ABSTRACT
METHODS: The study employed a retrospective survey of 458 older individuals with T2D residing in a Chinese community, conducted between June 2020 and May 2021, to develop a predictive model for frailty. Among the participants, 83 individuals (18.1%) were diagnosed with frailty using modified frailty phenotypic criteria. The predictors of frailty in this community-dwelling older population with T2D were determined using least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression. These predictors were utilized to construct a nomogram. The discrimination, calibration, and medical usefulness of the prediction model were assessed through the C-index, calibration plot, and decision curve analysis (DCA), respectively. Additionally, internal validation of the prediction model was conducted using bootstrapping validation. RESULTS: The developed nomogram for frailty prediction predominantly incorporated age, smoking status, regular exercise, depression, albumin (ALB) levels, sleep condition, HbA1c, and polypharmacy as significant predictors. Our prediction model demonstrated excellent discrimination and calibration, as evidenced by a C-index of 0.768 (95% CI, 0.714-0.822) and strong calibration. Internal validation yielded a C-index of 0.732, further confirming the reliability of the model. DCA indicated the utility of the nomogram in identifying frailty among the studied population. CONCLUSION: The development of a predictive model enables a valuable estimation of frailty among community-dwelling older individuals with type 2 diabetes. This evidence-based tool provides crucial guidance to community healthcare professionals in implementing timely preventive measures to mitigate the occurrence of frailty in high-risk patients. By identifying established predictors of frailty, interventions and resources can be appropriately targeted, promoting better overall health outcomes and improved quality of life in this vulnerable population.
ABSTRACT
Importance: There are wide disparities in neonatal mortality rates (NMRs, deaths <28 days of life after live birth per 1000 live births) between countries in Europe, indicating potential for improvement. Comparing country-specific patterns of births and deaths with countries with low mortality rates can facilitate the development of effective intervention strategies. Objective: To investigate how these disparities are associated with the distribution of gestational age (GA) and GA-specific mortality rates. Design, Setting, and Participants: This was a cross-sectional study of all live births in 14 participating European countries using routine data compiled by the Euro-Peristat Network. Live births with a GA of 22 weeks or higher from 2015 to 2020 were included. Data were analyzed from May to October 2023. Exposures: GA at birth. Main Outcomes and Measures: The study investigated excess neonatal mortality, defined as a rate difference relative to the pooled rate in the 3 countries with the lowest NMRs (Norway, Sweden, and Finland; hereafter termed the top 3). The Kitagawa method was used to divide this excess into the proportion explained by the GA distribution of births and by GA-specific mortality rates. A sensitivity analysis was conducted among births 24 weeks' GA or greater. Results: There were 35â¯094 neonatal deaths among 15â¯123â¯428 live births for an overall NMR of 2.32 per 1000. The pooled NMR in the top 3 was 1.44 per 1000 (1937 of 1â¯342â¯528). Excess neonatal mortality compared with the top 3 ranged from 0.17 per 1000 in the Czech Republic to 1.82 per 1000 in Romania. Excess deaths were predominantly concentrated among births less than 28 weeks' GA (57.6% overall). Full-term births represented 22.7% of the excess deaths in Belgium, 17.8% in France, 40.6% in Romania and 17.3% in the United Kingdom. Heterogeneous patterns were observed when partitioning excess mortality into the proportion associated with the GA distribution vs GA-specific mortality. For example, these proportions were 9.2% and 90.8% in France, 58.4% and 41.6% in the United Kingdom, and 92.9% and 7.1% in Austria, respectively. These associations remained stable after removing births under 24 weeks' GA in most, but not all, countries. Conclusions and Relevance: This cohort study of 14 European countries found wide NMR disparities with varying patterns by GA. This knowledge is important for developing effective strategies to reduce neonatal mortality.
