Glucagon-Like Peptide 1 Receptor Agonists and 13 Obesity-Associated Cancers in Patients With Type 2 Diabetes.

Importance: Thirteen human malignant neoplasms have been identified as obesity-associated cancers (OACs), ie, the presence of excess body fat is associated with increased risk of developing cancer and worse prognosis in patients with these specific tumors. The glucagon-like peptide receptor agonist (GLP-1RA) class of pharmaceuticals are effective agents for the treatment of type 2 diabetes (T2D) and for achieving weight loss, but the association of GLP-1RAs with the incident risk of 13 OACs is unclear. Objective: To compare the incident risk of each of the 13 OACs in patients with T2D who were prescribed GLP-1RAs vs insulins or metformin. Design, Setting, and Participants: This retrospective cohort study was based on a nationwide multicenter database of electronic health records (EHRs) of 113 million US patients. The study population included 1 651 452 patients with T2D who had no prior diagnosis of OACs and were prescribed GLP-1RAs, insulins, or metformin during March 2005 to November 2018. Data analysis was conducted on April 26, 2024. Exposures: Prescription of GLP-1RAs, insulins, or metformin. Main Outcomes and Measures: Incident (first-time) diagnosis of each of the 13 OACs occurring during a 15-year follow-up after the exposure was examined using Cox proportional hazard and Kaplan-Meier survival analyses with censoring applied. Hazard ratios (HRs), cumulative incidences, and 95% CIs were calculated. All models were adjusted for confounders at baseline by propensity-score matching baseline covariates. Results: In the study population of 1 651 452 patients with T2D (mean [SD] age, 59.8 [15.1] years; 827 873 [50.1%] male and 775 687 [47.0%] female participants; 5780 [0.4%] American Indian or Alaska Native, 65 893 [4.0%] Asian, 281 242 [17.0%] Black, 13 707 [0.8%] Native Hawaiian or Other Pacific Islander, and 1 000 780 [60.6%] White participants), GLP-1RAs compared with insulin were associated with a significant risk reduction in 10 of 13 OACs, including in gallbladder cancer (HR, 0.35; 95% CI, 0.15-0.83), meningioma (HR, 0.37; 95% CI, 0.18-0.74), pancreatic cancer (HR, 0.41; 95% CI, 0.33-0.50), hepatocellular carcinoma (HR, 0.47; 95% CI, 0.36-0.61), ovarian cancer (HR, 0.52; 95% CI, 0.03-0.74), colorectal cancer (HR, 0.54; 95% CI, 0.46-0.64), multiple myeloma (HR, 0.59; 95% CI, 0.44-0.77), esophageal cancer (HR, 0.60; 95% CI, 0.42-0.86), endometrial cancer (HR, 0.74; 95% CI, 0.60-0.91), and kidney cancer (HR, 0.76; 95% CI, 0.64-0.91). Although not statistically significant, the HR for stomach cancer was less than 1 among patients who took GLP-1RAs compared with those who took insulin (HR, 0.73; 95% CI, 0.51-1.03). GLP-1RAs were not associated with a reduced risk of postmenopausal breast cancer or thyroid cancer. Of those cancers that showed a decreased risk among patients taking GLP-1RAs compared with those taking insulin, HRs for patients taking GLP-1RAs vs those taking metformin for colorectal and gallbladder cancer were less than 1, but the risk reduction was not statistically significant. Compared with metformin, GLP-1RAs were not associated with a decreased risk of any cancers, but were associated with an increased risk of kidney cancer (HR, 1.54; 95% CI, 1.27-1.87). Conclusions and Relevance: In this study, GLP-1RAs were associated with lower risks of specific types of OACs compared with insulins or metformin in patients with T2D. These findings provide preliminary evidence of the potential benefit of GLP-1RAs for cancer prevention in high-risk populations and support further preclinical and clinical studies for the prevention of certain OACs.

Relationship between critical thinking ability and medication safety competence among clinical nurses: A multicenter cross-sectional study.

