Aptamer-Functionalized Magnetic Ti3C2 Based Nanoplatform for Simultaneous Enrichment and Detection of Exosomes.

Exosomes are nanovesicles secreted by cells, which play a crucial role in various pathological processes. Exosomes have shown great promise as tumor biomarkers because of the abundant secretion during tumor formation. The development of a convenient, efficient, and cost-effective method for simultaneously enriching and detecting exosomes is of utmost importance for both basic research and clinical applications. In this study, an aptamer-functionalized magnetic Ti3C2 composite material (Fe3O4@Ti3C2@PEI@DSP@aptamer@FAM-ssDNA) is prepared for the simultaneous enrichment and detection of exosomes. CD63 aptamers are utilized to recognize and capture the exosomes, followed by magnetic separation. The exosomes are then released by cleaving the disulfide bonds of DSP. Compared to traditional methods, Fe3O4@Ti3C2@PEI@DSP@aptamer@FAM-ssDNA exhibited superior efficiency in enriching exosomes while preserving their structural and functional integrity. Detection of exosome concentration is achieved through the fluorescence quenching of Ti3C2 and the competitive binding between the exosomes and a fluorescently labeled probe. This method exhibited a low detection limit of 4.21 × 104 particles mL-1, a number that is comparable to the state-of-the-art method in the detection of exosomes. The present study demonstrates a method of simultaneous enrichment and detection of exosomes with a high sensitivity, accuracy, specificity, and cost-effectiveness providing significant potential for clinical research and diagnosis.

The Association between Serum Level of Vitamin D and Inflammatory Biomarkers in Hospitalized Adult Patients: A Cross-Sectional Study Based on Real-World Data.

Objective: The association between vitamin D status and inflammation remains unclear in hospitalized patients. Materials and Methods: We performed the current study based on real-world data from two teaching hospitals. Serum level of vitamin D (assessed by 25-hydroxyvitamin D) was evaluated within 2 days after admission. All the patients were further classified into three groups: deficiency (<12 ng/mL), insufficiency (12-20 ng/mL), and adequate (≥20 ng/mL). White blood cell (WBC) count, serum level of C-reactive protein (CRP), and procalcitonin were also measured and used to evaluate inflammation. Other potential covariates were abstracted from medical records. Charlson comorbidity index (CCI) was calculated to assess the severity of disease. Results: A total number of 35,528 hospitalized adult patients (21,171 men and 14,357 women) were included. The average age and BMI were 57.5 ± 16.2 years and 23.4 ± 3.7 kg/m2, respectively, while medium vitamin D level was 16.1 ng/mL (interquartile range: 11.4 ng/mL, 21.6 ng/mL) and median CCI was one point (interquartile range: 0 point, two points). The prevalence of deficiency and insufficiency was 28.0% and 40.5%. Multivariate linear regression model showed that serum level of vitamin D was significantly associated with WBC and CRP but not associated with procalcitonin. Each standard deviation (≈7.4 ng/mL) increase in vitamin D was associated with a decrease in WBC by 0.13 × 109/mL (95% CI: 0.2 × 109/mL, 0.06 × 109/mL) and 0.62 mg/L (95% CI: 0.88 mg/L, 0.37 mg/L) for CRP. Subgroup analysis and sensitivity analysis (excluding those whose eGFR <60 ml/min/1.73 m2, those whose daily calorie intake <1,000 kcal, and those who were recruited from Xin Hua hospital) generated similar results. Conclusions: The deficiency and insufficiency of vitamin D in the hospitalized adult patients was very common. However, the results should be interpreted with caution for limited representation of the whole inpatients. Low level of vitamin D was associated with inflammatory biomarkers, which provide the evidences to early intervention for lower the risk of infection.

Clinical characteristics and survival prediction of surgical patients with invasive pancreatic cystic neoplasm: a large retrospective study over two decades.

