hucMSC-Derived Exosomes Alleviate the Deterioration of Colitis via the miR-146a/SUMO1 Axis.

Human umbilical cord mesenchymal stem cell-derived exosome (hucMSC-Ex) plays an important role in tissue repair and immunomodulation, leading to the mitigation of inflammatory bowel disease. However, the preventive function of hucMSC-Ex in the onset and progression of colitis-associated colon cancer (CAC) is poorly understood. In the current study, dextran sodium sulfate/azoxymethane-induced colitis mouse model was established, and the mice disease activity index, body weight, colon length, tumor counts, survival curve, tissue H&E/immunohistochemistry, and cytokines expression were analyzed to evaluate the effects of hucMSC-Ex on CAC. In addition, miR-146a mimics were transfected into colonic epithelial cells (fetal human cells) to evaluate their role in the hucMSC-Ex-mediated regulation of SUMO1. The results showed that hucMSC-Ex inhibits the expression of SUMO1 to reduce the process of CAC progression. Further analysis indicated that miR-146a targets and inhibits SUMO1 expression and its binding to ß-catenin. In conclusion, our findings showed that hucMSC-Ex is effective in alleviating the deterioration of colitis via the miR-146a-mediated inhibition of SUMO1, which is crucial in this disease process.

A Descriptive Analysis of the Epidemiology and Motivations for Laser Tattoo Removal in an Underserved Population.

Tattoos of formerly gang-involved and incarcerated individuals can negatively impact their ability to reintegrate into society. Laser tattoo removal is essential to helping individuals obtain employment, re-cultivate positive relationships, and disengage from gangs. The objective of this study is to describe the demographics and motivations for laser tattoo removal at a large nonprofit clinic. This was a single center retrospective study conducted on patients presenting to Ya'stuvo Tattoo Removal between January 2016-December 2018 and had at least three laser tattoo removal sessions. Data was recorded on patient demographics, geographic location of residence (e.g. zipcode), comorbidities, probation/parole status, referral source, transportation mode, and motivations for receiving and removing tattoos. A representative sample of 862 patients was used to conduct our analysis. Average age at first visit was 30. 16% (n = 134) were on probation, 8% (n = 66) were on parole, and 63% (n = 544) did not report their probation/parole status. Reasons for receiving a tattoo included gangs (46%, n = 368), a current or ex-relationship (28%, n = 223), and decoration (20%, n = 159). The most common reasons for tattoo removal were employment (66%, n = 546), readiness to change life (47%, n = 392), maturity (47%, n = 392), family (43%, n = 356), and negative attention from tattoos (37%, n = 303). The current study highlights the importance of laser tattoo removal in reintegration and gang disengagement. Expanding cost efficient laser tattoo removal is paramount to meet the safety and socioeconomic needs of this population.

Cellular and molecular mediators of lymphangiogenesis in inflammatory bowel disease.

BACKGROUND: Recent studies reporting the intricate crosstalk between cellular and molecular mediators and the lymphatic endothelium in the development of inflammatory bowel diseases (IBD) suggest altered inflammatory cell drainage and lymphatic vasculature, implicating the lymphatic system as a player in the occurrence, development, and recurrence of intestinal diseases. This article aims to review recent data on the modulatory functions of cellular and molecular components of the IBD microenvironment on the lymphatic system, particularly lymphangiogenesis. It serves as a promising therapeutic target for IBD management and treatment. The interaction with gut microbiota is also explored. MAIN TEXT: Evidence shows that cells of the innate and adaptive immune system and certain non-immune cells participate in the complex processes of inflammatory-induced lymphangiogenesis through the secretion of a wide spectrum of molecular factors, which vary greatly among the various cells. Lymphangiogenesis enhances lymphatic fluid drainage, hence reduced infiltration of immunomodulatory cells and associated-inflammatory cytokines. Interestingly, some of the cellular mediators, including mast cells, neutrophils, basophils, monocytes, and lymphatic endothelial cells (LECs), are a source of lymphangiogenic molecules, and a target as they express specific receptors for lymphangiogenic factors. CONCLUSION: The effective target of lymphangiogenesis is expected to provide novel therapeutic interventions for intestinal inflammatory conditions, including IBD, through both immune and non-immune cells and based on cellular and molecular mechanisms of lymphangiogenesis that facilitate inflammation resolution.

Improved therapeutics of modified mesenchymal stem cells: an update.

