Mechanism, and treatment of anti-CV2/CRMP5 autoimmune pain.

Paraneoplastic neurological syndromes arise from autoimmune reactions against nervous system antigens due to a maladaptive immune response to a peripheral cancer. Patients with small cell lung carcinoma or malignant thymoma can develop an autoimmune response against the CV2/collapsin response mediator protein 5 (CRMP5) antigen. For reasons that are not understood, approximately 80% of patients experience painful neuropathies. Here, we investigated the mechanisms underlying anti-CV2/CRMP5 autoantibodies (CV2/CRMP5-Abs)-related pain. We found that patient-derived CV2/CRMP5-Abs can bind to their target in rodent dorsal root ganglia (DRG) and superficial laminae of the spinal cord. CV2/CRMP5-Abs induced DRG neuron hyperexcitability and mechanical hypersensitivity in rats that were abolished by preventing binding to their cognate autoantigen CRMP5. The effect of CV2/CRMP5-Abs on sensory neuron hyperexcitability and mechanical hypersensitivity observed in patients was recapitulated in rats using genetic immunization providing an approach to rapidly identify possible therapeutic choices for treating autoantibody-induced pain including the repurposing of a monoclonal anti-CD20 antibody that selectively deplete B-lymphocytes. These data reveal a previously unknown neuronal mechanism of neuropathic pain in patients with paraneoplastic neurological syndromes resulting directly from CV2/CRMP5-Abs-induced nociceptor excitability. CV2/CRMP5-Abs directly sensitize pain responses by increasing sensory neuron excitability and strategies aiming at either blocking or reducing CV2/CRMP5-Abs can treat pain as a comorbidity in patients with paraneoplastic neurological syndromes.

Temperature-Induced Variations in Slip Behavior of Single Crystal Aluminum: Microstructural Analysis.

The simultaneous increase in strength and plasticity of aluminum and its alloys at cryogenic temperatures has been shown in previous research, but the deformation mechanism was still unclear. Therefore, the purpose of this investigation was to reveal the relationship between slip behavior and mechanical response at low temperatures. A quasi-in situ scanning electron microscope was used to observe the evolution of slip bands in the selected aluminum single crystals with two typical orientations at 25 °C, -100 °C, and -180 °C. The results showed that irrespective of orientation, the density of the slip plane was increased with the decline in temperature, which inhibited slip localization and significantly improved plasticity and work hardening. In detail, at RT, the slip bands were widening until the micro-cracks were generated, causing early failure during deformation. When the temperature was decreased to -180 °C, the slip plane density was increased, and the deformation was more homogenous. Moreover, the slip mode was influenced by orientation and temperature. In particular, a single slip system was activated in the sample with the [112] orientation at all the temperatures investigated. Multiple slip systems were found to activate at 25 °C and -100 °C, and only the primary slip system was activated in the sample with [114] orientation at -180 °C. These findings deepen the understanding of slip behavior at cryogenic temperatures, providing new insights into the deformation mechanism of aluminum and its alloys.

Mineralization of SF6 and NF3 fluorinated compounds for greenhouse gas abatement by oxalates.