PURPOSES: Invasive pancreatic cystic neoplasms (iPCNs) are an uncommon and biologically heterogeneous group of malignant neoplasms. We aimed to investigate the clinicopathological characteristics of iPCN patients and to develop nomograms for individual survival prediction after radical surgery. METHODS: Data of patients diagnosed with iPCN and pancreatic ductal adenocarcinoma (PDAC) between 2000 and 2018 from the SEER database were retrieved. The differences in clinical outcomes were evaluated using the Kaplan-Meier analysis. Nomograms were proposed based on the Cox regression model and internally validated by C-index, area under the curve (AUC) value, and calibration plot. RESULTS: A total of 7777 iPCN patients and 154,336 PDAC patients were enrolled. Most neoplasms were advanced, with 63.1% at stage IV. The 3-year overall survival (OS) and cancer-specific survival (CSS) rates in surgical patients were as follows: 45.7% and 50.1% for invasive intraductal papillary mucinous neoplasm (IPMN), 54.8% and 59.3% for invasive mucinous cystic neoplasm (MCN), 97.8% and 98.2% for invasive solid pseudopapillary neoplasm (SPN), 88.9% and 88.9% for invasive serous cystic neoplasm (SCN), and 27.3% and 30.5% for PDAC. Subgroup analyses showed no clinical benefit from chemotherapy or radiotherapy in lymph node-negative iPCN patients who underwent surgery. The following variables associated with OS and CSS were identified: age, race, chemotherapy, radiotherapy, histologic type, pathological grade, regional nodes examined, and T, N, and M stage. The nomograms had good discrimination and calibration by internal validation, with an AUC value of 0.800 for 3-year OS and 0.814 for 3-year CSS. CONCLUSION: Our study showed that the prognosis of iPCN patients was significantly better than PDAC patients. The proposed nomograms demonstrated substantially better discrimination and calibration.

Development and Assessment of Assisted Diagnosis Models Using Machine Learning for Identifying Elderly Patients With Malnutrition: Cohort Study.

BACKGROUND: Older patients are at an increased risk of malnutrition due to many factors related to poor clinical outcomes. OBJECTIVE: This study aims to develop an assisted diagnosis model using machine learning (ML) for identifying older patients with malnutrition and providing the focus of individualized treatment. METHODS: We reanalyzed a multicenter, observational cohort study including 2660 older patients. Baseline malnutrition was defined using the global leadership initiative on malnutrition (GLIM) criteria, and the study population was randomly divided into a derivation group (2128/2660, 80%) and a validation group (532/2660, 20%). We applied 5 ML algorithms and further explored the relationship between features and the risk of malnutrition by using the Shapley additive explanations visualization method. RESULTS: The proposed ML models were capable to identify older patients with malnutrition. In the external validation cohort, the top 3 models by the area under the receiver operating characteristic curve were light gradient boosting machine (92.1%), extreme gradient boosting (91.9%), and the random forest model (91.5%). Additionally, the analysis of the importance of features revealed that BMI, weight loss, and calf circumference were the strongest predictors to affect GLIM. A BMI of below 21 kg/m2 was associated with a higher risk of GLIM in older people. CONCLUSIONS: We developed ML models for assisting diagnosis of malnutrition based on the GLIM criteria. The cutoff values of laboratory tests generated by Shapley additive explanations could provide references for the identification of malnutrition. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-EPC-14005253; https://www.chictr.org.cn/showproj.aspx?proj=9542.

Identifying optimal candidates for tumor resection among borderline and locally advanced pancreatic cancer: A population-based predictive model.

BACKGROUND: Whether patients with borderline resectable and locally advanced pancreatic cancer (BR/LAPC) benefit from resection of the primary cancer is controversial. We developed a nomogram to screen who would benefit from surgery for the primary tumor. METHODS: We identified patients from the Surveillance, Epidemiology, and End Results (SEER) database and then divided them into surgical and non-surgical groups. A 1:1 propensity score matching (PSM) was used to mitigate the bias. We hypothesized that patients who underwent surgery would benefit from surgery by having a longer median overall survival (OS) than patients who did not undergo surgery. Univariate and multivariate logistic regression analyses were used to determine the variables affecting surgical outcomes, and a nomogram was created based on the multivariate logistic results. Finally, we verified the discrimination and calibration of the nomogram with receiver operator characteristic (ROC) curve and calibration plots. RESULTS: A total of 518 pairs of surgical and non-surgical pancreatic cancer patients were matched after PSM. Survival curves showed longer OS in the surgical group than in the non-surgical group, median survival times were 14 months versus 8 months. In the surgical group, 340 (65.63%) patients have a longer survival time than 8 months (beneficial group). Multifactorial logit regression results showed that including age, tumor size, degree of differentiation, and chemotherapy were significant influences on the benefit of surgery for primary tumors and were used as predictors to construct a nomogram. The area under the ROC curve (AUC) reached 0.747 and 0.706 in the training and validation sets. CONCLUSION: We developed a practical predictive model to support clinical decision-making that can be used to help clinicians determine if there is a benefit to surgical resection of the primary tumor in patients with BR/LAPC.