AIMS AND OBJECTIVES: This study investigated the relationship between clinical nurses' critical thinking ability and medication safety competence, as well as the factors related to medication safety competence. BACKGROUND: Nurses can have an active role in promoting medication safety. However, the main factors associating with nurses' competence in medication safety are uncertain. DESIGN: This was a descriptive, multicenter cross-sectional survey study. METHODS: A total of 1196 nurses from four different tertiary hospital in China were included in this study. A demographic information questionnaire, the Critical Thinking Diagnostic for nurses, and the Medication Safety Competence Scale for nurses were used to survey. Descriptive statistics, comparisons, correlation and regression analysis of the collected data were performed using SPSS 26.00 software. The study was reported using STROBE checklist. RESULTS: Included nurses obtained satisfactory scores on the critical thinking and medication safety scales and subscales. There was a strong statistically significant positive correlation between critical thinking ability and medication safety competence. Multiple linear regression analysis indicated that personal critical thinking scores and working years were positively associated with nurses' medication safety scores, accounting for 62.50% of the variance. CONCLUSION: Clinical nurses' critical thinking ability is positively associated with medication safety competence. RELEVANCE TO CLINICAL PRACTICE: As critical thinking ability positively predicts nurses' medication safety competence, hospitals and nursing administrators should consider continuing nursing education and training to improve critical thinking skills, thereby promoting medication safety competence among clinical nurses.

An Ultrasensitive Biosensor for Probing Subcellular Distribution and Mitochondrial Transport of l-2-Hydroxyglutarate.

l-2-Hydroxyglutarate (l-2-HG) is a functionally compartmentalized metabolite involved in various physiological processes. However, its subcellular distribution and mitochondrial transport remain unclear owing to technical limitations. In the present study, an ultrasensitive l-2-HG biosensor, sfLHGFRH, composed of circularly permuted yellow fluorescent protein and l-2-HG-specific transcriptional regulator, is developed. The ability of sfLHGFRH to be used for analyzing l-2-HG metabolism is first determined in human embryonic kidney cells (HEK293FT) and macrophages. Then, the subcellular distribution of l-2-HG in HEK293FT cells and the lower abundance of mitochondrial l-2-HG are identified by the sfLHGFRH-supported spatiotemporal l-2-HG monitoring. Finally, the role of the l-glutamate transporter SLC1A1 in mitochondrial l-2-HG uptake is elucidated using sfLHGFRH. Based on the design of sfLHGFRH, another highly sensitive biosensor with a low limit of detection, sfLHGFRL, is developed for the point-of-care diagnosis of l-2-HG-related diseases. The accumulation of l-2-HG in the urine of patients with kidney cancer is determined using the sfLHGFRL biosensor.

Non-Insulin Antidiabetic Agents and Lung Cancer Risk in Drug-Naive Patients with Type 2 Diabetes Mellitus: A Nationwide Retrospective Cohort Study.

Lung cancer (LC) is the second most common cancer and the leading cause of cancer deaths in the U.S. Insulin therapy, a key treatment for managing Type 2 Diabetes Mellitus (T2DM), is associated with increased LC risk. The impact of non-insulin antidiabetic drugs, particularly GLP-1 receptor agonists (GLP-1RAs), on LC risk is not well understood. This study evaluated LC risk in T2DM patients, comparing seven non-insulin antidiabetic agents to insulin. Using the TriNetX Analytics platform, we analyzed the de-identified electronic health records of 1,040,341 T2DM patients treated between 2005 and 2019, excluding those with prior antidiabetic use or LC diagnoses. We calculated hazard ratios and confidence intervals for LC risk and used propensity score matching to control for confounding factors. All non-insulin antidiabetic drugs, except alpha-glucosidase inhibitors, were associated with significantly reduced LC risk compared to insulin, with GLP-1RAs showing the greatest reduction (HR: 0.49, 95% CI: 0.41, 0.59). GLP-1RAs were consistently associated with lowered LC risk across all histological types, races, genders, and smoking statuses. These findings suggest that non-insulin antidiabetic drugs, particularly GLP-1RAs, may be preferable for managing T2DM while reducing LC risk.

Design and Discovery of New Collagen V-Derived FGF2-Blocking Natural Peptides Inhibiting Lung Squamous Cell Carcinoma In Vitro and In Vivo.

Aberrant FGF2/FGFR signaling is implicated in lung squamous cell carcinoma (LSCC), posing treatment challenges due to the lack of targeted therapeutic options. Designing drugs that block FGF2 signaling presents a promising strategy different from traditional kinase inhibitors. We previously reported a ColVα1-derived fragment, HEPV (127AA), that inhibits FGF2-induced angiogenesis. However, its large size may limit therapeutic application. This study combines rational peptide design, molecular dynamics simulations, knowledge-based prediction, and GUV and FRET assays to identify smaller peptides with FGF2-blocking properties. We synthesized two novel peptides, HBS-P1 (45AA) and HBS-P2 (66AA), that retained the heparin-binding site. Both peptides demonstrated anti-LSCC and antiangiogenesis properties in cell viability and microvessel network induction assays. In two LSCC subcutaneous models, HBS-P1, with its affinity for FGF2 and enhanced penetration ability, demonstrated substantial therapeutic potential without apparent toxicities. Our study provides the first evidence supporting the development of collagen V-derived natural peptides as FGF2-blocking agents for LSCC treatment.