BACKGROUND: Mesenchymal stromal cells (MSCs) have attracted intense interest due to their powerful intrinsic properties of self-regeneration, immunomodulation and multi-potency, as well as being readily available and easy to isolate and culture. Notwithstanding, MSC based therapy suffers reduced efficacy due to several challenges which include unfavorable microenvironmental factors in vitro and in vivo. BODY: In the quest to circumvent these challenges, several modification techniques have been applied to the naïve MSC to improve its inherent therapeutic properties. These modification approaches can be broadly divided into two groups to include genetic modification and preconditioning modification (using drugs, growth factors and other molecules). This field has witnessed great progress and continues to gather interest and novelty. We review these innovative approaches in not only maintaining, but also enhancing the inherent biological activities and therapeutics of MSCs with respect to migration, homing to target site, adhesion, survival and reduced premature senescence. We discuss the application of the improved modified MSC in some selected human diseases. Possible ways of yet better enhancing the therapeutic outcome and overcoming challenges of MSC modification in the future are also elaborated. CONCLUSION: The importance of prosurvival and promigratory abilities of MSCs in their therapeutic applications can never be overemphasized. These abilities are maintained and even further enhanced via MSC modifications against the inhospitable microenvironment during culture and transplantation. This is a turning point in MSC-based therapy with promising preclinical studies and higher future prospect.

The ignored emission of volatile organic compounds from iron ore sinter process.

Iron ore sintering is a major source of gaseous and particulate pollutants emission in iron smelt plant. The aim of present study is to characterize the volatile organic compounds (VOCs) emission profiles from iron ore sintering process. Both sinter pot test and sinter simulation experiment were conducted and compared. Out results showed that sinter process produced large quantity of VOCs together with NOx and SO2. VOCs and NO were produced simultaneously in sinter pot test from 3 to 24 min after ignition, flowed by SO2 production from 15 min to the end of sintering. Total VOCs (TVOC) concentration in sinter flue gas was affected by the coal and coke ratio in sinter raw material. The maximum TVOC concentration was 34.5 ppm when using 100% coal as fuel. Sinter simulation experiments found that the number of VOCs species and their concentrations were found by sinter temperature. The largest VOCs species varieties were obtained at 500 °C. Benzene, toluene, xylene and ethylbenzene were major VOCs in sinter flue gas based on the results from both simulation test and sinter pot. It thus demonstrated that in addition to NOx, SO2 and metal oxide particles, sinter flue gas also contained significant amount of VOCs whose environmental impact cannot be ignored. Based on our work, it is timely needed to establish a new VOC emission standard for sinter flue gas and develop advanced techniques to simultaneously eliminate multi-pollutants in iron ore sinter process.

Quercetin ameliorates ischemia/reperfusion-induced cognitive deficits by inhibiting ASK1/JNK3/caspase-3 by enhancing the Akt signaling pathway.

Cerebral ischemia/reperfusion (I/R) is a major cause of severe disability and death all worldwide. However, therapeutic options to minimize the detrimental effects of cerebral I/R injury are limited. Recent research has demonstrated that quercetin mediates neuroprotective effects associated with the activation of the Akt signaling pathway in the cerebral I/R brain. Therefore, the aim of this study was to further investigate the mechanisms of cognitive deficits induced by cerebral I/R injury and the effects of quercetin on these mechanisms. First, we assessed anxiety-like behavioral and cognitive impairment using the open field test and the Morris water maze test, respectively. Next, we examined the severity of apoptosis by staining hippocampal neurons by the Cresyl violet method. Third, we used western blot analysis to investigate the expression of total and phosphorylated Akt, ASK1, JNK3, c-Jun and caspase-3 after I/R injury. Our results revealed that mice subjected to bilateral common carotid occlusion exhibited severe anxiety-like behavior, learning and memory impairment, cell damage and apoptosis. These severe effects were attenuated by administration of quercetin. Further, western blot analysis revealed that quercetin increased p-Akt expression and decreased p-ASK1, p-JNK3 and cleaved caspase-3 expression after cerebral I/R injury and led to inhibition of neuronal apoptosis. Conversely, treatment with LY294002 (a selective inhibitor of Akt1) reversed the effects of quercetin. In conclusion, these findings highlight the important role of quercetin in protecting against cognitive deficits and inhibiting neuronal apoptosis via the Akt signaling pathway. We believe that quercetin might prove to be a useful therapeutic component in treating cerebral I/R diseases in the near future.