Malnutrition dynamics according to GLIM criteria in hospitalized elderly.

BACKGROUND AND OBJECTIVES: Assess the different nutritional status between admission and discharged in older adult patients using the GLIM criteria. METHODS AND STUDY DESIGN: A retrospective analysis was conducted on a multicenter study which initiated in 34 hospitals in China with 2734 hospitalized older patients. The dynamic changes of malnutrition according to GLIM criteria were performed between at admission and discharge, and their significance was analyzed using the chi-square test. The association between malnutrition and clinical outcomes was analyzed using the chi-square test, t-test, or rank sum test, and divided into different disease types for further analysis. RESULTS: The incidence of nutritional risk in elderly patients was 51.6% at admission and 48.4% at discharge. The prevalence of malnutrition according to the GLIM criteria was 19.6% at admission and increased to 33.4% at discharge, which was significantly different. Different age and disease type were related with nutrition status. Malnutrition is significantly association with adverse clinical outcomes such as increased risk of complications and prolonged length of hospital stay. CONCLUSIONS: The GLIM criteria can be used in elderly patients to assess malnutrition. The prevalence of malnutrition in elderly inpatients is high, and the prevalence of malnutrition at discharge is higher than that observed at admission. Attention should be paid to the dynamic changes of malnutrition in elderly patients during hospitalization.

Clinical characteristics and risk factors of fatal patients with COVID-19: a retrospective cohort study in Wuhan, China.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has caused a global pandemic, resulting in considerable mortality. The risk factors, clinical treatments, especially comprehensive risk models for COVID-19 death are urgently warranted. METHODS: In this retrospective study, 281 non-survivors and 712 survivors with propensity score matching by age, sex, and comorbidities were enrolled from January 13, 2020 to March 31, 2020. RESULTS: Higher SOFA, qSOFA, APACHE II and SIRS scores, hypoxia, elevated inflammatory cytokines, multi-organ dysfunction, decreased immune cell subsets, and complications were significantly associated with the higher COVID-19 death risk. In addition to traditional predictors for death risk, including APACHE II (AUC = 0.83), SIRS (AUC = 0.75), SOFA (AUC = 0.70) and qSOFA scores (AUC = 0.61), another four prediction models that included immune cells subsets (AUC = 0.90), multiple organ damage biomarkers (AUC = 0.89), complications (AUC = 0.88) and inflammatory-related indexes (AUC = 0.75) were established. Additionally, the predictive accuracy of combining these risk factors (AUC = 0.950) was also significantly higher than that of each risk group alone, which was significant for early clinical management for COVID-19. CONCLUSIONS: The potential risk factors could help to predict the clinical prognosis of COVID-19 patients at an early stage. The combined model might be more suitable for the death risk evaluation of COVID-19.

Effect of oral nutritional supplementation on the post-discharge nutritional status and quality of life of gastrointestinal cancer patients after surgery: a multi-center study.

