Trametinib boosts palbociclib's efficacy in breast cancer via autophagy inhibition.

Breast cancer, a predominant global health issue, requires ongoing exploration of new therapeutic strategies. Palbociclib (PAL), a well-known cyclin-dependent kinase (CDK) inhibitor, plays a critical role in breast cancer treatment. While its efficacy is recognized, the interplay between PAL and cellular autophagy, particularly in the context of the RAF/MEK/ERK signaling pathway, remains insufficiently explored. This study investigates PAL's inhibitory effects on breast cancer using both in vitro (MCF7 and MDA-MB-468 cells) and in vivo (tumor-bearing nude mice) models. Aimed at elucidating the impact of PAL on autophagic processes and exploring the potential of combining it with trametinib (TRA), an MEK inhibitor, our research seeks to address the challenge of PAL-induced drug resistance. Our findings reveal that PAL significantly decreases the viability of MCF7 and MDA-MB-468 cells and reduces tumor size in mice while showing minimal cytotoxicity in MCF10A cells. However, PAL also induces protective autophagy, potentially leading to drug resistance via the RAF/MEK/ERK pathway activation. Introducing TRA effectively neutralized this autophagy, enhancing PAL's anti-tumor efficacy. A combination of PAL and TRA synergistically reduced cell viability and proliferation, and in vivo studies showed notable tumor size reduction. In conclusion, the PAL and TRA combination emerges as a promising strategy for overcoming PAL-induced resistance, offering a new horizon in breast cancer treatment.

Staged surgical treatment of the giant Pituitary Neuroendocrine Tumors.

OBJECTIVE: To investigate the long-term clinical outcomes of staged surgical resection in giant Pituitary Neuroendocrine Tumors(pitNET).Method We performed a retrospective analysis of the clinical data of 16 patients who underwent surgery. The patients were diagnosed and underwent surgery at the Department of Neurosurgery of Shiyan Taihe Hospital from January 2013 to March 2021. Among the cases, 12 patients underwent primarily transsphenoidal surgery followed by secondary transcranial surgery, while 4 patients underwent primarily transsphenoidal surgery followed by secondary transsphenoidal surgery. Before the surgery, all patients underwent a pituitary MRI scan, pituitary hormone level examination, visual acuity, and visual field examination. A pituitary MRI was rechecked within 1 week after the operation. A tumor resection rate of 100% on MRI was considered as a total resection, between 90% to 100% as a subtotal resection, and lower than 90% as a partial resection. After the surgery, regular clinical visits and telephone or internet platform follow-ups were conducted. Outcome In our clinical investigation, after staged surgery 10 patients had a total resection, 5 had a subtotal resection, and 1 had a partial resection depending on the tumor size and invasion. The clinical outcomes showed that 1 case suffered from postoperative intracranial infection, 1 case had decreased visual acuity, and 6 cases experienced decreased pituitary function after surgery.Postoperative complications were cured after symptomatic treatment, except for 1 patient who experienced decreased vision and 1 patient sufferred hypopituitarism required long-term oral levothyroxine tablet treatment. No cases of intracranial hemorrhage or death were caused by intentionally staged resection surgery. Conclusion Staged surgery for giant pitNET is a safe and effective clinical surgery strategy.

Co-adsorption enhancement of formaldehyde/carbon dioxide over modified hexagonal boron nitride for whole-surface capture purification.

Simultaneous capture of formaldehyde (HCHO) and carbon dioxide (CO2) in indoor air is promising of achieving indoor-air purification. Of all potential adsorbents, hexagonal boron nitride (h-BN) is one of the most suitable species owing to facile formation of attraction points. Therefore, in this study, performances of HCHO and CO2 being adsorbed over pure/modified h-BN are systematically investigated via density functional theory (DFT) calculations. Minutely speaking, direct interaction between HCHO and CO2, single-point adsorption enhancement of HCHO over modified h-BN, co-adsorption reinforcement of HCHO/CO2 as well as relevant thermodynamic characteristics are major research contents. According to calculation results, there is relatively strong attraction between HCHO and CO2 owing to hydrogen bonds, which is in favor of co-adsorption of HCHO/CO2. As to single-adsorption of HCHO, C-doped h-BN shows better adsorption features than P-doped h-BN and C/P-doped h-BN is slightly weakened in adsorption ability due to surficial deformation caused by P atoms. For co-adsorption of HCHO/CO2, CO2 is the protagonist via formation of quasi-carbonate with the help of delocalized π-orbital electrons. Regarding effects of temperatures on adsorption strengths, they depend on interelectronic interactions among dopant atoms and finally derives from dispersion of π bonds across adsorbents. Overall, this study provides detailed mechanisms for co-capture of HCHO/CO2 to accomplish indoor-air purification.

