Contralateral approach using microscope and tubular retractor system for ipsilateral decompression of lumbar degenerative lateral recess stenosis associated with narrow spinal canal.

Objective: To summarize the clinical effect of a single-center retrospective analysis of the contralateral approach with a microscope and tubular retractor system for ipsilateral decompression in patients with lumbar lateral recess stenosis and a narrow spinal canal. Methods: A total of 25 patients who underwent ipsilateral decompression surgery via a contralateral approach with microscope and tubular retractor system, performed by one surgeon at a single center were retrospectively examined. The width of the lamina fenestration was compared with the preoperative distance from the root of the spinous process to the dorsal articular facet, the bilateral articular facet change in the suprapedicle notch section on CT scan, and with the changes in transverse and sagittal diameters of the canal area on MRI. Clinical efficacy was assessed using the Japanese Orthopedic Association (JOA), Visual Analog Scale (VAS), and Oswestry Disability Index (ODI) scores. Results: In total, 25 patients were treated and the mean intraoperative time was 82.04 ± 12.48 min. There was no nerve injury, cerebrospinal fluid leakage, and infection complications. The postoperative CT revealed that the width of the contralateral laminar fenestration was less than the distance from the root of the spinous process to the dorsal articular facet. The residual widths of the ipsilateral articular facet and contralateral articular facet were greater than 2/3 of the preoperative articular facet width. The transverse and sagittal diameter of canal were significantly increased. The mean follow-up period was 12-16 months, and no recurrence or reoperation incidence were found at the last follow-up. When compared to pre-surgery, the ODI, VAS, and JOA scores were significantly improved after surgery (p < 0.05). Conclusion: Based on our single-center retrospective observation of 25 cases and combined with previous literature, the contralateral approach with a microscope and tubular retractor system for ipsilateral decompression in patients with lumbar lateral recess stenosis and a narrow spinal canal can reduce damage to the articular processes, and probably more conducive to the postoperative stability of the lumbar spine. This was a single center retrospective analysis with a small sample size and lacked randomized controlled trials (RCTs). However, larger-scale, multicenter RTCs are required for additional validation.

Neutrophil Targeting Platform Reduces Neutrophil Extracellular Traps for Improved Traumatic Brain Injury and Stroke Theranostics.

Traumatic brain injuries (TBI) and stroke are major causes of morbidity and mortality in both developing and developed countries. The complex and heterogeneous pathophysiology of TBI and cerebral ischemia-reperfusion injury (CIRI), in addition to the blood-brain barrier (BBB) resistance, is a major barrier to the advancement of diagnostics and therapeutics. Clinical data showed that the severity of TBI and stroke is positively correlated with the number of neutrophils in peripheral blood and brain injury sites. Furthermore, neutrophil extracellular traps (NETs) released by neutrophils correlate with worse TBI and stroke outcomes by impairing revascularization and vascular remodeling. Therefore, targeting neutrophils to deliver NETs inhibitors to brain injury sites and reduce the formation of NETs can be an optimal strategy for TBI and stroke therapy. Herein, the study designs and synthesizes a reactive oxygen species (ROS)-responsive neutrophil-targeting delivery system loaded with peptidyl arginine deiminase 4 (PAD4) inhibitor, GSK484, to prevent the formation of NETs in brain injury sites, which significantly inhibited neuroinflammation and improved neurological deficits, and improved the survival rate of TBI and CIRI. This strategy may provide a groundwork for the development of targeted theranostics of TBI and stroke.

B cell memory: from generation to reactivation: a multipronged defense wall against pathogens.

Development of B cell memory is a conundrum that scientists are still exploring. Studies have been conducted in vitro and using advanced animal models to elucidate the mechanism underlying the generation of memory B cells (MBCs), the precise roles of MBCs against pathogens, and their protective functions against repeated infections throughout life. Lifelong immunity against invading diseases is mainly the result of overcoming a single infection. This protection is largely mediated by the two main components of B cell memory-MBCs and long-lived plasma cells (PCs). The chemical and cellular mechanisms that encourage fat selection for MBCs or long-lived PCs are an area of active research. Despite the fact that nearly all available vaccinations rely on the capacity to elicit B-cell memory, we have yet to develop successful vaccines that can induce broad-scale protective MBCs against some of the deadliest diseases, including malaria and AIDS. A deeper understanding of the specific cellular and molecular pathways that govern the generation, function, and reactivation of MBCs is critical for overcoming the challenges associated with vaccine development. Here, we reviewed literature on the development of MBCs and their reactivation, interaction with other cell types, strategies against invading pathogens, and function throughout life and discussed the recent advances regarding the key signals and transcription factors which regulate B cell memory and their relevance to the quest for vaccine development.