Subject(s)
Gestational Age , Infant Mortality , Humans , Infant Mortality/trends , Cross-Sectional Studies , Infant, Newborn , Europe/epidemiology , Infant , Female , Male , Health Status Disparities , Live Birth/epidemiologyABSTRACT
OBJECTIVES: To examine the influence of social disengagement and depressive symptoms on sleep disturbance among dementia caregiving dyads and the actor-partner interdependence nature of these influences. DESIGN: Actor-partner interdependence model through structural equation modeling for dyadic analyses. SETTING AND PARTICIPANTS: A total of 310 dyads of older adults with dementia and their care partners from 2 national representative studies in the United States, the National Health and Aging Trends Study (NHATS) and its companion study, the National Study of Caregiving (NSOC). METHODS: Data from the NHATS Round 11 and NSOC IV were analyzed using descriptive statistics, Pearson correlation analysis, and the actor-partner interdependence model. Structural equation modeling was used to assess the mediation effects of depressive symptoms within the actor-partner interdependence models. RESULTS: In the model of caregivers, social disengagement had a direct impact on sleep disturbance (ß = 0.49, P < .001) and an indirect impact through depressive symptoms (ß = 0.25, P < .001). In the model of older adults with dementia, social disengagement only had an indirect effect on sleep disturbance through depressive symptoms. In models examining partner effects, caregivers' social disengagement directly influenced their care partners' depressive symptoms (ß = 0.20, P = .019), which subsequently affected caregivers' sleep disturbance (ß = 0.17, P < .001). Social disengagement (ß = 0.17, P = .001) and depressive symptoms (ß = 0.17, P < .001) in older adults with dementia directly impacted their caregivers' sleep disturbance. Depressive symptoms of older adults with dementia served as multiple mediators linking one member's social disengagement to both their own and partner's sleep. CONCLUSIONS AND IMPLICATIONS: This study represents one of the first attempts to investigate the influencing mechanism of sleep disturbances among older adults with dementia and their informal caregivers through a dyadic perspective. The sleep disturbance of caregivers may be directly influenced by the social disengagement and depressive symptoms exhibited by both members of the dyad, whereas the sleep disturbance experienced by older adults with dementia can only be indirectly influenced by the dyad's social disengagement via their own depressive symptoms. Dyadic social activities targeting depressive symptoms could be designed to address sleep disturbances in dementia caregiving dyads.
ABSTRACT
Targeting tumor-infiltrating regulatory T (TI-Treg) cells is a potential strategy for cancer therapy. The ATPase p97 in complex with cofactors (such as Npl4) has been investigated as an antitumor drug target; however, it is unclear whether p97 has a function in immune cells or immunotherapy. Here we show that thonzonium bromide is an inhibitor of the interaction of p97 and Npl4 and that this p97-Npl4 complex has a critical function in TI-Treg cells. Thonzonium bromide boosts antitumor immunity without affecting peripheral Treg cell homeostasis. The p97-Npl4 complex bridges Stat3 with E3 ligases PDLIM2 and PDLIM5, thereby promoting Stat3 degradation and enabling TI-Treg cell development. Collectively, this work shows an important role for the p97-Npl4 complex in controlling Treg-TH17 cell balance in tumors and identifies possible targets for immunotherapy.
Subject(s)
T-Lymphocytes, Regulatory , T-Lymphocytes, Regulatory/immunology , Animals , Mice , Humans , Mice, Inbred C57BL , STAT3 Transcription Factor/metabolism , Nuclear Proteins/metabolism , Neoplasms/immunology , Cell Line, Tumor , Th17 Cells/immunology , Immunotherapy/methods , LIM Domain Proteins/metabolism , Adenosine Triphosphatases/metabolism , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Adaptor Proteins, Signal Transducing/metabolism , FemaleABSTRACT
Long noncoding RNAs (lncRNAs) are strongly associated with glucose homeostasis, but their roles remain largely unknown. In this study, the potential role of lncRNA-Snhg3 in glucose metabolism was evaluated both in vitro and in vivo. Here, we found a positive relationship between Snhg3 and hepatic glycogenesis. Glucose tolerance improved in hepatocyte-specific Snhg3 knock-in (Snhg3-HKI) mice, while it worsened in hepatocyte-specific Snhg3 knockout (Snhg3-HKO) mice. Furthermore, hepatic glycogenesis had shown remarkable increase in Snhg3-HKI mice and reduction in Snhg3-HKO mice, respectively. Mechanistically, Snhg3 increased mRNA and protein expression levels of PPP1R3B through inducing chromatin remodeling and promoting the phosphorylation of protein kinase B. Collectively, these results suggested that lncRNA-Snhg3 plays a critical role in hepatic glycogenesis.