Cimetidine Attenuates Therapeutic Effect of Anti-PD-1 and Anti-PD-L1 and Modulates Tumor Microenvironment in Colon Cancer.

Histamine modulates immunity by binding to histamine receptor 2 (H2R). Cimetidine, an H2R antagonist that inhibits gastric acid secretion and treats gastrointestinal ulcers, interferes with histamine-mediated immunomodulation and may have anticancer activity. This study examined cimetidine's effect on the anticancer effect of anti-PD-L1 in colon cancer. The MTT assay, colony formation assay, and DNA histograms assessed cell viability, clonogenicity, and cell cycle distribution, respectively. Flow cytometry measured H2R and PD-L1 expression and estimated specific immune cell lineages. For the in vivo study, tumor cells were subcutaneously implanted into the right flank of BALB/c mice. Cimetidine had no significant effect on CT26 cell viability, clonogenicity, or cell cycle distribution. It also did not affect H2R and PD-L1 expression levels in CT26 cells. In vivo, anti-PD-1 and anti-PD-L1 suppressed CT26 tumor growth, whereas cimetidine showed mild antitumor activity. In the combined experiment, cimetidine significantly attenuated anti-PD-1 and anti-PD-L1' antitumor effects without major toxicity. In the tumor microenvironment, anti-PD-L1 increased CD3+ T, CD4+ T, and CD8+ T cells and M1 macrophages. Combined treatment with cimetidine reversed this. Cimetidine also reversed anti-PD-1 and anti-PD-L1's decrease in circulating and tumor-associated neutrophils. Cimetidine attenuated anti-PD-L1's antitumor effect and modulated the tumor microenvironment in colon cancer.

Matching Patients to Accelerate Clinical Trials (MPACT): Enabling Technology for Oncology Clinical Trial Workflow.

Clinical trial enrollment is impeded by the significant time burden placed on research coordinators screening eligible patients. With 50,000 new cancer cases every year, the Veterans Health Administration (VHA) has made increased access for Veterans to high-quality clinical trials a priority. To aid in this effort, we worked with research coordinators to build the MPACT (Matching Patients to Accelerate Clinical Trials) platform with a goal of improving efficiency in the screening process. MPACT supports both a trial prescreening workflow and a screening workflow, employing Natural Language Processing and Data Science methods to produce reliable phenotypes of trial eligibility criteria. MPACT also has a functionality to track a patient's eligibility status over time. Qualitative feedback has been promising with users reporting a reduction in time spent on identifying eligible patients.

Impaired cerebral interstitial fluid dynamics in cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy, caused by cysteine-altering variants in NOTCH3, is the most prevalent inherited cerebral small vessel disease. Impaired cerebral interstitial fluid dynamics has been proposed as one of the potential culprits of neurodegeneration and may play a critical role in the initiation and progression of cerebral small vessel disease. In the present study, we aimed to explore the cerebral interstitial fluid dynamics in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy and to evaluate its association with clinical features, imaging biomarkers and disease severity of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy. Eighty-one participants carrying a cysteine-altering variant in NOTCH3, including 44 symptomatic cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy patients and 37 preclinical carriers, and 21 age- and sex-matched healthy control individuals were recruited. All participants underwent brain MRI studies and neuropsychological evaluations. Cerebral interstitial fluid dynamics was investigated by using the non-invasive diffusion tensor image analysis along the perivascular space method. We found that cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy patients exhibited significantly lower values of diffusion tensor image analysis along the perivascular space index comparing to preclinical carriers and healthy controls. For the 81 subjects carrying NOTCH3 variants, older age and presence of hypertension were independently associated with decreased diffusion tensor image analysis along the perivascular space index. The degree of cerebral interstitial fluid dynamics was strongly related to the severity of cerebral small vessel disease imaging markers, with a positive correlation between diffusion tensor image analysis along the perivascular space index and brain parenchymal fraction and negative correlations between diffusion tensor image analysis along the perivascular space index and total volume of white matter hyperintensity, peak width of skeletonized mean diffusivity, lacune numbers and cerebral microbleed counts. In addition, diffusion tensor image analysis along the perivascular space index was a significant risk factor associated with the development of clinical symptoms of stroke or cognitive dysfunction in individuals carrying NOTCH3 variants. In cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy patients, diffusion tensor image analysis along the perivascular space index was significantly associated with Mini-Mental State Examination scores. Mediation analysis showed that compromised cerebral interstitial fluid dynamics was not only directly associated with cognitive dysfunction but also had an indirect effect on cognition by influencing brain atrophy, white matter disruption, lacunar lesions and cerebral microbleeds. In conclusion, cerebral interstitial fluid dynamics is impaired in cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy and its disruption may play an important role in the pathogenesis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy. Diffusion tensor image analysis along the perivascular space index may serve as a biomarker of disease severity for cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy.

