hg and 1.53 (95% CI, 0.74–2.33) mm Hg among those taking angiotensin receptor blocker or not, respectively ( P interaction , 0.0229). In conclusion, although PM 2.5 exposure would increase BP, keeping well-controlled BP status and using angiotensin receptor blockers might attenuate these adverse impacts, which might provide supporting evidence for guiding hypertensive patients who live in areas with high level of PM 2.5 .

Introduction Studies investigating the effect of high-density lipoprotein cholesterol (HDL-C) on stroke and stroke subtypes have reached inconsistent conclusions. The purpose of our study was to clarify the dose–response association between HDL-C level and risk of total stroke and stroke subtypes by a systematic review and meta-analysis. Methods We performed a systematic search of PubMed, Embase, and Web of Science databases through July 30, 2020, for prospective cohort studies that reported the HDL-C–stroke association and extracted the estimate that was adjusted for the greatest number of confounding factors. Restricted cubic splines were used to evaluate the linear and nonlinear dose–response associations. Results We included 29 articles, which reported on 62 prospective cohort studies including 900,501 study participants and 25,678 with stroke. The summary relative risk per 1-mmol/L increase in HDL-C level for total stroke was 0.82 (95% CI, 0.76–0.89; I 2 = 42.9%; n = 18); ischemic stroke (IS), 0.75 (95% CI, 0.69–0.82; I 2 = 50.1%; n = 22); intracerebral hemorrhage (ICH), 1.21 (95% CI, 1.04–1.42; I 2 = 33.4%; n = 10); and subarachnoid hemorrhage (SAH), 0.98 (95% CI, 0.96–1.00; I 2 = 0%; n = 7). We found a linear inverse association between HDL-C level and risk of total stroke and SAH, a nonlinear inverse association for IS risk, but a linear positive association for ICH risk. The strength and the direction of the effect size estimate for total stroke, IS, ICH, and SAH remained stable for most subgroups. We found no publication bias with Begg’s test and Egger’s test for the association of HDL-C level with risk of total stroke, IS, and ICH. Conclusion A high HDL-C level is associated with reduced risk of total stroke and IS and an increased risk of ICH.

Aims. To compare the relationship between the nonperfusion area (NPA) on ultra-widefield fluorescein angiography (UWFFA) and the nonflow area (NFA) on optical coherence tomographic angiography (OCTA) in retinal vein occlusion (RVO). Methods. Cross-sectional study. 46 eyes of 46 RVO patients who underwent UWFFA and OCTA. NPA and ischemic index (ISI) were quantified on UWWFA. NFA, vessel density (VD) of the superficial capillary plexus (SCP), the deep capillary plexus (DCP), and the size foveal avascular zone (FAZ) on 3 ∗ 3 mm OCTA were measured. The association of the NPA and ISI on UWWFA and the parameters on OCTA were analyzed. Spearman correlation was used for statistical testing. Results. The NPA and ISI on UWFFA were significantly correlated with the NFA on OCTA in RVO, and r values were 0.688 ( p < 0.01 ) and 0.680 ( p < 0.01 ), respectively. VD in the SCP of the temporal quadrant was negatively correlated with NPA and ISI, and r values were −0.346 ( p < 0.05 ) and −0.337 ( p < 0.05 ), respectively. VD in the DCP of the temporal quadrant was negatively correlated with the NPA, and the r value was −0.246 ( p < 0.05 ). No significant correlation was found between the NPA and ISI on UWFFA and VD of other quadrants in the SCP or DCP and the FAZ area on OCTA. Conclusion. NPA in the peripheral retina was correlated with NFA in macula. NFA detected by OCTA could be an indicator of the ischemic status in RVO.

As one of the essential indicators for the development of a city, urban vibrancy plays an important role in evaluating the quality of urban areas and guiding urban construction. The development of spatial big data makes it possible to obtain information on user trajectories and the built environment, providing support for the evaluation of urban vibrancy. However, previous studies focused on the number of regional activities when evaluating urban vibrancy and ignored diversity, which was produced by diverse economic landscapes. In this paper, using mobile phone trajectory data, we propose a method for evaluating urban vibrancy from two dimensions: busyness and diversity, based on the improved PageRank algorithm and an index of entropy. Furthermore, in order to explore the relationship between urban vibrancy and the economic landscape, we construct an economic landscape index system based on multi-source data, including points of interest (POIs), roads, building footprints, house prices, the gross domestic product (GDP), and population data. Then, multiple linear regression is utilized to model the relationship between urban vibrancy and the urban economic landscape. The results show that combining busyness and diversity can better characterize urban vibrancy than any single indicator, and the adjusted R-squared (R2) of the regression with economic landscape reaches 0.59.