Subject(s)
Liver , RNA, Long Noncoding , Animals , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Mice , Liver/metabolism , Mice, Knockout , Glucose/metabolism , Male , Hepatocytes/metabolism , Mice, Inbred C57BL , Liver Glycogen/metabolismABSTRACT
The current polyvinyl chloride (PVC) gel flexible actuators are facing challenges of high input voltage and an insufficient elastic modulus. In this study, we conducted a detailed study on the properties of PVC gel prepared by introducing the modifier polyvinyl chloride-vinyl acetate (P(VC-VA)). We compared a modified PVC gel with the traditional one in terms of the relative dielectric constant, mechanical modulus, and electromechanical actuation performance. Experimental results demonstrated that the introduction of P(VC-VA) enhanced the dielectric constant and reduced the driving electric field strength of PVC gels. The dielectric constant increased from 4.77 to 7.3. The electromechanical actuation performance increased by 150%. We employed the Gent model to fit the experimental results, and the actual experimental data aligned well with the expectations of the Gent model. The research results show that this type of plasticizing method effectively balanced the mechanical and electrical performance of PVC gels. This study summarizes the experimental results and performance analysis of PVC gels prepared using innovative plasticization methods, revealing the potential engineering applications of polymeric gels.
ABSTRACT
Elucidating the formation mechanism of plastisphere antibiotic resistance genes (ARGs) on different polymers is necessary to understand the ecological risks of plastisphere ARGs. Here, we explored the turnover and assembly mechanism of plastisphere ARGs on 8 different microplastic polymers (4 biodegradable (bMPs) and 4 non-biodegradable microplastics (nMPs)) by metagenomic sequencing. Our study revealed the presence of 479 ARGs with abundance ranging from 41.37 to 58.17 copies/16S rRNA gene in all plastispheres. These ARGs were predominantly multidrug resistance genes. The richness of plastisphere ARGs on different polymers had a significant correlation with the contribution of species turnover to plastisphere ARGs ß diversity. Furthermore, polymer type was the most critical factor affecting the composition of plastisphere ARGs. More opportunistic pathogens carrying diverse ARGs on BMPs (PBAT, PBS, and PHA) with higher horizontal gene transfer potential may further magnify the ecological risks and human health threats. For example, the opportunistic pathogens Riemerella anatipestifer, Vibrio campbellii, and Vibrio cholerae are closely related to human production and life, which were the important potential hosts of many plastisphere ARGs and mobile genetic elements on BMPs. Thus, we emphasize the urgency of developing the formation mechanism of plastisphere ARGs and the necessity of controlling BMPs and ARG pollution, especially BMPs, with ever-increasing usage in daily life.
Subject(s)
Microplastics , Microplastics/toxicity , Drug Resistance, Microbial/genetics , Bacteria/genetics , Bacteria/drug effects , Genes, BacterialABSTRACT
BACKGROUND: Zellweger Syndrome (ZS), or cerebrohepatorenal syndrome, is a rare disorder due to PEX gene mutations affecting peroxisome function. While PEX6 coding mutations are known to cause ZS, the impact of noncoding mutations is less clear. METHODS: A Chinese neonate and his family were subjected to whole exome sequencing (WES) and bioinformatics to assess variant pathogenicity. A minigene assay was also performed for detailed splicing variant analysis. RESULTS: WES identified compound heterozygous PEX6 variants: c.315G>A (p. Trp105Ter) and c.2095-3 T>G. Minigene assays indicated that the latter variant led to abnormal mRNA splicing and the loss of exon 11 in PEX6 expression, potentially causing nonsense-mediated mRNA decay (NMD) or truncated protein structure. CONCLUSION: The study suggests that PEX6: c.2095-3 T>G might be a genetic contributor to the patient's condition, broadening the known mutation spectrum of PEX6. These insights lay groundwork for potential gene therapy for such variants.
