Online decision tools for personalized survival prediction and treatment optimization in elderly patients with lung squamous cell carcinoma: a retrospective cohort study.

BACKGROUND: Despite major advances in cancer therapeutics, the therapeutic options of Lung Squamous Cell Carcinoma (LSCC)-specific remain limited. Furthermore, the current staging system is imperfect for defining a prognosis and guiding treatment due to its simplicity and heterogeneity. We sought to develop prognostic decision tools for individualized survival prediction and treatment optimization in elderly patients with LSCC. METHODS: Clinical data of 4564 patients (stageIB-IIIB) diagnosed from 2010 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database for prognostic nomograms development. The proposed models were externally validated using a separate group consisting of 1299 patients (stage IB-IIIB) diagnosed from 2012-2015 in China. The prognostic performance was measured using the concordance index (C-index), calibration curves, the average time-dependent area under the receiver operator characteristic curves (AUC), and decision curve analysis. RESULTS: Eleven candidate prognostic variables were identified by the univariable and multivariable Cox regression analysis. The calibration curves showed satisfactory agreement between the actual and nomogram-estimated Lung Cancer-Specific Survival (LCSS) rates. By calculating the c-indices and average AUC, our nomograms presented a higher prognostic accuracy than the current staging system. Clinical usefulness was revealed by the decision curve analysis. User-friendly online decision tools integrating proposed nomograms were created to estimate survival for patients with different treatment regimens. CONCLUSIONS: The decision tools for individualized survival prediction and treatment optimization might facilitate clinicians with decision-making, medical teaching, and experimental design. Online tools are expected to be integrated into clinical practice by using the freely available website ( https://loyal-brand-611803.framer.app/ ).

Transcriptome evidence reveals enhanced autophagy-lysosomal function in centenarians.

Centenarians (CENs) are excellent subjects to study the mechanisms of human longevity and healthy aging. Here, we analyzed the transcriptomes of 76 centenarians, 54 centenarian-children, and 41 spouses of centenarian-children by RNA sequencing and found that, among the significantly differentially expressed genes (SDEGs) exhibited by CENs, the autophagy-lysosomal pathway is significantly up-regulated. Overexpression of several genes from this pathway, CTSB, ATP6V0C, ATG4D, and WIPI1, could promote autophagy and delay senescence in cultured IMR-90 cells, while overexpression of the Drosophila homolog of WIPI1, Atg18a, extended the life span in transgenic flies. Interestingly, the enhanced autophagy-lysosomal activity could be partially passed on to their offspring, as manifested by their higher levels of both autophagy-encoding genes and serum beclin 1 (BECN1). In light of the normal age-related decline of autophagy-lysosomal functions, these findings provide a compelling explanation for achieving longevity in, at least, female CENs, given the gender bias in our collected samples, and suggest that the enhanced waste-cleaning activity via autophagy may serve as a conserved mechanism to prolong the life span from Drosophila to humans.

River Valleys Shaped the Maternal Genetic Landscape of Han Chinese.

A general south-north genetic divergence has been observed among Han Chinese in previous studies. However, these studies, especially those on mitochondrial DNA (mtDNA), are based either on partial mtDNA sequences or on limited samples. Given that Han Chinese comprise the world's largest population and reside around the whole China, whether the north-south divergence can be observed after all regional populations are considered remains unknown. Moreover, factors involved in shaping the genetic landscape of Han Chinese need further investigation. In this study, we dissected the matrilineal landscape of Han Chinese by studying 4,004 mtDNA haplogroup-defining variants in 21,668 Han samples from virtually all provinces in China. Our results confirmed the genetic divergence between southern and northern Han populations. However, we found a significant genetic divergence among populations from the three main river systems, that is, the Yangtze, the Yellow, and the Zhujiang (Pearl) rivers, which largely attributed to the prevalent distribution of haplogroups D4, B4, and M7 in these river valleys. Further analyses based on 4,986 mitogenomes, including 218 newly generated sequences, indicated that this divergence was already established during the early Holocene and may have resulted from population expansion facilitated by ancient agricultures along these rivers. These results imply that the maternal gene pools of the contemporary Han populations have retained the genetic imprint of early Neolithic farmers from different river basins, or that river valleys represented relative migration barriers that facilitated genetic differentiation, thus highlighting the importance of the three ancient agricultures in shaping the genetic landscape of the Han Chinese.