Hesperetin promotes bladder cancer cells death via the PI3K/AKT pathway by network pharmacology and molecular docking.

Patients with bladder cancer (BLCA) still show high recurrence after surgery and chemotherapy. Hesperetin (HE), as a natural compound, has attracted researchers' attention due to its low toxicity and easy access. However, the inhibitory effect of HE on BLCA remains unknown. The hub genes and enrichment pathways regulated by HE in the treatment of BLCA were predicted by network pharmacology. The molecular docking of HE and hub proteins was visualized. Colony and CCK8 assays were used to test cell proliferation, and BLCA migration was confirmed by transwell and wound healing assays. In addition, the occurrence of apoptosis and ferroptosis was demonstrated by Hoechst staining, transmission electron microscopy (TEM) and ROS (reactive oxygen species) assay. Western Blotting was performed to validate the hub proteins, target functions and pathways. SRC, PIK3R1 and MAPK1 were identified as hub targets for HE in BLCA, involving the PI3k/AKT pathway. Furthermore, HE inhibited the proliferation and migration of BLCA cells. The MMP2/MMP9 proteins were significantly inhibited by HE. The increased expression of Bax and cleaved caspase-3 indicated that HE could promote BLCA cell apoptosis. In addition, Hoechst staining revealed concentrated and illuminated apoptotic nuclei. The activation of ROS and the decline of GPX4 expression suggested that HE might induce ferroptosis as an anti-BLCA process. Shrunk mitochondria and apoptotic bodies were observed in BLCA cells treated with HE, with reduced or absent mitochondrial cristae. We propose for the first time that HE could inhibit the proliferation and migration of BLCA cells and promote apoptosis and ferroptosis. HE may act by targeting proteins such as SRC, PIK3R1 and MAPK1 and the PI3K/AKT pathway.

En Bloc Resection for Spinal Cord Hemangioblastomas: Surgical Technique and Clinical Outcomes.

BACKGROUND: Spinal cord hemangioblastomas are rare benign and highly vascular tumors that develop either sporadically or as part of von Hippel-Lindau (VHL) disease. Generally, complete resection without significant neurologic deficit remains considerably challenging due to the risk of massive bleeding. The current study therefore aimed to describe en bloc resection of spinal cord hemangioblastomas according to the typical anatomical structures of peripheral lesions and evaluate the neurofunctional prognosis of this technique. METHODS: A total of 39 spinal cord hemangioblastomas from a series of 19 patients who underwent en bloc resection were retrospectively analyzed. In all cases, clinical and radiologic characteristics, as well as surgical tenets, were retrospectively determined and analyzed. Short- and long-term outcomes were analyzed using the McCormick grade and Odom's criteria. Factors significantly associated with poor neurologic function after en bloc resection were also determined. RESULTS: All 39 spinal cord hemangioblastomas, including 28 intramedullary, 2 intramedullary-extramedullary, and 9 extramedullary lesions, were located dorsally or dorsolaterally (100.0%). The most common lesion location was the thoracic segment (53.8%), with most of the lesions being accompanied by syringomyelia (94.7%). Long-term follow-up (mean: 103 ± 50.4 months) for prognosis determination revealed that 88.2% (15/17) of all cases had stable or improved neurofunctional outcomes according to the McCormick grade and Odom's criteria. Only one case with VHL disease developed recurrence 4 years after surgery. Additionally, statistical analysis showed that VHL disease was an independent prognostic factor associated with deteriorating neurologic function (p = 0.015). CONCLUSIONS: En bloc resection facilitated satisfactory long-term functional outcomes in patients with spinal cord hemangioblastomas. Given that VHL disease was identified as a predictor of poor long-term outcomes, regular long-term follow-up of patients with VHL-associated spinal cord hemangioblastoma seems necessary.

Ligustrazine Nanoparticle Hitchhiking on Neutrophils for Enhanced Therapy of Cerebral Ischemia-Reperfusion Injury.