Subject(s)
ATPases Associated with Diverse Cellular Activities , Introns , Zellweger Syndrome , Humans , Zellweger Syndrome/genetics , Infant, Newborn , Male , ATPases Associated with Diverse Cellular Activities/genetics , Exome Sequencing , Mutation , RNA Splicing , Membrane Proteins/genetics , Pedigree , Asian People/genetics , Peroxins/genetics , China , Female , East Asian PeopleABSTRACT
Gastric cancer (GC) is a major cause of cancer-related mortality worldwide. GC is determined by multiple (epi)genetic and environmental factors; can occur at distinct anatomic positions of the stomach; and displays high heterogeneity, with different cellular origins and diverse histological and molecular features. This heterogeneity has hindered efforts to fully understand the pathology of GC and develop efficient therapeutics. In the past decade, great progress has been made in the study of GC, particularly in molecular subtyping, investigation of the immune microenvironment, and defining the evolutionary path and dynamics. Preclinical mouse models, particularly immunocompetent models that mimic the cellular and molecular features of human GC, in combination with organoid culture and clinical studies, have provided powerful tools for elucidating the molecular and cellular mechanisms underlying GC pathology and immune evasion, and the development of novel therapeutic strategies. Herein, we first briefly introduce current progress and challenges in GC study and subsequently summarize immunocompetent GC mouse models, emphasizing the potential application of genetically engineered mouse models in antitumor immunity and immunotherapy studies.
Subject(s)
Disease Models, Animal , Stomach Neoplasms , Tumor Microenvironment , Animals , Stomach Neoplasms/pathology , Stomach Neoplasms/immunology , Stomach Neoplasms/genetics , Stomach Neoplasms/therapy , Mice , Humans , Tumor Microenvironment/immunology , Immunocompetence , Immunotherapy/methods , Organoids/pathologyABSTRACT
BACKGROUND: Anti-neutrophil cytoplasmic antibody (ANCA) is a type of autoantibodies associated with vasculitis. ANCA positivity is commonly observed in interstitial lung disease (ILD) patients. 7%-10% of ANCA-positive ILD patients don't present any symptoms of systemic vasculitis and are termed ANCA-positive idiopathic interstitial pneumonia (ANCA-IIP). Some researchers propose that ANCA-IIP should be categorized as interstitial pneumonia with autoimmune features (IPAF), although the official ATS/ERS statements exclude ANCA-IIP from this classification. Whether ANCA-IIP should be categorized into the entity of IPAF is still debatable. METHODS: Patients diagnosed with ANCA-IIP and those with IPAF were analyzed in a retrospective study of ILD. The clinical outcomes were determined through pulmonary function tests (PFTs) after a one-year follow-up, as well as assessing all-cause mortality. RESULTS: 27 patients with ANCA-IIP and 143 patients with IPAF were analyzed from a cohort of 995 patients with ILD. Patients in the ANCA-IIP group had an older age and a high proportion of males compared to those in the IPAF group. PFT results at baseline were similar between the two groups, except for a better FEV1% in the ANCA-IIP group. Glucocorticoid and immunosuppressive therapy improved pulmonary function in patients with IPAF, but it continued to deteriorate after one year of treatment in the ANCA-IIP group. Furthermore, the all-cause mortality rate was significantly higher in the ANCA-IIP group than in the IPAF group (22.2% vs. 6.3%, P = 0.017). CONCLUSION: The responses to glucocorticoid and immunosuppressive therapy differ between the ANCA-IIP and IPAF groups, leading to divergent prognoses. Therefore, it is inappropriate to classify ANCA-IIP as part of IPAF.
ABSTRACT
OBJECTIVE: To identify and categorize home- and community-based services used by older adults and the distribution of their utilization, and to examine their utilization patterns in terms of region, time trends, and older adults' characteristics. DESIGN: Systematic review and meta-analysis. METHODS: We conducted a systematic search of six databases for studies published up to January 12, 2023, and performed meta-analyses and subgroup analyses to identify the utilization of home- and community-based services and analyze utilization patterns concerning region, time trends, and individual characteristics. RESULTS: We included 42 studies from 10 countries worldwide, involving a total of 2,942,069 older adults. Home- and community-based services were grouped into three categories: health services, social services, and family caregiver services. Regional differences were consistently evident across all three categories of services, reflecting diverse patterns of home- and community-based service adoption worldwide. Notably, there was a significant increase in the utilization of social services, as distinct from health services and family caregiver services, during the post-2010 period (2010-2018) in comparison with the pre-2010 period (before 2010). In addition, age and cognitive function also played an important role in the utilization of home- and community-based services. CONCLUSION: These findings highlight the importance of tailoring home- and community-based services to specific populations and understanding the needs of older adults over time. Further research should be undertaken to gain a deeper understanding of the reasons behind these variations and differences and to provide more targeted and effective services to older adults worldwide.
