Plasma SMOC2 Predicts Prognosis in Patients with Heart Failure: A Prospective Cohort.

Background: Heart failure (HF) is a chronic disease with a poor prognosis, making it extremely important to assess the prognosis of patients with HF for accurate treatment. Secreted modular calcium-binding protein 2 (SMOC2) is a cysteine-rich acidic secreted protein that plays a pathophysiological role in many diseases, including regulation of vascular growth factor activity. It has previously been found that SMOC2 plays an essential role in cardiac fibrosis in our previous preclinical study, but whether it can be used as a clinical marker in heart failure patients remains unclear. The purpose of this research was to evaluate the correlation between plasma levels of SMOC2 and the prognosis for individuals with HF. Methods: HF patients diagnosed with ischemic cardiomyopathy were enrolled from January to December 2021. Baseline plasma levels of SMOC2 were measured after demographic and clinical features were collected. Linear and nonlinear multivariate Cox regression models were used to determine the association between plasma SMOC2 and patient outcomes during follow-up. All analysis was performed using SPSS, EmpowerStats, and R software. Results: The study included 188 patients, and the average follow-up time was 489.5±88.3 days. The plasma SMOC2 concentrations were positively correlated with N-terminal pro-B-type Natriuretic Peptide (NT-proBNP), left ventricular end-diastolic diameter (LVEDd), and length of hospital stay and were negatively correlated with left ventricular ejection fraction (LVEF) at baseline. A total of 53 patients (28.2%) were rehospitalized due to cardiac deterioration, 14 (7.4%) died, and 37 (19.7%) developed malignant arrhythmias. A fully adjusted multivariate COX regression model showed that SMOC2 is associated with readmission (HR = 1.02, 95% CI:1.012-1.655). A significant increase in rehospitalization risk was observed in group Q2 (HR =1.064, 95% CI: 1.037, 3.662, p=0.005) and group Q3 (HR =1.085, 95% CI:1.086, 3.792, p=0.009) in comparison with group Q1. The p for trend also shows a linear correlation across the three models (P < 0.001). SMOC2 was associated with the severity of HF in patients, but not with all-cause deaths and arrhythmias during follow-up. Conclusion: Plasma SMOC2 is associated with the severity of HF and readmission rate, and is a good predictor of the risk of readmission in patients.

Microecology of aerobic denitrification system construction driven by cyclic stress of sulfamethoxazole.

The construction of aerobic denitrification (AD) systems in an antibiotic-stressed environment is a serious challenge. This study investigated strategy of cyclic stress with concentration gradient (5-30 mg/L) of sulfamethoxazole (SMX) in a sequencing batch reactor (SBR), to achieve operation of AD. Total nitrogen removal efficiency of system increased from about 10 % to 95 %. Original response of abundant-rare genera to antibiotics was changed by SMX stress, particularly conditionally rare or abundant taxa (CRAT). AD process depends on synergistic effect of heterotrophic nitrifying aerobic denitrification bacteria (Paracoccus, Thauera, Hypomicrobium, etc). AmoABC, napA, and nirK were functionally co-expressed with multiple antibiotic resistance genes (ARGs) (acrR, ereAB, and mdtO), facilitating AD process. ARGs and TCA cycling synergistically enhance the antioxidant and electron transport capacities of AD process. Antibiotic efflux pump mechanism played an important role in operation of AD. The study provides strong support for regulating activated sludge to achieve in situ AD function.

A new perspective on prostate cancer treatment: the interplay between cellular senescence and treatment resistance.

The emergence of resistance to prostate cancer (PCa) treatment, particularly to androgen deprivation therapy (ADT), has posed a significant challenge in the field of PCa management. Among the therapeutic options for PCa, radiotherapy, chemotherapy, and hormone therapy are commonly used modalities. However, these therapeutic approaches, while inducing apoptosis in tumor cells, may also trigger stress-induced premature senescence (SIPS). Cellular senescence, an entropy-driven transition from an ordered to a disordered state, ultimately leading to cell growth arrest, exhibits a dual role in PCa treatment. On one hand, senescent tumor cells may withdraw from the cell cycle, thereby reducing tumor growth rate and exerting a positive effect on treatment. On the other hand, senescent tumor cells may secrete a plethora of cytokines, growth factors and proteases that can affect neighboring tumor cells, thereby exerting a negative impact on treatment. This review explores how radiotherapy, chemotherapy, and hormone therapy trigger SIPS and the nuanced impact of senescent tumor cells on PCa treatment. Additionally, we aim to identify novel therapeutic strategies to overcome resistance in PCa treatment, thereby enhancing patient outcomes.

