Face-to-face Assembly Strategy of Au Nanocubes: Induced Generation of Broad Hotspot Regions for SERS-Fluorescence Dual-Signal Detection of Intracellular miRNAs.

While designing anisotropic noble metal nanoparticles (NPs) can enhance the signal intensity of Raman dyes, more sensitive surface-enhanced Raman scattering (SERS) probes can be designed by oriented self-assembly of noble metal nanomaterials into dimers or higher-order nanoclusters. In this study, we engineered a self-assembly strategy in living cells for real-time fluorescence and SERS dual-channel detection of intracellular microRNAs (miRNAs), using Mg2+-dependent 8-17E DNAzyme sequences as the driving motors, gold nanocubes (AuNCs) as the driver components, and three-branched double-stranded DNA as the linking tool. The assembly selects adenine in DNA as a reporter molecule, simplifying the labeling process of Raman reporter molecules and reducing the synthesis process. In addition, adenine is stably distributed between the faces of AuNCs and the wide hotspot region gives good reproducibility of the adenine SERS signal. In this strategy, the SERS channel was consistently stable and more sensitive compared to the fluorescence channel. Among them, the detection limit of the SERS channel was 2.1 pM and the coefficient of variation was 1.26% in the in vitro liquid phase and 1.49% in MCF-7 cells. The strategy successfully achieved accurate tracking and quantification of miRNA-21 in cancer cells, showing good reproducibility in complex samples as well as cells. The reported strategy provides ideas for exploring intracellular specific triggering of nanoparticles for precise control of self-assembly.

Comparing surgical and endoscopic resection approaches for colorectal neuroendocrine tumors within the diameter range of 10-20mm: an inverse probability weighting analysis based on the SEER database.

Background: Currently, the primary treatment modalities for colorectal neuroendocrine tumors (CRNET) with a diameter between 10mm and 20mm are surgical resection (SR) and endoscopic resection (ER). However, it remains unclear which surgical approach yields the greatest survival benefit for patients. Methods: This study included data from patients diagnosed with CRNET with tumor diameters ranging from 10mm to 20mm between the years 2004 and 2019, obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized into ER and SR groups based on the respective surgical approaches. Inverse probability weighting (IPTW) was employed to mitigate selection bias. Kaplan-Meier analysis and log-rank tests were utilized to estimate overall survival (OS) and cancer-specific survival (CSS). Cox regression analysis (univariate and multivariate) was performed to evaluate potential factors influencing survival. Results: A total of 292 CRNET patients were included in this study (ER group: 108 individuals, SR group: 184 individuals). Prior to IPTW adjustment, Kaplan-Meier analysis and Cox proportional hazard regression analysis demonstrated that the OS and CSS of the SR group were inferior to those of the ER group. However, after IPTW adjustment, no statistically significant differences in prognosis were observed between the two groups. Subgroup analyses revealed that patients with muscular invasion, positive lymph nodes, or distant metastasis derived greater survival benefits from SR. Significant differences in OS and CSS between the two groups were also observed across different age groups. Conclusion: For patients with mucosal-limited lesions and without local lymph node or distant metastasis, ER is the preferred surgical approach. However, for patients with muscular invasion or positive lymph nodes/distant metastasis, SR offers a better prognosis. The choice of surgical approach should be based on the specific clinical characteristics of patients within different subgroups.

An ultrasound-based nomogram for predicting axillary node pathologic complete response after neoadjuvant chemotherapy in breast cancer: Modeling and external validation.

INTRODUCTION: The staging and treatment of axillary nodes in breast cancer have become a focus of research. For breast cancer patients with fine-needle aspiration-or core needle biopsy-confirmed positive nodes, axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC) is still a standard treatment. However, some patients achieve an axillary pathologic complete response (pCR) after NAC. In this study, the authors sought to construct a model to predict axillary pCR in patients with positive axillary lymph nodes (cN+) breast cancer. METHODS: Data from patients with pathologically proven cN+ breast cancer treated with NAC followed by ALND between January 2010 and April 2019 at the Peking University Cancer Hospital were reviewed. Axillary lymph node status was assessed using ultrasonography before and after NAC. The patient cohort was assigned to the construction and internal validation cohorts according to admission time. A nomogram was constructed based on the significant factors associated with axillary pCR. The predictive performance of the model was externally validated using data from Peking University First Hospital. RESULTS: This study included 953 and 267 patients from Peking University Cancer Hospital and Peking University First Hospital, respectively. In the construction cohort, 39.7% (238 of 600) of patients achieved axillary pCR after NAC. The result of multivariate logistic regression analysis showed that tumor grade, clinical nodal response, NAC regimen, tumor pCR, lymphovascular invasion, and tumor biologic subtype were significant independent predictors of ypN0 (p < 0.05). The areas under the receiver operating characteristic curves for the construction, validation, and independent testing cohorts were 0.87 (95% confidence interval [CI], 0.84-0.90), 0.83 (95% CI, 0.79-0.87), and 0.84 (0.79-0.89), respectively. CONCLUSIONS: A nomogram was constructed to predict the pCR of axillary lymph nodes after NAC for breast cancer. Validation of both the internal and external cohorts achieved good predictive performance, indicating that the model has preliminary clinical application prospects.