Subject(s)
Community Health Services , Health Services for the Aged , Home Care Services , Aged , Humans , Community Health Services/statistics & numerical data , Home Care Services/statistics & numerical data , Health Services for the Aged/statistics & numerical dataABSTRACT
BACKGROUND: Currently, different guidelines recommend using different methods to determine whether deduplication is necessary when determining the detection rates of multidrug-resistant organisms (MDROs). However, few studies have investigated the effect of deduplication on MDRO monitoring data. In this study, we aimed to investigate the influence of deduplication on the detection rates of MDROs in different specimens to assess its impact on infection surveillance outcomes. METHODS: Samples were collected from hospitalized patients admitted between January 2022 and December 2022; four types of specimens were collected from key monitored MDROs, including sputum samples, urine samples, blood samples, and bronchoalveolar lavage fluid (BALF) samples. In this study, we compared and analysed the detection rates of carbapenem-resistant Klebsiella pneumoniae (CRKP), carbapenem-resistant Escherichia coli (CRECO), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and methicillin-resistant Staphylococcus aureus (MRSA) under two conditions: with and without deduplication. RESULTS: When all specimens were included, the detection rates of CRKP, CRAB, CRPA, and MRSA without deduplication (33.52%, 77.24%, 44.56%, and 56.58%, respectively) were significantly greater than those with deduplication (24.78%, 66.25%, 36.24%, and 50.83%, respectively) (all P < 0.05). The detection rates in sputum samples were significantly different between samples without duplication (28.39%, 76.19%, 46.95%, and 70.43%) and those with deduplication (19.99%, 63.00%, 38.05%, and 64.50%) (all P < 0.05). When deduplication was not performed, the rate of detection of CRKP in urine samples reached 30.05%, surpassing the rate observed with deduplication (21.56%) (P < 0.05). In BALF specimens, the detection rates of CRKP and CRPA without deduplication (39.78% and 53.23%, respectively) were greater than those with deduplication (31.62% and 42.20%, respectively) (P < 0.05). In blood samples, deduplication did not have a significant impact on the detection rates of MDROs. CONCLUSION: Deduplication had a significant effect on the detection rates of MDROs in sputum, urine, and BALF samples. Based on these data, we call for the Infection Prevention and Control Organization to align its analysis rules with those of the Bacterial Resistance Surveillance Organization when monitoring MDRO detection rates.
Subject(s)
Cross Infection , Drug Resistance, Multiple, Bacterial , Klebsiella pneumoniae , Sputum , Humans , Cross Infection/microbiology , Cross Infection/epidemiology , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/isolation & purification , Klebsiella pneumoniae/drug effects , Sputum/microbiology , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Methicillin-Resistant Staphylococcus aureus/genetics , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/isolation & purification , Acinetobacter baumannii/genetics , Anti-Bacterial Agents/pharmacology , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/isolation & purification , Pseudomonas aeruginosa/genetics , Bronchoalveolar Lavage Fluid/microbiology , Carbapenems/pharmacology , Escherichia coli/isolation & purification , Escherichia coli/drug effects , Escherichia coli/genetics , Epidemiological Monitoring , HospitalsABSTRACT
Succession is a fundamental aspect of ecological theory, but studies on temporal succession trajectories and ecological driving mechanisms of plastisphere microbial communities across diverse colonization environments remain scarce and poorly understood. To fill this knowledge gap, we assessed the primary colonizers, succession trajectories, assembly, and turnover mechanisms of plastisphere prokaryotes and eukaryotes from four freshwater lakes. Our results show that differences in microbial composition similarity, temporal turnover rate, and assembly processes in the plastisphere do not exclusively occur at the kingdom level (prokaryotes and eukaryotes), but also depend on environmental conditions and colonization time. Thereby, the time of plastisphere colonization has a stronger impact on community composition and assembly of prokaryotes than eukaryotes, whereas for environmental conditions, the opposite pattern holds true. Across all lakes, deterministic processes shaped the assembly of the prokaryotes, but stochastic processes influenced that of the eukaryotes. Yet, they share similar assembly processes throughout the temporal succession: species turnover over time causes the loss of any priority effect, which leads to a convergent succession of plastisphere microbial communities. The increase and loss of microbial diversity in different kingdoms during succession in the plastisphere potentially impact the stability of entire microbial communities and related biogeochemical cycles. Therefore, research needs to integrate temporal dynamics along with spatial turnovers of the plastisphere microbiome. Taking the heterogeneity of global lakes and the diversity of global climate patterns into account, we highlight the urgency to investigate the spatiotemporal succession mechanism of plastisphere prokaryotes and eukaryotes in more lakes around the world.