Ischemic stroke is a refractory disease that endangers human health and safety owing to cerebral ischemia. Brain ischemia induces a series of inflammatory reactions. Neutrophils migrate from the circulatory system to the site of cerebral ischemia and accumulate in large numbers at the site of inflammation across the blood-brain barrier. Therefore, hitchhiking on neutrophils to deliver drugs to ischemic brain sites could be an optimal strategy. Since the surface of neutrophils has a formyl peptide receptor (FPR), this work modifies a nanoplatform surface by the peptide cinnamyl-F-(D)L-F-(D)L-F (CFLFLF), which can specifically bind to the FPR receptor. After intravenous injection, the fabricated nanoparticles effectively adhered to the surface of neutrophils in peripheral blood mediated by FPR, thereby hitchhiking with neutrophils to achieve higher accumulation at the inflammatory site of cerebral ischemia. In addition, the nanoparticle shell is composed of a polymer with reactive oxygen species (ROS)-responsive bond breaking and is encased in ligustrazine, a natural product with neuroprotective properties. In conclusion, the strategy of hitching the delivered drugs to neutrophils in this study could improve drug enrichment in the brain, thereby providing a general delivery platform for ischemic stroke or other inflammation-related diseases.

Investigation of macrophage polarization in herniated nucleus pulposus of patients with lumbar intervertebral disc herniation.

Macrophage infiltration and polarization during lumbar intervertebral disc herniation (LDH) have attracted increased attention but their role remains unclear. To explore macrophage polarization in herniated nucleus pulposus (NP) tissue of patients with LDH and investigate the association between cell frequency and different clinical characteristics or symptoms, we conducted a retrospective study by analyzing NP tissue samples from 79 patients. Clinical features and symptoms, using the visual analog scale (VAS) and Oswestry disability index (ODI), were collected. The macrophage markers CD68, CCR7, CD163, and CD206; pro-inflammatory cytokine TNF-α; and anti-inflammatory factor IL-4 were analyzed by immunohistochemistry. The frequency of polarized macrophages and positivity rate of pro- and anti-inflammatory cytokines showed significant differences in some of clinical characteristics. Specifically, higher CCR7+ and TNF-α + proportions were identified in the high-intensity zone (HIZ) and the type of extrusion and sequestration NP tissue than in non-HIZ and protrude NP tissue. Higher CD206+ and IL-4+ proportion were detected in Modic changes. However, no differences in gender, age, smoking status, Pfirrmann grade, analgesic use, leg pain duration, and segments were found between groups. CD68+ , CCR7+ , and CD206+ cell proportions, and TNF-α and IL-4 showed positive associations with VAS scores preoperation. Associations between ODI and the macrophages markers were weak/insignificant. Our results indicated that macrophage polarization or macrophage-like cells contribute to LDH pathological features. Macrophage populations displaying significant associations with VAS score reflected continuous M1/M2 transition contributing to pain during LDH. These findings may contribute to enhanced/personalized pharmacological interventions for patients with LDH considering pain heterogeneity.

Intracranial hemorrhage after spinal surgery: a literature review.

Background and Objective: Intracranial hemorrhage following spinal surgery is an infrequent but severe complication. Due to its rarity, the etiology, clinical characteristics, and treatment have not yet been fully elucidated. This literature review analyzed the incidence, clinical manifestations, hemorrhage location, current therapeutic strategies, location of operation, and interval time between surgery and bleeding. The objectives of the article were to provide insights for clinicians to promptly identify and prevent potential cases of intracranial hemorrhage. Methods: The authors queried PubMed and Web of Science databases using predefined keywords and included published literature reporting on intracranial hemorrhage after spinal surgery. Relevant case reports, case series, and reviews describing the mechanism of intracranial hemorrhage after spinal surgery and meeting diagnostic criteria for intracranial hemorrhage related to spinal surgery were included. Clinico-demographc data, presentations symptoms, location, index surgery type, and neurological outcomes after brain hemorrhage. Oxford Centre Level of Evidence guidelines was used to evaluate the quality of included studies. Descriptive statistics were used to synthesize the results. Key Content and Findings: A total of 80 publications of level of evidence IV involving 108 patients with median age at diagnosis was 58.5 years (inter-quartile range: 6-85) were analyzed. The incidence of intracranial hemorrhage was 0.08-0.37% among patients who underwent spinal surgery, and this complication occurred predominantly within 48 hours postoperatively. The initial presentation included headache, reduced level of consciousness, dysarthria, nausea, vomiting, hearing loss, blurred vision, neck rigidity, and delayed recovery from anesthesia. More than half (58.3%) of patients improved, while 23.1% still experienced neurological dysfunctions, and 7.4% died. Conclusions: The present study is limited by the levels of evidence of the included studies. There is heterogeneity among cases with respect to patient demographics and medical history. Angiography is critical in assessing the presence and extent of underlying vascular diseases. Intracranial hemorrages may be caused by intraoperative or postoperative cerebrospinal fluid leakage that will lead to intracranial pressure change and induced by intracranial venous or arterial bleeding. The treatment strategies include conservative medical management and surgical treatment. Individualized treatment should be emphasized.