Background World Health Organization (WHO) released region-specific cardiovascular disease (CVD) risk prediction charts recently, but the extent to which the charts can apply to Chinese population is unknown. We aimed to validate the WHO CVD risk charts for East Asia, and evaluate their practicability combining with China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) equations among Chinese adults. Methods The China-PAR cohort with 93,234 participants aged 40–80 years was followed up during 1992–2015, including 29,337 participants from three sub-cohorts with follow-up period of over 10 years. We validated the WHO CVD risk charts using the China-PAR cohort by assessment of the predicted number of events, C index, calibration χ², and calibration plots, further elaborated the concordance between the China-PAR equations and the WHO risk charts. Findings During an average follow-up of 13•64 years, 1849 incident CVD cases were identified from 29,337 participants. Both the laboratory-based and non-laboratory-based charts overestimated CVD events by 59% and 58% in men, and by 72% and 85% in women, respectively. However, 92% of participants identified as high risk by the China-PAR equations could be successfully detected by the laboratory-based charts at the cut-off point of 10%. We also observed that the non-laboratory-based charts demonstrated the poor performance for diabetic population, with high proportion of high-risk individuals (17% for men, 31% for women) would be missed. Interpretation Although the WHO CVD risk charts for East Asia apparently overestimated CVD risk among Chinese population, they could be pragmatic pre-selection tools, as potential supplement to the China-PAR equations. The widespread use of the WHO risk charts along with the China-PAR equations might facilitate the implementation of the risk-based CVD prevention in China. Funding Full funding sources are listed at the end of the paper (see Acknowledgments).

Background Glycine-N-acyltransferase-like 1 (GLYATL1), which is involved in the detoxification of endogenous and exogenous acyl-CoA, promotes glutamine metabolism in xenobiotic metabolism. Recent evidence suggests an association between GLYATL1 and tumors. However, there are few comprehensive analyses of GLYATL1 in cancers. We evaluated the expression and prognostic value of GLYATL1 and explored the mechanism underlying the association between GLYATL1 and cancers. Methods GLYATL1 mRNA expression across cancers was investigated in the Oncomine database and confirmed in the UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) databases. Next, its prognostic value in different cancers was revealed by PrognoScan and Kaplan-Meier plotter. According to clinicopathologic features, we conducted a subgroup analysis of the prognosis of GLYATL1 in a cohort of hepatocellular carcinoma (HCC) patients from The Cancer Genome Atlas (TCGA) and the GSE116174 dataset. We further investigated the GLYATL1 promoter methylation profile in HCC. Next, a protein-protein interaction (PPI) network was constructed via the Search Tool for the Retrieval of Interacting Genes (STRING) database. Finally, we utilized gene set enrichment analysis (GSEA) to identify significantly enriched pathways and confirmed their associations using the Tumor Immune Estimation Resource (TIMER) and GEPIA databases. Results GLYATL1 is downregulated in many cancers and indicates a poor prognosis. Specifically, low GLYATL1 expression was associated with short overall survival (OS) in HCC patients. Interestingly, GLYATL1 expression was associated with poor OS in stage I-II HCC patients and was revealed as an independent prognostic factor. The promoter methylation level of GLYATL1 in HCC tissue was significantly higher than that in normal liver tissue. The PPI network suggested that GLYATL1 is co-expressed with ten genes, including CNGA3 and GNB5. GSEA revealed that GLYATL1 is predominantly negatively enriched in xenobiotic metabolism, and the gene association analysis in TIMER and GEPIA showed a significantly negative association between the expression of GLYATL1 and the expression of most genes involved in mitochondrial glutamine metabolism, including SLC1A5 and SLC1A11. Conclusions Our study is the first to shed light on the expression and prognostic value of GLYATL1 in cancers and provide a potential regulatory mechanism underlying HCC development.