Short-echo-time magnitude image derived from quantitative susceptibility mapping could resemble neuromelanin-sensitive MRI image in substantia nigra.

BACKGROUND: In this study, we explored whether the proposed short-echo-time magnitude (setMag) image derived from quantitative susceptibility mapping (QSM) could resemble NM-MRI image in substantia nigra (SN), by quantitatively comparing the spatial similarity and diagnosis performances for Parkinson's disease (PD). METHODS: QSM and NM-MRI were performed in 18 PD patients and 15 healthy controls (HCs). The setMag images were calculated using the short-echo-time magnitude images. Bilateral hyperintensity areas of SN (SNhyper) were manually segmented on setMag and NM-MRI images by two raters in a blinded manner. The inter-rater reliability was evaluated by the intraclass correlation coefficients (ICC) and the Dice similarity coefficient (DSC). Then the inter-modality (i.e. setMag and NM-MRI) spatial similarity was quantitatively assessed using DSC and volume of the consensual voxels identified by both of two raters. The performances of mean SNhyper volume for PD diagnosis on setMag and NM-MRI images were evaluated using receiver operating characteristic (ROC) analysis. RESULTS: The SNhyper segmented by two raters showed substantial to excellent inter-rater reliability for both setMag and NM-MRI images. The DSCs of SNhyper between setMag and NM-MRI images showed substantial to excellent voxel-wise overlap in HCs (0.80 ~ 0.83) and PD (0.73 ~ 0.76), and no significant difference was found between the SNhyper volumes of setMag and NM-MRI images in either HCs or PD (p > 0.05). The mean SNhyper volume was significantly decreased in PD patients in comparison with HCs on both setMag images (77.61 mm3 vs 95.99 mm3, p < 0.0001) and NM-MRI images (79.06 mm3 vs 96.00 mm3, p < 0.0001). Areas under the curve (AUCs) of mean SNhyper volume for PD diagnosis were 0.904 on setMag and 0.906 on NM-MRI images. No significant difference was found between the two curves (p = 0.96). CONCLUSIONS: SNhyper on setMag derived from QSM demonstrated substantial spatial overlap with that on NM-MRI and provided comparable PD diagnostic performance, providing a new QSM-based multi-contrast imaging strategy for future PD studies.

Molecular phylogenetics and historical biogeography of the tribe Lilieae (Liliaceae): bi-directional dispersal between biodiversity hotspots in Eurasia.

Background and Aims: The role played by the Qinghai-Tibet Plateau (QTP) in the organismal diversification and biogeography of plants in the Northern Hemisphere has attracted much attention from evolutionary biologists. Here we use tribe Lilieae (Liliaceae), including primarily temperate and alpine lineages with disjunct distributions in the North Temperate Zone, as a case study to shed light upon these processes. Methods: Using 191 taxa (five outgroup taxa) comprising more than 60 % of extant Lilieae species across the entire geographical range, we analyse phylogenetic relationships based on three plastid markers (matK, rbcL, rpl16) and nuclear ITS. Divergence time estimation and ancestral range reconstruction were further inferred. Key Results: The results support a monophyletic Lilieae divided into four clades. Lilium is nested within Fritillaria, which is paraphyletic and partitioned into two clades, New World and Old World, in the chloroplast DNA (cpDNA) analysis. Incongruences between the ITS and cpDNA trees may be explained by divergent ITS paralogues and hybridization. Lilieae originated around 40-49 (28-67) Mya and probably diversified in the QTP region with four major clades that were established during the Oligocene and the Early Miocene. Uplift of the QTP and climatic changes probably drove early diversification of Lilieae in the QTP region. A rapid radiation occurred during the Late Miocene and the Pleistocene, coinciding temporally with recent orogenic process in the QTP region and climatic oscillations. Several lineages dispersed out of the QTP. Conclusions: Lineage persistence and explosive radiation were important processes for establishing high species diversity of Lilieae in the QTP region. Both long-distance dispersal and migration across Beringia probably contributed to the modern distribution range of Lilieae. Our study shows that biotic interchanges between the QTP region and Irano-Turanian region and the Mediterranean Basin were bi-directional, suggesting the latter was a secondary centre of diversity.