ABSTRACT
INTRODUCTION: Despite the widespread provision of free contraceptives and post-abortion care (PAC) services, China grapples with a high rate of unintended pregnancies and subsequent abortions. We aimed to study the evolving characteristics of women seeking abortion and their contraceptive practices before and after abortions, to shed light on the optimisation of Chinese PAC services. METHODS: This study utilised data from an abortion cohort between 2019 and 2021. We studied their demographic features, contraception and abortion histories, reasons and choices using chi-square or linear-by-linear tests. We also explored the potential impact of receiving services at PAC facilities on post-abortion contraception use and repeat abortions using logistic regression models. RESULTS: Among the 9005 participants, 43.4% experienced repeat abortion, without a discernible trend over the 3 years. Noteworthy increases were observed in the percentages of college students (from 1.7% to 6.6%, p<0.01) and middle-aged women (from 23.2% to 26.8%, p<0.01) seeking abortions. Surgical abortion was chosen by nearly 90% of participants with a continuously increasing trend (p trend <0.01). Nearly half of the participants experienced unintended pregnancies due to non-use of contraception. Of the remainder, the majority preferred less or the least effective methods both before and after abortion. Women residing in moderate-gross domestic product (GDP) regions faced a higher risk of repeat abortions (OR 1.33, 95% CI 1.16 to 1.54). Despite this, high-quality PAC services may encourage the use of reliable contraceptive methods, with 86.8% of women changing from least effective or no methods to (most) effective methods post-abortion, and prevent repeat abortions (OR 0.65, 95% CI 0.56 to 0.75). CONCLUSIONS: Increased proportions of college students and middle-aged multiparous women seeking abortions were observed, together with inappropriate preferences for less effective contraception and increasing choice of surgical abortions. Future research should extend the focus to cover the entire abortion period, advocate the rational selection of contraceptive methods, and emphasise the specified PAC services tailored to different socioeconomic groups.
ABSTRACT
PURPOSE: To identify radiological characteristics that could help differentiate cystic lung diseases between primary Sjögren syndrome (pSS) and idiopathic multicentric Castleman disease (iMCD). PATIENTS AND METHODS: Patients with pSS or iMCD who had cysts were enrolled. Cyst characteristics (number, size, morphology, and distribution) and other accompanying manifestations (nodules, ground-glass opacities, calcification, and thickening of the bronchovascular bundles and interlobular septa) were compared between them. RESULTS: Eleven patients with pSS and 25 patients with iMCD were eligible for our study. Eleven patients with pSS (100.0%) and 23 patients with iMCD (92.0%) had round or oval cysts. None of the patients with pSS had irregular cysts, but 21 (84.0%) patients with iMCD had irregular cysts ( P = 0.005). Smooth-walled cysts were present in 11 patients with pSS (100.0%) and 18 patients with iMCD (72.0%). Only 1 patient with pSS (9.1%) exhibited non-smooth-walled cysts, whereas 23 patients with iMCD (92.0%) had non-smooth-walled cysts ( P = 0.003). The presence of nodules was common in both groups ( P = 1.000). However, the nodules were more likely to be larger and more numerous in patients with iMCD ( P < 0.001). Cysts with mural nodules (52.2%) and central nodules (47.8%) were only observed in iMCD ( P = 0.007). CONCLUSION: Although regular and smooth-walled cysts were common in the 2 diseases, irregular and non-smooth-walled cysts were more often associated with iMCD than pSS. Nodules in iMCD tended to be larger and more numerous, and a close positional relationship between nodules and cysts was only observed in iMCD.