Endovascular Management of Post-Irradiated Carotid Blowout Syndrome in Patients with Lower Neck Cancers.

OBJECTIVE: Lower neck cancers (LNCs) include specific tumour types and have some different vascular supply or collaterals from other head and neck cancers. This prospective study evaluated the outcome of endovascular management of post-irradiated carotid blowout syndrome (PCBS) in patients with LNC by comparing reconstructive management (RE) and deconstructive management (DE). METHODS: This was a single centre, prospective cohort study. Patients with LNC complicated by PCBS between 2015 and 2021 were enrolled for RE or DE. RE was performed by stent graft placement covering the pathological lesion and preventive external carotid artery (ECA) embolisation without balloon test occlusion (BTO). DE was performed after successful BTO by permanent coil or adhesive agent embolisation of the internal carotid artery (ICA) and ECA to common carotid artery, or ICA occlusion alone if the pathological lesion was ICA only. Cross occlusion included the proximal and distal ends of the pathological lesion in all patients. Re-bleeding events, haemostatic period, and neurological complications were evaluated. RESULTS: Fifty-nine patients (mean age 58.5 years; 56 male) were enrolled, including 28 patients undergoing RE and 31 patients undergoing DE. Three patients originally grouped to DE were transferred to RE owing to failed BTO. The results of RE vs. DE were as follows: rebleeding events, 13/28 (46%) vs. 10/31 (32%) (p = .27); haemostatic period, 9.4 ± 14.0 months vs. 14.2 ± 27.8 months (p = .59); neurological complication, 4/28 (14%) vs. 5/31 (16%) (p = .84); and survival time, 11.8 ± 14.6 months vs. 15.1 ± 27.5 months (p = .61). CONCLUSION: No difference in rebleeding risk or neurological complications was observed between the DE and RE groups. RE could be used as a potential routine treatment for PCBS in patients with LNC.

Percutaneous transluminal angioplasty and stenting of post-irradiated stenosis of subclavian artery: A matched case-control study.

BACKGROUND: Although radiotherapy is common for head/neck and chest cancers (HNCC), it can result in post-irradiation stenosis of the subclavian artery (PISSA). The efficacy of percutaneous transluminal angioplasty and stenting (PTAS) to treat severe PISSA is not well-clarified. AIMS: To compare the technical safety and outcomes of PTAS between patients with severe PISSA (RT group) and radiation-naïve counterparts (non-RT group). METHODS: During 2000 and 2021, we retrospectively enrolled patients with severe symptomatic stenosis (>60%) of the subclavian artery who underwent PTAS. The rate of new recent vertebrobasilar ischaemic lesions (NRVBIL), diagnosed on diffusion-weight imaging (DWI) within 24 h of postprocedural brain MRI; symptom relief; and long-term stent patency were compared between the two groups. RESULTS: Technical success was achieved in all 61 patients in the two groups. Compared with the non-RT group (44 cases, 44 lesions), the RT group (17 cases, 18 lesions) had longer stenoses (22.1 vs 11.1 mm, P = 0.003), more ulcerative plaques (38.9% vs 9.1%, P = 0.010), and more medial- or distal-segment stenoses (44.4% vs 9.1%, P<0.001). The technical safety and outcome between the non-RT group and the RT group were NRVBIL on DWI of periprocedural brain MRI 30.0% vs 23.1%, P = 0.727; symptom recurrence rate (mean follow-up 67.1 ± 50.0 months) 2.3% vs 11.8%, P = 0.185; and significant in-stent restenosis rate (>50%) 2.3% vs 11.1%, P = 0.200. CONCLUSION: The technical safety and outcome of PTAS for PISSA were not inferior to those of radiation-naïve counterparts. PTAS for PISSA is an effective treatment for medically refractory ischaemic symptoms of HNCC patients with PISSA.