[Application of Fetal Magnetic Resonance Imaging in Prognosis Assessment of Fetuses With Congenital Pulmonary Cystic Diseases]. / äº§å‰ç£å ±æŒ¯åœ¨å ˆå¤©æ€§è‚ºå›Šæ€§ç–¾ç— èƒŽå„¿é¢„åŽè¯„ä¼°ä¸­çš„åº”ç”¨ç ”ç©¶.

Objective: The aim of this study is to explore the practical value of prenatal magnetic resonance imaging (MRI) in the assessment of congenital cystic lung disease in fetuses, to evaluate the relative size of the lesion and the status of lung development, and to make an attempt at utilizing the strength of MRI in post-processing to obtain assessment indicators of the size of the lesion and the status of lung development, with which predictions can be made for the prognosis that these fetuses may face after birth. We retrospectively collected and analyzed the data of fetuses diagnosed with congenital cystic lung disease. Prenatal ultrasound examination of these fetuses led to the diagnosis that they were suspected of having congenital cystic lung disease and the diagnosis was confirmed by subsequent prenatal MRI. The fetuses were followed up to track their condition at birth (postnatal respiratory distress, mechanical ventilation, etc.), whether the fetuses underwent surgical treatment, and the recovery of the fetuses after surgical treatment. The recovery of the fetuses was followed up to explore the feasibility of prenatal MRI examination to assess fetal congenital pulmonary cystic disease, and to preliminarily explore the predictive value of prenatal MRI for the prognosis of fetuses with congenital pulmonary cystic disease. Methods: MRI fetal images were collected from pregnant women who attended the West China Second University Hospital of Sichuan University between May 2018 and March 2023 and who were diagnosed with fetal congenital pulmonary cystic disease by prenatal ultrasound and subsequent MRI. Fetal MRI images of congenital cystic lung disease were post-processed to obtain the fetal lung lesion volume, the fetal affected lung volume, the healthy lung volume, and the fetal head circumference measurements. The signal intensity of both lungs and livers, the lesion volume/the affected lung volume, the lesion volume/total lung volume, the cystic volume ratio (CVR), and the bilateral lung-liver signal intensity ratio were measured. The feasibility and value of MRI post-processing acquisition indexes for evaluating the prognosis of fetuses with congenital cystic lung disease were further analyzed by combining the follow-up results obtained 6 months after the birth of the fetus. Logistic regression models were used to quantify the differences in maternal age, gestational week at the time of MRI, CVR, and bilateral lung-to-liver signal intensity ratio, and to assess whether these metrics correlate with poor prognosis. Receiver operating characteristic (ROC) curves were used to assess the value of the parameters obtained by MRI calculations alone and in combination with multiple metrics for predicting poor prognosis after birth. Results: We collected a total of 67 cases of fetuses diagnosed with congenital cystic lung disease by fetal MRI between May 2018 and March 2023, and excluded 6 cases with no normal lung tissue in the affected lungs, 11 cases of fetal induction, and 3 cases of loss of pregnancy. In the end, 47 cases of fetuses with congenital cystic lung disease were included, of which 30 cases had a good prognosis and 17 cases had a poor prognosis. The difference in the difference between the signal intensity ratios of the affected and healthy sides of the lungs and livers of the fetuses in the good prognosis group and that in the poor prognosis group was statistically significant (P<0.05), and the signal intensity ratio of the healthy side of the lungs and livers was higher than the signal intensity ratio of the affected side of the lungs and livers. Further analysis showed that CVR (odds ratio [OR]=1.058, 95% confidence interval [CI]: 1.014-1.104), and the difference between the lung-to-liver signal intensity ratios of the affected and healthy sides (OR=0.814, 95% CI: 0.700-0.947) were correlated with poor prognosis of birth in fetuses with congenital cystic lung disease. In addition, ROC curve analysis showed that the combined application of lesion volume/affected lung volume and the observed difference in the signal intensity ratio between the affected and healthy lungs and liver predicted the prognosis of children with congenital cystic lung disease more accurately than the single-parameter judgment did, with the area under the curve being 0.988, and the cut-off value being 0.33, which corresponded to a sensitivity of 100%, a specificity of 93.3%, and a 95% CI of 0.966-1.000. Conclusions: Based on the MRI of fetuses with congenital cystic lung disease, we obtained information on lesion volume, lesion volume/affected lung volume, lesion volume/total lung volume, CVR, and bilateral lung-to-liver signal intensity ratio difference, all of which showing some clinical value in predicting the poor prognosis in fetuses with congenital cystic lung disease. Furthermore, among the combined indexes, the lesion volume/affected lung volume and bilateral lung-to-liver signal intensity ratio difference are more effective predictors for the poor prognosis of fetuses with congenital cystic lung disease, and show better efficacy in predicting the poor prognosis of fetuses with congenital cystic lung disease. This provides a new and effective predictive method for further assessment of pulmonary lung development in fetuses with congenital cystic lung disease, and helps improve the assessment and prediction of the prognosis of fetuses with congenital cystic lung disease.