BACKGROUND AND OBJECTIVES: To evaluate the effect of oral nutritional supplementation (ONS) on the postdischarge nutritional status and quality of life (QoL) of gastrointestinal cancer patients after surgery. METHODS AND STUDY DESIGN: A multi-center study was conducted on gastrointestinal cancer patients who received surgical treatment from 2013-2015. All patients were screened using the Nutrition Risk Screening 2002 (NRS 2002) to assess nutritional risk. Patients with nutritional risk were randomized into two groups: patients in the study group (n=55) were given dietary guidance and ONS, control group (n=59) received only dietary guidance. Anthropometric measurements, nutrition-related laboratory tests, and gastrointestinal function scores were also collected and analyzed using Student's t test and analysis of variance (ANOVA). In addition, the EQ-5D was used to evaluate patients' QoL. RESULTS: Compared with baseline measurements, the body weight of patients in the study group increased by 1.35±0.53 kg and 1.35±0.73 kg at 60 and 90 days, which were significantly higher than those in the control group (-1.01±0.54 kg, and -1.60±0.81 kg at 60 and 90 days). The results from ANOVA showed that only weight and BMI differed significantly between the study and control groups and also between different measurement times (p<0.01). No differences were found for the other indicators or QoL between the study groups. CONCLUSIONS: ONS may improve the weight and BMI of surgically treated gastrointestinal cancer patients postdischarge. However, these effects had little impact on patients' QoL.

Nutritional Risk and Nutritional Status at Admission and Discharge among Chinese Hospitalized Patients: A Prospective, Nationwide, Multicenter Study.

OBJECTIVE: The objective of this study was to assess nutritional risk and status of Chinese hospitalized patients at admission and discharge and relations with clinical outcomes. METHODS: A prospective, nationwide, multicenter study was conducted from June to September 2014 in 34 large hospitals in 18 cities in China. Patients ≥ 18 years with a hospital stay of 7-30 days were recruited. Anthropometric and laboratory indicators, nutritional risk screening, and assessment by Nutritional Risk Screening 2002 (NRS 2002) and subjective global assessment (SGA) were performed within 24 hours of admission and discharge. Clinical data during hospitalization were collected. RESULTS: A total of 6,638 patients met the criteria with a male: female ratio of 1.39:1 and an average age of 59.72 ± 15.40 years. At admission, the proportion of patients with nutritional risk, body mass index (BMI) < 18.5 kg/m2, and moderate to severe malnutrition was 40.12%, 8.92%, and 26.45%, respectively, whereas at discharge, these percentages were 42.28%, 8.91%, and 30.57%, respectively. The values of all of these indicators were higher in patients 65 years of age and older. Patients with nutritional risk at admission had a longer average hospital stay (14.02 ± 6.42 vs 13.09 ± 5.703 days), higher incidence of total complications (6.90% vs 1.52%), and greater total medical expenses (3.39 ± 7.50 vs 3.00 ± 3.38 million RMB; all p < 0.01) than patients without nutritional risk. Similar results were obtained for the patients with nutritional risk at discharge. CONCLUSION: The prevalence of nutritional risk and malnutrition, including moderate to severe malnutrition, at discharge is higher than that observed at admission; the clinical outcome of patients with nutritional risk is poor.

Perioperative and Post-Hospital Whole-Course nutrition management in patients with pancreatoduodenectomy - a Single-Center prospective randomized controlled trial.

OBJECTIVE: Whole-course nutrition management (WNM) has been proven to improve outcomes and reduce complications. We conducted this randomized controlled trial to validate its effectiveness in patients undergoing pancreatoduodenectomy. METHODS: From December 1, 2020, to November 30, 2023, this single-center randomized clinical trial was conducted at the Department of Hepatobiliopancreatic Surgery in a major hospital in Beijing, China. Participants who were undergoing pancreatoduodenectomy were enrolled and randomly allocated to either the WNM group or the control group. The primary outcome was the incidence of postoperative complications. Subgroup analysis in patients who were at nutritional risk was performed. Finally, a six-month follow-up was conducted and the economic benefit was evaluated using an incremental cost-effectiveness ratio (ICER). RESULTS: A total of 84 patients were randomly assigned (1:1) into the WNM group and the control group. The incidences of total complications (47.6% vs. 69.0%, P=0.046), total infections (14.3% vs. 33.3%, P= 0.040) and abdominal infection (11.9% vs. 31.0%, P= 0.033) were significantly lower in the WNM group. In the subgroup analysis of patients at nutritional risk, 66 cases were included (35 cases in the WNM group and 31 cases in the control group). The rate of abdominal infection (11.4% vs. 32.3%, P= 0.039) and postoperative length of stay (23.1±10.3 vs. 30.4±17.2, P= 0.046) were statistically different between the two subgroups. In the six-month follow-up, more patients reached the energy target in the WNM group (97.0% vs. 79.4%, P=0.049) and got a higher daily energy intake (1761.3±339.5 vs. 1599.6±321.5, P=0.045). The ICER suggested that WNM saved 31,511 Chinese Yuan (CNY) while reducing the rate of total infections by 1% in the ITT population and saved 117,490 CNY in patients at nutritional risk, while WNM saved 31,511 CNY while reducing the rate of abdominal infections by 1% in the ITT population and saved 101,359 CNY in patients at nutritional risk. CONCLUSION: In this trial, whole-course nutrition management was associated with fewer total postoperative complications, total and abdominal infections, and was cost-effective, especially in patients at nutritional risk. It seems to be a favorable strategy for patients undergoing PD.