Fluorinated compounds (FCs) such as sulfur hexafluoride (SF6) and nitrogen trifluoride (NF3) have garnered attention due to their environmental impact. This study investigates the mineralization and removal of two potent FCs: SF6 and NF3. The results confirm that utilizing various oxalate salts leads to the formation of corresponding metallic fluorides: lithium fluoride (LiF), sodium fluoride (NaF), and potassium fluoride (KF), validating the occurrence of mineralization reactions. Among the oxalate salts, sodium oxalate demonstrates the highest mineralization efficiency in both SF6 and NF3 removal. Real-time Fourier transform infrared spectroscopy (FT-IR) gas-phase analysis confirms rapid and complete gas removal within a short reaction time using the selected oxalate salts. Meticulous mass balance calculations revealed that oxalates (LiF, NaF, and KF) yielded sulfur (S) at rates of 92.09%, 91.85%, and 84.98% following SF6 mineralization. Additionally, the conversion rates of oxalates to the corresponding metallic fluorides (LiF, NaF, and KF) after SF6 mineralization were 98.18%, 95.82%, and 95.21%, respectively. Similarly, after NF3 mineralization, these conversion rates stood at 92.18%, 90.67%, and 90.02%, respectively. The removal efficiencies for SF6 (1000 ppm) were 4.98, 12.01, and 7.23 L/g, while those for NF3 (1000 ppm) were 14.1, 12.6, and 11.7 L/g, respectively. Notably, sodium oxalate exhibits superior effectiveness, achieving 100% SF6 conversion within 30 min and 100% NF3 conversion within 50 min. This work underscores the potential of oxalate mineralization as a promising strategy for efficient and rapid removal of potent fluorinated compounds, paving the way for environmentally benign FC remediation techniques with broader implications for sustainable gas treatment technologies.

Impact of previous S-1 treatment on efficacy of liposomal irinotecan plus 5-fluorouracil and leucovorin in patients with metastatic pancreatic cancer.

BACKGROUND/OBJECTIVES: Liposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI + 5-FU/LV) provides survival benefits for metastatic pancreatic adenocarcinoma (mPDAC) refractory to gemcitabine-based treatment, mainly gemcitabine plus nab-paclitaxel (GA), in current practice. Gemcitabine plus S-1 (GS) is another commonly administered first-line regimen before nab-paclitaxel reimbursement; however, the efficacy and safety of nal-IRI + 5-FU/LV for mPDAC after failed GS treatment has not been reported and was therefore explored in this study. METHODS: In total, 177 patients with mPDAC received first-line GS or GA treatment, followed by second-line nal-IRI + 5-FU/LV treatment (identified from a multicenter retrospective cohort in Taiwan from 2018 to 2020); 85 and 92 patients were allocated to the GS and GA groups, respectively. Overall survival (OS), time-to-treatment failure (TTF), and adverse events were compared between the two groups. RESULTS: The baseline characteristics of the two groups were generally similar; however, a higher median age (67 versus 62 years, p < 0.001) and fewer liver metastases (52% versus 78%, p < 0.001) were observed in the GS versus GA group. The median OS was 15.0 and 15.9 months in the GS and GA groups, respectively (p = 0.58). The TTF (3.1 versus 2.8 months, p = 0.36) and OS (7.6 versus 6.7 months, p = 0.83) after nal-IRI treatment were similar between the two groups. More patients in the GS group developed mucositis during nal-IRI treatment (15% versus 4%, p = 0.02). CONCLUSIONS: The efficacy of second-line nal-IRI +5-FU/LV treatment was unaffected by prior S-1 exposure. GS followed by nal-IRI treatment is an alternative treatment sequence for patients with mPDAC.

An injectable active hydrogel based on BMSC-derived extracellular matrix for cartilage regeneration enhancement.

Articular cartilage injury impairs joint function and necessitates orthopedic intervention to restore the structure and function of the cartilage. Extracellular matrix (ECM) scaffolds derived from bone marrow mesenchymal stem cells (BMSCs) can effectively promote cell adhesion, proliferation, and chondrogenesis. However, pre-shaped ECM scaffolds have limited applicability due to their poor fit with the irregular surface of most articular cartilage defects. In this study, we fabricated an injectable active ECM hydrogel from autologous BMSCs-derived ECM by freeze-drying, liquid nitrogen milling, and enzymatic digestion. Moreover, our in vitro and in vivo results demonstrated that the prepared hydrogel enhanced chondrocyte adhesion and proliferation, chondrogenesis, cartilage regeneration, and integration with host tissue, respectively. These findings indicate that active ECM components can provide trophic support for cell proliferation and differentiation, restoring the structure and function of damaged cartilage.

Effect of bariatric surgery on metabolism in diabetes and obesity comorbidity: Insight from recent research.