Biomechanical effects of posterior lumbar interbody fusion with vertical placement of pedicle screws compared to traditional placement.

BACKGROUND: The pedicle screw technique is widely employed for vertebral body fixation in the treatment of spinal disorders. However, traditional screw placement methods require the dissection of paraspinal muscles and the insertion of pedicle screws at specific transverse section angles (TSA). Larger TSA angles require more force to pull the muscle tissue, which can increase the risk of surgical trauma and ischemic injury to the lumbar muscles. AIM: To study the feasibility of zero-degree TSA vertical pedicle screw technique in the lumbosacral segment. METHODS: Finite element models of vertebral bodies and pedicle screw-rod systems were established for the L4-S1 spinal segments. A standard axial load of 500 N and a rotational torque of 10 N/m were applied. Simulated screw pull-out experiment was conducted to observe pedicle screw resistance to pull-out, maximum stress, load-displacement ratio, maximum stress in vertebral bodies, load-displacement ratio in vertebral bodies, and the stress distribution in pedicle screws and vertebral bodies. Differences between the 0-degree and 17-degree TSA were compared. RESULTS: At 0-degree TSA, the screw pull-out force decreased by 11.35% compared to that at 17-degree TSA (P < 0.05). At 0-degree and 17-degree TSA, the stress range in the screw-rod system was 335.1-657.5 MPa and 242.8-648.5 MPa, separately, which were below the fracture threshold for the screw-rod system (924 MPa). At 0-degree and 17-degree TSA, the stress range in the vertebral bodies was 68.45-78.91 MPa and 39.08-72.73 MPa, separately, which were below the typical bone yield stress range for vertebral bodies (110-125 MPa). At 0-degree TSA, the load-displacement ratio for the vertebral bodies and pedicle screws was slightly lower compared to that at 17-degree TSA, indicating slightly lower stability (P < 0.05). CONCLUSION: The safety and stability of 0-degree TSA are slightly lower, but the risks of screw-rod system fracture, vertebral body fracture, and rupture are within acceptable limits.

Intranasal administration of DSM 32444 Bacillus subtilis spores: safety and tolerability.

Introduction. Administered nasally, spores of the Gram-positive bacterium Bacillus subtilis have been shown to be able to induce innate immunity sufficient to confer protection to influenza and respiratory syncytial virus.Hypothesis. Although members of the aerobiome, intranasal delivery of high numbers of live spores carries potential safety issues.Aim. To address the potential safety risk of using live spores, we assessed the safety of spores that had been completely inactivated using heat sterilization.Methodology. Using autoclaved, and therefore killed, spores of a generally recognized as safe-notified B. subtilis strain (DSM 32444), safety was assessed in vitro (biotype, genome and cell based cytoxicity) and in vivo, using intranasal administration in rodent models and lastly in human volunteers.Results. Using a 15-day, repeat-dose, regimen in a rodent model, no indication of toxicity was observed. In a registered human study (NCT05984004), a formulated preparation of inactivated DSM 32444 spores referred to as SPEROVID was developed, and tolerance in human volunteers was assessed following 7 days of nasal dosing (2-4 times/day).Conclusion. Our study demonstrated that in humans an intranasal dose of up to 3×108 killed spores was safe and well tolerated.