Hydrogels with ultra-highly additive adjustable toughness under quasi-isochoric conditions.

Bioinspired smart hydrogels with additive-switchable mechanical properties have been attracting increasing attention in recent years. However, most existing hydrogel systems suffer from limited stiffening amplitude and dramatic volume change upon response to environmental triggers. Herein, we propose a novel strategy to prepare additive-responsive hydrogels with ultra-highly adjustable toughness under quasi-isochoric conditions. The key point lies in tuning the softening transition temperature of the hydrogels with non-covalent interactions between the polymer networks and additives, shifting the hydrogels from glassy to rubbery states. As a proof of concept, a variety of glassy hydrogels are prepared and exposed to additives to trigger responsive performances. Young's modulus of the same hydrogel demonstrates up to 36 000 times ultra-broad-range tunability, ranging from 0.0042 to 150 MPa in response to different additives. Meanwhile, negligible volume changes occur, keeping the hydrogels in quasi-isochoric conditions. Interestingly, the mechanical behaviors of the hydrogels manifest remarkable dependence on the additive type and concentration since both the Hofmeister effect and hydrophobicity of the additives play pivotal roles according to mechanism investigations. Furthermore, the regulation with additives reveals satisfactory reversibility and universality. Taken together, this simple and effective approach provides a novel strategy to fabricate hydrogels with highly tunable toughness for versatile applications, including spatially patterned conductive gels and anti-icing coatings.

DFT Study of Zn-Modified SnP3: A H2S Gas Sensor with Superior Sensitivity, Selectivity, and Fast Recovery Time.

The adsorption properties of Cu, Ag, Zn, and Cd-modified SnP3 monolayers for H2S have been studied using density functional theory (DFT). Based on phonon spectrum calculations, a structurally stable intrinsic SnP3 monolayer was obtained, based on which four metal-modified SnP3 monolayers were constructed, and the band gaps of the modified SnP3 monolayers were significantly reduced. The adsorption capacity of Cu, Zn-modified SnP3 was better than that of Ag, Cd-modified SnP3. The adsorption energies of Cu-modified SnP3 and Zn-modified SnP3 for H2S were -0.749 eV and -0.639 eV, respectively. In addition, Cu-modified SnP3 exhibited chemisorption for H2S, while Zn-modified SnP3 exhibited strong physisorption, indicating that it can be used as a sensor substrate. Co-adsorption studies showed that ambient gases such as N2, O2, and H2O had little effect on H2S. The band gap change rate of Zn-modified SnP3 after adsorption of H2S was as high as -28.52%. Recovery time studies based on Zn-modified SnP3 showed that the desorption time of H2S was 0.064 s at 298 K. Therefore, Zn-modified SnP3 can be used as a promising sensor substrate for H2S due to its good selectivity, sensitivity, and fast recovery time.

The Osteogenic Role of Barium Titanate/Polylactic Acid Piezoelectric Composite Membranes as Guiding Membranes for Bone Tissue Regeneration.