Paradoxical herniation associated with hyperbaric oxygen therapy after decompressive craniectomy: A case report.

BACKGROUND: Whether hyperbaric oxygen therapy (HBOT) can cause paradoxical herniation is still unclear. CASE SUMMARY: A 65-year-old patient who was comatose due to brain trauma underwent decompressive craniotomy and gradually regained consciousness after surgery. HBOT was administered 22 d after surgery due to speech impairment. Paradoxical herniation appeared on the second day after treatment, and the patient's condition worsened after receiving mannitol treatment at the rehabilitation hospital. After timely skull repair, the paradoxical herniation was resolved, and the patient regained consciousness and had a good recovery as observed at the follow-up visit. CONCLUSION: Paradoxical herniation is rare and may be caused by HBOT. However, the underlying mechanism is unknown, and the understanding of this phenomenon is insufficient. The use of mannitol may worsen this condition. Timely skull repair can treat paradoxical herniation and prevent serious complications.

Enhanced cellular therapy: revolutionizing adoptive cellular therapy.

Enhanced cellular therapy has emerged as a novel concept following the basis of cellular therapy. This treatment modality applied drugs or biotechnology to directly enhance or genetically modify cells to enhance the efficacy of adoptive cellular therapy (ACT). Drugs or biotechnology that enhance the killing ability of immune cells include immune checkpoint inhibitors (ICIs) / antibody drugs, small molecule inhibitors, immunomodulatory factors, proteolysis targeting chimera (PROTAC), oncolytic virus (OV), etc. Firstly, overcoming the inhibitory tumor microenvironment (TME) can enhance the efficacy of ACT, which can be achieved by blocking the immune checkpoint. Secondly, cytokines or cytokine receptors can be expressed by genetic engineering or added directly to adoptive cells to enhance the migration and infiltration of adoptive cells to tumor cells. Moreover, multi-antigen chimeric antigen receptors (CARs) can be designed to enhance the specific recognition of tumor cell-related antigens, and OVs can also stimulate antigen release. In addition to inserting suicide genes into adoptive cells, PROTAC technology can be used as a safety switch or degradation agent of immunosuppressive factors to enhance the safety and efficacy of adoptive cells. This article comprehensively summarizes the mechanism, current situation, and clinical application of enhanced cellular therapy, describing potential improvements to adoptive cellular therapy.

Quantitative evaluation of meniscus injury using synthetic magnetic resonance imaging.

BACKGROUND: Magnetic resonance imaging (MRI) can diagnose meniscal lesions anatomically, while quantitative MRI can reflect the changes of meniscal histology and biochemical structure. Our study aims to explore the association between the measurement values obtained from synthetic magnetic resonance imaging (SyMRI) and Stoller grades. Additionally, we aim to assess the diagnostic accuracy of SyMRI in determining the extent of meniscus injury. This potential accuracy could contribute to minimizing unnecessary invasive examinations and providing guidance for clinical treatment. METHODS: Total of 60 (n=60) patients requiring knee arthroscopic surgery and 20 (n=20) healthy subjects were collected from July 2022 to November 2022. All subjects underwent conventional MRI and SyMRI. Manual measurements of the T1, T2 and proton density (PD) values were conducted for both normal menisci and the most severely affected position of injured menisci. These measurements corresponded to the Stoller grade of meniscus injuries observed in the conventional MRI. All patients and healthy subjects were divided into normal group, degeneration group and torn group according to the Stoller grade on conventional MRI. One-way analysis of variance (ANOVA) was employed to compare the T1, T2 and PD values of the meniscus among 3 groups. The accuracy of SyMRI in diagnosing meniscus injury was assessed by comparing the findings with arthroscopic observations. The diagnostic efficiency of meniscus degeneration and tear between conventional MRI and SyMRI were analyzed using McNemar test. Furthermore, a receiver operating characteristic curve (ROC curve) was constructed and the area under the curve (AUC) was utilized for evaluation. RESULTS: According to the measurements of SyMRI, there was no statistical difference of T1 value or PD value measured by SyMRI among the normal group, degeneration group and torn group, while the difference of T2 value was statistically significant among 3 groups (P=0.001). The arthroscopic findings showed that 11 patients were meniscal degeneration and 49 patients were meniscal tears. The arthroscopic findings were used as the gold standard, and the difference of T1 and PD values among the 3 groups was not statistically significant, while the difference of T2 values (32.81±2.51 of normal group, 44.85±3.98 of degeneration group and 54.42±3.82 of torn group) was statistically significant (P=0.001). When the threshold of T2 value was 51.67 (ms), the maximum Yoden index was 0.787 and the AUC value was 0.934. CONCLUSIONS: The measurement values derived from SyMRI could reflect the Stoller grade, illustrating that SyMRI has good consistency with conventional MRI. Moreover, the notable consistency observed between SyMRI and arthroscopy suggests a potential role for SyMRI in guiding clinical diagnoses.