A smart nanoplatform for enhanced photo-ferrotherapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Emerging therapies, such as ferroptosis mediated cancer therapy and phototherapy, offer new opportunities for HCC treatment. The combination of multiple treatments is often more effective than monotherapy, but many of the current treatments are prone to serious side effects, resulting in a serious decline in patients' quality of life. Therefore, the combination therapy of tumor in situ controllable activation will improve the efficacy and reduce side effects for precise treatment of tumor. Herein, we synthesized a GSH-activatable nanomedicine to synergize photothermal therapy (PTT) and ferrotherapy. We utilized a near-infrared dye SQ890 as both an iron-chelating and a photothermal converter agent, which was encapsulated with a GSH-sensitive polymer (PLGA-SS-mPEG), to attain the biocompatible SQ890@Fe nanoparticles (NPs). In the tumor microenvironment (TME), SQ890@Fe NPs showed a GSH-activated photothermal effect that could increase the Fenton reaction rate. Meanwhile, the depletion of GSH could further increase ferroptosis effect. In turn, the increasing radical generated by ferrotherapy could impair the formation of heat shock proteins (HSPs) which could amplify PTT effects by limiting the self-protection mechanism. Overall, the intelligent nanomedicine SQ890@Fe NPs combines ferrotherapy and PTT to enhance the efficacy and safety of cancer treatment through the mutual promotion of the two treatment mechanisms, providing a new dimension for tumor combination therapy.

Research progress on the mechanism of action of hesperetin in cerebral ischemia: a narrative review.

Background and Objective: Ischemic cerebrovascular disease is one of the main diseases threatening human health and survival and is a commonly occurring disease in neurology. Due to its high disability rate, ischemic cerebrovascular disease is one of the most important diseases to be prevented and treated at present. The risk factors of cerebral ischemia include atherosclerosis, hypertension, hyperlipidemia, and blood viscosity caused by thrombocytosis. After cerebral ischemia, cerebral ischemia-reperfusion injury may be induced by oxidative stress (OS), inflammatory reaction, nitric oxide damage, apoptosis, excitatory amino acid toxicity, calcium (Ca2+) overload, and other mechanisms. Hesperidin is a flavanone compound and is a key component in citrus plants. It is a kind of traditional Chinese medicine extract with high levels of Pericarpium, shell, fruit, and green peel. In recent years, Hesperidin has received great attention, compelling evidence has indicated Hesperidin plays a beneficial role in cerebral ischemia. Methods: We conducted a literature search for published manuscripts hesperidin in ischemia/reperfusion up to December 2021 in common English databases (i.e., PubMed, EMBASE, Web of Science, SpringerLink, Wiley, Cochrane Library) and Chinese databases [Chinese BioMedical Literature Service System (CBM), WANFANG database, China Knowledge Resource Integrated Database (CNKI)]. Key Content and Findings: In this article, we reviewed the mechanisms of action of hesperidin in the treatment of cerebral ischemia, including antioxidant stress, anti-inflammatory reaction, anti-atherosclerosis, anti-thrombosis, anti-apoptosis, and nitric oxide regulation. Conclusions: In this narrative review, Hesperidin exhibits antioxidant stress, anti-platelet aggregation, vasodilation, anti-atherosclerotic, anti-inflammatory, anti-apoptotic, hypolipidemic, anti-tumor, cardiovascular protection, and nitric oxide-release regulatory properties Such a comprehension of the recent progress of hesperidin will help identify biomarkers for diagnosis and therapeutic targets to cerebral ischemia.

Hesperetin ameliorates glioblastoma by inhibiting proliferation, inducing apoptosis, and suppressing metastasis.