Prostate cancer patient stratification by molecular signatures in the Veterans Precision Oncology Data Commons.

Veterans are at an increased risk for prostate cancer, a disease with extraordinary clinical and molecular heterogeneity, compared with the general population. However, little is known about the underlying molecular heterogeneity within the veteran population and its impact on patient management and treatment. Using clinical and targeted tumor sequencing data from the National Veterans Affairs health system, we conducted a retrospective cohort study on 45 patients with advanced prostate cancer in the Veterans Precision Oncology Data Commons (VPODC), most of whom were metastatic castration-resistant. We characterized the mutational burden in this cohort and conducted unsupervised clustering analysis to stratify patients by molecular alterations. Veterans with prostate cancer exhibited a mutational landscape broadly similar to prior studies, including KMT2A and NOTCH1 mutations associated with neuroendocrine prostate cancer phenotype, previously reported to be enriched in veterans. We also identified several potential novel mutations in PTEN, MSH6, VHL, SMO, and ABL1 Hierarchical clustering analysis revealed two subgroups containing therapeutically targetable molecular features with novel mutational signatures distinct from those reported in the Catalogue of Somatic Mutations in Cancer database. The clustering approach presented in this study can potentially be used to clinically stratify patients based on their distinct mutational profiles and identify actionable somatic mutations for precision oncology.

Research on nonsteady-state adsorption and regulation towards stabler adsorption for benzene over single-wall carbon materials.

With the intention of separating benzene (C6H6) from indoor polluted air and collecting it in a cleaner way, it is promising of getting C6H6 adsorbed on activated carbon materials with outstanding physicochemical properties. In this study, how C6H6 is adsorbed over single-wall carbon materials and relevant adsorption processes are enhanced is thoroughly investigated via density functional theory (DFT). Especially, distinction between partial and whole effects of adsorbents on C6H6 adsorption, features of electron distribution across section of adsorption forms, and regulation mechanism of nonsteady-state adsorption for C6H6 are key points. According to calculation results, C6H6 molecules could be captured by pure single-wall carbon nanotube (CNT) through repulsive forces (quantified as 103.42 kJ/mol) from all quarters, which makes it stay in nonsteady-state adsorption forms and easily run into free state. Therefore, when external temperature increases from 0 to 300 K, molecular movement will be intense enough to help C6H6 break into another random positions instead of statistically remaining immobile. As for this problem, single-wall CNTs are modified through making defects and replacing some C atoms with N atoms, respectively. In this way, surficial electron distribution of modified adsorbents is regulated to tremendously cut down repulsive forces (quantified as 50.30 kJ/mol) and reverse nonsteady-state adsorption into near-equilibrium quasi-steady-state adsorption (single-side attraction near 100 kJ/mol). Therefore, this research would provide useful information for exploiting single-wall carbon materials as effective adsorbents of C6H6 in order to quickly achieve indoor air purification.

Aflatoxin B1-induced early developmental hepatotoxicity in larvae zebrafish.