Obesity is a prevalent cause of diabetes mellitus (DM) and is a serious danger to human health. Type 2 DM (T2DM) mostly occurs along with obesity. Foodborne obesity-induced DM is caused by an excessive long-term diet and surplus energy. Bariatric surgery can improve the symptoms of T2DM in some obese patients. But different types of bariatric surgery may have different effects. There are some models built by researchers to discuss the surgical procedures' effects on metabolism in diabetes animal models and diabetes patients. It is high time to conclude all this effects and recommend procedures that can better improve metabolism.

The Role of Copper-Induced M2 Macrophage Polarization in Protecting Cartilage Matrix in Osteoarthritis.

BACKGROUND The pathological mechanism of osteoarthritis is still unclear. The regulation of the immune microenvironment has been of growing interest in the progression and treatment of osteoarthritis. Macrophages with different phenotypes, producing different cytokines, have been linked to the mechanism of cartilage injury in osteoarthritis. Copper ions play a role in the immune response and are involved in the pathological mechanisms of osteoarthritis by affecting the metabolism of the cartilage matrix. Bioactive glass (BG) is an osteogenic material with superior biocompatibility. Here, we report on the regulatory behavior of macrophages using a copper-based composite BG material. MATERIAL AND METHODS Cu-BGC powder was prepared by sol-gel method, and scaffolds were fabricated and characterized using 3D printing. Macrophage cultures grown with Cu-BGC were examined for cell culture and proliferation. The effect of Cu-BGC on the degradation metabolism of chondrocytes, cultured in the environment of inflammatory cytokine IL-1ß, was determined. In addition, the morphology of macrophages, secretion of inflammatory cytokines, and expression of surface markers were examined. RESULTS The results show that Cu-BGC promotes macrophage proliferation at a range of concentrations and increases the secretion of anti-inflammatory cytokines while inhibiting proinflammatory cytokines. At the same time, M2-type cell surface markers are definitely expressed and the morphology of macrophages is altered. In addition, Cu-BGC inhibited the degradation metabolism of chondrocytes in the inflammatory environment induced by IL-1ß. CONCLUSIONS These results suggest that Cu-BGC induced macrophage polarization into an M2 type anti-inflammatory phenotype, and inhibition of immune injury response may play a role in delaying cartilage matrix damage in osteoarthritis.

Application of the magnetic resonance 3D multiecho Dixon sequence for quantifying hepatic iron overload and steatosis in patients with thalassemia.

OBJECTIVE: To investigate the feasibility and diagnostic efficacy of a 3D multiecho Dixon (qDixon) research application for simultaneously quantifying the liver iron concentration (LIC) and steatosis in thalassemia patients. MATERIALS AND METHODS: This prospective study enrolled participants with thalassemia who underwent 3 T MRI of the liver for the evaluation of hepatic iron overload. The imaging protocol including qDixon and conventional T2* mapping based on 2D multiecho gradient echo (ME GRE) sequences respectively. Regions of interest (ROIs) were drawn in the liver on the qDixon maps to obtain R2* and proton density fat fraction (PDFF). The reference R2* value was measured and calculated on conventional T2* mapping using the CMRtools software. Correlation analysis, Linear regression analysis, and Bland-Altman analysis were performed. RESULTS: 84 patients were finally included in this study. The median R2*-ME-GRE was 366.97 (1/s), range [206.68 (1/s), 522.20 (1/s)]. 8 patients had normal hepatic iron deposition, 16 had Insignificant, 42 had mild, 18 had moderate. The median of R2*-qDixon was 376.88 (1/s) [219.33 (1/s), 491.75 (1/s)]. A strong correlation was found between the liver R2*-qDixon and the R2*-ME-GRE (r = 0.959, P < 0.001). The median value of PDFF was 1.76% (1.10%, 2.95%). 8 patients had mild fatty liver, and 1 had severe fatty liver. CONCLUSION: MR qDixon research sequence can rapidly and accurately quantify liver iron overload, that highly consistent with the measured via conventional GRE sequence, and it can also simultaneously detect hepatic steatosis, this has great potential for clinical evaluation of thalassemia patients.