Background: Glioblastoma is the most common type of malignant tumor of the brain. Despite substantial improvements in therapy, the 5-year survival rate of patients with glioblastoma remains low. Antitumor drug development has encountered considerable obstacles, which can be attributed to metastasis and the blood-brain barrier (BBB). Hesperetin (HSP), derived from citrus fruits, exhibits several biological properties, including anticancer and anti-inflammatory activities. In addition, in vitro models have shown that HSP can easily cross the BBB. The purpose of the present study was to explore the effects and underlying mechanisms of HSP on glioblastoma cells. Methods: GL261 cell were cultured and treated with different dose HSP. The cell viability was assessed with Cell Counting Kit-8 (CCK-8) assay. The cell apoptosis was determined using an Annexin V/propidine iodide (PI) staining and Hoechst staining and detection assay, cell migration and invasion were observed on GL261 cells using Matrigel-coated Transwells and Wound-Healing assay. The expression of proteins was detected by Western blotting. Results: HSP suppressed cell proliferation and could induce apoptosis, the latter of which might be regulated through the Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and nuclear factor-kappa B (NF-κB) pathways. Furthermore, HSP inhibited cell migration and invasion by downregulating the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9, and inhibited epithelial-mesenchymal transition (EMT) by upregulating the expression of E-cadherin while downregulating N-cadherin and vimentin expression. Conclusions: These findings suggest HSP to be an alternative preventive and therapeutic antiglioblastoma drug that may be especially useful for patients with recurrent glioblastoma.

Analysis of DWI in the classification of glioma pathology and its therapeutic application in clinical surgery: a case-control study.

Background: Glioma is a common primary craniocerebral malignant tumor, due to the lack of specificity of imaging examination and clinical manifestations, its diagnostic accuracy is relatively low, which may result in misdiagnosis and missed diagnosis. The apparent diffusion coefficient (ADC) in magnetic resonance diffusion weighted imaging (DWI) can reflect the histological characteristics of gliomas, which can be widely applied to classify gliomas and evaluate the extent of metastasis of glioma. The present study aimed to assess the clinical value of magnetic resonance DWI in the pathological grading of glioma and its therapeutic application in clinical surgery. Methods: This article retrospectively analyzed the clinical data of 41 patients with glioma confirmed by surgical pathology results from January 1, 2019 to March 31, 2020 in the People's Hospital of Gaozhou. Among them, 16 patients had low-grade gliomas [World Health Organization (WHO) grade I-II] and 25 patients had high-grade gliomas (WHO grade III-IV). They were subjected to conventional T1WI and T2WI plain scans, along with DWI and enhanced scans before surgery. The ADC values of the glioma parenchyma, the peritumoral edema area, the surrounding white matter, and the contralateral normal white matter were measured. We selected some tumor tissues for pathological analysis as well, and conducted pathological grading according to WHO grading standards. Results: We compared and evaluated the ADC values of the observed areas for low-grade gliomas and high-grade gliomas. The ADC values of low-grade gliomas in the tumor parenchyma, peritumoral edema, and white matter around the edema area were significantly lower than those of high-grade gliomas, and the differences were statistically significant (P<0.05). The difference in ADC values of normal white matter between the two groups of patients was not statistically significant (P=0.125). Conclusions: DWI has prognostic predictive value in the preoperative differential diagnosis and pathological classification of gliomas. This advanced technology can verify the extent of glioma infiltration in the surrounding brain tissue. It can help clinicians formulate a safer and more effective therapeutic strategy by providing accurate information on prognostic evaluation before the successful surgical intervention of gliomas.

Dynamic Adjust of Non-Radiative and Radiative Attenuation of AIE Molecules Reinforces NIR-II Imaging Mediated Photothermal Therapy and Immunotherapy.