Prediction of Potential Distribution of Carposina coreana in China under the Current and Future Climate Change.

Carposina coreana is an important pest of Cornus officinalis, distributed in China, Korea, and Japan. In recent years, its damage to C. officinalis has become increasingly serious, causing enormous economic losses in China. This study and prediction of current and future suitable habitats for C. coreana in China can provide an important reference for the monitoring, early warning, prevention, and control of the pest. In this study, the potential distributions of C. coreana in China under current climate and future climate models were predicted using the maximum entropy (MaxEnt) model with ArcGIS software. The distribution point data of C. coreana were screened using the buffer screening method. Nineteen environmental variables were screened using the knife-cut method and variable correlation analysis. The parameters of the MaxEnt model were optimized using the kuenm package in R software. The MaxEnt model, combined with key environmental variables, was used to predict the distribution range of the suitable area for C. coreana under the current (1971-2000) and four future scenarios. The buffer screening method screened data from 41 distribution points that could be used for modeling. The main factors affecting the distribution of C. coreana were precipitation in the driest month (Bio14), precipitation in the warmest quarter (Bio18), precipitation in the coldest quarter (Bio19), the standard deviation of seasonal variation of temperature (Bio4), minimum temperature in the coldest month (Bio6), and average temperature in the coldest quarter (Bio11). The feature class (FC) after the kuenm package optimization was a Q-quadratic T-threshold combination, and the regularization multiplier (RM) was 0.8. The suitable areas for C. coreana under the current climate model were mainly distributed in central China, and the highly suitable areas were distributed in southern Shaanxi, southwestern Henan, and northwestern Hubei. The lowest temperature in the coldest month (Bio6), the average temperature in the coldest quarter (Bio11), and the precipitation in the warmest quarter (Bio18) all had good predictive ability. In future climate scenarios, the boundary of the suitable area for C. coreana in China is expected to shift northward, and thus, most of the future climate scenarios would shift northward.

Multi-parametric thrombus profiling microfluidics detects intensified biomechanical thrombogenesis associated with hypertension and aging.

Arterial thrombosis, which represents a critical complication of cardiovascular diseases, is a leading cause of death and disability worldwide with no effective bioassay for clinical prediction. As a symbolic feature of arterial thrombosis, severe stenosis in the blood vessel creates a high-shear, high-gradient flow environment that effectively facilitates platelet aggregation towards vessel occlusion even with platelet amplification loops inhibited. However, no approach is currently available to comprehensively characterize the size, composition and platelet activation status of thrombi forming under this biorheological condition. Here, we present a thrombus profiling assay that monitors the multi-dimensional attributes of thrombi forming in conditions mimicking the physiological scenario of arterial thrombosis. Using this platform, we demonstrate that different receptor-ligand interactions contribute distinctively to the composition and activation status of the thrombus. Our investigation into hypertensive and older individuals reveals intensified biomechanical thrombogenesis and multi-dimensional thrombus profile abnormalities, demonstrating a direct contribution of mechanobiology to arterial thrombosis and endorsing the diagnostic potential of the assay. Furthermore, we identify the hyperactivity of GPIbα-integrin αIIbß3 mechanosensing axis as a molecular mechanism that contributes to hypertension-associated arterial thrombosis. By studying the interactions between anti-thrombotic inhibitors and hypertension, and the inter-individual variability in personal thrombus profiles, our work reveals a critical need for personalized anti-thrombotic drug selection that accommodates each patient's pathological profile.

Development of Plasmonic Attapulgite/Co(Ti)Ox Nanocomposite Using Spent Batteries toward Photothermal Reduction of CO2.

The rapid development of the battery industry has brought about a large amount of waste battery pollution. How to realize the high-value utilization of waste batteries is an urgent problem to be solved. Herein, cobalt and titanium compounds (LTCO) were firstly recovered from spent lithium-ion batteries (LIBs) using the carbon thermal reduction approach, and plasmonic attapulgite/Co(Ti)Ox (H-ATP/Co(Ti)Ox) nanocomposites were prepared by the microwave hydrothermal technique. H-ATP had a large specific surface area and enough active sites to capture CO2 molecules. The biochar not only reduced the spinel phase of waste LIBs into metal oxides including Co3O4 and TiO2 but also increased the separation and transmission of the carriers, thereby accelerating the adsorption and reduction of CO2. In addition, H-ATP/Co(Ti)Ox exhibited a localized surface plasmon resonance effect (LSPR) in the visible to near-infrared region and released high-energy hot electrons, enhancing the surface temperature of the catalyst and further improving the catalytic reduction of CO2 with a high CO yield of 14.7 µmol·g-1·h-1. The current work demonstrates the potential for CO2 reduction by taking advantage of natural mineral and spent batteries.

