Carbon dioxide capture from open air using covalent organic frameworks.

Capture of CO2 from the air offers a promising approach to addressing climate change and achieving carbon neutrality goals1,2. However, the development of a durable material with high capacity, fast kinetics and low regeneration temperature for CO2 capture, especially from the intricate and dynamic atmosphere, is still lacking. Here a porous, crystalline covalent organic framework (COF) with olefin linkages has been synthesized, structurally characterized and post-synthetically modified by the covalent attachment of amine initiators for producing polyamines within the pores. This COF (termed COF-999) can capture CO2 from open air. COF-999 has a capacity of 0.96 mmol g-1 under dry conditions and 2.05 mmol g-1 under 50% relative humidity, both from 400 ppm CO2. This COF was tested for more than 100 adsorption-desorption cycles in the open air of Berkeley, California, and found to fully retain its performance. COF-999 is an exceptional material for the capture of CO2 from open air as evidenced by its cycling stability, facile uptake of CO2 (reaches half capacity in 18.8 min) and low regeneration temperature (60 °C).

Nucleic acid degradation as barrier to gene delivery: a guide to understand and overcome nuclease activity.

Gene therapy is on its way to revolutionize the treatment of both inherited and acquired diseases, by transferring nucleic acids to correct a disease-causing gene in the target cells of patients. In the fight against infectious diseases, mRNA-based therapeutics have proven to be a viable strategy in the recent Covid-19 pandemic. Although a growing number of gene therapies have been approved, the success rate is limited when compared to the large number of preclinical and clinical trials that have been/are being performed. In this review, we highlight some of the hurdles which gene therapies encounter after administration into the human body, with a focus on nucleic acid degradation by nucleases that are extremely abundant in mammalian organs, biological fluids as well as in subcellular compartments. We overview the available strategies to reduce the biodegradation of gene therapeutics after administration, including chemical modifications of the nucleic acids, encapsulation into vectors and co-administration with nuclease inhibitors and discuss which strategies are applied for clinically approved nucleic acid therapeutics. In the final part, we discuss the currently available methods and techniques to qualify and quantify the integrity of nucleic acids, with their own strengths and limitations.

Crystalline Polyphenylene Covalent Organic Frameworks.

The synthesis of crystalline polyphenylene covalent organic frameworks (COFs) was accomplished by linking fluorinated tris(4-acetylphenyl)benzene building units using aldol cyclotrimerization. The structures of the two COFs, reported here, were confirmed by powder X-ray diffraction techniques, Fourier transform infrared, and solid-state 13C CP/MAS NMR spectroscopy. The results showed that the COFs were porous and chemically stable in corrosive, harsh environments for at least 1 week. Accordingly, postsynthetically modified derivatives of these COFs using primary amines showed CO2 uptake from air and flue gas.

Deconvolving Passive and Active Targeting of Liposomes Bearing LDL Receptor Binding Peptides Using the Zebrafish Embryo Model.

Improving target versus off-target ratio in nanomedicine remains a major challenge for increasing drug bioavailability and reducing toxicity. Active targeting using ligands on nanoparticle surfaces is a key approach but has limited clinical success. A potential issue is the integration of targeting ligands also changes the physicochemical properties of nanoparticles (passive targeting). Direct studies to understand the mechanisms of active targeting and off-targeting in vivo are limited by the lack of suitable tools. Here, the biodistribution of a representative active targeting liposome is analyzed, modified with an apolipoprotein E (ApoE) peptide that binds to the low-density lipoprotein receptor (LDLR), using zebrafish embryos. The ApoE liposomes demonstrated the expected liver targeting effect but also accumulated in the kidney glomerulus. The ldlra-/- zebrafish is developed to explore the LDLR-specificity of ApoE liposomes. Interestingly, liver targeting depends on the LDLR-specific interaction, while glomerular accumulation is independent of LDLR and peptide sequence. It is found that cationic charges of peptides and the size of liposomes govern glomerular targeting. Increasing the size of ApoE liposomes can avoid this off-targeting. Taken together, the study shows the potential of the zebrafish embryo model for understanding active and passive targeting mechanisms, that can be used to optimize the design of nanoparticles.

The Prognostic Utility of the Triceps Skinfold Thickness Albumin Index in Colorectal Cancer Patients with Cachexia.