Subject(s)
Castleman Disease , Cysts , Lung Diseases , Sjogren's Syndrome , Tomography, X-Ray Computed , Humans , Castleman Disease/diagnostic imaging , Castleman Disease/complications , Sjogren's Syndrome/diagnostic imaging , Sjogren's Syndrome/complications , Female , Male , Diagnosis, Differential , Middle Aged , Adult , Cysts/diagnostic imaging , Lung Diseases/diagnostic imaging , Tomography, X-Ray Computed/methods , Aged , Lung/diagnostic imaging , Retrospective StudiesABSTRACT
BACKGROUND: The indications for splenic hilar lymph node dissection in advanced proximal gastric cancer without invasion of the greater curvature are controversial. We aimed to develop a preoperative nomogram for individualized prediction of splenic hilar lymph node metastasis in non-greater curvature advanced proximal gastric cancer. METHODS: From January 2014 to December 2021, 558 patients with non-greater curvature advanced proximal gastric cancer who underwent D2 lymphadenectomy (including splenic hilar lymph node) were retrospectively analyzed and divided into a training cohort (n = 361) and validation cohort (n = 197), depending on the admission time. A preoperative predictive nomogram of splenic hilar lymph node metastasis was established based on independent predictors identified by multivariate analysis, and the performance and prognostic value were confirmed. RESULTS: In the training and validation cohorts, 48 (13.3%) and 24 patients (12.2%) had pathologically confirmed splenic hilar lymph node metastasis, respectively. Tumor located in the posterior wall, tumor size ≥5 cm, Borrmann type IV, and splenic hilar lymph node lymphadenectasis on computed tomography were preoperative factors independently associated with splenic hilar lymph node metastasis. The nomogram developed based on these four parameters had a high concordance index of 0.850 (95% confidence interval, 0.793-0.907) and 0.825 (95% confidence interval, 0.743-0.908) in the training and validation cohorts, respectively, with well-fitting calibration plots and better net benefits in the decision curve analysis. In addition, disease-free survival and overall survival were significantly shorter in the high-risk group, with hazard ratios of 3.660 (95% confidence interval, 2.228-6.011; log-rank P < .0001) and 3.769 (95% confidence interval, 2.279-6.231; log-rank P < .0001), respectively. CONCLUSION: The nomogram has good performance in predicting the risk of splenic hilar lymph node metastasis in non-greater curvature advanced proximal gastric cancer preoperatively, which can help surgeons make rational clinical decisions.
Subject(s)
Lymph Node Excision , Lymph Nodes , Lymphatic Metastasis , Nomograms , Spleen , Stomach Neoplasms , Humans , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Stomach Neoplasms/mortality , Male , Female , Middle Aged , Lymphatic Metastasis/pathology , Retrospective Studies , Aged , Lymph Nodes/pathology , Lymph Nodes/diagnostic imaging , Lymph Nodes/surgery , Spleen/pathology , Gastrectomy/methods , Prognosis , Neoplasm Invasiveness/pathology , Neoplasm Staging , Preoperative Period , Adult , Preoperative Care/methods , Tomography, X-Ray ComputedABSTRACT
Microorganisms in rivers indeed play a crucial role in nutrient cycling within aquatic ecosystems. Understanding the assembly mechanisms of bacterial communities in river networks is essential for predicting their special composition and functional characteristics in natural rivers. This study employed 16S rRNA gene amplicon sequence variation (ASVs) to scrutinize the bacterial community within the uniquely topographical Ili River network. The bacterial community composition varied across the three tributaries with distinct sources and the mainstream. The confluence of various sources diminished the diversity of the bacterial community and altered the functionality of within mainstream. We suggest that strong dispersal limitation predominantly shaped the community at the regional scale (46.6 %), underscoring the significant contribution of headwater sites to bacterial community composition. Contrary to expectation, the bacterial resources in the mainstream were not enriched by the higher diversity in three tributaries. Instead, confluence disturbance potentially increased the undominated processes (36.7 %) and alter the bacterial community composition at the local scale of the mainstream. The intricate coalescence at the confluence could potentially be an intriguing causative factor. Our research indicates that the composition of bacterial communities within intricate river networks exhibits biogeographic patterns, simultaneously influenced by river confluence and geographical features, necessitating multi-scale analysis.