Analysis of Risk Factors for the Association of Sarcopenia in Patients with Type 2 Diabetes Mellitus.

Background: Previous studies have shown that the prevalence of sarcopenia in patients with type 2 diabetes mellitus (T2DM) has increased significantly over the years. However, the risk factors for the association of sarcopenia in patients with T2DM are unknown. Therefore, we attempted to investigate the risk factors through measurement and analysis of the patients' data from April 2020 to April 2022. Methods: A total of 334 hospitalized patients with T2DM were divided into sarcopenia group (n=101) and non-sarcopenia group (n=233). Clinical factors were compared between the two groups and also between the two genders. Receiver operating characteristic curve (ROC) was used to analyze the ROC diagnostic ability of related factors in sarcopenia. Results: (1) Among the 334 patients, the overall prevalence of sarcopenia was 30.2%; 41.3% in men and 20.1% in women. (2) The multifactorial logistic regression analysis showed that gender (specifically for men; OR=4.997, 95% CI: 2.611-9.564), low body mass index (BMI) (OR=1.525, 95% CI: 1.353-1.718), lower 25(OH)D levels (OR=1.076, 95% CI:1.036-1.117), and lower IGF-1 (OR=1.013, 95% CI:1.006-1.020) were independent risk factors (P < 0.05). (3) ROC curve analysis results showed that BMI, 25 (OH) D, IGF-1, and testosterone (for men) had predictive significance for sarcopenia with T2DM (P < 0.05). However, the AUC of 25 (OH) D, IGF-1 and testosterone (for men) were all <0.7, while the AUC of BMI and the combined factors were all >0.7, has great predictive significance. Conclusion: The prevalence of sarcopenia in hospitalized patients with T2DM is higher in men than in women. Low BMI and lower serum levels of 25 (OH) D and IGF-1 are risk factors of sarcopenia in patients with T2DM. Low BMI, 25(OH)D, IGF-1, and testosterone (for men) all contributed to the prediction of sarcopenia, among which BMI and combined factors were more significant.

An in-situ method for SERS substrate preparation and optimization based on galvanic replacement reaction.

BACKGROUND: Various surface-enhanced Raman spectroscopy (SERS) substrate preparation methods have been reported, however, how to tune the "gap" between nanostructures to make more "hot spots" is still a barrier that restricts their application. The gap between nanostructures is usually fixed when the substrates are prepared. In other words, it is hard to tune interparticle distances for maximum electromagnetic coupling during substrate preparation process. Therefore, an in-situ substrate optimization method that could monitor the SERS signal intensity changes, i.e., to find the optimum gap width and particle size, during substrate preparation process is needed. RESULTS: A method based on the galvanic replacement reaction (GRR) is proposed for the in-situ gap width tuning between nanostructures as well as for the optimization of SERS substrates. Noble metal nanoparticles (NPs) form and grow on the sacrificial templates' surface while noble metal ions are reduced by sacrificial metal (oxides) in GRR. Along with the fresh and clean NPs' surface generated, the gap between two noble metal NPs decreases with the growth of the NPs. To demonstrate this strategy, cuprous oxide/Ti (Cu2O/Ti) sacrificial templates were prepared, and then a GRR was carried out with HAuCl4. The real-time SERS detection during GRR show that the optimum reaction time (ORT) is 300 ± 30 s. Furthermore, SERS performance testing was conducted on the optimized substrate, revealing that the detection limit for crystal violet can reach 1.96 × 10-11 M, confirming the feasibility of this method. SIGNIFICANCE AND NOVELTY: By monitoring the in-situ SERS signal of probes during GRR will obtain an "optimal state" of the SERS substrate with optimal gap width and particle size. The SERS substrate preparation and optimization strategy proposed in this article not only provides a simple, efficient, and low-cost method to fabricate surface-clean noble NPs but also paves the way for the in-situ optimization of NPs size and gap width between NPs which could achieve wider applications of SERS.