PURPOSE: To develop a simple and convenient inflammation-nutrition-adiposity biomarker to complement the TNM staging system, further assess the prognosis of patients with colorectal cancer cachexia. METHODS: This study was a multi-centre cohort study. The triceps skinfold thickness-albumin index (TA) was calculated by combining the triceps skinfold thickness (TSF) and serum albumin levels. Kaplan-Meier analysis and Cox proportional risk regression models were used to assess the relationship between the TA and all-cause mortality. Internal validation was carried out. RESULTS: We included 1025 patients with colorectal cancer cachexia, 61.2% of whom were male, with a mean age of 58.91 (12.45) years. As the TA increased, overall mortality decreased in female patients (hazard ratio [HR], 0.95) but not in male patients (HR, 0.99). Multivariate Cox analysis showed that patients in the normal TA group had a significantly lower risk of death than those in the low TA group (HR, 0.53, 95% CI, 0.40-0.72). Patients with a normal TA had a lower risk of malnutrition, poor quality of life, and poor short-term prognosis than those with a low TA. CONCLUSIONS: TA index enables clinicians to assess the prognosis of patients as early as possible to improve the survival of patients with colorectal cancer cachexia.

Miktoarm Star-polypept(o)ide-Based Polyion Complex Micelles for the Delivery of Large Nucleic Acids.

Miktoarm star polymers exhibit a captivating range of physicochemical properties, setting them apart from their linear counterparts. This study devised a synthetic pathway to synthesize cationic miktoarm stars utilizing polypept(o)ides (PeptoMiktoStars), comprising 3 or 6 polysarcosine (pSar) arms (AB3×100, AB6×50, overall 300) for shielding and a cross-linkable poly(S-ethylsulfonyl-l-homocysteine) (pHcy(SO2Et)20) block and a poly(l-lysine) ((pLys)20) block for nucleic acid complexation. Precise control over the DPn and narrow molecular weight distributions (D̵ ≈ 1.2) were achieved for both structures. Both PeptoMiktoStars efficiently complexed mRNA and pDNA into polyion complex micelles (PICMs). AB6-PICMs provided modest (mRNA) to high (pDNA) stability against glutathione and heparin sulfate (HS), while even cross-linked AB3-PICMs were susceptible to HS. All PICMs delivered pDNA and mRNA into D1 cells (over 80%) and Jurkat T cells (over 50%) in vitro. Despite payload- and cell-dependency, AB3 showed overall higher transfection efficiency, while AB6 demonstrated better shielding and enhanced stability.

Association of systemic inflammation with the obesity paradox in cancer: results from multi-cohort studies.

AIMS: This study aimed to explore whether the obesity paradox exists in overall and specific cancers and to investigate the role of systemic inflammation in the obesity paradox. METHODS: The Cox proportional hazard model was used to explore the relationship between body mass index (BMI) and all-cause mortality. The mediated effect was used to investigate the proportion of systemic inflammation mediating the relationship between BMI and cancer survival risk. RESULTS: The survival probability showed a step-like increase with an increase in BMI regardless of pathological stage. Approximately 10.8%-24.0% of the overall association between BMI and all-cause mortality in cancer was mediated by inflammation. In the internal validation, we found evidence of the obesity paradox in all body composition obtained using BIA, with inflammation remaining an important mediating factor. Furthermore, we also validated the existence of the obesity paradox of cancer in NHANES. Systemic inflammation remains an important factor in mediating the association between BMI and prognosis in cancer patients. CONCLUSIONS: The obesity paradox is prevalent in most cancers, except for hepatic biliary cancer and breast cancer. Inflammation may be one of the true features of the obesity paradox in cancer.

Machine learning to identify precachexia and cachexia: a multicenter, retrospective cohort study.