Purpose: Biopiezoelectric materials have good biocompatibility and excellent piezoelectric properties, and they can generate local currents in vivo to restore the physiological electrical microenvironment of the defect and promote bone regeneration. Previous studies of guided bone regeneration membranes have rarely addressed the point of restoring it, so this study prepared a Barium titanate/Polylactic acid (BT/PLA) piezoelectric composite membrane and investigated its bone-formation, with a view to providing an experimental basis for clinical studies of guided bone tissue regeneration membranes. Methods: BT/PLA composite membranes with different BT ratio were prepared by solution casting method, and piezoelectric properties were performed after corona polarization treatment. The optimal BT ratio was selected and then subjected to in vitro cytological experiments and in vivo osteogenic studies in rats. The effects on adhesion, proliferation and osteogenic differentiation of the pre-osteoblastic cell line (MC3T3-E1) were investigated. The effect of composite membranes on bone repair of cranial defects in rats was investigated after 4 and 12 weeks. Results: The highest piezoelectric coefficient d33 were obtained when the BT content was 20%, reaching (7.03 ± 0.26) pC/N. The value could still be maintained at (4.47±0.17) pC/N after 12 weeks, meeting the piezoelectric constant range of bone. In vitro, the MC3T3-E1 cells showed better adhesion and proliferative activity in the group of polarized 20%BT. The highest alkaline phosphatase (ALP) content was observed in cells of this group. In vivo, it promoted rapid bone regeneration. At 4 weeks postoperatively, new bone formation was evident at the edges of the defect, with extensive marrow cavity formation; after 12 weeks, the defect was essentially completely closed, with density approximating normal bone tissue and significant mineralization. Conclusion: The BT/PLA piezoelectric composite membrane has good osteogenic properties and provides a new idea for guiding the research of membrane materials for bone tissue regeneration.

Lymph node ratio is a superior predictor in surgically treated early-onset pancreatic cancer.

Background: The prognostic performance of four lymph node classifications, the 8th American Joint Committee on Cancer (AJCC) Tumor Node Metastasis (TNM) N stage, lymph node ratio (LNR), log odds of positive lymph nodes (LODDS), and examined lymph nodes (ELN) in early-onset pancreatic cancer (EOPC) remains unclear. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was searched for patients with EOPC from 2004 to 2016. 1048 patients were randomly divided into training (n = 733) and validation sets (n = 315). The predictive abilities of the four lymph node staging systems were compared using the Akaike information criteria (AIC), receiver operating characteristic area under the curve (AUC), and C-index. Multivariate Cox analysis was performed to identify independent risk factors. A nomogram based on lymph node classification with the strongest predictive ability was established. The nomogram's precision was verified by the C-index, calibration curves, and AUC. Kaplan-Meier analysis and log-rank tests were used to compare differences in survival at each stage of the nomogram. Results: Compared with the 8th N stage, LODDS, and ELN, LNR had the highest C-index and AUC and the lowest AIC. Multivariate analysis showed that N stage, LODDS, LNR were independent risk factors associated with cancer specific survival (CSS), but not ELN. In the training set, the AUC values for the 1-, 3-, and 5-year CSS of the nomogram were 0.663, 0.728, and 0.760, respectively and similar results were observed in the validation set. In addition, Kaplan-Meier survival analysis showed that the nomogram was also an important factor in the risk stratification of EOPC. Conclusion: We analyzed the predictive power of the four lymph node staging systems and found that LNR had the strongest predictive ability. Furthermore, the novel nomogram prognostic staging mode based on LNR was also an important factor in the risk stratification of EOPC.

DNA N6-Adenine methylation in HBV-related hepatocellular carcinoma.

DNA methylation on N6-adenine (6mA) has recently been found to be a potential epigenetic marker in prokaryotes and eukaryotes. However, its distribution patterns and potential functions in human tumorigenesis remain largely unknown. Here, we reported global profiling of 6mA sites in the genome of hepatocellular carcinoma at single-nucleotide resolution using Nanopore sequencing. 6mA was widely distributed throughout the human genome. The 6mA sites were related to the porphyrin and chlorophyll metabolism in autosomes and were related to oxidative phosphorylation and ATP metabolism in mitochondria. AGG was the most significant motif associated with 6mA modification and the prevalent motifs in tumors were mainly distributed in mitochondria. The density of 6mA was related to the activation of gene transcription and 6mA density in repetitive sequences decreased in hepatocellular carcinoma. DNA 6mA methylation modification may also be a potential biomarker for cancer diagnosis and treatment.