Due to the aggregation-caused quenching effect and near-infrared I poor penetration capabilities of common fluorescent molecules, their applications in visualized imaging and photoactivated treatment are limited. Therefore, new near-infrared II (NIR-II) molecule (named TST), which had the abilities of aggregation-induced emission (AIE) and photothermal therapy are synthesized. Moreover, in order to further improve its fluorescent yield and therapeutic effect, camptothecin prodrug (CPT-S-PEG) and novel immune checkpoint inhibitor AZD4635 are used to co-assemble with TST into nanoparticles for drug delivery. On account of the strong interaction of camptothecin and TST, the intramolecular rotation of TST is limited, thereby inhibiting non-radiation attenuation and promoting fluorescence generation when the nanoparticles are intact. As nanoparticles uptake by cancer cells, redox sensitive CPT-S-PEG is degraded and the nanoparticles disintegrate. The released TST enhances non-radiative attenuation and expedites photothermal conversion because of the removal of the constraint of camptothecin. Furthermore, photothermal therapy induces immunogenic cell death of cancer cells and releases abundant ATP into the tumor microenvironment to recruit immune cells. However, superfluous ATP is converted into immunosuppressive adenosine through the CD39-CD73-A2AR pathway. The AZD4635 released by photothermal disintegration of the nanoparticles just blocks this pathway timely, achieving favorable synergistic effect of photothermal therapy, chemotherapy, and immunotherapy.

Nanotherapeutics Overcoming the Blood-Brain Barrier for Glioblastoma Treatment.

Glioblastoma (GBM) is the most common malignant primary brain tumor with a poor prognosis. The current standard treatment regimen represented by temozolomide/radiotherapy has an average survival time of 14.6 months, while the 5-year survival rate is still less than 5%. New therapeutics are still highly needed to improve the therapeutic outcome of GBM treatment. The blood-brain barrier (BBB) is the main barrier that prevents therapeutic drugs from reaching the brain. Nanotechnologies that enable drug delivery across the BBB hold great promise for the treatment of GBM. This review summarizes various drug delivery systems used to treat glioma and focuses on their approaches for overcoming the BBB to enhance the accumulation of small molecules, protein and gene drugs, etc. in the brain.

Delivery of Cationic Platinum Prodrugs via Reduction Sensitive Polymer for Improved Chemotherapy.

A cationic monofunctional platinum anticancer drug, phenanthriplatin (PhenPt(II)), exhibits promising anticancer effect on various cancer cell lines. Unlike the conventional platinum(II) drugs, PhenPt(II) is more likely to bind the N7 adenosine base of DNA in situ, and consequently resulting in a unique cellular response profile and unusual potency. However, since this drug is positively charged, it can easily bind to plasma protein that leads to rapid systematic clearance and deleterious toxicities, which greatly limits its in vivo application. Herein, a lipophilic phenanthriplatin (PhenPt(IV)) prodrug is synthesized. To further reduce its toxicity, a negatively charged polymer P1 with reduction responsiveness is assembled with PhenPt(IV) to form PhenPt(IV) NPs. In comparison to cisplatin, PhenPt(IV) NPs exhibit up to 30 times greater in vitro potency against various cancer cell lines. Additionally, in vivo, no obvious side effect is found on PhenPt(IV) NPs. Significant enhancement in tumor accumulation and improvement of drug efficacy in 4T1 tumor model are demonstrated. Taken together, this study provides a promising strategy for the clinical translation of phenanthriplatin.

Research Progress on the Functions and Mechanism of circRNA in Cisplatin Resistance in Tumors.

Cisplatin is a common chemotherapeutic drug that has been used to treat of numerous tumors, including testicular, lung, bladder, ovarian, liver and head and neck cancers. Although clinical chemotherapy based on cisplatin has shown a remarkable therapeutic effect, the resistance to cisplatin becomes increasingly obvious as a patient uses it for a prolonged period. It not only affects the prognosis of these tumors, but also causes the recurrence of cancer and decreases the overall survival rate. The development of cisplatin resistance involves several mechanisms, including DNA damage repair, ATP-binding cassette (ABC) transporter, autophagy, cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), and other related signaling pathways. Interestingly, these mechanisms have been found to be influenced by circular RNAs (circRNAs) to regulate tumor proliferation, invasion, chemosensitivity, and other biological behaviors in the tumor microenvironment (TME). In recent years, circRNAs in cisplatin resistance in tumors, especially lung cancer and gastric cancer, have gradually drawn peoples' attention. This review summarizes recent studies on the functions and mechanisms of circRNAs in cisplatin resistance. We emphasize that circRNA can be used as a promising target gene to improve drug resistance and therapeutic efficacy.

Safety Evaluation and Flow Modification in the Anterior Cerebral Artery after Pipeline Embolization Device Deployment across the Internal Carotid Artery Terminus.