[3D hemodynamic numerical simulation of carotid artery aneurysm before and after surgery based on CT date].

Hemodynamic situation is an important factor of recurrence of postoperative carotid artery aneurysm. In order to investigate the hemodynamic factors of postoperative carotid artery aneurysm affect carotid artery aneurysm recurrence, we established a 3D finite element carotid artery aneurysm for the preoperative and postoperative periods using the three-dimensional reconstruction techniques. And then we measured the hemodynamic factors of carotid artery aneurysm of preoperative and postoperative by the finite element method. The carotid artery aneurysm model has an accurate and realistic shape; the pressure of the recurrence of aneurysm was reduced significantly after surgery,wall shear stress increased significantly at residual neck, and blood flow velocity increased significantly, which will increase the risk of recurrence. The hemodynamic analysis provides a reference for development of aneurysm clinical treatment programs and prevention of recurrence.

DNA methylation markers in esophageal cancer.

Background: Esophageal cancer (EC) is a prevalent malignancy characterized by a low 5-year survival rate, primarily attributed to delayed diagnosis and limited therapeutic options. Currently, early detection of EC heavily relies on endoscopy and pathological examination, which pose challenges due to their invasiveness and high costs, leading to low patient compliance. The detection of DNA methylation offers a non-endoscopic, cost-effective, and secure approach that holds promising prospects for early EC detection. Methods: To identify improved methylation markers for early EC detection, we conducted a comprehensive review of relevant literature, summarized the performance of DNA methylation markers based on different input samples and analytical methods in EC early detection and screening. Findings: This review reveals that blood cell free DNA methylation-based method is an effective non-invasive method for early detection of EC, although there is still a need to improve its sensitivity and specificity. Another highly sensitive and specific non-endoscopic approach for early detection of EC is the esophageal exfoliated cells based-DNA methylation analysis. However, while there are substantial studies in esophageal adenocarcinoma, further more validation is required in esophageal squamous cell carcinoma. Conclusion: In conclusion, DNA methylation detection holds significant potential as an early detection and screening technology for EC.

Radical Decarboxylation-Initiated SH2' Reaction of ß,ß-Difluoroenol Sulfonates: Access to α,α-Difluoroketones.

Reported herein is a novel radical decarboxylation-initiated SH2' reaction of ß,ß-difluoroenol sulfonates. This transformation is characterized by mild reaction conditions, a broad substrate scope, and late-stage modification of drug molecules, providing general and mechanistically distinct access to bioactive and synthetically versatile α,α-difluoroketones. Preliminary mechanistic studies demonstrate that this reaction proceeds through a succession of silver-mediated decarboxylative radical generation and radical-addition-induced ß-elimination of the sulfonyl radical.

The global burden of gynecological diseases from 1990 to 2019.

INTRODUCTION: Gynecological diseases ranked second among new cases of noncommunicable diseases in women of reproductive age in 1990 and 2019 globally. The aim of this study was to estimate the disease burden of gynecological diseases and describe their trends in women of all ages from 1990 to 2019. METHODS: Using data from the Global Burden of Diseases, Injuries and Risk Factors Study (GBD 2019), we examined the incidence, disability-adjusted life years (DALYs) and deaths from gynecological diseases by age in 204 countries and territories worldwide from 1990 to 2019. Analyses were conducted in 2022. RESULTS: Globally, the age-standardized incidence rate (ASIR) and age-standardized DALY rate (ASDR) of gynecological diseases decreased by -0.176 % and -0.245 %, respectively from 1990 to 2019. Low socioeconomic development index (SDI) countries had the highest ASIR and ASDR in 2019. The age-specific incidence rate of gynecological diseases in women aged 15-29 years increased from 1990 to 2019, and the 20-24-year age group increased the greatest by 0.21%. Polycystic ovary syndrome and other types of benign disorders contributed to the major increase. CONCLUSIONS: Although the disease burden of gynecological diseases decreased slightly between 1990 and 2019 globally, it remained highest in low SDI countries. The disease burden in 20-24-year age group exhibited the fastest growth, with polycystic ovary syndrome and other types of benign disorders playing a significant role. Urgent and effective measures should be taken to target different age groups, types of gynecological disease and regions with high disease burdens.