BACKGROUND: Detection of precachexia is important for the prevention and treatment of cachexia. However, how to identify precachexia is still a challenge. OBJECTIVE: This study aimed to detect cancer precachexia using a simple method and distinguish the different characteristics of precachexia and cachexia. METHODS: We included 3896 participants in this study. We used all baseline characteristics as input variables and trained machine learning (ML) models to calculate the importance of the variables. After filtering the variables based on their importance, the models were retrained. The best model was selected based on the receiver operating characteristic value. Subsequently, we used the same method and process to identify patients with precachexia in a noncachexia population using the same method and process. RESULTS: Participants in this study included 2228 men (57.2%) and 1668 women (42.8%), of whom 471 were diagnosed with precachexia, 1178 with cachexia, and the remainder with noncachexia. The most important characteristics of cachexia were eating changes, arm circumference, high-density lipoprotein (HDL) level, and C-reactive protein albumin ratio (CAR). The most important features distinguishing precachexia were eating changes, serum creatinine, HDL, handgrip strength, and CAR. The two logistic regression models for screening for cachexia and diagnosing precachexia had the highest area under the curve values of 0.830 and 0.701, respectively. Calibration and decision curves showed that the models had good accuracy. CONCLUSION: We developed two models for identifying precachexia and cachexia, which will help clinicians detect and diagnose precachexia.

Remnant cholesterol is an effective biomarker for predicting survival in patients with breast cancer.

BACKGROUND: Breast cancer is the most common malignancy in women worldwide. The relationship between remnant cholesterol (RC) and the prognosis of patients with breast cancer has not been clearly reported. This study investigated the prognostic value of RC in predicting mortality in patients with breast cancer. METHODS: This study prospectively analysed 709 women patients with breast cancer from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) project. Restricted cubic splines were used to analyse the dose-response relationship between RC and breast cancer mortality. The Kaplan-Meier method was used to evaluate the overall survival of patients with breast cancer. A Cox regression analyses was performed to assess the independent association between RC and breast cancer mortality. Inverse probability of treatment weighting (IPTW) using the propensity score was used to reduce confounding. Sensitivity analysis was performed after excluding patients with underlying diseases and survival times shorter than one year. RESULTS: A linear dose-response relationship was identified between RC and the risk of all-cause mortality in patients with breast cancer (p = 0.036). Kaplan-Meier survival analysis and log-rank test showed that patients with high RC levels had poorer survival than those with low RC levels (p = 0.007). Univariate and multivariate Cox regression analyses showed that RC was an independent risk factor for mortality in women patients with breast cancer. IPTW-adjusted analyses and sensitivity analyses showed that CR remained a prognostic factor. CONCLUSIONS: RC is an independent risk factor for the prognosis of patients with breast cancer, and patients with higher RC levels have poorer survival.

Exploring the impact of women-specific reproductive factors on phenotypic aging and the role of life's essential 8.

BACKGROUND: Aging is an inevitable biological process. Accelerated aging renders adults more susceptible to chronic diseases and increases their mortality rates. Previous studies have reported the relationship between lifestyle factors and phenotypic aging. However, the relationship between intrinsic factors, such as reproductive factors, and phenotypic aging remains unclear. METHODS: This study utilized data from the National Health and Nutrition Examination Survey (NHANES), spanning from 1999 to 2010 and 2015-2018, with 14,736 adult women. Random forest imputation was used to handle missing covariate values in the final cohort. Weighted linear regression was utilized to analyze the relationship between women-specific reproductive factors and PhenoAgeAccel. Considering the potential impact of menopausal status on the results, additional analyses were conducted on premenopausal and postmenopausal participants. Additionally, the Life's Essential 8 (LE8) was used to investigate the impact of healthy lifestyle and other factors on the relationship between women-specific reproductive factors and PhenoAgeAccel. Stratified analyses were conducted based on significant interaction p-values. RESULTS: In the fully adjusted models, delayed menarche and gynecological surgery were associated with increased PhenoAgeAccel, whereas pregnancy history were associated with a decrease. Additionally, early or late ages of menopause, first live birth, and last live birth can all negatively impact PhenoAgeAccel. The relationship between women-specific reproductive factors and PhenoAgeAccel differs between premenopausal and postmenopausal women. High LE8 scores positively impacted the relationship between certain reproductive factors (age at menarche, age at menopause, age at first live birth, and age at last live birth) and phenotypic age acceleration. Stratified analysis showed significant interactions for the following variables: BMI with age at menarche, pregnancy history, and age at menopause; ethnicity with age at menopause, age at first live birth, and parity; smoking status with use of contraceptive pills and gynecologic surgery; hypertension with use of contraceptive pills, pregnancy history, and age at menopause. CONCLUSION: Delayed menarche, gynecological surgery, and early or late ages of menopause, first live birth, and last live birth are associated with accelerated phenotypic aging. High LE8 score may alleviate the adverse effects of reproductive factors on phenotypic aging.

miR-134-5p inhibits osteoclastogenesis through a novel miR-134-5p/Itgb1/MAPK pathway.