AHNAK2 Regulates NF-κB/MMP-9 Signaling to Promote Pancreatic Cancer Progression.

Early metastasis of pancreatic cancer (PaC) is a major cause of its high mortality rate. Previous studies have shown that AHNAK2 is involved in the progression of some tumors and is predicted to be an independent prognostic factor for PaC; however, the specific mechanisms through which AHNAK2 regulates PaC remain unclear. In this study, we examined the role of AHNAK2 in PaC and its potential molecular mechanisms. AHNAK2 mRNA and protein expression in PaC tissues and cells were measured using qRT-PCR and western blot analysis. After AHNAK2 knockdown using small interfering RNA, PaC cells were subjected to CCK-8 scratch, and Transwell assays to assess cell proliferation, migration, and invasion, respectively. Furthermore, the validation of the mechanistic pathway was achieved by western blot analysis. AHNAK2 mRNA and protein levels were up-regulated in PaC and silencing AHNAK2 significantly inhibited the proliferation, migration, and invasion of PaC cells. Mechanistically, AHNAK2 knockdown decreased the expression of phosphorylated p65, phosphorylated IκBα, and matrix metalloproteinase-9 (MMP-9), suggesting that activation of the NF-κB/MMP-9 signaling pathway was inhibited. Importantly, activation of NF-κB reversed the effects of AHNAK2 knockdown. Our findings indicate that AHNAK2 promotes PaC progression through the NF-kB/MMP-9 pathway and provides a theoretical basis for targeting AHNAK2 for the treatment of PaC.

Distance-related functional reorganization predicts motor outcome in stroke patients.

BACKGROUND: Analyzing distance-dependent functional connectivity density (FCD) yields valuable insights into patterns of brain activity. Nevertheless, whether alterations of FCD in non-acute stroke patients are associated with the anatomical distance between brain regions remains unclear. This study aimed to explore the distance-related functional reorganization in non-acute stroke patients following left and right hemisphere subcortical lesions, and its relationship with clinical assessments. METHODS: In this study, we used resting-state fMRI to calculate distance-dependent (i.e., short- and long-range) FCD in 25 left subcortical stroke (LSS) patients, 22 right subcortical stroke (RSS) patients, and 39 well-matched healthy controls (HCs). Then, we compared FCD differences among the three groups and assessed the correlation between FCD alterations and paralyzed motor function using linear regression analysis. RESULTS: Our findings demonstrated that the left inferior frontal gyrus displayed distance-independent FCD changes, while the bilateral supplementary motor area, cerebellum, and left middle occipital gyrus exhibited distance-dependent FCD alterations in two patient subgroups compared with HCs. Furthermore, we observed a positive correlation between increased FCD in the bilateral supplementary motor area and the motor function of lower limbs, and a negative correlation between increased FCD in the left inferior frontal gyrus and the motor function of both upper and lower limbs across all stroke patients. These associations were validated by using a longitudinal dataset. CONCLUSIONS: The FCD in the cerebral and cerebellar cortices shows distance-related changes in non-acute stroke patients with motor dysfunction, which may serve as potential biomarkers for predicting motor outcomes after stroke. These findings enhance our comprehension of the neurobiological mechanisms driving non-acute stroke. TRIAL REGISTRATION: All data used in the present study were obtained from a research trial registered with the ClinicalTrials.gov database (NCT05648552, registered 05 December 2022, starting from 01 January 2022).

Application value of 18F-FDG PET/CT in primary spleen angiosarcoma with liver metastasis: a case report and literature review.