An ultrasensitive and multiplexed miRNA one-step real time RT-qPCR detection system and its application in esophageal cancer serum.

MicroRNAs (miRNAs) are increasingly recognized as promising biomarkers for early disease diagnosis and prognosis. Therefore, the need for rapid, robust methods for multiplex miRNA detection in biological research and clinical diagnosis is crucial. This study introduces a novel multiplex miRNA detection method, SMOS-qPCR (Sensitive and Multiplexed One-Step RT-qPCR). The method integrates multiplexed reverse transcription and TaqMan-based qPCR into a single tube, employing a one-step operation on a real-time PCR system. We investigated the effect of 3' end phosphorylation of the Linker, Linker concentration and probe concentration on the SMOS-qPCR, resulted in a wide linear range from 1 fM to 0.1 zM (R2 ≥ 0.99 for each miRNA), surpassing the capabilities of stem-loop RT-qPCR and SYBR Green One-step RT-qPCR. The method showed excellent performance in distinguishing mature miRNA from miRNA precursor, and successfully detected four miRNAs in a single tube without cross-interference. Its high specificity enables precise differentiation of less than 1% nonspecific signal. Finally, we demonstrated the effectiveness of the SMOS-qPCR system in detecting circulating miRNAs in serum samples, distinguishing between esophageal cancers and health individuals with high AUC values (>0.940). In conclusion, the proposed SMOS-qPCR system offers a straightforward and promising approach for miRNA profiling in future clinical applications.

[Role of small-dose recombinant human coagulation factor VIIa for coagulopathy in patients with isolated traumatic brain injury].

OBJECTIVE: To explore the role of small-dose recombinant human coagulation factor VIIa (rFVIIa) for coagulopathy in patients with isolated traumatic brain injury. METHODS: A total of 86 isolated traumatic brain patients with coagulopathy were treated at our neurosurgery intensive care unit (NICU) from January 2010 to December 2012. Their trauma registry data included mortality, pre-and post-rFVIIa coagulation parameters. Two-tailed paired t-test was used to determine significant changes in coagulation parameters and other major clinical parameters. RESULTS: Twenty-seven patients made up the low-dose rFVIIa (20 µg/kg) group. And the control group had 59 well-matched subjects. At admission, age, blood pressure, Glasgow coma scale score, hemoglobin, platelets and international normalize ratio were similar in both groups. After treatment, the INR of patients on rFVIIa was lower than that of the conventional treatment group (1.1 ± 0.2 vs 1.2 ± 0.2, P < 0.01) and it declined more in the rFVIIa group (0.3 ± 0.2 vs 0.1 ± 0.4, P = 0.05). No significant difference existed in mortality or length of stay between two groups.There was no occurrence of subsequent thromboembolic events. CONCLUSION: The application of small-dose rFVIIa can effectively reduce the value of INR and improve the coagulation status of patients. During the course of treatment, no major adverse events occur.

Expression And Prognostic Role of PRDX1 In Gastrointestinal Cancers.

Esophageal, gastric, liver, and colorectal cancers represent four prevalent gastrointestinal cancers that pose substantial threats to global health due to their high morbidity and mortality rates. Peroxiredoxin 1 (PRDX1), a significant component of the PRDXs family, primarily functions to counteract the peroxides produced by metabolic activities in the body, thereby maintaining the dynamic equilibrium of peroxides in vivo. Intriguingly, PRDX1 expression correlates strongly with cancer's onset, progression, and prognosis. This study mainly applied bioinformatics methods to analyze PRDX1's expression, diagnosis, and prognosis in gastrointestinal cancers and to summarize current research advancements. Evidence from the bioinformatics database suggested that the high expression of PRDX1 was a prominent characteristic of these four gastrointestinal cancers, with this observation reaching statistical significance. The high expression of PRDX1 in gastrointestinal cancer cells also confirms this result. Notably, the primary alteration in PRDX1 within these cancers is the presence of genetic mutations. PRDX1 demonstrated the highest diagnostic efficacy for colorectal cancer. Nevertheless, elevated PRDX1 levels only significantly diminished the survival time of liver cancer patients, exerting no statistically significant impact on the survival duration of patients afflicted by the other three types of gastrointestinal cancers. Recent research has indicated variability in PRDX1 expression across different cancer types, with high expression being predominantly observed in these four gastrointestinal cancers and, in most instances, unfavorable prognosis. These findings broadly align with the results derived from bioinformatics. This research underscores the high expression of PRDX1 in gastrointestinal cancers, its relevance to the diagnosis and prognosis monitoring of these cancers, and its potential to guide clinical treatment for these cancers.