Molecular phylogeny, biogeography and ecological niche modelling of Cardiocrinum (Liliaceae): insights into the evolutionary history of endemic genera distributed across the Sino-Japanese floristic region.

BACKGROUND AND AIMS: The patterns of evolutionary assembly in the Sino-Japanese floristic region (SJFR) remain largely unknown due to a lack of integrative multidimensional studies throughout the region. To address this issue, we elucidated the evolutionary history of Cardiocrinum (Liliaceae), a genus containing four taxa distributed across the SJFR. METHODS: Fifty-four populations were sampled throughout the geographical range of Cardiocrinum to assess genetic structure, analyse phylogenetic relationships and reconstruct ancestral area based on six chloroplast DNA (cpDNA) fragments and three low copy nuclear genes (LCNG). Ecological niche modelling was used to examine the potential range shifts of Cardiocrinum in response to climatic change. KEY RESULTS: The molecular data showed high genetic similarity in the cpDNA (98·37 %) and LCNG (94·53 %) sequences. The biogeographical analyses revealed that the ancestor of Cardiocrinum diversified during the late Miocene (approx. 7·32 Mya) in Central China. The ancestor of the C. giganteum lineage dispersed westward to the Himalayas and south-west China with the split between C. giganteum and C. giganteum var. yunnanense occurring around 4·11 Mya consistent with the period of orogeny of the Hengduan Mountains. Some populations of the C. cathayanum lineage dispersed eastward to south Japan via the land bridge approx. 4·97 Mya, providing opportunities for allopatric speciation of C. cordatum The predicted suitable habitats of Cardiocrinum have become smaller and more fragmented since the Last Glacial Maximum. CONCLUSIONS: Our study provides evidence of a biogeographical pattern of dispersal from Central China to the Himalayas in the west and Japan in the east for genera distributed across the SJFR, and highlights that the orogeny of the Hengduan Mountains and fluctuations of the sea level of the East China Sea played important roles in promoting species divergence.

Characterization of SXT/R391 Integrative and Conjugative Elements in Proteus mirabilis Isolates from Food-Producing Animals in China.

SXT/R391 integrative and conjugative elements (ICEs) were detected in 8 out of 125 Proteus mirabilis isolates from food-producing animals in China. Whole-genome sequencing revealed that seven ICEs were identical to ICEPmiJpn1, carrying the cephalosporinase gene blaCMY-2. Another one, designated ICEPmiChn1, carried five resistance genes. All eight ICEs could be transferred to Escherichia coli via conjugation. The results highlight the idea that animal farms are important reservoir of the SXT/R391 ICE-containing P. mirabilis.

Two novel Salmonella genomic island 1 variants in Proteus mirabilis isolates from swine farms in China.

Four different Salmonella genomic island 1 (SGI1) variants, including two novel variants, were characterized in one Salmonella enterica serovar Rissen sequence type ST1917 isolate and three Proteus mirabilis isolates from swine farms in China. One novel variant was derived from SGI1-B with the backbone gene S021 disrupted by a 12.72-kb IS26 composite transposon containing the dfrA17-aadA5 cassettes and macrolide inactivation gene cluster mphA-mrx-mphR. The other one was an integron-free SGI1 and contained a 183-bp truncated S025 next to IS6100 and S044.

[Relevant studies on effect of Fuzheng Sanjie recipe in regulating immune microenvironment remodeling of TAMs in Lewis lung cancer mice].