Model-based simulation of glycaemic effect and body weight loss when switching from semaglutide or dulaglutide to once weekly tirzepatide.

OBJECTIVE: To evaluate the efficacy endpoints of HbA1c and body weight loss after switching from the GLP-1 receptor agonists, semaglutide or dulaglutide, to treatment with the GIP/GLP-1 receptor agonist (RA) tirzepatide. METHODS: Models were developed and validated to describe the HbA1c and weight loss time course for semaglutide (SUSTAIN 1-10), dulaglutide (AWARD-11) and tirzepatide (SURPASS 1-5, phase 3 global T2D program). The impact of switching from once weekly GLP-1 RAs to tirzepatide was described by simulating the efficacy time course. Semaglutide and dulaglutide doses were escalated in accordance with their respective labels. RESULTS: Model-predicted mean decreases from baseline in HbA1c and body weight for semaglutide 0.5 mg, 1 mg, and 2 mg were 1.22 to 1.79% and 3.62 to 6.87 kg respectively, at Week 26. Model-predicted mean decreases from baseline in HbA1c and body weight for dulaglutide 1.5 mg, 3 mg and 4.5 mg were 1.53 to 1.84% and 2.55 to 3.71 kg respectively, at Week 26. After switching to tirzepatide 5, 10 and 15 mg HbA1c reductions were predicted to range between 1.95 to 2.46% and body weight reductions between 6.50 to 12.1 kg by Week 66. CONCLUSION: In this model-based simulation, switching from approved maintenance doses of semaglutide or dulaglutide to tirzepatide, even at the lowest approved maintenance dose of 5 mg, showed the potential to further improve HbA1c and body weight reductions.

Type 2 diabetes is a disease of elevated blood sugar levels. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a type of medication used to treat type 2 diabetes that work on GLP-1 receptors in the body. Semaglutide and dulaglutide are examples of GLP-1 RAs, which lower blood sugar and body weight. Tirzepatide is a newer medication, which works on both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors. It reduces blood sugar and body weight in people living with type 2 diabetes. Healthcare professionals and patients are interested in how switching medication from semaglutide or dulaglutide to tirzepatide might change blood glucose levels and body weight. However, because tirzepatide is a newer medication, there is not much information available on this aspect. Data from clinical trials of these medications were used to predict the effects of switching from semaglutide or dulaglutide to tirzepatide. These model-based simulations showed that switching to tirzepatide may further reduce HbA1c (a measure of blood sugar) and body weight. This may provide useful information to healthcare professionals and patients when making decisions about treatment with these medications.

Oncological features and prognosis of colorectal cancer in human immunodeficiency virus-positive patients: A retrospective study.

BACKGROUND: Due to the prolonged life expectancy and increased risk of colorectal cancer (CRC) among patients with human immunodeficiency virus (HIV) infection, the prognosis and pathological features of CRC in HIV-positive patients require examination. AIM: To compare the differences in oncological features, surgical safety, and prognosis between patients with and without HIV infection who have CRC at the same tumor stage and site. METHODS: In this retrospective study, we collected data from HIV-positive and -negative patients who underwent radical resection for CRC. Using random stratified sampling, 24 HIV-positive and 363 HIV-negative patients with colorectal adenocarcinoma after radical resection were selected. Using propensity score matching, we selected 72 patients, matched 1:2 (HIV-positive:negative = 24:48). Differences in basic characteristics, HIV acquisition, perioperative serological indicators, surgical safety, oncological features, and long-term prognosis were compared between the two groups. RESULTS: Fewer patients with HIV infection underwent chemotherapy compared to patients without. HIV-positive patients had fewer preoperative and postoperative leukocytes, fewer preoperative lymphocytes, lower carcinoembryonic antigen levels, more intraoperative blood loss, more metastatic lymph nodes, higher node stage, higher tumor node metastasis stage, shorter overall survival, and shorter progression-free survival compared to patients who were HIV-negative. CONCLUSION: Compared with CRC patients who are HIV-negative, patients with HIV infection have more metastatic lymph nodes and worse long-term survival after surgery. Standard treatment options for HIV-positive patients with CRC should be explored.

