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The Huainan mining area is rich in coal resources and has sparse vegetation and many collapsed waterways. Large-scale and long-term underground coal mining has led to a fragile ecological environment in the mining area, and it is urgent to solve the contradiction between coal development and ecological environmental protection. The Huainan mining area was selected as the research object, and the vegetation cover was extracted using 10-phase Landsat multispectral remote sensing images from 1989 to 2021 to analyze its spatial and temporal changes and driving forces to provide a scientific basis for the guided restoration of the ecological environment in the region. Combined with the image dichotomous model, regression slope, correlation coefficient, and standard deviation of vegetation cover grid points in different time series, standard deviation ellipse, and center of gravity migration, we analyzed the spatial and temporal variation pattern of vegetation cover for 33 years and revealed the responses of temperature, precipitation, population density, GDP, and afforestation area to vegetation cover. Results show the following: (1) from 1989 to 2021, the overall vegetation cover in the study area tended to decrease with 36.48% of the areas increasing and 63.52% of the areas decreasing, primarily in the very low and medium range; (2) the center of gravity of different types of vegetation cover generally shifted from north to south during 33 years; (3) climate and social activities had a substantial effect on the spatial heterogeneity of the vegetation cover in the study area. There is significant spatial heterogeneity in the effects of climate and social activities on the vegetation in the study area with human activities negatively correlating with vegetation cover. Mining activities are the primary driver of the evolution of regional vegetation cover, with climate change serving as a secondary driver.

Ku70 and Topo IIα are hopeful targets of anticancer drugs. Platinum complex OPPC shows high antiproliferative activity towards cancer cells, which is associated with the damage to DNA, downregulation of Ku70, and inhibition of Topo IIα.

Graphical Abstract Redox-responsive drug delivery system emerges as a hopeful platform for tumor treatment. Dihydroartemisinin (DHA) has been investigated as an innovative tumor therapeutic agent. Herein, a DHA dimeric prodrug bridged with disulfide bond as linker (DHA2-SS) has been designed and synthesized. The prepared prodrugs could self-assemble into nanoparticles (SS NPs) with high DHA content (> 90%) and robust stability. These SS NPs display sensitive redox responsive capability and can release DHA under the tumor heterogeneity microenvironment. SS NPs possess preferable antitumor therapeutic activity in contrast with free DHA. Moreover, the possible anti-cancer mechanism of SS NPs was investigated through RNA-seq analysis, bioinformatics and molecular biological method. SS NPs could induce apoptosis via mitochondrial apoptosis pathway, as well as glycolysis inhibition associate with the regulation of PI3K/AKT/HIF-1α signal path, which may offer an underlying therapeutic target for liver cancer. Our study highlights the potential of using redox responsive prodrug nanoparticles to treat cancer, meanwhile provides insights into the anti-cancer mechanism of DHA prodrug. Supplementary Information The online version contains supplementary material available at 10.1186/s12951-021-01200-z.

Background BMP9-stimulated DPSCs, SCAPs and PDLSCs are effective candidates for repairing maxillofacial bone defects in tissue engineering, while the most suitable seed cell source among these three hDMSCs and the optimal combination of most suitable type of hDMSCs and BMP9 have rarely been explored. Moreover, the orthotopic maxillofacial bone defect model should be valuable but laborious and time-consuming to evaluate various candidates for bone regeneration. Thus, inspired from the maxillofacial bone defects and the traditional in vivo ectopic systems, we developed an intrabony defect repair model to recapitulate the healing events of orthotopic maxillofacial bone defect repair and further explore the optimized combinations of most suitable hDMSCs and BMP9 for bone defect repair based on this modified ectopic system. Methods Intrabony defect repair model was developed by using decellularized bone matrix (DBM) constructs prepared from the cancellous part of porcine lumbar vertebral body. We implanted DBM constructs subcutaneously on the flank of each male NU/NU athymic nude mouse, followed by directly injecting the cell suspension of different combinations of hDMSCs and BMP9 into the central hollow area of the constructs 7 days later. Then, the quality of the bony mass, including bone volume fraction (BV/TV), radiographic density (in Hounsfield units (HU)) and the height of newly formed bone, was measured by micro-CT. Furthermore, the H&E staining and immunohistochemical staining were performed to exam new bone and new blood vessel formation in DBM constructs. Results BMP9-stimulated periodontal ligament stem cells (PDLSCs) exhibited the most effective bone regeneration among the three types of hDMSCs in DBM constructs. Furthermore, an optimal dose of PDLSCs with a specific extent of BMP9 stimulation was confirmed for efficacious new bone and new blood vessel formation in DBM constructs. Conclusions The reported intrabony defect repair model can be used to identify optimized combinations of suitable seed cells and biological factors for bone defect repair and subsequent development of efficacious bone tissue engineering therapies.

Early recognition of cachexia is essential for ensuring the prompt intervention and treatment of cancer patients. However, the diagnosis of cancer cachexia (CC) usually is delayed. This study aimed to establish an accurate and high-efficiency diagnostic system for CC.A total of 4834 cancer inpatients were enrolled in the INSCOC project from July 2013 to June 2020. All cancer patients in the study were randomly assigned to a development cohort (n=3384, 70%) and a validation cohort (n=1450, 30%). The least absolute shrinkage and selection operator (LASSO) method and multivariable logistic regression were used to identify the independent predictors for developing the dynamic nomogram. Discrimination and calibration were adopted to evaluate the ability of nomogram. A decision curve analysis (DCA) was used to evaluate clinical use.We combined 5 independent predictive factors (age, NRS2002, PG-SGA, QOL by the QLQ-C30, and cancer categories) to establish the online dynamic nomogram system. The C-index, sensitivity, and specificity of the nomo-system to predict CC was 0.925 (95%CI, 0.916-0.934, P0.001), 0.826, and 0.862 in the development set, while the values were 0.923 (95%CI, 0.909-0.937, P0.001), 0.854, and 0.829 in the validation set. In addition, the calibration curves of the diagnostic nomogram also presented good agreement with the actual situation. DCA showed that the model is clinically useful and can increase the clinical benefit in cancer patients.This study developed an online dynamic nomogram system with outstanding accuracy to help clinicians and dieticians estimate the probability of cachexia. This simple-to-use online nomogram can increase the clinical benefit in cancer patients and is expected to be widely adopted.

Inflammatory cytokines has been of great interest in the field of colorectal cancer (CRC) tumor immunology in recent years. As an anti-inflammatory interleukin (IL), IL-38 may contribute to the ear...

Copy number variations (CNVs) in cell‐free DNA (cfDNA) are emerging as noninvasive biomarkers for various cancers. However, multiple‐level analysis of cfDNA CNVs for hepatocellular carcinoma (HCC) patients with radical treatments remains uninvestigated. Here, CNVs at genome‐wide, chromosomal‐arm, and bin levels were analyzed in cfDNA from 117 HCC patients receiving radical treatments. Then, the relationship between cfDNA CNVs and clinical outcomes was explored. Our results showed that a concordant profile of CNVs was observed between cfDNA and tumor tissue DNA. Three genome‐wide CNV indicators including tumor fraction (TFx), prediction score (P‐score), and stability score (S‐score) were calculated and demonstrated to exhibit significant correlation with poorer overall survival (OS) and recurrence‐free survival (RFS). Furthermore, the high‐frequency cfDNA CNVs at chromosomal‐arm level including the loss of 4q, 17p, and 19p and the gain of 8q and 1q clearly predicted HCC prognosis. Finally, a bin‐level risk score was constructed to improve the ability of CNVs in predicting prognosis. Altogether, our study indicates that the multiple‐level cfDNA CNVs are significantly associated with OS and RFS in HCC patients with radical treatments, suggesting that cfDNA CNVs detected by low‐coverage whole‐genome sequencing (WGS) may be used as potential prognostic biomarkers of HCC patients., The circulating free DNA (cfDNA) copy number variation (CNV) indicators at different levels provide important prognosis information for hepatocellular carcinoma (HCC) patients with radical treatments beyond clinicopathologic factors and cfDNA concentration. This approach is helpful for broadening the applicable strategy to reveal clinically useful biomarkers based on cfDNA CNV analysis.