OBJECTIVE: To study the effect of Fuzheng Sanjie recipe in regulating tumor-associated macrophages (TAMs) in Lewis lung cancer mice. METHOD: Efforts were made to establish the Lewis lung cancer mouse model, weigh tumors and calculate the anti-tumor rate. The immunohistochemical method was used to examine the infiltration degree of CD68 + in tumor tissues in each group. ELISA was used to examine the content of IFN-γ, TGF-ß, IL-4, IL-13, IL-6, IL-10, IL-12, TNF-α in mice serum. RESULT: Compared with the tumor-bearing model group, all of the other groups showed higher tumor inhibition rates, i. e. 50.28% for the DDP group, 34.37% for the TCM-preventing group and 66.76% for the Chinese and western medicine group, with statistical difference (P < 0.05), but without statistical difference in the infiltration degree of CD68+. The expressions of the IFN-γ, IL-6, IL-12 in tumor-bearing groups were lower than that in the blank control group, but with higher contents of IL-4, IL-13, TGF-ß. Intervened with different drugs, there were significant differences in content among some relevant cytokines (P < 0.05), as well as statistical differences among the TCM prevention group, the Chinese and western medicine group and the tumor-bearing control group (P <0. 05) , but without statistical difference in TNF-α and IL-10 content from the tumor-bearing control group (P < 0.05). CONCLUSION: Fuzheng Sanjie recipe could reverse the immune remodeling effect and control the tumor growth by down-regulating the expressions of IL-4, IL-13, TGF-α in lung cancer immune microenvironment and up-regulating the expression of IFN-γ.

Methylation entropy landscape of Chinese long-lived individuals reveals lower epigenetic noise related to human healthy aging.

The transition from ordered to noisy is a significant epigenetic signature of aging and age-related disease. As a paradigm of healthy human aging and longevity, long-lived individuals (LLI, >90 years old) may possess characteristic strategies in coping with the disordered epigenetic regulation. In this study, we constructed high-resolution blood epigenetic noise landscapes for this cohort by a methylation entropy (ME) method using whole genome bisulfite sequencing (WGBS). Although a universal increase in global ME occurred with chronological age in general control samples, this trend was suppressed in LLIs. Importantly, we identified 38,923 genomic regions with LLI-specific lower ME (LLI-specific lower entropy regions, for short, LLI-specific LERs). These regions were overrepresented in promoters, which likely function in transcriptional noise suppression. Genes associated with LLI-specific LERs have a considerable impact on SNP-based heritability of some aging-related disorders (e.g., asthma and stroke). Furthermore, neutrophil was identified as the primary cell type sustaining LLI-specific LERs. Our results highlight the stability of epigenetic order in promoters of genes involved with aging and age-related disorders within LLI epigenomes. This unique epigenetic feature reveals a previously unknown role of epigenetic order maintenance in specific genomic regions of LLIs, which helps open a new avenue on the epigenetic regulation mechanism in human healthy aging and longevity.

[Spatiotemporal Response of Ecosystem Service Value to Land Use Change in the Lanzhou-Xining Urban Agglomeration over the Past 20 Years].

With rapid urbanization and human activities exacerbating threats to the degradation of various ecosystem services in modern urban agglomerations, the exploration of the state of ecological security at the scale of urban agglomerations is of great significance. This study considered the Lanzhou-Xining Urban Agglomeration as the research area, based on the land use data in 2000, 2005, 2010, 2015, and 2020. At the same time, the landscape ecological risk index was introduced. The land use change characteristics of the Lanzhou-Xining Urban Agglomeration were analyzed by using the land use transfer matrix, the value per unit area equivalent factor method, and the bivariate spatial autocorrelation analysis method to elucidate the impacts of the changes in the ecological risk index induced by the land use transition on the value of ecosystem services. This study analyzed the land use change characteristics of the Lanzhou-Xining Urban Agglomeration and elucidated the impacts of changes in the ecological risk index on the value of ecosystem services caused by land use transformation. The results showed that:① During the period from 2000 to 2020, the land use types of the Lanzhou-Xining Urban Agglomeration were mainly dominated by grassland, cropland, and forest land. The construction land area had expanded significantly mainly from cropland and grassland, and the six land use types had strong cross-transformation. The total area of land use change was 6 646.05 km2. ② In terms of spatial changes, the spatial pattern of ecosystem service value in the Lanzhou-Xining Urban Agglomeration had not undergone obvious transformation. However, the regional variability was significant, generally showing the distribution characteristics of high in the northwest and low in the southeast. ③From the perspective of temporal change, the value of ecosystem services in the Lanzhou-Xining Urban Agglomeration showed an upward trend, with the total flow of value increasing from 186.459 billion yuan to 192.156 billion yuan, with a total value-added of 5.697 billion yuan. ④ There was a rising trend in the overall ecological risk index of the Lanzhou-Xining Urban Agglomeration over the past 20 years. Low ecological risk areas and lower ecological risk areas dominated the ecological risk areas. There was a significant positive correlation between the value of ecosystem services and the ecological risk index. This study aimed to reveal the understanding of the impacts of land-use practices on ecosystem service values and ecological risks, to provide important references for regional ecological risk management and land-use policy formulation, and thus to promote the high-quality development of the ecological environment in the Yellow River Basin.