3D-printed antibiotic-loaded bone cement spacers as adjunctive therapy for hip periprosthetic infection after arthroplasty: A clinical assessment.

OBJECTIVE: To explore the effect of three-dimensional (3D) printing to create personalized antibiotic-loaded bone cement (ALBC) spacers to assist in treatment of periprosthetic infection after total hip arthroplasty (THA). METHODS: The data of 40 patients with postoperative infection after THA were analysed retrospectively. The patients were divided into two groups: the 3D-printing group (age 47-78 years, n = 20) and the conventional group (age 57-78 years, n = 20). In stage I surgery, 3D-printed silicone moulds were used to create ALBC spacers for the 3D-printing group, while traditional manual methods were used to create spacers for the conventional group. After the infection was controlled, both groups underwent conventional hip revision surgery (stage II surgery). All patients were evaluated using the Harris Hip Score (HHS) (primary outcome) for hip function. RESULTS: All 40 patients had follow-up data from 3 months after stage I surgery and 12 months after stage II surgery. The intergroup difference in HHS was 11.25 points [97.5% confidence interval (CI) 7.92-14.58; P < 0.01] at 3 months after stage I surgery, and 9.15 points (97.5% CI 4.82-13.48; P < 0.01) at 12 months after stage II surgery. The overall difference between the two groups was 9.55 points (97.5% CI 5.83-13.27; P < 0.01), which was significant (P < 0.05). CONCLUSION: During the follow-up period, the hip function of the 3D-printing group was superior to that of the conventional group following the treatment of infections after THA.

Icariin inhibits osteoblast ferroptosis via Nrf2/HO-1 signaling and enhances healing of osteoporotic fractures.

The incidence of osteoporotic fractures is increasing every year because of population aging around the world. The reduced osteoblast activity in osteoporotic fracture has been associated with ferroptosis. A recent study showed that the antioxidant icariin (ICA) reduced iron deposition in the bone marrow of osteoporotic mice, although the underlying regulatory mechanisms were not explored. The objective of present study was to assess the therapeutic effects of ICA in a rat osteoporotic fracture model, with particular focus on its impact on ferroptosis. Primary rat osteoblasts were exposed to the ferroptosis inducer erastin, and then treated with ICA or the ferroptosis inhibitor ferrostatin-1 (Fer-1) as the positive control group. The levels of Nrf2 signaling factors and osteogenesis-related factors were examined by RT-PCR and western blotting. An osteoporotic fracture model was established in rats, and the effect of ICA on bone formation was evaluated by X-ray, Micro CT analysis, histological examination and Safranin O staining. Furthermore, the levels of GPX4, Bax, Nrf2 and Runx2 proteins at the fracture site were examined by immunohistochemistry. ICA significantly reduced ROS levels in the erastin-treated osteoblasts, and downregulated glutathione peroxidase 4 (GPX4) and cystine glutamate antiporter (SLC7A11). Moreover, ICA also upregulated Nrf2, NQO-1, HO-1, Runx2, ALP, OPG and OCN in these cells, which was reversed by inhibitors of the Nrf2 signaling pathway and Nrf2 silencing. X-ray and Micro CT analysis showed that ICA increased the trabecular bone and promoted callus formation in the osteoporotic fracture model, and also enhanced the transition from fibrous to osseous callus. Furthermore, ICA upregulated GPX4, Nrf2 and Runx2 at the fracture site, and significantly reduced the expression of the apoptotic genes of Bax. Taken together, our findings indicate that ICA promotes osteoporotic fracture healing by inhibiting osteoblast ferroptosis via activation of the antioxidant Nrf2/HO-1 signaling pathway.

Immunogenicity and protective efficacy of recombinant adenovirus expressing a novel genotype G2b PEDV spike protein in protecting newborn piglets against PEDV.