Background: To investigate the intergenerational effects of grandmaternal smoking during pregnancy (GMSDP) on the DNA methylation of grandchildren. Methods: Data from the Isle of Wight birth cohort with information regarding GMSDP and DNA methylation profiling at the birth of grandchildren (n = 161) were used. Differentially methylated CpG sites related to GMSDP were identified using testing–training screening, analysis of variance and multivariate analysis of covariance. The association between identified CpG sites and expression levels of neighboring genes was tested by linear regression. Results: Twenty-three CpG sites were differentially methylated in grandchildren because of GMSDP, and eight of these were associated with expression levels of 13 neighboring genes. Conclusion: GMSDP has an intergenerational effect on the DNA methylation profile of grandchildren independent of maternal smoking during pregnancy.

In the updated consensus, low muscle strength overtook the role of low muscle mass, and probable sarcopenia was diagnosed once low muscle strength was detected. Whether the modified creatinine index (mCI) could identify persons with probable sarcopenia who may be at risk of adverse outcomes remains unknown. We aimed to evaluate the association of the mCI with probable sarcopenia and mortality in patients undergoing hemodialysis.In the cross-sectional study (Cross-sectional results showed that after adjusting for confounders, the association of mCI with low muscle strength remained significant. The area under the curve (AUC) of the mCI to predict probable sarcopenia was 0.804 (95% CI, 0.744-0.863;The mCI is a predictor of muscle strength and survival in hemodialysis patients, and is preferable to the MQSGA for predicting death. Assessment of mCI could provide additional predictive and prognostic information to sarcopenia.

Background Breast cancer is one of the most common cancers in women. It is necessary to classify breast cancer subtypes because different subtypes need specific treatment. Identifying biomarkers and classifying breast cancer subtypes is essential for developing appropriate treatment methods for patients. MiRNAs can be easily detected in tumor biopsy and play an inhibitory or promoting role in breast cancer, which are considered promising biomarkers for distinguishing subtypes. Results A new method combing ensemble regularized multinomial logistic regression and Cox regression was proposed for identifying miRNA biomarkers in breast cancer. After adopting stratified sampling and bootstrap sampling, the most suitable sample subset for miRNA feature screening was determined via ensemble 100 regularized multinomial logistic regression models. 124 miRNAs that participated in the classification of at least 3 subtypes and appeared at least 50 times in 100 integrations were screened as features. 22 miRNAs from the proposed feature set were further identified as the biomarkers for breast cancer by using Cox regression based on survival analysis. The accuracy of 5 methods on the proposed feature set was significantly higher than on the other two feature sets. The results of 7 biological analyses illustrated the rationality of the identified biomarkers. Conclusions The screened features can better distinguish breast cancer subtypes. Notably, the genes and proteins related to the proposed 22 miRNAs were considered oncogenes or inhibitors of breast cancer. 9 of the 22 miRNAs have been proved to be markers of breast cancer. Therefore, our results can be considered in future related research.

ObjectiveCoal mining activities have continuously introduced heavy metals into the soil–crop system, causing increasing damage to crops. This study integrated the analysis of the heavy metal contamination status and human health risk in soil and maize near coal mines to help formulate control strategies for soil quality, maize production, and safe consumption.MethodThis study was carried out on maize agricultural land near a coal mining plant. Heavy metal contamination was assessed by the geo-accumulation index (Igeo), enrichment factor (EF), and bioaccumulation factor (BCF). The Monte Carlo simulation was used to estimate the probabilistic health risk of heavy metals exposure in soil and maize. The relationship between the concentration of heavy metal in the soil and that in maize was further visualized by correlation analysis and random forest analysis.ResultsThe results revealed that the mean concentrations of soil Ni, Cu, As, Cd, Sn, Zn, Pb, and Hg were all above the local background level. Ni was the most severely polluted heavy metal in maize and had a concentration higher than the risk control standard for corn in China (NY 861-2004). The Igeo values of all heavy metals were low, and EF values showed enrichment in V, Cr, Ti, Ni, and As. The assessment of probabilistic health risk exposed by heavy metals in soil and maize indicated that 1.16 and 1.46% of residents exceeded the carcinogenic risk level due to heavy metal exposure from soil and maize, respectively. Children were the most sensitive to maize and soil heavy metal exposure in the contaminated area. Ingestion of heavy metals was associated with the highest health risk to residents, followed by dermal contact and inhalation. As and Cr in soil and Cr and Ni in maize had the greatest impact on human health risk. Furthermore, maize heavy metals were affected the most by soil Cr, Cd, and V.ConclusionThese results may provide useful information for human carcinogenic risk associated with soil and maize heavy metal exposure due to coal mining activities.

Background: Childhood food allergy (FA) and food allergen sensitization (FAS) are associated with allergic airway disease(s) [AAD] (asthma and rhinitis) in childhood. However, the associations between childhood FA/FAS and AAD in adulthood are not well described. Methods: We investigated the longitudinal relationship between childhood FA/FAS to common food allergens and AAD at 18 and 26 years, in the Isle of Wight birth cohort. Study subjects (N = 1456) were followed up at fixed time points from ages 1–26 years for FA/FAS status. AAD were evaluated from 4 years onwards. The associations between FA/FAS and AAD were assessed with univariate analyses and then multivariable logistic regression, adjusting for clinically relevant co-variates. Results: Food allergy at 4 years was significantly associated with asthma at 18 years [adjusted odds ratio (aOR): 2.75, 95% CI: 1.53–4.92, p =.001] and 26 years (aOR: 2.62, 95% CI: 1.32–5.20, p =.006). Conversely, childhood FA was not associated with adulthood rhinitis whatsoever. While FAS at ages 4 and 10 were associated with both AAD, the associations between FAS and rhinitis were less robust relative to asthma. Conclusion: Childhood FA increased the odds of asthma during adulthood by nearly threefold. Additionally, childhood FAS was also associated with increased odds of asthma in adulthood. Conversely, FAS but not FA in childhood was associated with rhinitis in adulthood. We suggest that children with FA/FAS should be followed up to facilitate early detection and intervention of subsequent AAD, particularly asthma.

The present study evaluated whether fat mass assessment using the triceps skinfold (TSF) thickness provides additional prognostic value to the Global Leadership Initiative on Malnutrition (GLIM) framework in patients with lung cancer (LC). We performed an observational cohort study including 2672 LC patients in China. Comprehensive demographic, disease and nutritional characteristics were collected. Malnutrition was retrospectively defined using the GLIM criteria, and optimal stratification was used to determine the best thresholds for the TSF. The associations of malnutrition and TSF categories with survival were estimated independently and jointly by calculating multivariable-adjusted hazard ratios (HR). Malnutrition was identified in 808 (30·2 %) patients, and the best TSF thresholds were 9·5 mm in men and 12 mm in women. Accordingly, 496 (18·6 %) patients were identified as having a low TSF. Patients with concurrent malnutrition and a low TSF had a 54 % (HR = 1·54, 95 % CI = 1·25, 1·88) greater death hazard compared with well-nourished individuals, which was also greater compared with malnourished patients with a normal TSF (HR = 1·23, 95 % CI = 1·06, 1·43) or malnourished patients without TSF assessment (HR = 1·31, 95 % CI = 1·14, 1·50). These associations were concentrated among those patients with adequate muscle mass (as indicated by the calf circumference). Additional fat mass assessment using the TSF enhances the prognostic value of the GLIM criteria. Using the population-derived thresholds for the TSF may provide significant prognostic value when used in combination with the GLIM criteria to guide strategies to optimise the long-term outcomes in patients with LC.