Background: Primary splenic angiosarcoma (PSA) is a rare neoplasm. It is a malignant tumor derived from endothelial cells of the splenic sinuses. PSA has an unknown etiology, a high degree of malignancy, easy early metastasis, atypical clinical symptoms and imaging findings, and difficult early diagnosis. This paper reports the 18F-FDG PET/CT findings of a case of PSA with intrahepatic metastasis; summarizes its clinical, imaging, and pathological data; and reviews the literature. Case description: A 64-year-old male patient presented with left lower abdominal distending pain without obvious causes on 13 March 2022. The pain was persistent and dull and worsened after sitting and eating. Blood routine examination results were RBC ↓ 3.33 × 1012/L, WBC ↑ 12.32 × 109/L, and PLT ↓ 40 × 109/L. The tumor markers indicated CA125 ↑ 47.0 U/ml, AFP (-), CEA (-), CA199 (-), and CA724 (-). Non-contrast-enhanced CT scan of the abdomen showed that the spleen was significantly enlarged in volume and irregular in shape and had multiple nodules and clumpy low-density shadows, unclear boundaries, uneven density, and multiple necrotic areas. Enhanced CT showed diffuse uneven mild enhancement of the spleen, and the degree of enhancement increased with time. Multiple nodular low-density shadows were seen in the liver, which were slightly enhanced by the enhanced scan.18F-FDG PET/CT showed multiple nodular and massive lesions in the spleen with multiple necrotic areas. There were multiple nodular lesions in the liver, the level of FDG metabolism increased, the SUVmax of the spleen lesions was 9.0, and the SUVmax of the liver lesions was 5.6. The 18F-FDG PET/CT diagnosis was splenic malignancy with liver metastasis. Finally, after a multidisciplinary discussion, it was decided to perform laparoscopic total splenectomy and portal vein infusion chemotherapy. Pathological examination showed that the tumor cells were round, oval, or fusiform, with obvious atypia, arranged into a cable or anastomosed vascular lumen. The final diagnosis was primary splenic angiosarcoma with massive necrosis. After surgery, the patient received antitumor combined therapy and died 5 months later. Conclusion: The incidence of PSA is very low, and its clinical and radiological manifestations lack specificity. 18F-FDG PET/CT imaging has a certain diagnostic value for PSA and significant utility in preoperative staging, guiding biopsy procedures, evaluating postoperative treatment response, and monitoring disease recurrence. PSA should be considered in the presence of a space-occupying lesion within the spleen that exhibits necrotic areas, shows progressive enhancement on contrast-enhanced scans, and demonstrates heterogeneous increases in FDG uptake.

Obinutuzumab in untreated primary membranous nephropathy: An observational case series.

BACKGROUND: As an initial treatment for primary membranous nephropathy (PMN), there remains a significant proportion of patients for whom rituximab is not fully effective. Here, we aimed to assess the effectiveness and safety of obinutuzumab as initial treatment in patients with PMN. METHODS: In this observational case series, patients diagnosed with PMN and treated with obinutuzumab as initial treatment were included. Treatment response was assessed by 24-h urine total protein (24 h UTP) and serum albumin, and immunologic remission was assessed by phospholipase A2 receptor (PLA2R) antibodies. RESULTS: Twelve patients with PMN receiving obinutuzumab as initial treatment were included. Over 6 months, a statistically significant reduction in 24 h UTP levels (p = 0.003) and an increase in serum albumin levels were observed (p < 0.001). By the 6-month follow-up, two patients (16.7%) achieved complete remission, eight (66.6%) reached partial remission, and two (16.7%) showed no remission. Immunological remission was observed in 44.4% of evaluable patients (n = 9) after 3 months, increasing to 100% (6/6) at 6 months. Except for cases 1, 2, and 3, the total B cell counts in the remaining patients fell to less than 5 cells/µL before the administration of the second dose of obinutuzumab, including seven patients with counts as low as 0 cells/µL. Mild to moderate treatment-related adverse events (TRAEs) were reported in 58.3% (7/12) of the patients. No serious TRAEs were reported. CONCLUSIONS: Obinutuzumab demonstrates promising potential as an initial treatment for PMN, with good effectiveness and a manageable safety profile. Further large-scale prospective studies are needed to confirm these findings.

Indocyanine green-mediated fabrication of urchin-like hydroxyethyl starch nanocarriers for enhanced drug tumor EPR and deep penetration effects.