Scrutiny of genome-wide somatic mutation profiles in centenarians identifies the key genomic regions for human longevity.

Somatic mutations accumulate with age and are associated closely with human health, their characterization in longevity cohorts remains largely unknown. Here, by analyzing whole genome somatic mutation profiles in 73 centenarians and 51 younger controls in China, we found that centenarian genomes are characterized by a markedly skewed distribution of somatic mutations, with many genomic regions being specifically conserved but displaying a high function potential. This, together with the observed more efficient DNA repair ability in the long-lived individuals, supports the existence of key genomic regions for human survival during aging, with their integrity being of essential to human longevity.

Gut microbiota contributes to high-altitude hypoxia acclimatization of human populations.

BACKGROUND: The relationship between human gut microbiota and high-altitude hypoxia acclimatization remains highly controversial. This stems primarily from uncertainties regarding both the potential temporal changes in the microbiota under such conditions and the existence of any dominant or core bacteria that may assist in host acclimatization. RESULTS: To address these issues, and to control for variables commonly present in previous studies which significantly impact the results obtained, namely genetic background, ethnicity, lifestyle, and diet, we conducted a 108-day longitudinal study on the same cohort comprising 45 healthy Han adults who traveled from lowland Chongqing, 243 masl, to high-altitude plateau Lhasa, Xizang, 3658 masl, and back. Using shotgun metagenomic profiling, we study temporal changes in gut microbiota composition at different timepoints. The results show a significant reduction in the species and functional diversity of the gut microbiota, along with a marked increase in functional redundancy. These changes are primarily driven by the overgrowth of Blautia A, a genus that is also abundant in six independent Han cohorts with long-term duration in lower hypoxia environment in Shigatse, Xizang, at 4700 masl. Further animal experiments indicate that Blautia A-fed mice exhibit enhanced intestinal health and a better acclimatization phenotype to sustained hypoxic stress. CONCLUSIONS: Our study underscores the importance of Blautia A species in the gut microbiota's rapid response to high-altitude hypoxia and its potential role in maintaining intestinal health and aiding host adaptation to extreme environments, likely via anti-inflammation and intestinal barrier protection.

Appropriateness and Comprehensiveness of Using ChatGPT for Perioperative Patient Education in Thoracic Surgery in Different Language Contexts: Survey Study.