An overview of DNA methylation markers for early detection of gastric cancer: current status, challenges, and prospects.

Background: Gastric cancer (GC) is one of the most common malignancies, with a low 5-year survival rate. However, if diagnosed at an early stage, it can be cured by endoscopic treatment and has a good prognosis. While gastrointestinal X-ray and upper endoscopy are used as national GC screening methods in some GC high-risk countries, such as Japan and Korea, their radiation exposure, invasiveness, and high cost suggest that they are not the optimal tools for early detection of GC in many countries. Therefore, a cost-effective, and highly accurate method for GC early detection is urgently needed in clinical settings. DNA methylation plays a key role in cancer progression and metastasis and has been demonstrated as a promising marker for cancer early detection. Aims and methods: This review provides a comprehensive overview of the current status of DNA methylation markers associated with GC, the assays developed for GC early detection, challenges in methylation marker discovery and application, and the future prospects of utilizing methylation markers for early detection of GC. Through our analysis, we found that the currently reported DNA methylation markers related to GC are mainly in the early discovery stage. Most of them have only been evaluated in tissue samples. The majority of non-invasive assays developed based on blood lack standardized sampling protocols, pre-analytical procedures, and multicenter validation, and they exhibit insufficient sensitivity for early-stage GC detection. Meanwhile, the reported GC DNA methylation markers are generally considered pan-cancer markers. Conclusion: Therefore, future endeavors should focus on identifying additional methylation markers specific to GC and establishing non-invasive diagnostic assays that rely on these markers. These assays should undergo multicenter, large-scale prospective validation in diverse populations.

Resveratrol alleviates DSS-induced IBD in mice by regulating the intestinal microbiota-macrophage-arginine metabolism axis.

BACKGROUND: Inflammatory bowel disease (IBD) is a global disease with a growing public health concern and is associated with a complex interplay of factors, including the microbiota and immune system. Resveratrol, a natural anti-inflammatory and antioxidant agent, is known to relieve IBD but the mechanism involved is largely unexplored. METHODS: This study examines the modulatory effect of resveratrol on intestinal immunity, microbiota, metabolites, and related functions and pathways in the BALB/c mice model of IBD. Mouse RAW264.7 macrophage cell line was used to further explore the involvement of the macrophage-arginine metabolism axis. The treatment outcome was assessed through qRT-PCR, western blot, immunofluorescence, immunohistochemistry, and fecal 16S rDNA sequencing and UHPLC/Q-TOF-MS. RESULTS: Results showed that resveratrol treatment significantly reduced disease activity index (DAI), retained mice weight, repaired colon and spleen tissues, upregulated IL-10 and the tight junction proteins Occludin and Claudin 1, and decreased pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α. Resveratrol reduced the number of dysregulated metabolites and improved the gut microbial community structure and diversity, including reversing changes in the phyla Bacteroidetes, Proteobacteria, and Firmicutes, increasing 'beneficial' genera, and decreasing potential pathogens such as Lachnoclostridium, Acinobacter, and Serratia. Arginine-proline metabolism was significantly different between the colitis-treated and untreated groups. In the colon mucosa and RAW264.7 macrophage, resveratrol regulated arginine metabolism towards colon protection by increasing Arg1 and Slc6a8 and decreasing iNOS. CONCLUSION: This uncovers a previously unknown mechanism of resveratrol treatment in IBD and provides the microbiota-macrophage-arginine metabolism axis as a potential therapeutic target for intestinal inflammation.

Identifying potential DNA methylation markers for the detection of esophageal cancer in plasma.