To evaluate the baseline MRI characteristics for predicting survival outcomes and construct survival models for risk stratification to facilitate personalized treatment and follow-up strategies in patients with MRI-defined T3 (mrT3) locally advanced rectal cancer (LARC). We retrospectively reviewed 256 mrT3 LARC patients evaluated between 2008 and 2012 in our institution, with an average follow-up period of 6.8 ± 1.2 years. The baseline MRI characteristics, clinical data, and follow-up information were evaluated. The patients were randomized into a training cohort (TC, 186 patients) and validation cohort (VC, 70 patients). The TC dataset was used to develop multivariate nomograms for disease-free survival (DFS) and overall survival (OS), while the VC dataset was used for independent validation of the models. Harrell concordance (C) indices and Hosmer-Lemeshow calibration were used to evaluate the performances of the models. Baseline mrT3 substage, extramural venous invasion (EMVI) grading, mucinous adenocarcinoma, mesorectal fascia involvement, elevated pretreatment carcinoembryonic antigen level, and neoadjuvant chemoradiotherapy (NCRT) were independent predictors of DFS. T3 substage, EMVI grading, and NCRT were also independent predictors of OS. The nomograms constructed permitted the individualized prediction of 3-year and 5-year DFS and 5-year OS with high discrimination (C-index range, 0.833–0.892) and good calibration in the TC and VC. We have identified baseline MRI characteristics that help independently predict survival outcomes in patients with mrT3 LARC. The survival models based on these characteristics allow for the individualized pretreatment risk stratification in patients with mrT3 LARC. • Baseline MRI characteristics can independently stratify risk and predict survival outcomes in patients with mrT3 LARC. • The nomograms built using selected baseline MRI characteristics facilitate the individualized pretreatment risk stratification and help with clinical decision-making in patients with mrT3 LARC. • MR-defined risk factors should, therefore, be carefully reported in the baseline MRI evaluation.

Transcriptional regulator PRD1-BF-1-RIZ1 homology (PR) domain containing protein-16 (PRDM16) has a fundamental function in maintaining energy homeostasis and regulating glucose and lipid metabolism, which are responsible for the development of type 2 diabetes (T2D). However, the impact of genetic variation of PRDM16 gene on T2D risk remains to be investigated. Thus, we evaluated the possible association between genetic variants within PRDM16 region and T2D development in Chinese individuals.A total of 427 T2D patients and 408 healthy controls were enrolled. Ten single-nucleotide variants across PRDM16 gene were screened with the SNaPshot assay. The effect of genotypes and alleles of different variant on the T2D risk was examined under diverse genetic models. The impact of genetic variant on promoter activity was determined using an in vitro luciferase reporter gene assay.Genotypic frequency of rs2297828 in the PRDM16 promoter region was significantly different between patients with T2D and controls (P = 0.004). The minor allele A of rs2297828 was potentially associated with a higher T2D susceptibility in a dominant model (AG + AA vs GG: OR = 1.54, 95 % CI: 1.12-1.12; P = 0.007), and the subjects with either an AA homozygote or an AG heterozygote displayed increased fasting blood levels of glucose and lipids. Reporter gene assays demonstrated that rs2297828 can influence the activity of the PRDM16 promoter.We firstly observed that PRDM16 variation might influence T2D occurrence, and rs2297828 might be a functional variant that can influence the expression of PRDM16.

Background Body mass index (BMI) has been shown to be associated with lung function. Recent findings showed that DNA methylation (DNAm) variation is likely to be a consequence of changes in BMI. However, whether DNAm mediates the association of BMI with lung function is unknown. We examined the mediating role of DNAm on the association of pre-adolescent BMI trajectories with post-adolescent and adulthood lung function (forced expiratory volume (FEV1), forced vital capacity (FVC), and FEV1/FVC). Methods Analyses were undertaken in the Isle of Wight birth cohort (IOWBC). Group-based trajectory modelling was applied to infer latent BMI trajectories from age 1 to 10 years. An R package, ttscreening, was applied to identify CpGs at 10 years potentially associated with BMI trajectories for each sex. Linear regressions were implemented to further screen CpGs for their association with lung function at 18 years. Path analysis, stratified by sex, was applied to each screened CpG to assess its role of mediation. Internal validation was applied to further examine the mediation consistency of the detected CpGs based on lung function at 26 years. Mendelian randomization (MR-base) was used to test possible causal effects of the identified CpGs. Results Two BMI trajectories (high vs. low) were identified. Of the 442,475 CpG sites, 18 CpGs in males and 33 in females passed screening. Eight CpGs in males and 16 CpGs in females (none overlapping) were identified as mediators. For subjects with high BMI trajectory, high DNAm at all CpGs in males were associated with decreased lung function, while 8 CpGs in females were associated with increased lung function at 18 years. At 26 years, 6 CpGs in males and 14 CpGs in females showed the same direction of indirect effects as those at 18 years. DNAm at CpGs cg19088553 (GRIK2) and cg00612625 (HPSE2) showed a potential causal effect on FEV1. Conclusions The effects of BMI trajectory in early childhood on post-adolescence lung function were likely to be mediated by pre-adolescence DNAm in both males and females, but such mediation effects were likely to diminish over time.

While physical activity and diet behaviors are correlated, mechanisms underlying associations have rarely been examined. This study examined associations between physical activity identity and eating identity among college-aged adults in Hawai‘i to provide guidance for future multiple behavior change interventions. This study was a cross-sectional analysis of data collected between September 2013 and January 2014. Participants were 40 college students attending 4-year and 2-year institutions within the University of Hawai‘i system. Total physical activity identity score and dimensions were measured using the Athlete Identity Questionnaire. Eating identity subtypes were measured using the Eating Identity Type Inventory. Associations between physical activity identity total score, 4 physical activity identity dimensions (appearance, importance, competence, and encouragement), and 4 eating identity subtypes (healthy, emotional, meat, and picky) were examined using multiple linear regressions. A significant positive association was found between total physical activity identity score and the healthy eating subtype and a negative association with the picky eating subtype. The physical activity dimension importance had a significant positive association with the healthy eating subtype, appearance a negative association with the emotional eating subtype, and competence a positive association with the meat eating subtype but a negative association with the picky eating subtype. The findings suggest important overlap in identities for physical activity and diet. Measurement of physical activity identity and eating identity as well as tailored intervention strategies should be incorporated into more behavior change research.

Background To develop a radiomics model based on pretreatment whole-liver portal venous phase (PVP) contrast-enhanced CT (CE-CT) images for predicting metachronous liver metastases (MLM) within 24 months after rectal cancer (RC) surgery. Methods This study retrospectively analyzed 112 RC patients without preoperative liver metastases who underwent rectal surgery between January 2015 and December 2017 at our institution. Volume of interest (VOI) segmentation of the whole-liver was performed on the PVP CE-CT images. All 1316 radiomics features were extracted automatically. The maximum-relevance and minimum-redundancy and least absolute shrinkage and selection operator methods were used for features selection and radiomics signature constructing. Three models based on radiomics features (radiomics model), clinical features (clinical model), and radiomics combined with clinical features (combined model) were built by multivariable logistic regression analysis. Receiver operating characteristic (ROC) curves were used to assess the diagnostic performance of models, and calibration curve and the decision curve analysis were performed to evaluate the clinical application value. Results In total, 52 patients in the MLM group and 60 patients in the non-MLM group were enrolled in this study. The radscore was built using 16 selected features and the corresponding coefficients. Both the radiomics model and the combined model showed higher diagnostic performance than clinical model (AUCs of training set: radiomics model 0.84 (95% CI, 0.76–0.93), clinical model 0.65 (95% CI, 0.55–0.75), combined model 0.85 (95% CI, 0.77–0.94); AUCs of validation set: radiomics model 0.84 (95% CI, 0.70–0.98), clinical model 0.58 (95% CI, 0.40–0.76), combined model 0.85 (95% CI, 0.71–0.99)). The calibration curves showed great consistency between the predicted value and actual event probability. The DCA showed that both the radiomics and combined models could add a net benefit on a large scale. Conclusions The radiomics model based on preoperative whole-liver PVP CE-CT could predict MLM within 24 months after RC surgery. Clinical features could not significantly improve the prediction efficiency of the radiomics model.