Aflatoxin B1 (AFB1) is a ubiquitous mycotoxin that causes oxidative damage in various organs. At present, the research studies on AFB1 are primarily focused on its effects on the terrestrial environment and animals. However, its toxicity mechanism in aquatic environments and aquatic animals has not been largely explored. Thus, in this study, zebrafish was used as a model to study the toxicity mechanism of AFB1 on the liver of developing larvae. The results showed that AFB1 exposure inhibited liver development and promoted fat accumulation in the liver. Transcriptome sequencing analysis showed that AFB1 affected liver redox metabolism and oxidoreductase activity. KEGG analysis showed that AFB1 inhibited the expression of gsto1, gpx4a, mgst3a, and idh1 in the glutathione metabolizing enzyme gene pathway, resulting in hepatic oxidative stress. At the same time, AFB1 also inhibited the expression of acox1, acsl1b, pparα, fabp2, and cpt1 genes in peroxidase and PPAR metabolic pathways, inducing hepatic steatosis and lipid droplet accumulation. Antioxidant N-Acetyl-l-cysteine (NAC) preconditioning up-regulated gsto1, gpx4a and idh1 genes, and improved the AFB1-induced lipid droplet accumulation in the liver. In summary, AFB1 induced hepatic oxidative stress and steatosis, resulting in abnormal liver fat metabolism and accumulation of cellular lipid droplets. NAC could be used as a potential preventative drug to improve AFB1-induced fat accumulation.

Length and location of post-PIRCS predict percutaneous transluminal angioplasty and stenting-related restenosis in nasopharyngeal cancer.

PURPOSE: Post-irradiated carotid stenosis (PIRCS) commonly occurs in patients with nasopharyngeal cancer (NPC) after receiving radiotherapy. A high in-stent restenosis (ISR) is observed in these patients after percutaneous transluminal angioplasty and stenting (PTAS) for PIRCS. Risk factors for ISR in these patients remain unclear. METHODS: Data were retrospectively analyzed from 68 NPC patients with 70 lesions treated with PTAS for PIRCS. The median follow-up was 40 months (range: 4-120). Evaluations of demographic and clinical characteristics included stenotic severity, stenotic lesion length (SLL), stenotic lesion location, and ISR-related stroke during follow-up. The risk for ISR was evaluated using multiple Cox regression analysis. RESULTS: The median age of the patients was 61 (35-80) years and 94.1% were male. The median stenosis was 80% (60-99%) and the median SLL was 2.6 cm (0.6-12.0 cm) before PTAS. Compared to those without ISR, patients with longer SLL were at significantly greater risk of developing significant ISR, defined as > 50% after PTAS (hazard ratio [HR] and 95% confidence interval [CI]: 2.06 [1.30-3.28]). PTAS for lesions from the internal carotid artery (ICA) to common carotid artery (CCA) was associated with a significantly greater risk of ISR than lesions located only in the ICA (HR: 9.58 [1.79-51.34]). The baseline cut-off value for SLL that best predicted significant ISR was 1.6 cm (area under the curve 0.700, sensitivity 83.3% and specificity 62.5%). CONCLUSION: Stenotic lesions located from the ICA to CCA with longer SLL at baseline appear to predict ISR in NPC patients with PIRCS after PTAS. Intensive post-procedural follow-up is advised for this patient population.

Clinical and imaging findings for the evaluation of large Rathke's cleft cysts and cystic craniopharyngiomas.

PURPOSE: Large Rathke's cleft cysts (LRCCs) and cystic craniopharyngiomas (CCPs) arise from the same embryological origin and may have similar MR presentations. However, the two tumors have different management strategies and outcomes. This study was designed to evaluate the clinical and imaging findings of LRCCs and CCPs, aiming to evaluate their pretreatment diagnosis and outcomes. METHODS: We retrospectively enrolled 20 patients with LRCCs and 25 patients with CCPs. Both tumors had a maximal diameter of more than 20 mm. We evaluated the patients' clinical and MR imaging findings, including symptoms, management strategies, outcomes, anatomic growth patterns and signal changes. RESULTS: The age of onset for LRCCs versus CCPs was 49.0 ± 16.8 versus 34.2 ± 22.2 years (p = .022); the following outcomes were observed for LRCCs versus CCPs: (1) postoperative diabetes insipidus: 6/20 (30%) versus 17/25 (68%) (p = .006); and (2) posttreatment recurrence: 2/20 (10%) versus 10/25 (40%) (p = .025). The following MR findings were observed for LRCCs versus CCPs: (1) solid component: 7/20 (35%) versus 21/25 (84%) (p = .001); (2) thick cyst wall: 2/20 (10%) versus 12/25 (48%) (p = .009); (3) intracystic septation: 1/20 (5%) versus 8/25 (32%) (p = .030); (4) snowman shape: 18/20 (90%) versus 1/25 (4%) (p < .001); (5) off-midline extension: 0/0 (0%) versus 10/25 (40%) (p = .001); and (6) oblique angle of the sagittal long axis of the tumor: 89.9° versus 107.1° (p = .001). CONCLUSIONS: LRCCs can be differentiated from CCPs based on their clinical and imaging findings, especially their specific anatomical growth patterns. We suggest using the pretreatment diagnosis to select the appropriate surgical approach and thus improve the clinical outcome.