Comprehensive Analysis of DNA 5-Methylcytosine and N6-Adenine Methylation by Nanopore Sequencing in Hepatocellular Carcinoma.

DNA methylation is a widespread epigenetic signal in human genome. With Nanopore technology, differential methylation modifications including 5-methylcytosine (5mC) and 6-methyladenine (6mA) can be identified. 5mC is the most important modification in mammals, although 6mA may also function in growth and development as well as in pathogenesis. While the role of 5mC at CpG islands in promoter regions associated with transcriptional regulation has been well studied, but the relationship between 6mA and transcription is still unclear. Thus, we collected two pairs of tumor tissues and adjacent normal tissues from hepatocellular carcinoma (HCC) surgical samples for Nanopore sequencing and transcriptome sequencing. It was found that 2,373 genes had both 5mC and 6mA, along with up- and down-regulated methylation sites. These genes were regarded as unstable methylation genes. Compared with 6mA, 5mC had more inclined distribution of unstable methylation sites. Chi-square test showed that the levels of 5mC were consistent with both up- and down-regulated genes, but 6mA was not significant. Moreover, the top three unstable methylation genes, TBC1D3H, CSMD1, and ROBO2, were all related to cancer. Transcriptome and survival analyses revealed four potential tumor suppressor genes including KCNIP4, CACNA1C, PACRG, and ST6GALNAC3. In this study, we firstly proposed to combine 5mC and 6mA methylation sites to explore functional genes, and further research found top of these unstable methylation genes might be functional and some of them could serve as potential tumor suppressor genes. Our study provided a new solution for epigenetic regulation research and therapy of HCC.

2D titanium carbide nanosheets based fluorescent aptasensor for sensitive detection of thrombin.

The emerging two-dimensional titanium carbides (MXenes) have a large potential in biomedical sensing owing to their excellent electrical and optical properties. Herein, a fluorescence resonance energy transfer (FRET) aptasensor with high sensitivity and specificity was constructed with single layer Ti3C2 MXene for quantitative detection of thrombin. The dye labelled thrombin-binding aptamer (TBA) was deposited on the surface of Ti3C2, and the fluorescence of which was efficiently quenched owing to the FRET between the dye and Ti3C2. The fact that thrombin forms quadruplex with TBA on Ti3C2 surface is due to the high electronic affinity between thrombin and Ti3C2. This process will cause the subsequent detachment of dye from the surface of Ti3C2, resulting in the recovery of fluorescence. Because of the special structure and high fluorescence quenching efficiency of Ti3C2 MXene, the aptasensor shows a high sensitivity with a low detection limit for thrombin at 5.27 pM. Three different aptamers were compared, and the aptamer HD22 is most sensitive for detection of thrombin originated from its great specificity in the human plasma. Importantly, this Ti3C2 MXene-based FRET aptasensor can detect thrombin in human serum accurately. These results suggest that the Ti3C2 MXene-based FRET aptasensor hold a great prospect in clinical diagnosis in the real-world applications.

Controlling Nutritional Status Score as a Predictive Marker of In-hospital Mortality in Older Adult Patients.