Knowledge mapping of application of image-guided surgery in prostate cancer: a bibliometric analysis (2013-2023).

BACKGROUND: Image-guided surgery (IGS) refers to surgery navigated by medical imaging technology, helping doctors better clarify tumor boundaries, identify metastatic lymph nodes and preserve surrounding healthy tissue function. Recent studies have provided expectable momentum of the application of IGS in prostate cancer (PCa). The authors aim to comprehensively construct a bibliometric analysis of the application of IGS in PCa. METHOD: The authors searched publications related to application of IGS in PCa from 2013 to 2023 on the web of science core collection (WoSCC) databases. VOSviewer, CiteSpace, and R package 'bibliometrix' were used for bibliometric analysis. RESULTS: Two thousand three eighty-nine articles from 75 countries and 2883 institutions led by the United States were included. The number of publications related to the application of IGS in PCa kept high in the last decade. Johns Hopkins University is the top research institutions. Journal of Nuclear Medicine has the highest popularity as the selection of journal and co-cited journal. Pomper Martin G. had published the most paper. Ali Afshar-Oromieh was co-cited most frequently. The clinical efficacy of PSMA-PET/CT in PCa diagnosis and treatment are main topics in this research field, with emerging focuses on the use of fluorescence imaging guidance technology in PCa. 'PSMA' and 'PET/CT' are the main keywords as long-term research hotspots. CONCLUSION: This study is the first bibliometric analysis of researches on application of IGS in PCa with three recognized bibliometric software, providing an objective description and comprehensive guidance for the future relevant investigations.

Impact of metabolic syndrome on bone mineral density in men over 50 and postmenopausal women according to U.S. survey results.

Metabolic Syndrome (MetS) and bone mineral density (BMD) have shown a controversial link in some studies. This research aims to study their association in males over 50 and postmenopausal females using National Health and Nutrition Examination Survey (NHANES) data. Postmenopausal females and males over 50 were included in the study. MetS was defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines. BMD values were measured at the thoracic spine, lumbar spine, and pelvis as the primary outcome. Weighted multivariate general linear models have been employed to explore the status of BMD in patients with MetS. Additionally, interaction tests and subgroup analyses were conducted. Utilizing the NHANES database from 2003 to 2006 and 2011-2018, we included 1924 participants, with 1029 males and 895 females. In postmenopausal women, after adjusting for covariates, we found a positive correlation between MetS and pelvic (ß: 0.030 [95%CI 0.003, 0.06]) and thoracic (ß: 0.030 [95%CI 0.01, 0.06]) BMD, though not for lumbar spine BMD (ß: 0.020 [95%CI - 0.01, 0.05]). In males over 50 years old, MetS was positively correlated with BMD in both Model 1 (without adjusting for covariates) and Model 2 (considering age and ethnicity). Specifically, Model 2 revealed a positive correlation between MetS and BMD at the pelvis (ß: 0.046 [95%CI 0.02, 0.07]), thoracic spine (ß: 0.047 [95%CI 0.02, 0.07]), and lumbar spine (ß: 0.040 [95%CI 0.02, 0.06]). Subgroup analysis demonstrated that the relationship between MetS and BMD remained consistent in all strata, underscoring the stability of the findings. In postmenopausal women, after adjusting for all covariates, a significant positive correlation was observed between MetS and BMD in the pelvis and thoracic spine, whereas this correlation was not significant for lumbar spine BMD. Conversely, in males, positive correlations between MetS and BMD at the lumbar spine, thoracic spine, and pelvis were identified in Model 2, which adjusted for age and ethnicity; however, these correlations disappeared after fully adjusting for all covariates. These findings highlight the potential moderating role of gender in the impact of MetS on BMD.