Objective To investigate the association of fasting serum fructose concentrations and the incidence of GDM. Research design and methods Five hundred twenty six pregnant women who attended the obstetric clinic of Xinhua Hospital, Chongming Branch were recruited prospectively from September 2019 to November 2020. Fasting serum fructose concentrations were measured by a validated liquid chromatography–tandem mass spectrometry method. GDM was diagnosed according to the criteria of the IADPSG. Independent sample t-test was used to compare the differences between groups. Multiple stepwise regression analysis was used to estimate the associations of serum fructose and other variables. Multivariate logistic regression models were adopted to evaluate the odds ratios (ORs) for GDM. Results Of the 526 pregnant women, 110 were diagnosed with GDM. Fasting fructose concentrations were increased significantly in GDM patients compared to those without GDM (1.30 ug/ml vs 1.16 ug/ml, p Conclusions Increased fasting serum fructose levels were independently associated with the incidence of GDM.

Toll-like receptors (TLRs) participate in the induction and regulation of immune responses and are closely related to the occurrence and development of small-cell lung cancer (SCLC). This study aimed to investigate the impact of polymorphisms in the regulatory regions of TLRs on the susceptibility of SCLC.The case-control study included 304 SCLC patients and 304 healthy controls. TLRs gene polymorphisms were genotyped by PCR-restrictive fragment length polymorphism analysis and TaqMan assay. Unconditional logistic regression was used to estimate odds ratio (OR) and its 95% confidence interval (95% CI).Our results showed that TLR4 rs1927914 GG genotype and TLR4 rs7869402 TT genotype reduced the risk of SCLC with OR (95% CI) of 0.54 (0.32-0.90) and 0.47 (0.28-0.80), respectively. Stratified analysis suggested that TLR4 rs1927914 GG genotypes significantly reduced the risk of SCLC among male (OR = 0.35; 95% CI, 0.18-0.69; P0.01), the younger patients (OR = 0.49; 95% CI, 0.26-0.94; P = 0.03) and non-drinkers (OR = 0.47; 95% CI, 0.24-0.89; P = 0.02). TLR4 rs7869402 CT or TT genotype significantly reduced the susceptibility to SCLC among male patients (OR = 0.37; 95% CI, 0.19-0.71, P0.01), the younger patients (OR = 0.41; 95% CI, 0.22-0.79; P0.01), smokers (OR = 0.25; 95% CI, 0.10-0.60; P0.01) and drinkers (OR = 0.31; 95% CI, 0.11-0.88; P = 0.03). TLR3 rs5743303, TLR4 rs11536891, TLR5 rs1640816 and TLR7 rs3853839 had no significant correlation with the risk of SCLC.These findings emphasized the important role of TLR4 in the development of SCLC.

Background In this study, we aimed to explore whether COL1A2 and miR-1297 participated in the progression of diabetic nephropathy (DN) in vitro and classified the underlying mechanisms. Methods d-Glucose (30 mM; high glucose, HG)-stimulated HK-2 cells were used to mimic DN condition. RNA and non-coding RNA profiles were from Gene Expression Omnibus (GEO) database. The interaction between miR-1297 and COL1A2 was measured by dual-luciferase reporter assay. Gene Set Enrichment Analysis (GSEA) method was conducted to analyse COL1A2-associated signalling pathways. The role of miR-1297/COL1A2 in biological behaviours of HG-induced HK-2 cells were analysed by cell counting kit-8 and apoptosis assays. Results Bioinformatics analysis revealed that COL1A2 was up-regulated in DN tissues. We predicted and verified miR-1297 as the regulatory miRNA of COL1A2, and the expression of miR-1297 was decreased in DN tissues and HG-stimulated HK-2 cells. Overexpression of miR-1297 could promote cell proliferation and inhibit apoptosis to protect HK-2 cells from HG-induced damage. And knockdown of COL1A2 enhanced the protective effects of miR-1297 on HG-stimulated HK-2 cells. GSEA results revealed that several inflammatory pathways were enriched in COL1A2 high-expression group. Meanwhile, transfection of miR-1297 reduced the phosphorylation of NFκB and expression of three important pro-inflammatory genes including cytokine CCL5, adhesion molecules ICAM1 and VCAM1 via targeting COL1A2. These results suggested that miR-1297 protected HG-treated HK-2 cells probably through suppressing inflammation via targeting COL1A2. Conclusion This study sheds a light on the role miR-1297/COL1A2 in DN progression and provides a novel promising therapy strategy for suppressing DN progression.

Objective To update the prevalence of eating disorders in the general population before 2021 and to analyze the distribution characteristics at different times and in different regions and sexes, as well as the diagnostic criteria. Methods Based on the method from a previous report by the authors, studies were identified from the following databases: PubMed/Medline, PsycINFO, ISI Web of Knowledge, Ovid and the 4 most important Chinese databases. Articles in English and Chinese before 2021 were retrieved. The data retrieved at this time were pooled with the data from a previous report for analyses. Results Thirty-three studies were identified, which included 18 studies supplemented in this retrieval. The pooled lifetime and 12-month prevalence of eating disorders were 0.91% (95% CI, 0.48–1.71) and 0.43% (95% CI, 0.18–0.78), respectively. The pooled lifetime and 12-month prevalence of the subgroup EDs (any), which covers all types of eating disorders, were 1.69% and 0.72%, respectively. The lifetime prevalence of AN, BN and BED was 0.16% (95% CI, 0.06–0.31), 0.63% (95% CI, 0.33–1.02) and 1.53% (95% CI, 1.00–2.17), respectively. The lifetime prevalence of EDs in Western countries was 1.89%, and was high at 2.58% in females. Prevalence studies using DSM-5 criteria were scarce. Conclusions The prevalence of eating disorders might be underestimated thus far. Not all types of EDs were included in a majority of epidemiological surveys, and the prevalence rates of the new types of EDs were significantly higher. Eating disorders were especially common in Western countries and in females. New diagnostic criteria should be used to comprehensively assess all types of eating disorders. Level of evidence 1, systematic review and meta-analysis.