Highlights • Sedentary behavior is associated with higher risks of cancer incidence, cancer mortality and all-cause mortality, as well as earlier onset of cancer and shorter life expectancy, among the Chinese population. • J-shaped dose–response relationships were observed between daily sedentary time and risks of cancer incidence and mortality, and the lowest risks were seen at 6 h/day. • Significant adverse effects of sedentary behavior on cancer incidence and mortality are independent of the level of moderate-to-vigorous physical activity. • The present study indicates that a reduction in sedentary behavior, in addition to an increase in physical activity, is recommended for the prevention of cancer and mortality., Background Inconsistent results have been reported in developed countries for relationships between sedentary behavior and cancer incidence and mortality, and evidence from the Chinese population is scarce. This study aimed to investigate such relationships in large Chinese population-based prospective cohorts and to explore the joint effect and interaction of sedentary behavior and moderate-to-vigorous physical activity (MVPA) on these relationships. Methods We included 95,319 Chinese adults without cancer from 3 large cohorts and assessed their sedentary behavior and physical activity with a unified questionnaire. Cancer incidence and mortality were confirmed by interviewing participants or their proxies and checking hospital records and death certificates. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) for cancer and mortality were estimated using Cox proportional hazards regression models. Results During 559,002 person-years of follow-up, 2388 cancer events, 1571 cancer deaths, and 4562 all-cause deaths were recorded. Sedentary behavior was associated with increased risk of developing cancer and deaths in a dose–response manner. The multivariable-adjusted HRs (95%CIs) were the following: HR = 1.16, 95%CI: 1.01‒1.33; HR = 1.24, 95%CI: 1.04‒1.48; and HR = 1.15, 95%CI: 1.04‒1.28 for cancer incidence, cancer mortality, and all-cause mortality, respectively, for those having ≥10 h/day of sedentary time compared with those having, Graphical abstract Image, graphical abstract

Background: Pharmacologic targeting of components of the MAPK/ERK pathway in differentiated thyroid carcinoma (DTC) is often limited due to the development of adaptive resistance. However, the detailed mechanism of MEK inhibitor (MEKi) resistance is not fully understood. Methods: RNA-seq of the constructed MEKi-resistant DTC cell line BCPAP-R (compared with the BCPAP line) was performed to investigate the intrinsic mechanism of drug resistance. Colony formation assays, cell viability assays, and cell cycle analysis were performed, and various murine models, including xenograft models, long-term MEKi-treated models, and transgenic model were used to evaluate the treatment effect of combination therapy (SHP099 and selumetinib). Findings: MEKi-resistant models were constructed successfully, in which multiple receptor tyrosine kinases (RTKs) signaling pathways and Src-homology 2 domain-containing phosphatase 2 (SHP2) were activated in MEKi-resistant cells. Given the physiological role of SHP2 as the downstream target of many RTKs, we first found that blockade of SHP2 enhanced the sensitivity to MEKi in constructed MEKi-resistant thyroid cancer models (including constructed cell lines and a long-term MEKi-treated murine model). Interestingly, we also found that compared with MEKi treatment alone, MEKi in combination with an SHP2 inhibitor markedly suppressed the reactivation of the MEK/ERK pathway; thus, the addition of the SHP2 inhibitor significantly improved the anti-tumor effects of MEKi. The synergistic suppression of DTC upon treatment with both inhibitors was futher confirmed in xenograft models and transgenic models. Interpretation: RTKs activation leads to reactivation of the MAPK pathway and resistance to MEKi in DTC, which is reversed by SHP2 blockade. As a novel active inhibitor of SHP2, SHP099 in combination with selumetinib is a promising therapeutic approach for advanced DTC and MEKi-resistant one. Funding Statement: This work was partially supported by grants from the National Natural Science Foundation of China (GRANT no. 81872169), Tianjin Key Research and Development Program Science and Technology Support Key Projects (grant no. 17YFZCSY00690), and Tianjin Municipal Science and Technology Project (grant no. 19JCYBJC27400). Declaration of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethics Approval Statement: All animal experiments were approved by the Tianjin Medical University Cancer Institute and the Hospital Animal Care and Use Committee and performed according to the IACUC protocol.