Background: Esophageal cancer (EC) is a leading cause of cancer-related deaths in China, with the 5-year survival rate reaching less than 30%, because most cases were diagnosed and treated at the advanced stage. However, there is still a lack of low-cost, efficient, and accurate non-invasive methods for the early detection of EC at present. Methods: A total of 48 EC plasma and 101 control plasma samples were collected in a training cohort from 1 January 2021 to 31 December 2021, and seven cancer-related DNA methylation markers (ELMO1, ZNF582, FAM19A4, PAX1, C13orf18, JAM3 and TERT) were tested in these samples to select potential markers. In total, 20 EC, 10 gastric cancer (GC), 10 colorectal cancer (CRC), and 20 control plasma samples were collected in a validation cohort to evaluate the two-gene panel. Results: ZNF582, FAM19A4, JAM3, or TERT methylation in plasma was shown to significantly distinguish EC and control subjects (p < 0.05), and the combination of ZNF582 and FAM19A4 methylation was the two-gene panel that exhibited the best performance for the detection of EC with 60.4% sensitivity (95% CI: 45.3%-73.9%) and 83.2% specificity (95% CI: 74.1%-89.6%) in the training cohort. The performance of this two-gene panel showed no significant difference between different age and gender groups. When the two-gene panel was combined with CEA, the sensitivity for EC detection was further improved to 71.1%. In the validation cohort, the sensitivity of the two-gene panel for detecting EC, GC, and CRC was 60.0%, 30.0%, and 30.0%, respectively, with a specificity of 90.0%. Conclusion: The identified methylation marker panel provided a potential non-invasive strategy for EC detection, but further validation should be performed in more clinical centers.

Rapid quantitative detection of Klebsiella pneumoniae in infants with severe infection disease by point-of-care immunochromatographic technique based on nanofluorescent microspheres.

Background: Klebsiella pneumoniae (KP, K. pneumoniae) is one of the most important nosocomial pathogens that cause severe respiratory infections. As evolutionary high-toxic strains with drug resistance genes increase year by year, the infections caused by it are often accompanied by high mortality, which may be fatal to infants and can cause invasive infections in healthy adults. At present, the traditional clinical methods for detecting K. pneumoniae are cumbersome and time-consuming, and the accuracy and sensitivity are not high. In this study, nanofluorescent microsphere (nFM)-based immunochromatographic test strip (ICTS) quantitative testing platform were developed for point-of-care testing (POCT) method of K. pneumoniae. Methods: 19 clinical samples of infants were collected, the genus-specific gene of mdh was screened from K. pneumoniae. Polymerase chain reaction (PCR) combined with nFM-ICTS based on magnetic purification assay (PCR-ICTS) and strand exchange amplification (SEA) combined with nFM-ICTS based on magnetic purification assay (SEA-ICTS) were developed for the quantitative detection of K. pneumoniae. The sensitivity and specificity of SEA-ICTS and PCR-ICTS were demonstrated by the existing used classical microbiological methods, the real-time fluorescent quantitative PCR (RTFQ-PCR) and PCR assay based on agarose gel electrophoresis (PCR-GE). Results: Under optimum working conditions, the detection limits of PCR-GE, RTFQ-PCR, PCR-ICTS and SEA-ICTS are 7.7 × 10-3, 2.5 × 10-6, 7.7 × 10-6, 2.82 × 10-7 ng/µL, respectively. The SEA-ICTS and PCR-ICTS assays can quickly identify K. pneumoniae, and could specifically distinguish K. pneumoniae samples from non-K. pneumoniae samples. Experiments have shown a diagnostic agreement of 100% between immunochromatographic test strip methods and the traditional clinical methods on the detection of clinical samples. During the purification process, the Silicon coated magnetic nanoparticles (Si-MNPs) were used to removed false positive results effectively from the products, which showed of great screening ability. The SEA-ICTS method was developed based on PCR-ICTS, which is a more rapid (20 min), low-costed method compared with PCR-ICTS assay for the detection of K. pneumoniae in infants. Only need a cheap thermostatic water bath and takes a short detection time, this new method can potentially serve as an efficient point-of-care testing method for on-site detection of pathogens and disease outbreaks without fluorescent polymerase chain reaction instruments and professional technicians operation.

How to Keep the Balance between Red and Processed Meat Intake and Physical Activity Regarding Mortality: A Dose-Response Meta-Analysis.