IMPORTANCE: Porcine epidemic diarrhea (PED) is a highly infectious and economically significant gastrointestinal disorder that affects pigs of all ages. Preventing and controlling PED is achieved by immunizing sows with vaccines, enabling passive piglet immunization via colostrum. The prevalence of G2b porcine epidemic diarrhea virus (PEDV) continues in China despite the use of commercial vaccines, raising questions regarding current vaccine efficacy and the need for novel vaccine development. Adenovirus serotype 5 (Ad5) has several advantages, including high transduction efficiency, a wide range of host cells, and the ability to infect cells at various stages. In this study, we expressed the immunogenic proteins of spike (S) using an Ad5 vector and generated a PED vaccine candidate by inducing significant humoral immunity. The rAd5-PEDV-S prevented PED-induced weight loss, diarrhea, and intestinal damage in piglets. This novel vaccine candidate strain possesses the potential for use in the pig breeding industry.

Practical Applications of a Nausea and Vomiting Model in the Clinical Development of Additional Doses of Dulaglutide.

Dulaglutide 3.0 and 4.5 mg weekly doses were approved for additional glycemic control in adult patients with type 2 diabetes inadequately controlled with metformin and 0.75 or 1.5 mg weekly doses of dulaglutide. Effects such as nausea and vomiting are commonly reported with dulaglutide and other glucagon-like peptide-1 receptor agonist therapies. Based on a pharmacokinetic/pharmacodynamic model-informed approach, a stepwise dose-escalation scheme with 4-week intervals between dose increments was suggested to mitigate gastrointestinal events for dulaglutide. These gastrointestinal events are dose dependent and attenuate over time with repeated dosing. A Markov chain Monte Carlo pharmacokinetic/pharmacodynamic joint model was developed using AWARD-11 data (N = 1842) to optimize dulaglutide dose escalation to 3.0 and 4.5 mg to mitigate gastrointestinal events. Model simulations evaluated probabilities of nausea and vomiting events for various dosing scenarios in patients needing higher doses for additional glycemic control. The model indicated that patients may dose escalate from 1.5 to 3.0 mg, then 4.5 mg weekly after at least 4 weeks on each dose. No clinically meaningful differences in nausea or vomiting events were expected when patients escalated to 3.0 or 4.5 mg following initiation at 0.75 or 1.5 mg dulaglutide. Based on the findings of this model, a minimum 4-week duration at each dose before escalation was appropriate to reduce gastrointestinal events of dulaglutide, consistent with observed gastrointestinal events data from the AWARD-11 study and supporting the currently recommended dose-escalation regimen of dulaglutide doses of 3.0 and 4.5 mg for additional glycemic control.

Targeted transcriptional upregulation of SENP1 by CRISPR activation enhances deSUMOylation pathways to elicit antinociception in the spinal nerve ligation model of neuropathic pain.

ABSTRACT: The voltage-gated sodium channel Na V 1.7 is an essential component of human pain signaling. Changes in Na V 1.7 trafficking are considered critical in the development of neuropathic pain. SUMOylation of collapsin response mediator protein 2 (CRMP2) regulates the membrane trafficking and function of Na V 1.7. Enhanced CRMP2 SUMOylation in neuropathic pain correlates with increased Na V 1.7 activity. Pharmacological and genetic interventions that interfere with CRMP2 SUMOylation in rodents with neuropathic pain have been shown to reverse mechanical allodynia. Sentrin or SUMO-specific proteases (SENPs) are vital for balancing SUMOylation and deSUMOylation of substrates. Overexpression of SENP1 and/or SENP2 in CRMP2-expressing cells results in increased deSUMOylation and decreased membrane expression and currents of Na V 1.7. Although SENP1 is present in the spinal cord and dorsal root ganglia, its role in regulating Na V 1.7 function and pain is not known. We hypothesized that favoring SENP1 expression can enhance CRMP2 deSUMOylation to modulate Na V 1.7 channels. In this study, we used a clustered regularly interspaced short palindromic repeats activation (CRISPRa) SENP1 lentivirus to overexpress SENP1 in dorsal root ganglia neurons. We found that SENP1 lentivirus reduced CRMP2 SUMOylation, Na V 1.7-CRMP2 interaction, and Na V 1.7 membrane expression. SENP1 overexpression decreased Na V 1.7 currents through clathrin-mediated endocytosis, directly linked to CRMP2 deSUMOylation. Moreover, enhancing SENP1 expression did not affect the activity of TRPV1 channels or voltage-gated calcium and potassium channels. Intrathecal injection of CRISPRa SENP1 lentivirus reversed mechanical allodynia in male and female rats with spinal nerve injury. These results provide evidence that the pain-regulating effects of SENP1 overexpression involve, in part, the modulation of Na V 1.7 channels through the indirect mechanism of CRMP2 deSUMOylation.