To establish a radiomics nomogram based on relaxation maps for predicting the extramural venous invasion (EMVI) of rectal cancer (RC) and compare the diagnostic efficacy of the nomogram and subjective assessment by radiologists. Among 94 RC patients receiving direct surgical resection, 65 were randomly allocated to the training cohort and 29 to the validation cohort. Radiomics features were extracted from synthetic magnetic resonance imaging including T1, T2, and proton density (PD) maps. The least absolute shrinkage and selection operator methods were used for dimension reduction, feature selection, and radiomics model building. Multivariable logistic regression analysis was used for nomogram development. The performance of the nomogram was assessed with respect to its calibration, receiver operating characteristics (ROC) curve, and decision curve analysis. The radiomics model demonstrated good predictive efficacy for EMVI, with an area under the ROC curve (AUC), sensitivity, and specificity of 0.912 (95% confidence interval (CI), 0.837–0.986), 0.824, and 0.875 in the training cohort and 0.877 (95% CI 0.751–1.000), 0.833, and 0.826 in the validation cohort. The nomogram had good diagnostic performance, with AUCs of 0.925 (95% CI 0.862–0.988) and 0.899 (95% CI 0.782–1.000) in the training and validation cohort. Furthermore, the radiomics signature showed better diagnostic efficiency than the subjective assessment by both readers (AUC =0.912 vs. 0.732 and 0.763, P = 0.023 and 0.028, respectively). A radiomics nomogram was developed to preoperatively predict EMVI in RC patients. The application of the radiomics model based on relaxation maps could improve the diagnostic efficacy of EMVI.

Background Respect for patients’ autonomy is usually considered to be an important ethical principle in Western countries; privacy is one of the implications of such respect. Healthcare professionals frequently encounter ethical dilemmas during their practice. The past few decades have seen an increased use of courts to resolve intractable ethical dilemmas across both the developed and the developing world. However, Chinese and American bioethics differ largely due to the influence of Chinese Confucianism and Western religions, respectively, and there is a dearth of comparative studies that explore cases of ethical dilemmas between China and the United States. Methods This paper discusses four typical cases with significant social impact. First, it compares two cases concerning patient privacy: the “Shihezi University Hospital Case”, in which a patient was used as a clinical teaching object without her permission, and the “New York-Presbyterian Hospital Case”, in which the hospital allowed the filming of a patient’s treatment without his consent. Second, it compares two cases regarding patient autonomy and potentially life-saving medical procedures: the “Case of Ms. L”, concerning a cohabitant’s refusal to sign a consent form for a pregnant woman’s caesarean, and the “Case of Mrs. V”, concerning a hospital’s insistence upon a blood transfusion for a dissenting patient. This paper introduces the supporting and opposing views for each case and discusses their social impact. It then compares and analyses the differences between China and the United States from cultural and legislative perspectives. Conclusions Ethical dilemmas have often occurred in China due to the late development of bioethics. However, the presence of bioethics earlier in the US than in China has not spared the US of ethical dilemmas. This paper highlights lessons and inspiration from the cases for healthcare professionals and introduces readers to the role and weight of privacy and autonomy in China and in the US from the perspectives of different cultures, religions and laws.

BACKGROUND Malnutrition is prevalent that can impair multiple clinical outcomes in oncology populations. This study aimed to develop and utilize a tool to optimize the early identification of malnutrition in patients with cancer. METHODS We performed an observational cohort study including 3998 patients with cancer at two teaching hospitals in China. Hierarchical clustering was performed to classify the patients into well-nourished or malnourished clusters based on 17 features reflecting the phenotypic and etiologic dimensions of malnutrition. Associations between the identified clusters and patient characteristics were analyzed. A nomogram for predicting the malnutrition probability was constructed and independent validation was performed to explore its clinical significance. RESULTS The cluster analysis identified a well-nourished cluster (n = 2736, 68.4%) and a malnourished cluster (n = 1262, 31.6%) in the study population, which showed significant agreement with the Patient-Generated Subjective Global Assessment and the Global Leadership Initiative on Malnutrition criteria (both P

Topoisomerases are ubiquitous enzymes and important targets for DNA-oriented anticancer drugs. Two mitochondrion-targeted monofunctional platinum(ii) complexes, [Pt(ortho-PPh3CH2Py)(NH3)2Cl](NO3)2 (OPT) and [Pt(para-PPh3CH2Py)(NH3)2Cl](NO3)2 (PPT; PPh3 = triphenylphosphonium, Py = pyridine), show significant inhibition towards the activity of DNA topoisomerases in addition to their DNA binding and mitochondrial targeting capabilities. OPT exhibits strong cytotoxicity toward the human renal clear cell carcinoma 786-O and the murine prostate cancer RM-1 cell lines. The complex could bind to the minor groove of DNA, as well as DNA topoisomerases I and IIα, thereby acting as an inhibitor of topoisomerase I/IIα and causing DNA damage. The damage was evidenced by the enhanced expression of γ-H2AX, Chk1/2 phosphorylation, p53 and cell cycle arrest in the G2/M phase. In contrast, the inhibitory effect of PPT on DNA topoisomerases was largely limited to the isolated enzymes. The results demonstrate that the cellular inhibition of the complex towards the DNA topoisomerases positively correlated with its mitochondrial accumulation. Molecular docking provided more detailed structural insights into the interactions of OPT or PPT with DNA and topoisomerase I/IIα. The binding sites of OPT and PPT in topoisomerase-DNA complexes are different from each other. Aside from previously revealed DNA and mitochondrial targets, this study discovered new evidence that DNA topoisomerases may also serve as targets of monofunctional platinum(ii) complexes. For a multispecific platinum complex, strong DNA binding ability does not necessarily lead to potent cytotoxicity as other factors including the cell types, mitochondrial accumulation, and activity of DNA topoisomerases also affect the outcome of DNA damage.

Introduction: This study aimed to examine whether intraplaque neovascularization (IPN) of carotid plaques, as characterized by contrast-enhanced ultrasound (CEUS), is associated with ischemic stroke recurrence in patients with carotid atherosclerosis. Methods: We conducted a prospective study of consecutive patients with a recent stroke and at least one atherosclerotic plaque in the carotid artery on the side consistent with symptoms. All patients underwent CEUS after their first admission. IPN was graded on the basis of the presence and location of microbubbles within each plaque. Results: We eventually included 155 patients, all of whom underwent IPN analysis. After a follow-up of 24 months, we recorded 25 (16.1%) stroke recurrences in the whole population. All the recurrences occurred in patients presenting IPN. There was significant difference in the IPN between the 2 groups (p = 0.002). In the final Cox proportional-hazards multivariable models, IPN of grade 2 was independently associated with the risk of stroke recurrence (HR = 4.535; 95% CI: 1.892–10.870; p = 0.001). This association remained after adjusting for the degree of carotid stenosis (HR = 3.491; 95% CI: 1.410–8.646; p = 0.007). Conclusions: IPN was an independent predictor of stroke recurrence in patients with a recent ischemic stroke and carotid atherosclerosis. In predicting stroke recurrence, IPN may be an earlier indicator than carotid stenosis and may help stratify the risk of stroke recurrence.

Background: Hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) are key angiogenic regulatory factors. The aim of this study was to identify the most useful prognosti...

Long non-coding RNAs (lncRNAs) play important functional roles in many diverse biological processes. However, not all expressed lncRNAs are functional. Thus, it is necessary to manually collect all experimentally validated functional lncRNAs (EVlncRNA) with their sequences, structures, and functions annotated in a central database. The first release of such a database (EVLncRNAs) was made using the literature prior to 1 May 2016. Since then (till 15 May 2020), 19 245 articles related to lncRNAs have been published. In EVLncRNAs 2.0, these articles were manually examined for a major expansion of the data collected. Specifically, the number of annotated EVlncRNAs, associated diseases, lncRNA-disease associations, and interaction records were increased by 260%, 320%, 484% and 537%, respectively. Moreover, the database has added several new categories: 8 lncRNA structures, 33 exosomal lncRNAs, 188 circular RNAs, and 1079 drug-resistant, chemoresistant, and stress-resistant lncRNAs. All records have checked against known retraction and fake articles. This release also comes with a highly interactive visual interaction network that facilitates users to track the underlying relations among lncRNAs, miRNAs, proteins, genes and other functional elements. Furthermore, it provides links to four new bioinformatics tools with improved data browsing and searching functionality. EVLncRNAs 2.0 is freely available at https://www.sdklab-biophysics-dzu.net/EVLncRNAs2/.