BACKGROUND: Non-communicable diseases have become a major threat to public health, with cardiovascular diseases (CVDs) and cancer being the top two causes of death each year. OBJECTIVE: Our objective is to evaluate the balanced association between the effect of red and processed meat intake on the risk of death and the effect of physical activity on the risk of mortality, where the risk of death includes all causes, CVDs, and cancers. METHODS: We searched electronic databases, including PubMed, ISI Web of Science, Embase, and the Cochrane Library, for prospective studies reporting risk estimates for the association between the intake of red and processed meat, walking, and muscle-strengthening activity (MSA) and the risk of mortality from all causes, CVDs, and cancer. We extracted fully adjusted effect estimates from original studies and performed a summary analysis using the fixed and random-effect models. RESULTS: A conventional meta-analysis showed that red meat and processed meat were positively associated with the risk of mortality, and daily steps and MSA were negatively associated with the risk of death. Further analysis of the dose-response relationship showed that a risk reduction (20%) from 39.5 min/week of MSA or 4100 steps/d was equivalent to an increased risk of all-cause mortality from a daily intake of 103.4 g/d of red meat or 50 g/d of processed meat. The risk was further decreased as the number of steps per day increased, but the risk reversed when the MSA exceeded the threshold (39.5 min/week). CONCLUSIONS: Adherence to physical activity is an effective way to reduce the risk of mortality due to meat intake. However, the total intake of red meat and processed meat should be controlled, especially the latter. Walking is recommended as the main daily physical activity of choice, while MSAs are preferred when time is limited, but it should be noted that longer MSAs do not provide additional benefits.

A systematic review and meta-analysis of 90 cohort studies of social isolation, loneliness and mortality.

The associations between social isolation, loneliness and the risk of mortality from all causes, cardiovascular disease (CVD) and cancer are controversial. We systematically reviewed prospective studies on the association between social isolation, loneliness and mortality outcomes in adults aged 18 years or older, as well as studies on these relationships in individuals with CVD or cancer, and conducted a meta-analysis. The study protocol was registered with PROSPERO (reg. no. CRD42022299959). A total of 90 prospective cohort studies including 2,205,199 individuals were included. Here we show that, in the general population, both social isolation and loneliness were significantly associated with an increased risk of all-cause mortality (pooled effect size for social isolation, 1.32; 95% confidence interval (CI), 1.26 to 1.39; P < 0.001; pooled effect size for loneliness, 1.14; 95% CI, 1.08 to 1.20; P < 0.001) and cancer mortality (pooled effect size for social isolation, 1.24; 95% CI, 1.19 to 1.28; P < 0.001; pooled effect size for loneliness, 1.09; 95% CI, 1.01 to 1.17; P = 0.030). Social isolation also increased the risk of CVD mortality (1.34; 95% CI, 1.25 to 1.44; P < 0.001). There was an increased risk of all-cause mortality in socially isolated individuals with CVD (1.28; 95% CI, 1.10 to 1.48; P = 0.001) or breast cancer (1.51; 95% CI, 1.34 to 1.70; P < 0.001), and individuals with breast cancer had a higher cancer-specific mortality owing to social isolation (1.33; 95% CI, 1.02 to 1.75; P = 0.038). Greater focus on social isolation and loneliness may help improve people's well-being and mortality risk.

A sensitive and robust plasma-based DNA methylation panel for early detection of target gastrointestinal cancers.

BACKGROUND: Target gastrointestinal cancers (GICs), encompassing esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC), originate within a single readily accessible luminal organ system and are diagnosable using endoscopy. However, endoscopy is an invasive procedure with low compliance and no plasma-based DNA methylation assay for the early detection of GICs. METHODS: Nine potential DNA methylation markers were identified and evaluated in tissue (n=60) and plasma (n=155) cohorts to select the most suitable markers. A training cohort (n=244) and a validation cohort (n=199), including GICs patients, benign tumors, gastrointestinal polyps, and controls, were enrolled to develop and validate a DNA methylation panel. An independent prospective cohort (n=158) was used to validate the panel's performance and compare it with blood protein tumor markers. RESULTS: Six out of nine candidate methylation markers with excellent discrimination abilities in both tissue and plasma cohorts were selected for the DNA methylation panel. The panel demonstrated high AUC values of 0.937 (EC), 0.968 (GC), and 0.987 (CRC) in training cohort, and achieved AUC values of 0.921 (EC), 0.921 (GC), and 0.959 (CRC) in validation cohort. Notably, it achieved impressive AUC values of 0.971 and 0.843 for identifying stage I GICs in the training and validation cohorts, respectively. In the prospective cohort, the six-marker panel showed comparable AUC values to CEA, AFP, and CA19-9 (0.935, 0.769, 0.663, and 0.668, respectively). CONCLUSION: This study successfully developed and validated a novel, robust, sensitive, and specific plasma-based DNA methylation panel, offering a promising strategy for the early detection of GICs.