Circular RNAs in glioma: Molecular functions and pathological implications.

Circular RNAs (circRNAs) are a special class of non-coding RNAs with the ring structure. They are stable, abundant and conservative across mammals. The biogenesis and molecular properties of circRNAs are being elucidated, which exert regulatory functions not only through miRNA and protein sponge, but also via translation and exosomal interaction. Accumulating studies have demonstrated that circRNAs are aberrantly expressed in various diseases, especially in cancer. Glioma is one of the most common malignant cerebral neoplasms with poor prognosis. The accurate diagnosis and effective therapies of glioma have always been challenged, there is an urgent need for developing promising therapeutic intervention. Therefore, exploring novel biomarkers is crucial for diagnosis, treatment and prognosis of the glioma which can provide better assistance in guiding treatment. Recent findings found that circRNAs are systematically altered in glioma and may play critical roles in glioma tumorigenesis, proliferation, invasion and metastasis. Due to their distinct functional properties, they are considered as the potential therapeutic targets, diagnostic and prognostic biomarkers. This review elaborates on current advances towards the biogenesis, translation and interaction of circRNAs in many diseases and focused on the role of their involvement in glioma progression, highlighting the potential value of circRNAs in glioma.

Magnetic resonance imaging assessment of the changes of cardiac and hepatic iron load in thalassemia patients before and after hematopoietic stem cell transplantation.

To investigate the value of T2* technique on 3.0 T magnetic resonance imaging (MRI) in evaluating the changes of cardiac and hepatic iron load before and after hematopoietic stem cell transplantation (HSCT) in patients with thalassemia (TM), the 141 TM patients were divided into 6 group for subgroup analysis: 6, 12, 18, 24 and > 24 months group, according to the postoperative interval. The T2* values of heart and liver (H-T2*, L-T2*) were quantified in TM patients before and after HSCT using 3.0 T MRI T2* technology, and the corresponding serum ferritin (SF) was collected at the same time, and the changes of the three before and after HSCT were compared. The overall H-T2* (P = 0.001) and L-T2* (P = 0.041) of patients after HSCT were higher than those before HSCT (mean relative changes = 19.63%, 7.19%). The H-T2* (P < 0.001) and L-T2* (P < 0.001) > 24 months after HSCT were significantly higher than those before HSCT (mean relative changes = 69.19%, 93.73%). The SF of 6 months (P < 0.001), 12 months (P = 0.008), 18 months (P = 0.002) and > 24 months (P = 0.001) were significantly higher than those before HSCT (mean relative changes = 57.93%, 73.84%, 128.51%, 85.47%). There was no significant improvement in cardiac and liver iron content in TM patients within 24 months after HSCT, while the reduction of cardiac and liver iron content in patients is obvious when > 24 months after HSCT.

Fasting blood glucose predicts high risk of in-stent restenosis in patients undergoing primary percutaneous coronary intervention: a cohort study.