Recently, we identified that the atypical protein kinase C isoform ι (PKCι) enhances the expression of Yes-associated protein 1 (YAP1) to promote the tumorigenesis of pancreatic adenocarcinoma harboring mutant KRAS (mu-KRAS). To advance our understanding about underlying mechanisms, we analyze the transcription of YAP1 in pancreatic cancer cells and reveal that transcription factor specificity protein 1 (Sp1) is upregulated by PKCι and subsequently binds to multiple sites in YAP1 promoter to drive the transactivation of YAP1 in pancreatic cancer cells carrying mu-KRAS. The bioinformatics analysis further substantiates that the expression of PKCι, Sp1 and YAP1 is correlated and associated with the stages and prognosis of pancreatic tumors. Moreover, our apoptotic detection data demonstrate that combination of PKCι and Sp1 inhibitors at subtoxic doses displays synergistic effects on inducing apoptosis and reversing the immunosuppression of pancreatic cancer cells, establishing the combination of PKCι and Sp1 inhibitors as a promising novel therapeutic approach, or an adjuvant strategy to potentiate the antitumor effects of other immunotherapeutic agents in pancreatic cancer treatment.

Early childhood caries (ECC) is a significant chronic disease of childhood and a rising public health burden worldwide. ECC may cause a higher risk of new caries lesions in both primary and permanent dentition, affecting lifelong oral health. The occurrence of ECC has been closely related to the core microbiome change in the oral cavity, which may be influenced by diet habits, oral health management, fluoride use, and dental manipulations. So, it is essential to improve parental oral health and awareness of health care, to establish a dental home at the early stage of childhood, and make an individualized caries management plan. Dental interventions according to the minimally invasive concept should be carried out to treat dental caries. This expert consensus mainly discusses the etiology of ECC, caries-risk assessment of children, prevention and treatment plan of ECC, aiming to achieve lifelong oral health.

The prevalence of liver disease has been increasing worldwide. Moreover, the burden of end-stage liver disease, including cirrhosis and liver cancer, is high because of high mortality and suboptimal treatment. The pathological process of liver disease includes steatosis, hepatocyte death, and fibrosis, which ultimately lead to cirrhosis and liver cancer. Clinical and preclinical evidence indicates that non-neoplastic liver diseases, particularly cirrhosis, are major risk factors for liver cancer, although the mechanism underlying this association remains unclear. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are transcriptional activators that regulate organ size and cancer development. YAP and TAZ play important roles in liver development, regeneration, and homeostasis. Abnormal YAP and TAZ levels have also been implicated in non-neoplastic liver diseases (e.g., non-alcoholic fatty liver disease, alcoholic liver disease, liver injury, and liver fibrosis). Here, we review recent findings on the roles of YAP and TAZ in non-neoplastic liver diseases and discuss directions for future research. This review provides a basis for the study of non-neoplastic liver diseases.

Purpose: Lung adenocarcinoma is one of the most common malignancies. Though some historic breakthroughs have been made in lung adenocarcinoma, its molecular mechanisms of development remain elusive. The aim of this study was to identify the potential genes associated with the lung adenocarcinoma progression and to provide new ideas for the prognosis evaluation of lung adenocarcinoma.Methods: The transcriptional profiles of ten pairs of snap-frozen tumor and adjacent normal lung tissues were obtained by performing RNA-seq. Weighted gene co-expression network analysis (WGCNA) was used to construct free-scale gene co-expression networks in order to explore the associations of gene sets with the clinical features and to investigate the functional enrichment analysis of co-expression genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Gene Set Enrichment Analysis (GSEA) analyses were performed using clusterProfiler. The protein-protein network (PPI) was established using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and hub genes were identified using Cytohubba in Cytoscape. Transcription factor enrichment analysis was performed by the RcisTarget program in R language.Results: Based on RNA-seq data, 1,545 differentially expressed genes (DEGs) were found. Eight co-expression modules were identified among these DEGs. The blue module exhibited a strong correlation with LUAD, in which ADCY4, RXFP1, AVPR2, CALCRL, ADRB1, RAMP3, RAMP2 and VIPR1 were hub genes. A low expression level of RXFP1, AVPR2, ADRB1 and VIPR1 was detrimental to the survival of LUAD patients. Genes in the blue module enriched in 86 Gene Ontology terms and five KEGG pathways. We also found that transcription factors EGR3 and EXOSC3 were related to the biological function of the blue module. Overall, this study brings a new perspective to the understanding of LUAD and provides possible molecular biomarkers for prognosis evaluation of LUAD.

Glioma is the most common primary malignant brain tumors in adults. Despite considerable advances in treatment, the clinical outcome remains dismal. Translocator protein 18 kDa (TSPO), an evolutionarily conserved transmembrane protein, has always been found to be elevated in glioma, which predicts a poor prognosis. However, studies on the regulatory network of TSPO in glioma are limited. The Cancer Genome Atlas (TCGA) and our research group cohorts demonstrated that TSPO expression was also highly expressed in glioma tissues and glioma cell lines. Inhibition of TSPO expression significantly reduced glioma cell proliferation and mobility

Background Excessive salt intake is associated with the deterioration of chronic kidney disease (CKD). Aldosterone is also known as an independent risk factor for kidney injury. Dietary sodium intake acts as a main stimulator in aldosterone-mediated kidney injury. Hence, this study aimed to further investigate the renal protective effects and safety of a low-sodium diet in combination with spironolactone (SPL) in stage 1-3a CKD. Methods This single-center, SPL-blinded randomized controlled trial recruited patients with stage 1-3a CKD, randomized into three groups, low-sodium (3 g/d salt) + placebo, medium-sodium (5 g/d salt) + SPL, and low-sodium (3 g/d salt) + SPL. Patients received 12 weeks of intervention. The primary and secondary endpoints were 24-h urine protein and estimated glomerular filtration rate (eGFR) at the end of the intervention, respectively. Results A total of 74 patients were analyzed eventually. Significantly decreased 24-h urine protein was found in all three groups, from 0.37 to 0.23 g/d (P = 0.004) in the low-sodium+placebo group, from 0.44 to 0.29 g/d (P = 0.020) in the medium-sodium+SPL group, and from 0.35 to 0.31 g/d (P = 0.013) in the low-sodium +SPL group. There were no significant differences among the three groups in 24-h urine protein amount change after intervention from pre-treatment values (P = 0.760, ITT set). The results of the 24-h urine protein by using PP set analysis was similar to the ITT set. No significant differences in eGFR, nutritional, metabolic, inflammatory, and other biomarkers were observed across all three groups (P > 0.05). No safety signal was observed. Conclusion No additional benefit was observed when SPL was prescribed to patients already on a low-sodium diet (3.0 g/d). Still, small doses of SPL may benefit patients with poor sodium restriction. A combination of short-term low-dose SPL and ARB is safe for patients with stage 1-3a CKD, but blood potassium must be regularly monitored. Trial registration Name of the registry: Chinese clinical trial registry. Trial registration number: ChiCTR1900026991. Date of registration: Retrospectively registered 28 October 2019. URL of trial registry record: http://www.chictr.org.cn/searchproj.aspx?title=&officialname=&subjectid=&secondaryid=&applier=&studyleader=ðicalcommitteesanction=&spo