Synovial sarcoma of the viscera (lung and jejunum): a case report.

We report the case of a woman nearing 70 years old who was admitted to the hospital with a complaint of "epigastric distension for 1 month". Her main signs and symptoms were progressive abdominal distension and occasional abdominal pain. Computed tomography suggested an abdominal mass. She had a surgical history of synovial sarcoma (SS) of the lungs. After admission, she was diagnosed with jejunal SS following a puncture biopsy and laparoscopic surgery. This disease usually occurs in the soft tissues of the limbs, and it is extremely rare for SS to originate in the jejunum. The morphologic heterogeneity of SS overlaps with other tumors and makes the diagnosis particularly difficult. Imaging studies usually lack specificity; however, measuring multiple immunohistochemical markers can greatly assist in the diagnosis and differential diagnosis of SS. This case not only enriches our understanding of SS and describes a rare site of origin, but also emphasizes the importance and challenges of achieving an accurate diagnosis. Immunohistochemical and molecular biological testing have important roles in the definitive diagnosis, highlighting the need for precise and innovative diagnostic and therapeutic approaches in SS.

Prognostic implications of T stage in different pathological types of colorectal cancer: an observational study using SEER population-based data.

OBJECTIVES: Colorectal cancer (CRC) encompasses a spectrum of pathological types, each exhibiting distinct biological behaviours that challenge the conventional T-staging system's predictive efficiency. Thus, this study aims to explore the prognostic significance of the T stage across various CRC pathological types, seeking to unravel insights that could enhance prognostic assessment in this complex disease. STUDY DESIGN: We performed a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database for primary CRC cases from 2010 to 2017. SETTING: The SEER database, comprising data from various US regional and state cancer registries, identified 39 321 patients with CRC. Our analysis focused on the three most common CRC pathological types: adenocarcinoma (AC), mucinous adenocarcinoma (MC) and signet ring cell carcinoma (SR). PRIMARY OUTCOME MEASURES: The study used Cox regression models to evaluate how different pathological characteristics impact mortality risk in patients with CRC. Time-dependent receiver operating characteristic curves were also applied to assess the prognostic accuracy of various tumour node metastasis (TNM)/non-mucinous (NM) stages. RESULTS: We observed significant associations between T stage and mortality risk for patients with AC and MC. Notably, in comparison to those at T1 stage, patients with AC in the T4 stage demonstrated a 2.01-fold increase in mortality risk (HR=2.01, 95% CI: 1.89 to 2.15), while patients with MC at T4 stage showed a 1.42-fold increase (HR=1.42, 95% CI: 1.03 to 1.97). However, within the SR group, T stages did not independently impact survival, showing no significant distinction (HR=1.07, 95% CI: 0.59 to 1.95). Intriguingly, the traditional TNM staging systems demonstrated limited discriminatory power in predicting prognosis for patients with SR when compared with the more innovative NM staging systems. CONCLUSIONS: This study uncovers important insights about the prognostic significance of the T stage in different types of CRC, highlighting the need for personalised assessments based on specific histological subtypes.

IRF4 induces M1 macrophage polarization and aggravates ulcerative colitis progression by the Bcl6-dependent STAT3 pathway.

Ulcerative colitis (UC) is an idiopathic chronic intestinal inflammation. An increasing body of evidence shows that macrophages play an important role in the pathogenesis of UC. Interferon regulatory factor 4 (IRF4) is crucial for the development of autoimmune diseases via regulating immune cells. This research was designed to explore the function of IRF4 in UC and its association with macrophage polarization. The in vitro model of UC was established by stimulating colonic epithelial cells with tumor necrosis factor α (TNF-α). A mouse model of UC was constructed by injecting C57BL/6 mice with dextran sulfate sodium salt. Flow cytometry was used to assess percentage of CD11b+ CD86+ and CD11b+ CD206+ cells in bone marrow macrophages. Occult blood tests were used to detect hematochezia. Hematoxylin and eosin staining assay was used to assess colon pathological changes. Enzyme-linked immunosorbent assay (ELISA) was used to detect concentrations of inflammatory cytokines. The interaction of IRF4 and B-cell lymphoma 6 (Bcl6) was confirmed using GST pull-down and coimmunoprecipitation assays. Our findings revealed that IRF4 promoted cell apoptosis and stimulated M1 macrophage polarization in vitro. Furthermore, IRF4 aggravated symptoms of the mouse model of UC and aggravated M1 macrophage polarization in vivo. IRF4 negatively regulated Bcl6 expression. Downregulation of Bcl6 promoted apoptosis and M1 macrophage polarization in the presence of IRF4 in vitro and in vivo. Moreover, Bcl6 positively mediated the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. In conclusion, IRF4 aggravated UC progression through promoting M1 macrophage polarization via Bcl6/JAK2/STAT3 pathway. These findings suggested that IRF4 might be a good target to competitively inhibit or to treat with UC.