Objectives. Studies have shown that fasting blood glucose (FBG) is closely associated with poor prognosis in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI), but its association with in-stent restenosis (ISR) is still unclear. Therefore, this study was to explore the association between FBG with ISR in patients with CHD after PCI. Design. In this cohort study, we included 531 patients with CHD who underwent PCI. Logistic regression, receiver operating characteristic (ROC), subgroup analysis and restricted cubic spline (RCS) were used to assess the association between FBG with ISR. Results. A total of 124 (23.4%) patients had ISR. Patients with higher levels of FBG had higher incidence of ISR compared to those with lower levels of FBG (p = 0.002). In multivariable logistic regression analyses, higher levels of FBG remained strongly associated with higher risk of ISR (as a categorical variable, OR: 1.89, 95% CI: 1.21-2.94, p = 0.005; as a continuous variable, OR: 1.12, 95% CI: 1.03-1.23, p = 0.011). ROC analysis also showed that FBG might be associated with the occurrence of ISR (AUC = 0.577, 95% CI: 0.52-0.64, p = 0.013). Subgroup analyses showed the association of FBG with ISR was also stable in several subgroups (< 60 years or ≥ 60 years, male, with or without smoking, without diabetes and without hypertension). And RCS analysis showed that FBG was linearly and positively associated with the risk of ISR. Conclusions. Higher levels of FBG were closely associated with higher risk of ISR in patients with CHD after PCI.

Adjuvant Radiotherapy Is Not Necessary for Stage III Mucinous Rectal Cancer: Evidence Based on Long Survival Analysis from SEER Data.

BACKGROUND: Although rectal mucinous adenocarcinoma (RMC) is less sensitive to radiotherapy, adjuvant radiotherapy is still recommended for RMC patients. This study aimed to explore whether adjuvant radiotherapy is necessary for stage III RMC. METHODS: Data of patients with stage III RMC were obtained from the National Cancer Institute's SEER database (2004-2015). The survival rates were calculated by Kaplan-Meier method and compared by log-rank test. Univariate and multivariate Cox regression analyses were used to assess the impact of clinicopathological parameters on overall survival (OS) and cancer-specific survival (CSS). RESULTS: RMC has a worse T and N stage at diagnosis than rectal adenomatous carcinoma (RAC) (all p < 0.001). Multivariate Cox regression analyses revealed that histopathological type MC was an independent poor prognostic factor for OS (HR 1.27; 95%CI 1.14-1.41; p < 0.001) and CSS (HR 1.34; 95%CI 1.18-1.51; p < 0.001). Subgroup analysis based on different treatment regimens showed no significant difference between chemotherapy group and chemotherapy plus radiotherapy group. After the propensity score matching, no significant difference was also found in OS and CSS between chemotherapy group and chemotherapy plus radiotherapy group. CONCLUSIONS: RMC is an independent poor prognostic factor for OS and CSS. Adjuvant radiotherapy for RMC was not beneficial in improving survival outcomes.

Effects of suspended particles and dispersants on marine oil snow formation of crude oil/diesel oil.

Marine oil snow (MOS) potentially forms after an oil spill. To fully understand the mechanism of its formation, we investigated the effects of suspended particles (SP) and dispersants on MOS formation of crude oil and diesel oil by laboratory experiments. In the crude oil experiment, the SP concentration of 0.2 g L-1 was more suitable for crude oil MOS formation. The addition of dispersants significantly stimulated N and TV during MS/MOS formation of SP at 0.4 g L-1 and 0.8 g L-1 concentration (p < 0.05). Without SP, the dispersants also stimulated crude oil MOS formation. Furthermore, the concentration of SP had a significantly positive effect on the reduction of the total amount of N-alkanes (p < 0.05). In the diesel oil experiment, after adding dispersants to diesel oil, the maximum N, Dm, and TV values at a SP concentration of 0.2 g L-1 were significantly higher than those at 0.4 g L-1 and 0.8 g L-1 (p < 0.05). Besides, we found that dispersants stimulated MOS formation in diesel oil at a SP concentration of 0.2 g L-1. However, the dispersants had an inhibitory effect on diesel oil MOS formation without SP. Notably, the MOS formed by diesel oil appeared white, unlike the black MOS associated with crude oil. These findings are important for the environmental impact of oil spills and elevated SP concentrations.