To investigate the utility of histogram analysis of zoomed EPI diffusion-weighted imaging (DWI) for predicting the perineural invasion (PNI) status of rectal cancer (RC).This prospective study evaluated 94 patients diagnosed with histopathologically confirmed RC between July 2020 and July 2021. Patients underwent preoperative rectal magnetic resonance imaging (MRI) examinations, including the zoomed EPI DWI sequence. Ten whole-tumor histogram parameters of each patient were derived from zoomed EPI DWI. Reproducibility was evaluated according to the intra-class correlation coefficient (ICC). The association of the clinico-radiological and histogram features with PNI status was assessed using univariable analysis for trend and multivariable logistic regression analysis with β value calculation. Receiver operating characteristic (ROC) curve analysis was conducted to assess the diagnostic performance.Forty-two patients exhibited positive PNI. The inter- and intraobserver agreements were excellent for the histogram parameters (all ICCs 0.80). The maximum (p = 0.001), energy (p = 0.021), entropy (p = 0.021), kurtosis (p 0.001), and skewness (p 0.001) were significantly higher in the positive PNI group than in the negative PNI group. Multivariable analysis showed that higher MRI T stage [β = 2.154, 95% confidence interval (CI) 0.932-3.688; p = 0.002] and skewness (β = 0.779, 95% CI 0.255-1.382; p = 0.006) were associated with positive PNI. The model combining skewness and MRI T stage had an area under the ROC curve of 0.811 (95% CI 0.724-0.899) for predicting PNI status.Histogram parameters in zoomed EPI DWI can help predict the PNI status in RC.

Benzo[a]pyrene (B[a]P) is a known human carcinogen and plays a major function in the initiation of lung cancer at its first proximity. However, the underlying molecular mechanisms are less well understood. In this study, we investigated the impact of B[a]P treatment on the DNA methylation and mRNA levels of

Fangcang shelter (Cabin) hospitals were set up in order to cope with the rapid growth of confirmed cases of coronavirus disease 2019 (COVID‐19) in Wuhan, China at a time when there were insufficient beds in designated hospitals. This paper describes the layout and functioning of a typical Fangcang shelter hospital, Wuhan Dongxihu Fangcang shelter Hospital, where the author has worked, the working mechanism, experience and effectiveness. A set of patient management protocols was employed for daily practice, which included preset criteria and procedure for admission, examination, medication treatment, referral and discharge. WeChat platform with different groups was used for communication, ward round, test appointments and patient data communication. All these procedures and mechanisms of working enabled the effective management of a larger number of patients with relatively few doctors. As a result, 442 mild or moderate COVID‐19 patients in Hall C were successfully managed by a team of 40 doctors, with 246 (56%) patients were cured and discharged from the Fangcang shelter hospital while the remaining 196 (44%) patients were referred on to designated hospitals for further treatment. The reasons for referral included poor resolution in computerized tomography (CT) scan (59%), persistently positive severe acute respiratory syndrome coronavirus 2 by PCR after 9 days of admission (16%), deterioration in CT image (4%), development of dyspnoea (1%) and other (4%) or unclear reasons (16%) due to no record of reasons for referral on the document. There were no deaths and no complaints from the patients in Hall C. In summary, the Fangcang shelter hospital could be run successfully with a set of patient management protocols under conditions of limited facilities and medical staff. It was effective and safe in isolating patients, providing basic medical care and early identification of potential severe cases. This experience may provide a successful example of a working mechanism for the prevention and control of the COVID‐19 pandemic worldwide.

Enterostomy patients were exposed to various stressors, and self-care ability played an important role in their daily lives. This study aimed to examine the relationship between perceived social support and self-care ability among Chinese enterostomy patients and to explore whether perceived stress mediated this relationship. A sample of 410 enterostomy patients aged 59.68 ± 12.95 years old were recruited in the study. Participants completed a set of questionnaires including demographics, perceived stress scale, perceived social support scale, and ostomy self-care ability scale. A total of 392 valid questionnaires were finally used in the data analyses among 410 questionnaires; the effective response rate was 95.6%. Results demonstrated that the scores of perceived social support were positively correlated with scores of self-care ability scores and negatively with perceived stress scores. And the effect of perceived social support on self-care ability was partially mediated by perceived stress (51.53%). This study explained the mediating model that connects perceived social support with self-care ability through perceived stress, which enhances our understanding about the mediating role of perceived stress. Thus, when focusing on the self-care ability of enterostomy patients, perceived stress was as important as perceived social support.

OBJECTIVE To evaluate the clinical significance of serum and urinary microRNA-423-5p in the prediction of acute kidney injury onset and survival in patients with acute decompensated heart failure. METHODS A total of 180 acute decompensated heart failure patients, including 57 acute kidney injury cases and 123 non-acute kidney injury cases, were included in this study. Serum and urinary neutrophil gelatinase-associated lipocalin, a biomarker of renal injury of acute kidney injury, was detected using an enzyme-linked immunosorbent assay. Expression of microRNA-423-5p in serum and urine samples was examined using quantitative real-time polymerase chain reaction. The clinical significance of microRNA-423-5p was evaluated using receiver operating characteristic curve and Kaplan-Meier survival analysis. RESULTS The levels of neutrophil gelatinase-associated lipocalin and microRNA-423-5p in serum and urine samples were elevated in patients with acute kidney injury compared with the non-acute kidney injury cases (all P

Rationale and Objectives This study aimed to investigate the predictive value of pre-/postneoadjuvant chemoradiotherapy (nCRT) magnetic resonance imaging (MRI) characteristics for the long-term survival outcomes in patients with locally advanced rectal cancer (LARC). Materials and Methods We retrospectively evaluated pre- and post-nCRT MRI and clinicopathologic characteristics of LARC patients. The 3-year disease-free survival (DFS) was estimated using the Kaplan-Meier product-limit method. Associations between MRI variabilities and survival outcomes were assessed using Cox proportional hazards model. Results In total, 171 LARC patients (112 men and 59 women) with a median age of 55 years (range, 27–82 years) treated with nCRT were evaluated. The median follow-up was 47.6 months, and the 3-, 4-, and 5-year DFS in the overall cohort was 76.6%, 74.5%, and 73.7%, respectively. MRI assessment of extramural venous invasion (mrEMVI) positivity was a significant independent adverse factor of long-term survival (hazard ratio [HR] = 2.589, 95% confidence interval [CI] = 1.398–4.794, p = 0.002) on multivariate analysis. Patients with positive mrEMVI had significantly lower 3-year DFS than those with negative mrEMVI (52.6 months vs 65.1 months; p = 0.003). Moreover, the tumor regression grade on MRI (mrTRG) also significantly correlated with survival outcomes in patients with LARC. Patients with partial response on post-nCRT MRI (mrPR) showed short DFS than those with complete response (mrCR; HR = 4.914, 95% CI = 1.176–20.533, p = 0.029). The 3-year DFS of mrCR and mrPR patients were 74.3 months and 58.9 months, respectively (p = 0.011). Conclusion The pre-/post-nCRT MRI characteristics may be used to long-term survival stratification in LARC patients. mrEMVI positivity was an independent adverse prognostic indicator for 3-year DFS. Further, mrTRG may also be a predictive factor for the prognosis of LARC patients. The pre-/post-nCRT MR imaging may offer more information for providing individualized treatment.