Osteoporosis affects approximately 200 million people and severely affects quality of life, but the exact pathological mechanisms behind this disease remain unclear. Various miRNAs have been shown to play a predominant role in the regulation of osteoclast formation. In this study, we explored the role of miR-134-5p in osteoclastogenesis both in vivo and in vitro. We constructed an ovariectomized (OVX) mouse model and performed microarray analysis using bone tissue from OVX mice and their control counterparts. Quantitative RT-PCR data from bone tissue and bone marrow macrophages (BMMs) confirmed the decreased expression of miR-134-5p in OVX mice observed in microarray analysis. In addition, a decrease in miR-134-5p was also observed during induced osteoclastogenesis of BMMs collected from C57BL/6N mice. Through transfection with miR-134-5p agomirs and antagomirs, we found that miR-134-5p knockdown significantly accelerated osteoclast formation and cell proliferation and inhibited apoptosis. Furthermore, a luciferase reporter assay showed that miR-134-5p directly targets the integrin surface receptor gene Itgb1. Cotransfection with Itgb1 siRNA reversed the effect of the miR-134-5p antagomir in promoting osteoclastogenesis. Moreover, the abundance levels of MAPK pathway proteins phosphorylated-p38 (p-p38) and phosphorylated-ERK (p-ERK) were significantly increased after transfection with the miR-134-5p antagomir but decreased after transfection with the miR-134-5p agomir or Itgb1 siRNA, which indicated a potential relationship between the miR-134-5p/Itgb1 axis and the MAPK pathway. Collectively, these results revealed that miR-134-5p inhibits osteoclast differentiation of BMMs both in vivo and in vitro and that the miR-134-5p/Itgb1/MAPK pathway might be a potential target for osteoporosis therapy.

Hydrazonyl Sultones as Stable Tautomers of Highly Reactive Nitrile Imines for Fast Bioorthogonal Ligation Reaction.

Here we report the design and synthesis of a new class of bioorthogonal reagents called hydrazonyl sultones (HS) that serve as stable tautomers of highly reactive nitrile imines (NI). Compared to the photogenerated NI, HS display a broad range of aqueous stability and tunable reactivity in a 1,3-dipolar cycloaddition reaction, depending on substituents, sultone ring structure, and solvent conditions. DFT calculations have provided vital insights into the HS → NI tautomerism, including a base-mediated anionic tautomerization pathway and a small activation barrier. Comparative kinetic analysis of tetrazole vs HS-mediated cycloadditions reveals that a tiny fraction of the reactive NI (∼15 ppm) is present in the tautomeric mixture, underpinning the extraordinary stability of the six-membered HS. We further demonstrate the utilities of HS in selective modification of bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN)-lysine-containing nanobodies in phosphate buffered saline and fluorescent labeling of a BCN-lysine-encoded transmembrane glucagon receptor on live cells.

Cholesterol-modified prognostic nutritional index (CPNI) as an effective tool for assessing the nutrition status and predicting survival in patients with breast cancer.

BACKGROUND: Malnutrition is associated with poor overall survival (OS) in breast cancer patients; however, the most predictive nutritional indicators for the prognosis of patients with breast cancer are not well-established. This study aimed to compare the predictive effects of common nutritional indicators on OS and to refine existing nutritional indicators, thereby identifying a more effective nutritional evaluation indicator for predicting the prognosis in breast cancer patients. METHODS: This prospective study analyzed data from 776 breast cancer patients enrolled in the "Investigation on Nutritional Status and its Clinical Outcome of Common Cancers" (INSCOC) project, which was conducted in 40 hospitals in China. We used the time-dependent receiver operating characteristic curve (ROC), Kaplan-Meier survival curve, and Cox regression analysis to evaluate the predictive effects of several nutritional assessments. These assessments included the patient-generated subjective nutrition assessment (PGSGA), the global leadership initiative on malnutrition (GLIM), the controlling nutritional status (CONUT), the nutritional risk index (NRI), and the prognostic nutritional index (PNI). Utilizing machine learning, these nutritional indicators were screened through single-factor analysis, and relatively important variables were selected to modify the PNI. The modified PNI, termed the cholesterol-modified prognostic nutritional index (CPNI), was evaluated for its predictive effect on the prognosis of patients. RESULTS: Among the nutritional assessments (including PGSGA, GLIM, CONUT, NRI, and PNI), PNI showed the highest predictive ability for patient prognosis (time-dependent ROC = 0.58). CPNI, which evolved from PNI, emerged as the superior nutritional index for OS in breast cancer patients, with the time-dependent ROC of 0.65. It also acted as an independent risk factor for mortality (p < 0.05). Moreover, the risk of malnutrition and mortality was observed to increase gradually among both premenopausal and postmenopausal age women, as well as among women categorized as non-overweight, overweight, and obese. CONCLUSIONS: The CPNI proves to be an effective nutritional assessment tool for predicting the prognosis of patients with breast cancer.