The controlling nutritional status (CONUT) score assesses nutritional status and is associated with short- and long-term prognoses in some diseases, but the significance of the CONUT score for the prediction of in-hospital mortality in older adults is unknown. The purpose was to determine the importance of the CONUT score for the prediction of in-hospital mortality, short-term complications, length of hospital stay, and hospital costs in older adults. Our retrospective cohort study analyzed data from 11,795 older adult patients from two multicenter cohort studies. We performed receiver operating characteristic curve analysis using in-hospital mortality as the endpoint and determined the appropriate CONUT score cut-off by the Youden index. The patients were divided into two high and low groups according to the CONUT cut-off value, and the differences in clinical characteristics and in-hospital clinical outcomes between the two groups were compared. We compared the accuracy of the CONUT score and other nutrition-related tools in predicting in-hospital mortality by calculating the area under the receiver operating characteristic curve and performed univariate and multivariate analyses of predictors of in-hospital mortality. Among all the patients, 178 (1.5%) patients experienced in-hospital death. The optimal cut-off values was 5.5 for the CONUT score. The high CONUT group had a higher incidence of short-term complications and prolonged hospital stay than the low CONUT group (CONUT score <6), but hospital costs were not significantly higher. The CONUT score had the highest predictive ability for in-hospital mortality among the five nutrition-related parameters compared. Multivariate analysis showed that a high CONUT score (CONUT score ≥ 6) was an independent predictor of in-hospital mortality. In conclusion, the present study demonstrated that the CONUT score could be used to predict in-hospital mortality in older adults.

Influence of Malnutrition According to the GLIM Criteria on the Clinical Outcomes of Hospitalized Patients With Cancer.

Background: Malnutrition is prevalent among patients with cancer. The Global Leadership Initiative on Malnutrition (GLIM) released new universal criteria for diagnosing malnutrition in 2019. The objectives of this study were to assess the prevalence of malnutrition in patients with cancer using the GLIM criteria, explore the correlation between the GLIM criteria, and clinical outcomes, and compare the GLIM criteria with subjective global assessment (SGA). Methods: This retrospective analysis was conducted on 2,388 patients with cancer enrolled in a multicenter study. Nutritional risk was screened using the Nutritional Risk Screening-2002, and the nutritional status was assessed using SGA and GLIM criteria. Chi-square analysis and Wilcoxon rank sum test, stratified by age 65 years, were used to evaluate the effect of GLIM-defined malnutrition on clinical outcomes. Logistic regression analysis was used to analyze the nutritional status and complications, and the interrater reliability was measured using a kappa test. Results: The prevalence of malnutrition defined by the GLIM criteria was 38.9% (929/2,388). GLIM-defined malnutrition was significantly associated with in-hospital mortality (P = 0.001) and length of hospital stays (P = 0.001). Multivariate logistic regression analysis showed GLIM-defined malnutrition significantly increased complications (odds ratio [OR] 1.716, 95% CI 1.227-2.400, P = 0.002). The GLIM criteria had a "moderate agreement" (kappa = 0.426) compared with the SGA. Conclusions: The prevalence of malnutrition in hospitalized patients with cancer is high, and malnourishment in patients with cancer is associated with poorer clinical outcomes. The use of the GLIM criteria in assessing the nutritional status of inpatients with cancer is recommended and can be used as the basis for nutritional interventions.

Long-read sequencing reveals the structural complexity of genomic integration of HBV DNA in hepatocellular carcinoma.

The integration of HBV DNA into the human genome can disrupt its structure in hepatocellular carcinoma (HCC), but the complexity of HBV genomic integration remains elusive. Here we applied long-read sequencing to precisely elucidate the HBV integration pattern in the human hepatocellular genome. The DNA library was sequenced using the long-read sequencing on GridION and PacBio Sequel II, respectively. The DNA and mRNA were sequenced using next-generation sequencing on Illumina NextSeq. BLAST (Basic Local Alignment Search Tool) and local scripts were used to analyze HBV integration patterns. We established an analytical strategy based on the long-read sequences, and analyzed the complexity of HBV DNA integration into the hepatocellular genome. A total of 88 integrated breakpoints were identified. HBV DNA integration into human genomic DNA was mainly fragmented with different orientations, rarely with a complete genome. The same HBV integration breakpoints were identified among the three platforms. Most breakpoints were observed at P, X, and S genes in the HBV genome, and observed at introns, intergenic sequences, and exons in the human genome. Tumor tissue harbored a much higher integrated number than the adjacent tissue, and the distribution of HBV integrated into human chromosomes was more concentrated. HBV integration shows different patterns between cancer cells and adjacent normal cells. We for the first time obtained the entire HBV integration pattern through long-read sequencing and demonstrated the value of long-read sequencing in detecting the genomic integration structures of viruses in host cells.