BACKGROUND: ChatGPT, a dialogue-based artificial intelligence language model, has shown promise in assisting clinical workflows and patient-clinician communication. However, there is a lack of feasibility assessments regarding its use for perioperative patient education in thoracic surgery. OBJECTIVE: This study aimed to assess the appropriateness and comprehensiveness of using ChatGPT for perioperative patient education in thoracic surgery in both English and Chinese contexts. METHODS: This pilot study was conducted in February 2023. A total of 37 questions focused on perioperative patient education in thoracic surgery were created based on guidelines and clinical experience. Two sets of inquiries were made to ChatGPT for each question, one in English and the other in Chinese. The responses generated by ChatGPT were evaluated separately by experienced thoracic surgical clinicians for appropriateness and comprehensiveness based on a hypothetical draft response to a patient's question on the electronic information platform. For a response to be qualified, it required at least 80% of reviewers to deem it appropriate and 50% to deem it comprehensive. Statistical analyses were performed using the unpaired chi-square test or Fisher exact test, with a significance level set at P<.05. RESULTS: The set of 37 commonly asked questions covered topics such as disease information, diagnostic procedures, perioperative complications, treatment measures, disease prevention, and perioperative care considerations. In both the English and Chinese contexts, 34 (92%) out of 37 responses were qualified in terms of both appropriateness and comprehensiveness. The remaining 3 (8%) responses were unqualified in these 2 contexts. The unqualified responses primarily involved the diagnosis of disease symptoms and surgical-related complications symptoms. The reasons for determining the responses as unqualified were similar in both contexts. There was no statistically significant difference (34/37, 92% vs 34/37, 92%; P=.99) in the qualification rate between the 2 language sets. CONCLUSIONS: This pilot study demonstrates the potential feasibility of using ChatGPT for perioperative patient education in thoracic surgery in both English and Chinese contexts. ChatGPT is expected to enhance patient satisfaction, reduce anxiety, and improve compliance during the perioperative period. In the future, there will be remarkable potential application for using artificial intelligence, in conjunction with human review, for patient education and health consultation after patients have provided their informed consent.

Longevity-Associated Transcription Factor ATF7 Promotes Healthspan by Suppressing Cellular Senescence and Systematic Inflammation.

Aging is characterized by persistent low-grade systematic inflammation, which is largely responsible for the occurrence of various age-associated diseases. We and others have previously reported that long-lived people (such as centenarians) can delay the onset of or even escape certain major age-related diseases. Here, by screening blood transcriptome and inflammatory profiles, we found that long-lived individuals had a relatively lower inflammation level (IL6, TNFα), accompanied by up-regulation of activating transcription factor 7 (ATF7). Interestingly, ATF7 expression was gradually reduced during cellular senescence. Loss of ATF7 induced cellular senescence, while overexpression delayed senescence progress and senescence-associated secretory phenotype (SASP) secretion. We showed that the anti-senescence effects of ATF7 were achieved by inhibiting nuclear factor kappa B (NF-κB) signaling and increasing histone H3K9 dimethylation (H3K9me2). In Caenorhabditis elegans, ATF7 overexpression significantly suppressed aging biomarkers and extended lifespan. Our findings suggest that ATF7 is a longevity-promoting factor that lowers cellular senescence and inflammation in long-lived individuals.

Mitogenome evidence shows two radiation events and dispersals of matrilineal ancestry from northern coastal China to the Americas and Japan.

Although it is widely recognized that the ancestors of Native Americans (NAs) primarily came from Siberia, the link between mitochondrial DNA (mtDNA) lineage D4h3a (typical of NAs) and D4h3b (found so far only in East China and Thailand) raises the possibility that the ancestral sources for early NAs were more variegated than hypothesized. Here, we analyze 216 contemporary (including 106 newly sequenced) D4h mitogenomes and 39 previously reported ancient D4h data. The results reveal two radiation events of D4h in northern coastal China, one during the Last Glacial Maximum and the other within the last deglaciation, which facilitated the dispersals of D4h sub-branches to different areas including the Americas and the Japanese archipelago. The coastal distributions of the NA (D4h3a) and Japanese lineages (D4h1a and D4h2), in combination with the Paleolithic archaeological similarities among Northern China, the Americas, and Japan, lend support to the coastal dispersal scenario of early NAs.

Specific Gain and Loss of Co-Expression Modules in Long-Lived Individuals Indicate a Role of circRNAs in Human Longevity.

Deep RNA sequencing of 164 blood samples collected from long-lived families was performed to investigate the expression patterns of circular RNAs (circRNAs). Unlike that observed in previous studies, circRNA expression in long-lived elderly individuals (98.3 ± 3.4 year) did not exhibit an age-accumulating pattern. Based on weighted circRNA co-expression network analysis, we found that longevous elders specifically gained eight but lost seven conserved circRNA-circRNA co-expression modules (c-CCMs) compared with normal elder controls (spouses of offspring of long-lived individuals, age = 59.3 ± 5.8 year). Further analysis showed that these modules were associated with healthy aging-related pathways. These results together suggest an important role of circRNAs in regulating human lifespan extension.