Tuning the Cross-Linking Density and Cross-Linker in Core Cross-Linked Polymeric Micelles and Its Effects on the Particle Stability in Human Blood Plasma and Mice.

Core cross-linked polymeric micelles (CCPMs) are designed to improve the therapeutic profile of hydrophobic drugs, reduce or completely avoid protein corona formation, and offer prolonged circulation times, a prerequisite for passive or active targeting. In this study, we tuned the CCPM stability by using bifunctional or trifunctional cross-linkers and varying the cross-linkable polymer block length. For CCPMs, amphiphilic thiol-reactive polypept(o)ides of polysarcosine-block-poly(S-ethylsulfonyl-l-cysteine) [pSar-b-pCys(SO2Et)] were employed. While the pCys(SO2Et) chain lengths varied from Xn = 17 to 30, bivalent (derivatives of dihydrolipoic acid) and trivalent (sarcosine/cysteine pentapeptide) cross-linkers have been applied. Asymmetrical flow field-flow fraction (AF4) displayed the absence of aggregates in human plasma, yet for non-cross-linked PM and CCPMs cross-linked with dihydrolipoic acid at [pCys(SO2Et)]17, increasing the cross-linking density or the pCys(SO2Et) chain lengths led to stable CCPMs. Interestingly, circulation time and biodistribution in mice of non-cross-linked and bivalently cross-linked CCPMs are comparable, while the trivalent peptide cross-linkers enhance the circulation half-life from 11 to 19 h.

Association between the Dietary Inflammatory Index and All-Cause Mortality in Adults with Obesity.

INTRODUCTION: The dietary inflammatory index (DII) is associated with numerous chronic noncommunicable diseases. Previous studies have shown that the pro-inflammatory DII categories are associated with abdominal and simple obesity. However, the association between DII and mortality in patients with abdominal obesity and simple overweight or obesity remains unclear. METHODS: We used data from the US National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. A DII >0 (positive DII) was defined as a pro-inflammatory diet. A restricted cubic spline curve was used to describe the trend between DII and all-cause mortality. We then examined the association between DII and all-cause mortality in different body types using a Cox regression analysis and investigated the differences between sexes. Finally, the mediating effects of systemic inflammation were explored. RESULTS: A pro-inflammatory diet increased all-cause mortality in adults with abdominal obesity (aHR: 1.31, 95% confidence interval [CI]: 1.11-1.54; p < 0.001) and with simple overweight or obesity (aHR: 1.30, 95% CI: 1.11-1.53; p < 0.001). In addition, the most pro-inflammatory DII increased the risk of mortality by 43% (hazard ratio [HR]: Q4 vs. Q1 = 1.43, 95% CI = 1.14-1.79; p = 0.002; p for trend = 0.003) and 39% (HR: Q4 vs. Q1 = 1.39, 95% CI = 1.13-1.74; p = 0.003; p for trend = 0.009) in participants with abdominal obesity and with simple overweight or obesity, respectively. However, this association was not present in normal-sized participants. Compared with men, women resisted the effects of a pro-inflammatory diet. Mediation analysis showed that white blood cell and neutrophil were mediators of the association between DII and all-cause mortality (p < 0.001). CONCLUSION: A pro-inflammatory diet is associated with all-cause mortality in adults with abdominal obesity and simple overweight or obesity, and this effect differs between men and women. Systemic inflammation may mediate the association between DII and all-cause mortality.