Effective EPR and tumor penetration are bottlenecks in current nanomedicine therapy. Comosol software was utilized to analyze the motion process of nanoparticles (NPs) with different shapes, from blood vessels to tumor tissue, to address this. By calculation, urchin-like NPs experienced higher drag forces than spherical NPs, facilitating their EPR and tumor penetration effects. Thus, urchin-like indocyanine green-loaded hydroxyethyl starch-cholesterol (ICG@HES-CH) NPs were prepared by leveraging the instability of ICG responding to near-infrared light (NIR). Upon NIR exposure, ICG degraded and partly disintegrated ICG@HES-CH NPs, and its morphology transformed from spherical to urchin-like. Vincristine (VC), as a model drug, was loaded in urchin-like ICG@HES-CH NPs for the treatment of lymphoma. A20 lymphoma cells and 3T3-A20 tumor organoids were employed to investigate the influence of shape on NPs' cellular uptake, penetration pathway, and cytotoxicity. It demonstrated that urchin-like ICG@HES-CH NPs mainly transport across the extracellular matrix through intercellular pathways, easily reaching the deep tumor sites and achieving higher cytotoxicity. In vivo VC distribution and anti-tumor results indicated that urchin-like NPs increased VC EPR and penetration ability, lowering VC neurotoxicity and superior anti-tumor effect. Therefore, urchin-like ICG@HES-CH NPs have great translational potential to be used as chemotherapeutic nanocarriers in anticancer therapy.

Vapor/Vapor-Solid Interfacial Growth of Covalent Organic Framework Membranes on Alumina Hollow Fiber for Advanced Molecular Separation.

Covalent organic frameworks (COFs), known for their chemical stability and porous crystalline structure, hold promises as advanced separation membranes. However, fabricating high-quality COF membranes, particularly on industrial-preferred hollow fiber substrates, remains challenging. This study introduces a novel vapor/vapor-solid (V/V-S) method for growing ultrathin crystalline TpPa-1 COF membranes on the inner lumen surface of alumina hollow fibers (TpPa-1/Alumina). Through vapor-phase monomer introduction onto polydopamine-modified alumina at 170 °C and 1 atm, efficient polymerization and crystallization occur at the confined V-S interface. This enables one-step growth within 8 h, producing 100 nm thick COF membranes with strong substrate adhesion. TpPa-1/Alumina exhibits exceptional stability and performance over 80 h in continuous cross-flow organic solvent nanofiltration (OSN), with methanol permeance of about 200 L m-2 h-1 bar-1 and dye rejection with molecular weight cutoff (MWCO) of approximately 700 Da. Moreover, the versatile V/V-S method synthesizes two additional COF membranes (TpPa2Cl/Alumina and TpHz/Alumina) with different pore sizes and chemical environments. Adjusting the COF membrane thickness between 100-500 nm is achievable easily by varying the growth cycle numbers. Notably, TpPa2Cl/Alumina demonstrates excellent OSN performance in separating the model active pharmaceutical ingredient glycyrrhizic acid (GA) from dimethyl sulfoxide (DMSO), highlighting the method's potential for large-scale industrial applications.

DCPIB Attenuates Ischemia-Reperfusion Injury by Regulating Microglial M1/M2 Polarization and Oxidative Stress.

The inflammatory response plays an indispensable role in ischemia-reperfusion injury, the most significant of which is the inflammatory response caused by microglial polarization. Anti-inflammatory therapy is also an important remedial measure after failed vascular reconstruction. Maintaining the internal homeostasis of the brain is a crucial measure for suppressing the inflammatory response. The mechanism underlying the relationship between DCPIB, a selective blocker of volume-regulated anion channels (VRAC), and inflammation induced by cerebral ischemia-reperfusion injury is currently unclear. The purpose of this study was to investigate the relationship between DCPIB and microglial M1/M2 polarization-mediated inflammation after cerebral ischemia-reperfusion injury. C57BL/6 mice were subjected to transient middle cerebral artery occlusion (tMCAO). DCPIB was administered by a lateral ventricular injection within 5 min after reperfusion. Behavioral assessments were conducted at 1, 3, and 7 days after tMCAO/R. Pathological injuries were evaluated using TTC assay, HE and Nissl staining, brain water content measurement, and immunofluorescence staining. The levels of inflammatory cytokines were analyzed using qPCR and ELISA. Additionally, the phenotypic variations of microglia were examined using immunofluorescence staining. In mouse tMCAO/R model, DCPIB administration markably reduced mortality, improved behavioral performance, and alleviated pathological injury. DCPIB treatment significantly inhibited the inflammatory response, promoted the conversion of M1 microglia to M2 microglia via the MAPK signaling pathway, and ultimately protected neurons from the microglia-mediated inflammatory response. In addition, DCPIB inhibited oxidative stress induced by cerebral ischemia-reperfusion injury. In conclusion, DCPIB attenuates cerebral ischemia-reperfusion injury by regulating microglial M1/M2 polarization and oxidative stress.