Highlights • Epidemic dynamics of COVID-19 by age and gender groups in South Korea are different. • The epidemic process of COVID-19 was driven by young people aged 20-39, with two peaks from Feb 19 to May 2, 2020. • The epidemic in the elderly people had been declining steadily after Mar. 15, 2020, despite large fluctuations in daily new cases among young people. • Elderly people can be effectively protected during the COVID-19 pandemic., Objectives Elderly people had suffered disproportional burden of COVID-19. We hypothesized that males and females in different age groups might have different epidemic trajectories. Methods Using publicly available data from South Korea, daily new COVID-19 cases were fitted with generalized additive models, assuming Poisson and negative binomial distributions. Epidemic dynamics by age and gender groups were explored with interactions between smoothed time terms and age and gender. Results A negative binomial distribution fitted the daily case counts best. Interaction between the dynamic patterns of daily new cases and age groups was statistically significant (p

Dental mesenchymal stem cells (MSCs) are recognized as a critical factor in repair of defective craniofacial bone owing to the multiple differentiation potential, the ability to regenerate distinct tissues, and the advantage that they can be easily obtained by relatively noninvasive procedures. Special AT-rich sequence-binding protein 2 (SATB2) is a nuclear matrix protein, involved in chromatin remodeling and transcriptional regulation, and has been reported to be as a positive regulator of osteoblast differentiation, bone formation, and bone regeneration in MSCs. In this study, we systematically investigated the capability of SATB2 to promote the osteogenic differentiation of periodontal ligament stem cells (PDLSCs), dental pulp stem cells (DPSCs), and stem cells from human exfoliated deciduous teeth (SHED). RNA-seq analysis and quantitative real-time PCR (RT-PCR) revealed that genes regulating osteogenic differentiation were differentially expressed among three cell types and SATB2 was found to be expressed at a relatively high level. When the three cell types overexpressed SATB2 with AdSATB2 infection, alkaline phosphatase (ALP) staining, ALP activity, Alizarin Red S staining, and quantification tended to increase with an increasing infection rate. It showed opposite results after infection with AdsiSATB2. RNA-seq analysis indicated that the expression of downstream osteogenic genes was affected by AdSATB2 infection and quantitative RT-PCR confirmed that nine osteogenic genes (Spp1, Sema7a, Atf4, Ibsp, Col1a1, Sp7, Igfbp3, Dlx3, and Alpl) were upregulated, to various extents, following SATB2 overexpression. In addition, quantitative PCR results indicated that SATB2 affected the expression of MSC markers. These results suggested an important role of SATB2 in the osteogenesis of PDLSCs, DPSCs, and SHED. Further research is warranted to investigate SATB2-mediated regulation of osteogenic differentiation and to evaluate the therapeutic use of SATB2 for the regeneration of defective craniofacial bone tissue.

Distant metastasis (DM) is the main cause of treatment failure in locally advanced rectal cancer. Adjuvant chemotherapy is usually used for distant control. However, not all patients can benefit from adjuvant chemotherapy, and particularly, some patients may even get worse outcomes after the treatment. We develop and validate an MRI-based radiomic signature (RS) for prediction of DM within a multicenter dataset. The RS is proved to be an independent prognostic factor as it not only demonstrates good accuracy for discriminating patients into high and low risk of DM in all the four cohorts, but also outperforms clinical models. Within the stratified analysis, good chemotherapy efficacy is observed for patients with pN2 disease and low RS, whereas poor chemotherapy efficacy is detected in patients with pT1–2 or pN0 disease and high RS. The RS may help individualized treatment planning to select patients who may benefit from adjuvant chemotherapy for distant control., Distant metastasis (DM) is the main cause of treatment failure in locally advanced rectal cancer. Here, the authors developed and validated a radiomic signature (RS) for prediction of DM within a multicenter dataset, and suggest that it may help with stratification of patients who might benefit from adjuvant chemotherapy for DM.

The present study included 658 hospitalized patients with confirmed COVID‐19. Forty‐two (6.4%) out of 658 patients presented with ketosis on admission with no obvious fever or diarrhoea. They had a median (interquartile range [IQR]) age of 47.0 (38.0–70.3) years, and 16 (38.1%) were men. Patients with ketosis were younger (median age 47.0 vs. 58.0 years; P = 0.003) and had a greater prevalence of fatigue (31.0% vs. 10.6%; P

Cancer progression involves biomechanical changes within transformed cells and the surrounding extracellular matrix (ECM). The viscoelastic features of fluidity and elasticity that are based on a novel Kelvin–Voigt fractional derivative (KVFD) model were found capable of discriminating normal, benign and malignant breast biopsy tissues on the cellular scale. The improved specificity of KVFD model parameters derives from greater accuracy of fitting the entire approaching force-indentation measurement curve ( $$R^{2}$$ > 0.99) compared with traditional elastic models ( $$R^{2}$$

BackgroundAdolescence is a significant period for the gender-dependent development of lung function. Prior studies have shown that DNA methylation (DNA-M) is associated with lung function and DNA-M at some cytosine-phosphate-guanine dinucleotide sites (CpGs) changes over time. This study examined whether changes of DNA-M at lung-function-related CpGs are associated with changes in lung function during adolescence for each gender, and if so, the biological significance of the detected CpGs.MethodsGenome-scale DNA-M was measured in peripheral blood samples at ages 10 (n = 330) and 18 years (n = 476) from the Isle of Wight (IOW) birth cohort in United Kingdom, using Illumina Infinium arrays (450 K and EPIC). Spirometry was conducted at both ages. A training and testing method was used to screen 402,714 CpGs for their potential associations with lung function. Linear regressions were applied to assess the association of changes in lung function with changes of DNA-M at those CpGs potentially related to lung function. Adolescence-related and personal and family-related confounders were included in the model. The analyses were stratified by gender. Multiple testing was adjusted by controlling false discovery rate of 0.05. Findings were further examined in two independent birth cohorts, the Avon Longitudinal Study of Children and Parents (ALSPAC) and the Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) cohort. Pathway analyses were performed on genes to which the identified CpGs were mapped.ResultsFor females, 42 CpGs showed statistically significant associations with change in FEV1/FVC, but none for change in FEV1or FVC. No CpGs were identified for males. In replication analyses, 16 and 21 of the 42 CpGs showed the same direction of associations among the females in the ALSPAC and BAMSE cohorts, respectively, with 11 CpGs overlapping across all the three cohorts. Through pathway analyses, significant biological processes were identified that have previously been related to lung function development.ConclusionsThe detected 11 CpGs in all three cohorts have the potential to serve as the candidate epigenetic markers for changes in lung function during adolescence in females.

Lung adenocarcinoma is recognized as one of the most recurrent tumours in adults. Long non‐coding RNAs (lncRNAs) are non–protein‐coding transcripts and have been demonstrated to regulate biological functions during tumorigenesis. Our study aims to investigate the underlying molecular mechanisms of LINC00461/microRNA‐195 (miR‐195)/HOXA10 responsible for its involvement in lung adenocarcinoma. We firstly selected differentially expressed lncRNAs and genes by the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO). The functional role of LINC00461 in lung adenocarcinoma was then determined using ectopic expression, knockdown and reporter assay experiments. Besides, we detected the expression profiles of LINC00461, miR‐195, HOXA10 and apoptosis‐ and invasion‐related genes. Cell proliferation, migration and invasion were evaluated. In vivo tumour formation ability was analysed. Overexpressed LINC00461 and HOXA10 but down‐regulated miR‐195 were observed in primary and metastatic lung adenocarcinoma. LINC00461 negatively regulated miR‐195, while miR‐195 negatively regulated HOXA10. Forced LINC00461 expression decreased expression of miR‐195 and Bax, increased expression of HOXA10, MMP‐2, MMP‐9 and Bcl‐2, promoted cell proliferation, migration and invasion as well as tumour formation, and enhanced radiosensitivity of lung adenocarcinoma cells. However, these effects were reversed by lentivirus‐mediated miR‐195–forced expression, thereby suggesting that miR‐195 could antagonize the harmful effect of LINC00461 on lung adenocarcinoma cells. Collectively, the present study provides evidence supporting the inhibitory effect of LINC00461 silencing on lung adenocarcinoma, which suppresses lung adenocarcinoma cell migration, invasion and radiosensitivity via HOXA10 by binding to miR‐195, which provides a promising basis for the targeted intervention treatment for human lung adenocarcinoma.