Subject(s)
Bacteria , RNA, Ribosomal, 16S , Rivers , Rivers/microbiology , Bacteria/genetics , Bacteria/classification , RNA, Ribosomal, 16S/genetics , Biodiversity , Water MicrobiologyABSTRACT
BACKGROUND: The popularity of Muscovy ducks is attributed not only to their conformation traits but also to their slightly higher content of breast and leg meat, as well as their stronger-tasting meat compared to that of typical domestic ducks. However, there is a lack of comprehensive systematic research on the development of breast muscle in Muscovy ducks. In addition, since the number of skeletal muscle myofibers is established during the embryonic period, this study conducted a full-length transcriptome sequencing and microRNA sequencing of the breast muscle. Muscovy ducks at four developmental stages, namely Embryonic Day 21 (E21), Embryonic Day 27 (E27), Hatching Day (D0), and Post-hatching Day 7 (D7), were used to isolate total RNA for analysis. RESULTS: A total of 68,161 genes and 472 mature microRNAs were identified. In order to uncover deeper insights into the regulation of mRNA by miRNAs, we conducted an integration of the differentially expressed miRNAs (known as DEMs) with the differentially expressed genes (referred to as DEGs) across various developmental stages. This integration allowed us to make predictions regarding the interactions between miRNAs and mRNA. Through this analysis, we identified a total of 274 DEGs that may serve as potential targets for the 68 DEMs. In the predicted miRNAâmRNA interaction networks, let-7b, miR-133a-3p, miR-301a-3p, and miR-338-3p were the hub miRNAs. In addition, multiple DEMs also showed predicted target relationships with the DEGs associated with skeletal system development. These identified DEGs and DEMs as well as their predicted interaction networks involved in the regulation of energy homeostasis and muscle development were most likely to play critical roles in facilitating the embryo-to-hatchling transition. A candidate miRNA, miR-301a-3p, exhibited increased expression during the differentiation of satellite cells and was downregulated in the breast muscle tissues of Muscovy ducks at E21 compared to E27. A dual-luciferase reporter assay suggested that the ANKRD1 gene, which encodes a transcription factor, is a direct target of miR-301a-3p. CONCLUSIONS: miR-301a-3p suppressed the posttranscriptional activity of ANKRD1, which is an activator of satellite cell proliferation, as determined with gain- and loss-of-function experiments. miR-301a-3p functions as an inducer of myogenesis by targeting the ANKRD1 gene in Muscovy ducks. These results provide novel insights into the early developmental process of black Muscovy breast muscles and will improve understanding of the underlying molecular mechanisms.
Subject(s)
MicroRNAs , Animals , MicroRNAs/genetics , MicroRNAs/metabolism , Ducks/genetics , Ducks/metabolism , Gene Expression Profiling , Muscle, Skeletal/metabolism , RNA, Messenger/genetics , TranscriptomeABSTRACT
The spontaneous combustion of residual coal in abandoned mining areas severely affects the safe and efficient extraction of coal, employee occupational health, and regional environmental ecology. A technical measure for preventing and controlling the spontaneous combustion of residual coal involves injecting antispontaneous combustion materials into abandoned areas. In this study, the composition, preparation, and mechanism of action of silica gel foam, a material used to suppress spontaneous combustion during coal mining, were investigated to improve the performance of materials designed to prevent spontaneous combustion in abandoned areas. The inhibitory efficiency improved, and the mechanical strength and stability of the foam liquid film increased upon adding modified antioxidants and nanosilica particles to the gel foam. Macro performance tests, microstructural characterization, and chemical inhibition mechanism analyses verified the efficacy of silica gel foam for suppressing spontaneous combustion. The air leakage resistance of the silica gel foam effectively increased the air leakage resistance of the coal samples at different pressures. New radicals formed during the spontaneous combustion of coal comprising different inhibitors, as indicated by the g-factor results of electron paramagnetic resonance (EPR) spectroscopy analysis; the formation of radicals initially decreased and then increased when the inhibitor material changed. The concentration of free radicals decreased markedly during the spontaneous combustion process of both raw and inhibited coal samples at low oxidation temperatures (â¼60-100 °C), indicating a marked inhibitory effect.
ABSTRACT
Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6-18.0) for the immunotherapy group compared with 9.9 months (8.0-11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40-0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3-32.8) for the control group (HR, 0.57 [95% CI, 0.33-0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.