METHOD: The clinical and imaging data of PEDs in the postmarket multicenter registry study (PLUS) in China were retrospectively analyzed, and patients were divided into two groups on the basis of the follow-up angiographic results: group 1 (no significant change in A1 blood flow) and group 2 (A1 occlusion or decreased blood flow). We collected patients' baseline data and evaluated the following imaging indicators: diameter and ratio of bilateral A1, M1, and internal carotid artery (ICA) vessels before stenting and the ratio of the PED size (sPED) to the ipsilateral ICA (I-ICA) diameter on the implantation side. RESULTS: A total of 1171 patients were included, of whom 48 met the inclusion criteria (17 in group 1 and 31 in group 2). In group 2, three patients experienced neurological deterioration at follow-up. From the univariate analysis of outcomes, single PED without coils, incomplete aneurysm occlusion (IAO), maximum aneurysm diameter, aneurysms involving the ICA bifurcation (ICAb), and large sPED/I-ICA diameter ratio were included in the multivariate analysis (P < 0.20). The multivariate regression analysis results showed that the ratio of sPED/I-ICA diameter was the factor influencing A1 vessel occlusion. The area under the ROC curve was 73.2%. When the sPED/I-ICA diameter ratio was 1.14, sensitivity was 70.6%, and specificity was 77.4%. CONCLUSION: When an oversized PED is placed from M1 to the ICA, the higher porosity formed at the covered A1 orifice is conducive to maintaining stable A1 blood flow and reducing the risk of A1 vessel occlusion. This trial is registered with ClinicalTrials.gov identifier: NCT03831672.

Computational numerical analysis of different cannulation methods during cardiopulmonary bypass of type A aortic dissection model based on computational fluid dynamics.

BACKGROUND: The aim of the present study was to use a numerical simulation based on computational fluid dynamics (CFD) to analyze the difference of different cannulation methods on hemodynamics characteristic in a type A aortic dissection (TAAD) model. METHODS: A finite-element analysis based on the CFD model of a TAAD patient was used, and axillary artery cannulation (AAC), innominate artery cannulation (IAC), and femoral artery cannulation (FAC) were analyzed under different situations, including a cardiac output (CO) of 2.5 L/min and cardiopulmonary bypass (CPB) of 2.5 L/min (partial CPB before cross-clamping aorta, defined as condition A), and a CO of 0 L/min and CPB of 5 L/min (aortic cross-clamping phase, defined as condition B). The insertion of an 8-mm cannula into the different models was simulated. Hemodynamic characteristics, including wall shear stress, wall stress, blood flow, and velocity were analyzed. RESULTS: In condition A, the total flow of branches of the aortic arch was 2,009.5 mL/min (AAC), 1,855.47 mL/min (IAC), and 1,648.03 mL/min (FAC). All cannulation methods improved left renal blood perfusion. However, in relation to blood flow in the right renal artery, FAC showed the highest blood flow (105 mL/min). The results in condition B were similar to those of condition A. The velocity, shear stress, and stress of entry tear via AAC and IAC decreased in condition B compared with condition A. The velocity, shear stress, stress of tear via AAC was lower than that of IAC. CONCLUSIONS: Different cannulation modes have an effect on the hemodynamic characteristic of the tear, but this effect is related to different states of CPB. AAC was found to superior to IAC, especially in reducing velocity, stress, and shear stress of site of tear. However, IAC and AAC are more conductive to blood supply than FAC in branch vessels of the aortic arch without being affected by the CPB state.

Engineered Polymer Nanoplatforms for Targeted Tumor Cells and Controlled Release Cargos to Enhance Cancer Treatment.

Cancer is composed of a series of uncontrollable cells, which finally form tumors to negatively impact the functions of the body and induce other serious diseases, even leading to death. During the last decades, scientists have devoted great efforts to study cancer; however, there are no effective diagnoses and treatments. Nanomaterials have attracted great attention in the biomedical field in recent years, which are widely used as optical imaging probes and delivery systems for cancer therapy. Among the numerous nanomaterials, polymeric nanoparticles occupy a prominent position because of their tunable micro-size, multifunctional surface, prominent biocompatibility and high drug-carrying capacity. These significant advantages of polymeric nanomaterials have significance over the traditional nanomaterials and have become a potential therapy for cancer. In this review, we focus on the applications of polymeric nanoparticles in cancer theranostics, especially as the drug delivery systems for cancer treatment. This review provides an overview on the advancement of synthesis, application of polymeric nanoparticles- based drug delivery systems and highlights the evaluation for cancer therapy.