Monitoring ROS Responsive Fe3O4-based Nanoparticle Mediated Ferroptosis&Immunotherapy via 129Xe MRI.

The immune checkpoint blockade strategy has improved the survival rate of late-stage lung cancer patients. However, the low immune response rate limits the immunotherapy efficiency. Here, we report a ROS-responsive Fe3O4-based nanoparticle that undergoes charge reversal and disassembly in the tumor microenvironment, enhancing the uptake of Fe3O4 by tumor cells and triggering a more severe ferroptosis. In the tumor microenvironment, the nanoparticle rapidly disassembles and releases the loaded GOx and the immune-activating peptide Tuftsin under overexpressed H2O2. GOx can consume the glucose of tumor cells and generate more H2O2, promoting the disassembly of the nanoparticle and drug release, thereby enhancing the therapeutic effect of ferroptosis. Combined with Tuftsin, it can more effectively reverse the immune-suppressive microenvironment and promote the recruitment of effector T cells in tumor tissues. Ultimately, in combination with α-PD-L1, there is significant inhibition of the growth of lung metastases. Additionally, the hyperpolarized 129Xe method has been used to evaluate the Fe3O4 nanoparticle-mediated immunotherapy, where the ventilation defects in lung metastases have been significantly improved with complete lung structure and function recovered. The ferroptosis-enhanced immunotherapy combined with non-radiation evaluation methodology paves a new way for designing novel theranostic agents for cancer therapy.

Insulin Degludec in People with Type 2 Diabetes in China: A Non-interventional, Retrospective Chart Review Study (CN-TREAT).

INTRODUCTION: Insulin degludec (degludec), an ultra-long-acting basal insulin analogue, provides equivalent glycemic control to other basal insulin analogues, with lower risk of hypoglycemia and flexible dosing. Chinese TREsiba AudiT (CN-TREAT) investigated outcomes with degludec in people with type 2 diabetes (T2D) in routine clinical practice in China. METHODS: This was a retrospective chart review study in adults with T2D initiating or switching to degludec at 50 sites in China between January 2020 and July 2021. The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline to end of study (EOS; week 20). Secondary endpoints included change from baseline to EOS in fasting plasma glucose (FPG), self-measured plasma glucose (SMPG), daily insulin dose, and rate of hypoglycemia. RESULTS: Data from 936 participants were included (499 insulin-naïve; 437 insulin-experienced). Mean (95% confidence interval [CI]) HbA1c change from baseline to EOS was - 1.48%-points (- 1.57; - 1.38; P < 0.0001) overall: - 1.95%-points (- 2.08; - 1.81; P < 0.0001) in insulin-naïve participants and - 0.95%-points (- 1.08; - 0.82; P < 0.0001) in insulin-experienced participants. Mean (95% CI) changes in FPG and SMPG were - 2.27 mmol/L (- 2.69; - 1.85; P < 0.0001) and - 2.89 mmol/L (- 3.52; - 2.25; P < 0.0001), respectively, with similar reductions in insulin-naïve and insulin-experienced subgroups. Rate of hypoglycemia did not change statistically significantly from baseline to EOS overall, or in insulin-experienced participants, except when adjusted for baseline hypoglycemia. Basal insulin dose did not change statistically significantly in insulin-experienced participants. CONCLUSION: In routine clinical practice in China, initiation or switching to degludec was associated with improvements in glycemic control in people with T2D, with no increased risk of hypoglycemia. TRIAL REGISTRATION: ClinialTrials.gov, NCT04227431.

Development and validation of a model integrating clinical and coronary lesion-based functional assessment for long-term risk prediction in PCI patients.