Implementing the AAOS Guidelines for Screening of Developmental Dysplasia of the Hip Before the Age of 6 Months in Taiwan.

BACKGROUND: The prevalence of developmental dysplasia of the hip (DDH) has been considered to be low in East Asia, but this may be incorrect because of inconsistent diagnostic definitions and testing criteria. In 2015, the AAOS released guidelines for systematic screening for DDH in newborns. We implemented these guidelines and compared DDH incidence and outcomes before and after their implementation. METHODS: We used a historic comparison cohort of newborns with DDH between July 2015 and May 2017 before guideline implementation (the preguideline group); their data were retrieved using electronic medical records. In this group, the newborns received general hip screening without systemic follow-up. The postguideline group included newborns who were screened for hip dysplasia and followed up per the AAOS guidelines between July 2017 and May 2019. Their data were prospectively collected. The primary outcome in the postguideline group was DDH incidence. Other outcomes included rates of referral, surgery, and complications, and DDH prognosis. RESULTS: The preguideline and postguideline groups included 3534 and 2663 newborns, respectively, of whom 49 (1.1%) and 225 (8.4%), respectively, were referred to the pediatric orthopaedic clinic enrolled. In the postguideline group, 35 patients were diagnosed as having DDH (incidence: 1.3%, 95% CI: 0.8%-1.9%). Both the incidence and referral rates were significantly higher in the postguideline group than in the preguideline group. Furthermore, the mean age at referral was 6.7±10.06 months and 0.9±0.25 months in the preguideline and postguideline groups, respectively, indicating a potential for early treatment in the postguideline group. Finally, the female sex was identified as a risk factor for residual hip dysplasia at 6 months of age. CONCLUSION: DDH incidence in East Asia seems comparable to that in Western countries. Implementing the AAOS guidelines increased the diagnosis rate and opportunity for early treatment initiation, thus potentially avoiding surgical intervention. Nevertheless, residual DDH may be detected in some patients at 6 months of age, particularly in female infants. LEVEL OF EVIDENCE: Level IV.

MRI features of pediatric atypical teratoid rhabdoid tumors and medulloblastomas of the posterior fossa.

BACKGROUND: Atypical teratoid rhabdoid tumor (AT/RT) occurs at a younger age and is associated with a worse prognosis than medulloblastoma; however, these two tumor entities are mostly indistinguishable on neuroimaging. The aim of our study was to differentiate AT/RT and medulloblastoma based on their clinical and MRI features to enhance treatment planning and outcome prediction. METHODS: From 2005-2021, we retrospectively enrolled 16 patients with histopathologically diagnosed AT/RT and 57 patients with medulloblastoma at our institute. We evaluated their clinical data and MRI findings, including lesion signals, intratumoral morphologies, and peritumoral/distal involvement. RESULTS: The age of children with AT/RT was younger than that of children with medulloblastoma (2.8 ± 4.9 [0-17] vs. 6.5 ± 4.0 [0-18], p < 0.001), and the overall survival rate was lower (21.4% vs. 66.0%, p = 0.005). Regarding lesion signals on MRI, AT/RT had a lower ADCmin (cutoff value ≤544.7 × 10-6  mm2 /s, p < 0.001), a lower ADC ratio (cutoff value ≤0.705, p < 0.001), and a higher DWI ratio (cutoff value ≥1.595, p < 0.001) than medulloblastoma. Regarding intratumoral morphology, the "tumor central vein sign" was mostly exclusive to medulloblastoma (24/57, 42.1%; AT/RT 1/16, 6.3%; p = 0.007). Regarding peritumoral invasion on T2WI, AT/RT was more prone to invasion of the brainstem (p < 0.001) and middle cerebellar peduncle (p < 0.001) than medulloblastoma. CONCLUSIONS: MRI findings of a lower ADC value, more peritumoral invasion, and absence of the "tumor central vein sign" may be helpful to differentiate AT/RT from medulloblastoma. These distinct MRI findings together with the younger age of AT/RT patients may explain the worse outcomes in AT/RT patients.