Roles of the hsa_circ_0013880/USP32/Rap1b axis in the proliferation and apoptosis of acute myeloid leukemia cells.

Acute myeloid leukemia (AML) is a myeloid malignancy with generally high mortality. Although recent advances in AML research have revealed that circRNAs play significant roles in AML progression, our understanding of the leukemogenic mechanism of circRNAs remains very limited. In this study, increased expression of hsa_circ_0013880 was observed in bone marrow mononuclear cells (BMNCs) of AML patients. Overexpression of hsa_circ_0013880 promotes AML cell proliferation and migration and reduces cell apoptosis. Mechanistically, hsa_circ_0013880 could elevate the expression of USP32, a deubiquitinating enzyme that is highly expressed in the BMNCs of AML patients. Given the deubiquitination function of USP32, we further hypothesize that USP32 may mediate the malignant behaviors of AML cells by regulating the stability of Ras-related protein (Rap1b). At the molecular level, we find that silencing of USP32 increases ubiquitinated Rap1b. Overexpression of Rap1b restores the effects of USP32 knockdown, which further verifies our hypothesis. In addition, we propose another hypothesis that a potential regulatory network among hsa_circ_0013880, miR-148a-3p/miR-20a-5p and USP32 might exist in the development of AML, according to bioinformatics website predictions and our preliminary experimental verification. Overall, our findings will enrich the understanding of the hsa_circ_0013880/USP32/Rap1b axis in AML development, which may contribute to the development of novel therapeutic strategies for AML.

A novel inflammation-nutrition biomarker score for predicting prognosis of patients with cancer: results from a multicenter study.

BACKGROUND: This study aimed to develop an innovative inflammation-nutrition biomarker score (INS) system to stratify the prognoses of patients with cancer. METHODS: A total of 5,221 patients with cancer from multiple centers in China between June 2010 and December 2017 were enrolled in this prospective cohort study. We compared the commonly used inflammation and nutrition biomarkers and selected the most valuable to develop the novel INS system. Survival curves were assessed using the Kaplan-Meier method and the log-rank test to evaluate the difference in survival rates between groups. The Cox proportional hazards model was used to investigate the association between biomarkers and all-cause mortality. RESULTS: As the risk stratification of INS increased (1 to 5), the rate of death for cancer patients gradually increased (25.43% vs. 37.09% vs. 44.59% vs. 56.21% vs. 61.65%, p < 0.001). The INS system was associated with all-cause mortality in patients with cancer. Patients with both high inflammation and nutrition risk (INS = 5) were estimated to have much worse prognosis than those with neither (HR, 2.606; 95%CI, 2.261-3.003, p < 0.001). Subsequently, the results of randomized internal validation also confirmed that INS system had an ideal effect in identifying adverse outcomes. In addition, the INS system could be used as a supplement to pathological stages in prognosis assessment, and had a higher predictive value in comparison with the constitute biomarkers. Patients with a high INS had less functional ability, reduced quality of life, and were at high risk of malnutrition, cachexia, and poor short-term outcomes. CONCLUSION: The INS system based on inflammation and nutrition biomarkers is a simple and effective prognostic stratification tool for patients with cancer, which can provide a valuable reference for clinical prognosis assessment and treatment strategy formulation.

Prognostic importance of systemic inflammation and insulin resistance in patients with cancer: a prospective multicenter study.