OBJECTIVES: To establish a scoring system combining the ACEF score and the quantitative blood flow ratio (QFR) to improve the long-term risk prediction of patients undergoing percutaneous coronary intervention (PCI). METHODS: In this population-based cohort study, a total of 46 features, including patient clinical and coronary lesion characteristics, were assessed for analysis through machine learning models. The ACEF-QFR scoring system was developed using 1263 consecutive cases of CAD patients after PCI in PANDA III trial database. The newly developed score was then validated on the other remaining 542 patients in the cohort. RESULTS: In both the Random Forest Model and the DeepSurv Model, age, renal function (creatinine), cardiac function (LVEF) and post-PCI coronary physiological index (QFR) were identified and confirmed to be significant predictive factors for 2-year adverse cardiac events. The ACEF-QFR score was constructed based on the developmental dataset and computed as age (years)/EF (%) + 1 (if creatinine ≥ 2.0 mg/dL) + 1 (if post-PCI QFR ≤ 0.92). The performance of the ACEF-QFR scoring system was preliminarily evaluated in the developmental dataset, and then further explored in the validation dataset. The ACEF-QFR score showed superior discrimination (C-statistic = 0.651; 95% CI: 0.611-0.691, P < 0.05 versus post-PCI physiological index and other commonly used risk scores) and excellent calibration (Hosmer-Lemeshow χ2 = 7.070; P = 0.529) for predicting 2-year patient-oriented composite endpoint (POCE). The good prognostic value of the ACEF-QFR score was further validated by multivariable Cox regression and Kaplan-Meier analysis (adjusted HR = 1.89; 95% CI: 1.18-3.04; log-rank P < 0.01) after stratified the patients into high-risk group and low-risk group. CONCLUSIONS: An improved scoring system combining clinical and coronary lesion-based functional variables (ACEF-QFR) was developed, and its ability for prognostic prediction in patients with PCI was further validated to be significantly better than the post-PCI physiological index and other commonly used risk scores.

Simplified design method for optical imaging systems based on aberration characteristics of optical-digital joint optimization.

With the continuous improvement of imaging performance requirements, the design of imaging systems has become increasingly complex, making it more difficult and expensive to manufacture and test. To overcome these problems, a simplified design framework for imaging systems based on aberration characteristics of optical-digital joint optimization was built in this paper. Specifically, an improved total variation regularization restoration algorithm was proposed, and the difficulty of correction for different monochromatic aberrations was evaluated. With this evaluation, the proposed algorithm was combined with the traditional optical design method to jointly correct the aberration and simplify the optical system by relaxing the requirements for optical structures and surface shapes under the guarantee of the imaging performance. To demonstrate the feasibility and efficiency of the method, three design examples are provided, where the structure similarity index measure of the simulation imaging results is on the same level as that of the initial system, with a maximum error not exceeding 0.04. The simulation results demonstrate that our design method can effectively simplify the optical structure of imaging systems while maintaining high performance.

Incidence and survival of second primary non-Hodgkin lymphoma: A Surveillance, Epidemiology, and End Results-based cohort study.

BACKGROUND: The aim of this study was to investigate patient survival and factors associated with survival in second primary non-Hodgkin lymphoma (NHL) compared with the first primary NHL. METHODS: The retrospective cohort study used data from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2014. Demographic characteristics, histological types, Ann Arbor stage, and treatment information were collected. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for factors associated with overall survival (OS) and cancer-specific survival (CSS) in the first and second primary NHLs. RESULTS: Of 318,168 cases followed for 5 years, 299,248 patients developed the first primary NHL and 18,920 patients developed the second primary NHL. This study identified a rising incidence of first and second primary NHL from 2000 to 2014. For the second primary NHL, the OS risk was higher when compared to the first primary NHL (HR: 1.13, 95% CI: 1.11 to 1.15, P <0.001). Risk factors that negatively affected OS in the first primary NHL included being male, over 40 years of age, certain marital statuses, specific histological types, and advanced disease stages. In contrast, being of White race and having histological types such as Follicular Lymphoma (FL), Marginal Zone Lymphoma (MZL), and mantle B-cell NHL were associated with better OS outcomes. Treatments like surgery, radiation therapy, and chemotherapy were associated with a lower risk of OS and CSS in the first primary NHL. For the second primary NHL, the detrimental risk factors were similar but also included being over the age of 60. Certain histological types showed a lower OS risk relative to diffuse Large B-cell Lymphoma (DLBCL). While surgery and chemotherapy were beneficial for OS, radiation therapy did not improve survival in second primary NHL cases. Notably, undergoing chemotherapy for the first primary cancer increased the OS risk in the second primary NHL, whereas surgery and radiation seemed to offer a protective effect against OS risk in the second primary NHL (all P <0.05). CONCLUSION: Our findings emphasize the need for tailored strategies in managing the second primary NHL, given the distinct survival patterns and risk factor profiles compared to the first primary NHL. Future research should aim to further elucidate these differences to improve prognosis and treatment approaches for second primary NHL patients.