Background. The tumor microenvironment (TME) is associated with disease outcomes and treatment response in colon cancer. Here, we constructed a TME-related gene signature that is prognosis of disease survival and may predict response to immunotherapy in colon cancer. Methods. We calculated immune and stromal scores for 385 colon cancer samples from The Cancer Genome Atlas (TCGA) database using the ESTIMATE algorithm. We identified nine TME-related prognostic genes using Cox regression analysis. We evaluated associations between protein expression, extent of immune cell infiltrate, and patient survival. We calculated risk scores and built a clinical predictive model for the TME-related gene signature. Receiver operating characteristic (ROC) curves were generated to assess the predictive power of the signature. We estimated the half-maximal inhibitory concentration (IC50) of chemotherapeutic drugs in patients using the pRRophetic algorithm. The expression of immune checkpoint genes was evaluated. Results. High immune and stromal scores are significantly associated with poor overall survival ( p < 0.05 ). We identified 773 differential TME-related prognostic genes associated with survival; these genes were enriched in immune-related pathways. Nine key prognostic genes were identified and were used to construct a TME-related prognostic signature: CADM3, LEP, CD1B, PDE1B, CCL22, ABI3BP, IGLON5, SELE, and TGFB1. This signature identified a high-risk group with worse survival outcomes, based on Kaplan-Meier analysis. A nomogram composed of clinicopathological factors and risk score exhibited good accuracy. Drug sensitivity analysis identified no difference in sensitivity between the high-risk and low-risk groups. High-risk patients had higher expression of PD-1, PDL-1, and CTLA-4 and lower expression of LAG-3 and VSIR. Infiltration of dendritic cells was higher in the high-risk group. Conclusions. We identified a novel prognostic TME-related gene expression signature in colon cancer. Stratification of patients based on this gene signature could be used to improve outcomes and guide better therapy for colon cancer patients.

Background While the relationship between ambient air pollution and diabetes mellitus has recently been reported, data on the association between fine particulate matter (PM2.5) and diabetic complications are limited, especially in microvascular diseases such as diabetic retinopathy. Objectives To investigate the associations between long-term exposure to PM2.5 and the prevalence of diabetic retinopathy in adult diabetic patients in rural China. Methods The study population was based on the Rural Epidemiology for Glaucoma in China (REG-China), a national cross-sectional survey conducted in rural China. This analysis selected diabetic patients with or without diabetic retinopathy. A satellite-based spatiotemporal model was used to estimate personal PM2.5 exposure. Logistic regression models were used to investigate the effect of long-term PM2.5 exposure on diabetic retinopathy. Results The analysis included 3111 diabetic participants, 329 of whom were diagnosed with diabetic retinopathy. The median level of exposure to PM2.5 from 2000 to2016 was 59.9 μg/m3. For each 10 μg/m3 increase in PM2.5, the adjusted odds ratio (95% confidence interval) for diabetic retinopathy was 1.41 (1.27, 1.57). In subgroup analyses, the effect of PM2.5 on diabetic retinopathy was significantly stronger in participants who self-reported alcohol consumption. Conclusion These findings suggest that long-term exposure to high PM2.5 was associated with the risk of diabetic retinopathy among diabetic patients in rural China.

In order to explore the static contact problem between the rolling element and raceway of the elastic composite cylindrical roller bearing based on the locomotive wheel set, the mechanical analysis of the new type bearing of the locomotive wheel set is carried out by using the numerical simulation method and the theoretical analysis method. The contact stress, contact half width, contact displacement and contact stress of the elastic composite cylindrical roller bearing under the load of locomotive wheel pair are analyzed by finite element method The results show that: the contact displacement and contact half width of the elastic composite cylindrical rolling element applied to locomotive wheel set increase with the increase of filling degree; the contact stress and equivalent stress have minimum values with the increase of filling degree, and the minimum values change regularly. Compared with the solid cylindrical roller bearing, the elastic composite cylindrical roller bearing has obvious advantages in contact stress. Reasonable filling degree can reduce the contact stress and improve the "edge effect".

Based on the previous research on the ECCRB, this paper deeply analyzes the working load-bearing mechanism of the wheel set, studies the influence of the ECCRB on the wheel set from the perspective of comprehensive stress and stiffness, deeply analyzes the deep hole structure design of the ECCRB with specific size and type that can meet the working requirements of the wheel set, and deeply analyzes the wheel set based on locomotive In this paper, the bending stress of the ECCRB of locomotive wheelset axle box is analyzed, and the working reliability of the ECCRB based on the locomotive wheel set is analyzed. The above research and analysis are comprehensive, which has important practical significance for the application of ECCRB in locomotive wheel set.