BACKGROUND: Systemic inflammation and insulin resistance (IR) are often associated with poor prognosis in cancer. This study aimed to investigate the prognostic value of surrogate systemic inflammation and IR indices in patients with cancer. METHODS: This multicenter prospective study included 5,221 patients with cancer, with a mean age of 59.41±11.15 years, of whom 3,061 (58.6%) were male. The surrogate IR indices included low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LHR) ratio, total cholesterol to high-density lipoprotein cholesterol (TC/ HDL-c) ratio, triglyceride to high-density lipoprotein cholesterol (TG/HDL-c) ratio, and fasting triglyceride glucose (TyG). Prognostic receiver operator characteristic (ROC) curves and C-indices were used to select a better surrogate IR index in patients with cancer. The prognostic value of the indicators was evaluated using univariate and multivariate survival analyses. RESULTS: In this study, the median survival time of patients was 44.5 (40.5-51.4) months, and the overall mortality in the 12-month period was 1,115 (53.7%), with 196 mortality events per 1,000 patient-years of patients' follow-up. The prognostic ROC curve and C-index suggested that the prognostic value of LHR was better than that of the other IR indices. The multivariate-adjusted hazard ratios (HRs) for overall survival (OS) were higher in patients with high C-reactive protein (CRP) (HR, 1.51; 95% confidence interval [CI]: 1.38-1.65) and high LHR (HR, 1.20; 95% CI: 1.06-1.37), respectively. The mortality rate of patients with both high CRP and LHR was 1.75-fold higher than that of patients with both low CRP and LHR. CONCLUSION: Both CRP and LHR showed good survival predictions in patients with cancer. CRP combined with LHR can improve the predictive power of patients with cancer.

Lymphocyte to C-reactive protein ratio could better predict the prognosis of patients with stage IV cancer.

BACKGROUND: Systemic inflammation is currently regarded as a hallmark of cancer. This study aimed to accurately clarify the prognostic value of various inflammatory markers in patients with stage IV cancer. METHODS: This study assessed 2,424 patients with cancer diagnosed with cancer in tumor, node, metastasis (TNM) stage IV. After evaluating the predictive value of 13 inflammatory indicators for patient prognosis using the C index, the lymphocyte C-reactive protein ratio (LCR) was selected to elucidate the prognostic and predictive values in patients with stage IV cancer. Kaplan-Meier and Cox proportional hazards regression models were used to analyze long-term survival. RESULTS: A total of 1,457 men (60.1%) and 967 women (39.9%) diagnosed with TNM stage IV cancer were enrolled. A ratio of 2,814 was defined as the optimal cut-off value for the LCR. The LCR was the most accurate prognosis predictor for patients with stage IV cancer among the 13 inflammatory nutritional markers evaluated. The multivariate-adjusted restricted cubic spline plot suggested that LCR had an L-shaped dose-response association with all-cause mortality risk. Patients with lower LCR levels tended to present with worse prognoses. Kaplan-Meier curves and log-rank test results showed that the high LCR groups (LCR ≥ 2,814) exhibited a better prognosis, whereas patients with stage IV cancer of different sex and tumor types (for example, gastrointestinal tumor, non-gastrointestinal tumor, and lung cancer) had a worse survival time. CONCLUSION: The LCR score can be regarded as a stable and useful biomarker to predict prognosis in patients with TNM stage IV compared to other evaluated inflammation indicators.

TLS/FUS-ERG fusion gene in acute leukemia and myelodysplastic syndrome evolved to acute leukemia: report of six cases and a literature review.

To investigate the pathogenesis and the refractory/relapse mechanisms in patients with t(16;21)(p11;q22), we retrospectively analyzed the clinical data of six cases in our hospital and sixty-two cases reported in the literature. Among the patients in our hospital, five cases were diagnosed as acute leukemia, and one was myelodysplastic syndrome evolved to acute myeloid leukemia, harboring TLS/FUS-ERG fusion gene; all the cases were detected t(16;21)(p11;q22) translocation, and five cases showed additional chromosomal abnormalities. We firstly report a novel three-way translocation t(11;16;21)(q13;p11;q22), which may affect the prognosis of leukemia with TLS-ERG fusion gene because this patient shows a more satisfactory treatment effect and deeper remission. And we found patients with TLS-ERG are more likely to have bone and arthrosis pain. Besides, CD56 and CD123 were positive in these cases, which are related to poor prognosis and the character of refractory. Moreover, some gene mutations are involved, and GATA2 and SMAD4 mutations were identified when the disease progressed from myelodysplastic syndrome to leukemia. Among sixty-two patients reported in the literature, valid positive percent of CD56 and CD123 were 81% and 14.3%, respectively. Mutation of the RUNX1 gene was detected in four cases, and one patient had multiple mutations, including BCOR, PLCG1, DIS3, BRAF, JAK2, and JAK3. The prominent feature of leukemia carrying the TLS/FUS-ERG gene is its poor prognosis. The relevant mechanism includes new mutation, jumping translocation, different transcripts, and so on. The mechanism still acquaints scarcely, which requires further study.