Multiple time-series expression trajectories imply dynamic functional changes during cellular senescence.

Cellular senescence is a dynamic process driven by epigenetic and genetic changes. Although some transcriptomic signatures of senescent cells have been discovered, how these senescence-related signals change over time remains largely unclear. Here, we profiled the transcriptome dynamics of human dermal fibroblast (HDF) cells in successive stages of growth from proliferation to senescence. Based on time-series expression profile analysis, we discovered four trajectories (C1, C2, C3, C4) that are dynamically expressed as senescence progresses. While some genes were continuously up-regulated (C4) or down-regulated (C2) with aging, other genes did not change linearly with cell proliferation, but remained stable until entering the senescent state (C1, C3). Further analysis revealed that the four modes were enriched in different biological pathways, including regulation of cellular senescence. These findings provide a new perspective on understanding the dynamic regulatory mechanism of cellular senescence.

Combinations of liver lobe and spleen volumes obtained on magnetic resonance imaging to predict esophagogastric variceal bleeding in hepatitis B-related cirrhotic patients: A prospective cohort study.

To evaluate whether combinations of liver lobe and spleen volumes obtained on magnetic resonance imaging (MRI) could predict esophagogastric variceal bleeding (EVB) in hepatitis B-related cirrhotic patients. Ninety-six consecutive patients with hepatitis B-related cirrhosis underwent upper abdominal contrast-enhanced MRI within 1 week after initial hospitalization, and grouped based on outcomes of EVB during the 2 years' follow-up after being discharged. Total liver volume (TLV), spleen volume (SV) and 4 liver lobe volumes including right lobe volume (RV), left medial lobe volume (LMV), left lateral lobe volume (LLV), and caudate lobe volume (CV) were measured on MRI. Percentages of individual liver lobe volumes in TLV (including RV/TLV, LMV/TLV, LLV/TLV, and CV/TLV), ratios of SV to individual liver lobe volumes (including SV/RV, SV/LMV, SV/LLV, and SV/CV), and SV/TLV were statistically analyzed to predict EVB. Patients with EVB had lower RV than without EVB (P value = .001), whereas no differences in LMV, LLV, CV, and TLV were found (P values >.05 for all). Among percentages of individual liver lobe volumes in TLV, RV/TLV was lower whereas LMV/TLV and LLV/TLV were greater in patients with EVB than without EVB (P values <.05 for all). SV, ratios of SV to individual liver lobe volumes, and SV/TLV in patients with EVB were larger than without EVB (P values <.05 for all). Among parameters with difference between patients with and without EVB, SV/RV could best predict EVB with an area under receiver operating characteristic curve of 0.84. SV/RV could best predict EVB in hepatitis B-related cirrhotic patients.

ETS1 acts as a regulator of human healthy aging via decreasing ribosomal activity.

Adaptation to reduced energy production during aging is a fundamental issue for maintaining healthspan or prolonging life span. Currently, however, the underlying mechanism in long-lived people remains poorly understood. Here, we analyzed transcriptomes of 185 long-lived individuals (LLIs) and 86 spouses of their children from two independent Chinese longevity cohorts and found that the ribosome pathway was significantly down-regulated in LLIs. We found that the down-regulation is likely controlled by ETS1 (ETS proto-oncogene 1), a transcription factor down-regulated in LLIs and positively coexpressed with most ribosomal protein genes (RPGs). Functional assays showed that ETS1 can bind to RPG promoters, while ETS1 knockdown reduces RPG expression and alleviates cellular senescence in human dermal fibroblast (HDF) and embryonic lung fibroblast (IMR-90) cells. As protein synthesis/turnover in ribosomes is an energy-intensive cellular process, the decline in ribosomal biogenesis governed by ETS1 in certain female LLIs may serve as an alternative mechanism to achieve energy-saving and healthy aging.