MiR-221-5p regulates blood-brain barrier dysfunction through the angiopoietin-1/-2/Tie-2 signaling axis after subarachnoid hemorrhage.

AIM: To explore the potential role of microRNA miR-221-5p on the angiopoietin-1 (Ang-1)/Ang-2/Tie-2 signaling axis after subarachnoid hemorrhage (SAH) in a rat model. METHODS: Aspects of the rat's behavior were measured using the Kaoutzanis scoring system to test neurological responses. This included feeding behavior, body contraction, motor, and eye-opening responses. Brain sections were studied using transmission electron microscopy and Evans blue extravasation. Levels of Ang-1, Ang-2, and Tie-2 were determined by Western blot, while miR-221-5p was quantified using stem-loop real-time quantitative PCR (RT-qPCR). RESULTS: The SAH group responded worse to the neurological response test than the sham-operated group. The intercellular space was widened in the SAH group, but not in the sham-operated group. Evans blue dye leaked significantly more into brain tissue cells of the SAH group. Stem-loop qRT-PCR showed elevated miR-221-5p levels. Additionally, Ang-1 and Tie-2 were reduced but Ang-2 expression was increased after SAH. This led to a significant reduction of the Ang-1/Ang-2 ratio in the brain tissue, which was associated with the destruction of the blood-brain barrier. CONCLUSION: The data indicate that miR-221-5p might regulate blood-brain barrier dysfunction through the Ang-1/Ang-2/Tie-2 signaling axis, suggesting that it should be further investigated as a potential novel biomarker.

Jellyfish-inspired smart tetraphenylethene lipids with unique AIE fluorescence, thermal response, and cell membrane interaction.

Smart lipids with fluorescence emission, thermal response, and polyethylene glycolation (PEGylation) functions can be highly valuable for formulation, image-traceable delivery, and targeted release of payloads. Herein, a series of jellyfish-shaped amphiphiles with a tetraphenylethene (TPE) core and four symmetrical amphiphilic side chains were conveniently synthesized and systematically investigated as smart lipids. Compared with regular amphiphilic TPE lipids and phospholipids, the unprecedented jellyfish-shaped molecular geometry was found to enable a series of valuable capabilities, including sensitive and responsive aggregation-induced emission of fluorescence (AIE FL) and real-time FL monitoring of drug uptake. Furthermore, the jellyfish-shaped geometry facilitated the concentration-dependent aggregation from unimolecular micelles at low concentrations to "side-by-side" spherical aggregates at high concentrations and a unique mode of AIE. In addition, the size and the arrangement of the amphiphilic side chains were found to dominate the aggregate stability, cell uptake, and thus the cytotoxicity of the amphiphiles. This study has unprecedentedly developed versatile smart TPE lipids with precise structures, and unique physicochemical and biological properties while the peculiar structure-property relationship may shed new light on the design and application of AIE fluorophores and functional lipids in biomedicine and materials science.

Increased monocytic myeloid-derived suppressor cells in type 2 diabetes correlate with hyperglycemic and was a risk factor of infection and tumor occurrence.

To investigate the frequency of monocytic myeloid-derived suppressor cells (M-MDSCs) in type 2 diabetes mellitus (T2DM) patients and explore the potential associations between M-MDSCs, glycemic control, and the occurrence of infections and tumor. 102 healthy and 77 T2DM individuals were enrolled. We assessed the M-MDSCs frequency, levels of fasting plasma glucose (FPG), haemoglobin A1c (HbA1c), and other relevant indicators. Each patient underwent a follow-up of at least 6 months after M-MDSCs detection. The M-MDSCs frequency was significantly higher in patients with poor glycemic control (PGC) compared to the healthy population (P < 0.001), whereas there was no significant difference between patients with good glycemic control and the healthy (P > 0.05). There was a positive correlation between the M-MDSCs frequency and FPG, HbA1c (R = 0.517 and 0.315, P < 0.001, respectively). T2DM patients with abnormally increased M-MDSCs have a higher incidence of infection and tumor (48.57% and 11.43% respectively). Our results shed new light on the pathogenesis of T2DM, help to understand why T2DM patients are susceptible to infection and tumor and providing novel insights for future prevention and treatment of T2DM.