Rationale: Limited cohort studies have evaluated chronic effects of high fine particulate matter (particulate matter with an aerodynamic diameter ≤2.5 μm [PM(2.5)]) exposure on lung cancer. Objectives: To investigate the response pattern of lung cancer associated with high PM(2.5) exposure. Methods: A Chinese cohort of 118,551 participants was followed up from 1992 to 2015. By incorporating PM(2.5) exposure at 1 km spatial resolution generated using the satellite-based model during 2000–2015, we estimated the association between lung cancer and time-weighted average PM(2.5) concentration using Cox proportional hazard models. Measurements and Main Results: A total of 844 incident lung cancer cases were identified during 915,053 person-years of follow-up. Among them, 701 lung cancer deaths occurred later. The exposure–response curves for lung cancer associated with PM(2.5) exposure were nonlinear, with steeper slopes at the higher concentrations. Adjusted for age, sex, geographical region, urbanization, education level, smoking status, alcohol consumption, work-related physical activity, and body mass index, participants exposed to the second-fifth quintiles of PM(2.5) had higher risk for lung cancer incidence than those exposed to the first quintile, with hazard ratios of 1.44 (95% confidence interval [CI], 1.10–1.88), 1.49 (95% CI, 1.12–1.99), 2.08 (95% CI, 1.42–3.04), and 2.45 (95% CI, 1.83–3.29), respectively. The corresponding hazard ratios for lung cancer mortality were 1.83 (95% CI, 1.33–2.50), 1.80 (95% CI, 1.29–2.53), 2.50 (95% CI, 1.62–3.86), and 2.95 (95% CI, 2.09–4.17), respectively. Conclusions: We provide strong evidence that high PM(2.5) exposure leads to an elevated risk of lung cancer incidence and mortality, highlighting that remarkable public health benefits could be obtained from the improvement of air quality in highly polluted regions.

Tumor-associated macrophages (TAMs) are important components of the tumor microenvironment, which are characterized by pro-tumor M2 phenotype and correlate with poor survival of nasopharyngeal carcinoma (NPC). Heme oxygenase-1 (HO-1) plays a crucial role in macrophage polarization toward M2 phenotype, but its prognosis significance in NPC has been rarely determined. To gain insights into the HO-1 expression profile and to determine the clinical significance of HO-1 in NPC, we performed immunohistochemistry analyses in 126 NPC specimens. CD163, a highly specific marker of M2 macrophages, was used as a surrogate for the polarization state of TAMs. Our results showed that high expression of HO-1 and CD163 were detected in TAMs for 57.9% (73/126) and 61.9% (78/126) of the studied patients, and both of them were significantly associated with worse survival. Additionally, a significant correlation between the intensities of HO-1 and CD163 was identified, and HO-1 exhibited a superior ability in predicting survival compared with CD163. Our study revealed for the first time that overexpression of HO-1 characterized a poor-prognosis subtype in NPC. Individualized therapy targeting HO-1 might serve as a promising treatment modality for NPC.

Background: Blood pressure responses to dietary sodium intake vary among individuals. However, it is unknown whether sodium sensitivity and sodium resistance predict incidence of hypertension. Methods: We conducted a feeding study, including a 7-day low-sodium diet (51.3 mmol/day) and a 7-day high-sodium diet (307.8 mmol/day), among 1,718 Chinese individuals with normal blood pressure in 2003-2005 and follow-up studies in 2008-2009 and 2011-2012. Three blood-pressure measurements and 24-hour urinary sodium excretion were obtained on each of 3 days during baseline, low- and high-sodium interventions, and follow-up visits. Latent class models were used to identify subgroups that share a similar underlying trajectory in blood-pressure responses to dietary sodium intake. Results: Three trajectories of systolic blood pressure responses to dietary sodium intake were identified (Figure). Mean (standard deviation) changes in systolic blood pressure were -13.7 (5.5), -4.9 (3.0), and 2.4 (3.0) mmHg during the low-sodium intervention, and 11.2 (5.3), 4.4 (4.1) and -0.2 (4.1) mmHg during the high-sodium intervention ( P< 0.001 for group differences) in high sodium-sensitive, moderate sodium-sensitive, and sodium-resistant groups, respectively. Compared to individuals with moderate sodium sensitivity, multiple-adjusted odds ratio (95% confidence intervals) for incident hypertension were 1.44 (1.03 to 1.99) for those with high sodium sensitivity and 1.42 (1.02 to 1.97) for those with sodium resistance ( P P Conclusions: Individuals with either high sodium sensitivity or sodium resistance are at an increased risk for developing hypertension.