Prevention of in-stent restenosis with drug-eluting balloons in patients with postirradiated carotid stenosis accepting percutaneous angioplasty and stenting.

OBJECTIVE: To investigate the technical safety and outcome of in-stent restenosis (ISR) prevention with drug-eluting balloon (DEB) in patients with postirradiated carotid stenosis (PIRCS) undergoing percutaneous angioplasty and stenting (PTAS). METHODS: Between 2017 and 2021, we prospectively recruited patients with severe PIRCS for PTAS. They were randomly separated into two groups based on endovascular techniques performed with and without DEB. Preprocedural and early postprocedural (within 24 hours) MRI, short-term ultrasonography (6 months after PTAS), and long-term CT angiography (CTA)/MR angiography (MRA), 12 months after PTAS, were performed. Technical safety was evaluated based on periprocedural neurological complications and the number of recent embolic ischemic lesions (REIL) in the treated brain territory on diffusion-weighted imaging of early postprocedural MRI. RESULTS: Sixty-six (30 with and 36 without DEB) subjects were enrolled, with one failure in techniques. For 65 patients in the DEB versus conventional groups, technical neurological symptoms within 1 month (1/29 (3.4%) vs 0/36; P=0.197) and REIL numbers within 24 hours (1.0±2.1 vs 1.3±1.5; P=0.592) after PTAS showed no differences. Peak systolic velocity (PSVs) on short-term ultrasonography was significantly higher in the conventional group (104.13±42.76 vs .81.95±31.35; P=0.023). The degree of in-stent stenosis (45.93±20.86 vs 26.58±8.75; P<0.001) was higher, and there were more subjects (n=8, 38.9% vs 1, 3.4%; P=0.029) with significant ISR (≥ 50%) in the conventional group than in the DEB group on long-term CTA/MRA. CONCLUSIONS: We observed similar technical safety of carotid PTAS with and without DEBs. The number of cases of significant ISR were fewer and the degree of stenosis of ISR was less in primary DEB-PTAS of PIRCS than for conventional PTAS in the 12-month follow-up.

Advances in Boron Neutron Capture Therapy (BNCT) for Recurrent Intracranial Meningioma.

Meningiomas are the most frequently diagnosed primary intracranial tumors in adults. Surgical resection is preferred if the meningioma is accessible; for those that are not suitable for surgical resection, radiotherapy should be considered to improve local tumor control. However, recurrent meningiomas are challenging to treat, as the recurrent tumor might be located in the previously irradiated area. Boron Neutron Capture Therapy (BNCT) is a highly selective radiotherapy modality in which the cytotoxic effect focuses mainly on cells with increased uptake of boron-containing drugs. In this article, we describe four patients with recurrent meningiomas treated with BNCT in Taiwan. The mean boron-containing drug tumor-to-normal tissue uptake ratio was 4.125, and the tumor mean dose was 29.414 GyE, received via BNCT. The treatment response showed two stable diseases, one partial response, and one complete response. We also introduce and support the effectiveness and safety of BNCT as an alternative salvage treatment for recurrent meningiomas.

Percutaneous transluminal angioplasty and stenting of post-irradiation stenosis of the vertebral artery.