3D hierarchic interfacial assembly of Au nanocage@Au along with IS-AgMNPs for simultaneous, ultrasensitive, reliable, and quantitative SERS detection of colorectal cancer related miRNAs.

Simultaneous, reliable, and ultra-sensitive analysis of promising miRNA biomarkers of colorectal cancer (CRC) in serum is critical for early diagnosis and prognosis of CRC. In this work, we proposed a novel 3D hierarchic assembly clusters-based SERS strategy with dual enrichment and enhancement designed for the ultrasensitive and quantitative analysis of two upregulated CRC-related miRNAs (miR-21 and miR-31). The biosensor contains the following: (1) SERS probe, Au nanocage@Au nanoparticles (AuNC@Au NPs) labeled with Raman reporters (RaRs). (2) magnetic capture unit, Ag-coated Fe3O4 magnetic nanoparticles (AgMNPs) modified with internal standard (IS). (3) signal amplify probes (SA probes) for the formation of hierarchic assembly clusters. Based on this sensing strategy, the intensity ratio IRaRs/IIS with Lg miRNAs presents a wide linear range (10 aM-100 pM) with a limit of detection of 3.46 aM for miR-21, 6.49 aM for miR-31, respectively. Moreover, the biosensor shows good specificity and anti-interference ability, and the reliability and repeatability of the strategy were then verified by practical detection of clinical serum. Finally, the biosensor can distinguish CRC cancer subjects from normal ones and guide the distinct tumor, lymph node, and metastasis (TNM) stages. Overall, benefiting from the face-to-face coupling of hierarchic assembly clusters, rapid magnetic enrichment and IS signal calibration of AgMNPs, the established biosensor achieves ultra-sensitive and simultaneous detection of dual miRNAs and opens potential avenues for prediction and staging of CRC.

Association of HbA1c Variability with Vibrating Perception Threshold in Middle-Aged and Elderly Patients with Type 2 Diabetes Mellitus: A Retrospective Cohort Study.

Purpose: To investigate the relationship between HbA1c variability and vibrating perception threshold (VPT) in middle-aged and elderly patients with type 2 diabetes mellitus (T2DM). Patients and Methods: A total of 367 middle-aged and elderly patients with T2DM were enrolled. All patients were categorized into the control and vibration sensation deficiency group (VSD) based on VPT. Clinical data were collected. The coefficient of variation of glycated hemoglobin A1c (HbA1c-CV) and the mean glycated hemoglobin A1c(HbA1c-Mean) are considered as indexes of HbA1c variability. Multivariate logistic regression analysis, the generalized linear model and ROC curve correlation analysis were used to analyze the correlation of various factors and VPT. Results: The multivariate logistic regression analysis revealed that age, systolic blood pressure (SBP), and HbA1c-CV were identified as risk factors for vibration sensation deficiency in middle-aged and elderly patients with T2DM, while estimated glomerular filtration rate (eGFR), triiodothyronine (T3), and alanine aminotransferase (ALT) were considered as protective factors. In the unadjusted generalized linear model, a significant association was observed between HbA1c-CV and VPT values. After adjusting for age, diabetic duration, SBP, homeostatic model assessment for beta-cell function (HOMA-ß), ALT, eGFR, T3, 24-hour urinary protein excretion levels, and HbA1c-Mean, HbA1c-CV remained significantly correlated with VPT values on both sides. (left side, B=2.560, 95% CI 1.298~3.823; P<0.001; right side, B=2.608, 95% CI 1.498~3.718, P<0.001). The area under the curve (AUC) for HbA1c-CV and VSD prevalence was 0.723, with a sensitivity of 79.85%, specificity of 56.22%. Conclusion: The risk of developing VSD increases proportionally with higher HbA1c-CV levels in middle-aged and elderly patients with T2DM. Reaching and maintaining blood glucose stability is essential to the mitigation of diabetes peripheral neuropathy occurrence.