Eggs are nutrient-dense while also loaded with abundant cholesterol, thus making the public hesitant about their consumption. We conducted the study to investigate if egg consumption is associated with incident cardiovascular disease (CVD) and all-cause mortality. Using the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China, we included 102,136 adults free of CVD and assessed their egg consumption with food-frequency questionnaires. CVD endpoints and all-cause mortality were confirmed during follow-ups by interviewing participants or their proxies and checking hospital records/death certificates. The HRs (95% CIs) were calculated using the cohort-stratified Cox regression models. During 777,163 person-years of follow-up, we identified 4,848 incident CVD and 5,511 deaths. U-shaped associations of egg consumption with incident CVD and all-cause mortality were observed. Compared with consumption of 3–

Introduction The relationship between blood pressure categories and all-cause mortality has not been fully addressed in cohort studies, especially in the general Chinese population. Our study aimed to assess the sex-specific association of systolic blood pressure (SBP), diastolic blood pressure (DBP), and 2017 United States hypertension guidelines with all-cause mortality in China. Methods We conducted a prospective study of 13,760 rural Chinese adults aged 18 or older (41.1% men). Mean age overall was 49.4, 51.0 for men, and 48.3 for women. We analyzed the blood pressure-mortality relationship by using restricted cubic splines and Cox proportional-hazards regression analysis, estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Results During a mean follow-up of 5.95 years, 710 people died (60.3% men) from any cause. We found a U-shaped SBP-mortality or DBP-mortality relationship for both sexes. Mortality risk was increased for men with SBP 120-139 mm Hg (adjusted HR [aHR], 1.42; 95% CI, 1.10-1.82) or ≥140 mm Hg (aHR, 2.05; 95% CI, 1.54-2.72), and for DBP ≥90 mm Hg (aHR, 1.53; 95% CI, 1.10-2.13) as compared with SBP 100-119 mm Hg or DBP 70-79 mm Hg. Mortality risk also was increased for men with blood pressure status defined according to 2017 US hypertension guidelines as elevated, SBP 120-129 and DBP >80 mm Hg (aHR 1.48; 95% CI,1.11-1.98); stage 1 hypertension, SBP/DBP 130-139/80-89 mm Hg (aHR 1.53; CI, 1.19-1.97); and stage 2 hypertension, SBP/DBP ≥140/90 mm Hg (aHR 1.83; CI, 1.33-2.51). No significant relationship was observed for women. Conclusion Elevated blood pressure and stages 1 and 2 hypertension were positively associated with all-cause mortality for men but not women in rural China.

Aims. To quantify the capillary density of the optic nerve head in healthy control eyes and different stages of diabetic retinopathy (DR) eyes and identify the parameters to detect eyes with or without DR using optical coherence tomographic angiography (OCTA). Methods. In this cross-sectional study, 211 eyes of 121 participants with type 2 diabetes with different stages of DR or without DR and 73 eyes of 38 healthy age-matched controls were imaged by OCTA. Radial peripapillary capillary (RPC) plexus density and retinal nerve fiber layer (RNFL) thickness were examined. The mixed model binary logistic regression model was used to identify the parameters to detect eyes with or without DR. The area under the receiver operating characteristic (ROC) curve was calculated. Results. RPC density decreased significantly in diabetic patients without DR compared with the healthy controls, and it was negatively correlated with the severity of DR (P<0.01). RPC density was a significant parameter to distinguish diabetic eyes with or without DR (P<0.01). The area under the ROC curve was 0.743. Conclusions. Quantification of RPC density by OCTA provides evidence of microvascular changes in the optic nerve in diabetic patients. RPC density can serve as a possible biomarker in detecting eyes with DR. Larger cohort studies need to support this statement.