BACKGROUND: The outcomes of percutaneous transluminal angioplasty and stenting (PTAS) in patients with medically refractory post-irradiation stenosis of the vertebral artery (PISVA) have not been clarified. AIM: This retrospective study evaluated the safety and outcomes of PTAS in patients with severe PISVA compared with their radiation-naïve counterparts (non-RT group). METHODS: Patients with medically refractory severe symptomatic vertebral artery stenosis and undergoing PTAS between 2000 and 2021 were classified as the PISVA group or the non-RT group. The periprocedural neurological complications, periprocedural brain magnetic resonance imaging, the extent of symptom relief, and long-term stent patency were compared. RESULTS: As compared with the non-RT group (22 cases, 24 lesions), the PISVA group (10 cases, 10 lesions) was younger (62.0 ± 8.6 vs 72.4 ± 9.7 years, P = 0.006) and less frequently had hypertension (40.0% vs 86.4%, P = 0.013) and diabetes mellitus (10.0% vs 54.6%, P = 0.024). Periprocedural embolic infarction was not significantly different between the non-RT group and the PISVA group (37.5% vs 35.7%, P = 1.000). At a mean follow-up of 72.1 ± 58.7 (3-244) months, there was no significant between-group differences in the symptom recurrence rate (0.00% vs 4.55%, P = 1.000) and in-stent restenosis rate (10.0% vs 12.5%, P = 1.000). CONCLUSION: PTAS of severe medically refractory PISVA is effective in the management of vertebrobasilar ischemic symptoms in head and neck cancer patients. Technical safety and outcome of the procedure were like those features in radiation-naïve patients.

The Application of Biomaterials in Spinal Cord Injury.

The spinal cord and the brain form the central nervous system (CNS), which is the most important part of the body. However, spinal cord injury (SCI) caused by external forces is one of the most difficult types of neurological injury to treat, resulting in reduced or even absent motor, sensory and autonomic functions. It leads to the reduction or even disappearance of motor, sensory and self-organizing nerve functions. Currently, its incidence is increasing each year worldwide. Therefore, the development of treatments for SCI is urgently needed in the clinic. To date, surgery, drug therapy, stem cell transplantation, regenerative medicine, and rehabilitation therapy have been developed for the treatment of SCI. Among them, regenerative biomaterials that use tissue engineering and bioscaffolds to transport cells or drugs to the injured site are considered the most promising option. In this review, we briefly introduce SCI and its molecular mechanism and summarize the application of biomaterials in the repair and regeneration of tissue in various models of SCI. However, there is still limited evidence about the treatment of SCI with biomaterials in the clinic. Finally, this review will provide inspiration and direction for the future study and application of biomaterials in the treatment of SCI.

Huangqi decoction attenuates renal interstitial fibrosis transforming growth factor-ß1/mitogen-activated protein kinase signaling pathways in 5/6 nephrectomy mice.

OBJECTIVE: To investigate the effect of Huangqi decoction on renal interstitial fibrosis and its association with the transforming growth factor-ß1 (TGF-ß1) / mitogen-activated protein kinase (MAPK) signaling pathway. METHODS: 120 C57/BL mice were randomly divided into six groups: sham group, Enalapril (20 mg/kg) group, 5/6 nephrectomy model group, and 5/6 nephrectomy model plus Huangqicoction (0.12, 0.36 and 1.08 g/kg respectively) groups. Detecting 24hours urinary protein, blood pressure, serum creatinine, urea nitrogen content changes. Periodic Acid-Schiff stain (PAS) and Masson's trichrome staining was used to observe the renal tissue pathological changes. Protein expression of TGF-ß1, Phosphorylated P38 mitogen activated protein kinases (P-P38), Phosphorylated c-jun N-terminal kinase (P-JNK), Phosphorylated extracellular regulated proteinhnase (P-ERK), Fibroblast-specific protein-1 (FSP-1), Alpha smooth muscle actin (α-SMA), Type III collagen (Collagen III), Connective tissue growth factor (CTGF), Bcl-2 Assaciated X protein (Bax) and B cell lymphoma 2 (Bcl-2) were measured with western blot and immunohistochemical. RESULTS: Both Huangqi decoction and Enalapril improved the kidney function, 24 h urinary protein and the fibrosis in 5/6 nephrectomy mice, Huangqi decoction downregulated the expressions of TGF-ß1, FSP-1, α-SMA, Collagen III and CTGF in a dose-dependent manner, and it has a significant difference ( 0.01) compared with model group.Huangqi decoction downregulated the expressions of P-P38, P-JNK, P-ERK and Bcl-2 in a dose-dependent manner, while upregulated the expression of Bax. CONCLUSIONS: The protective effect of Huangqi decoction for renal interstitial fibrosis in 5/6 nep-hrectomized mice the inhibition of Epithelial-Mesenchymal Transitions and downregulating the TGF-ß1/ MAPK signaling pathway.