CYP1B1-AS1 Delays the Malignant Progression of Colorectal Cancer by Binding with NOP58.

BACKGROUND: Colorectal cancer (CRC) is a prevalent type of gastrointestinal cancer, and its poor prognosis is mainly attributed to the occurrence of invasion and metastasis. CYP1B1-AS1, as non-coding RNA, plays an important role in tumorigenesis and progression. However, the mechanism by which CYP1B1-AS1 acts in CRC is not yet understood. AIMS: The objective of this study was to investigate how CYP1B1-AS1 contributes to the development of CRC, and provide a base for CRC diagnosis and treatment. METHODS: RT-qPCR was used to detect the expression level of CYP1B1-AS1 in CRC and adjacent tissues. CCK-8, Edu, scratch healing, and transwell experiments were used to detect the changes of proliferation, migration, and invasion ability of CRC cells after overexpression or knockdown of CYP1B1-AS1 respectively. The RNA binding protein NOP58 combined with CYP1B1-AS1 was verified by RIP and RNA Pull-down experiments. Functional recovery experiments validated the interaction between CYP1B1-AS1 and NOP58 in CRC cells. The changes of EMT-related proteins were detected by Western blot, and the half-life of transcription factor SNAIL mRNA were detected by RT-qPCR after overexpression or knockdown of NOP58. RESULTS: CYP1B1-AS1 was found to be significantly downregulated in CRC compared to adjacent noncancerous tissues. Experiments conducted in vitro and in vivo confirmed that upregulation of CYP1B1-AS1 significantly inhibited the proliferation, migration, and invasion of CRC cells. In addition, CYP1B1-AS1 can directly bind to NOP58 and negatively regulate NOP58. The effect of overexpression CYP1B1-AS1 was reversed by NOP58 overexpression. NOP58 regulates the EMT process of CRC cells by affecting the stability of EMT-related transcription factor SNAIL mRNA, and then affects the progress of CRC. CONCLUSION: This research proves that CYP1B1-AS1 can inhibit the occurrence of EMT in CRC by binding with NOP58, thus delaying the progress of CRC. This finding indicates that CYP1B1-AS1 may be a novel biomarker to improve the diagnosis and treatment of CRC.

Fully Endoscopic Microvascular Decompression for Trigeminal Neuralgia Caused by Vertebrobasilar Artery: A Case Series Review: 2-Dimensional Operative Video.

BACKGROUND AND OBJECTIVE: Microvascular decompression (MVD) is the most definitive and preferred surgical treatment for trigeminal neuralgia (TN). Treatment of TN caused by the vertebrobasilar artery (VBA) has been reported to be challenging and less satisfactory in complications and recurrence. Endoscopy has been implemented to provide a comprehensive view of neurovascular conflicts and minimize brain tissue stretch injury while exploring the trigeminal nerve. However, there are few retrospective studies on the treatment of TN caused by VBA by fully endoscopic microvascular decompression (E-MVD). This article aimed to illustrate the safety and efficacy of E-MVD for TN caused by the VBA. METHODS: Clinical data for 26 patients with TN caused by the VBA who underwent E-MVD from 2019 to 2022 were retrospectively analyzed. The characteristics of vertebrobasilar-associated TN were summarized. The safety and efficacy of E-MVD for vertebrobasilar-associated TN were estimated based on the analysis of intraoperative manipulation, postoperative symptom relief, and complications. RESULTS: Intraoperatively, the vertebrobasilar artery was regarded as a direct offending vessel in all 26 patients with TN, the vertebral artery in 18 (69.23%) and the basilar artery in 10 (38.46%). In addition to the vertebrobasilar artery, other vessels involved included the superior cerebellar artery in 12 patients, anterior inferior cerebellar artery in 9, posterior inferior cerebellar artery in 1, and veins in 4. All patients underwent E-MVD, and TN was entirely resolved in 26 (100%) patients immediately postoperatively. During the follow-up period of 12-45 months, no recurrence or serious complications were found. There were no serious postoperative complications, such as cerebellar swelling, intracranial hemorrhage, or death. CONCLUSION: E-MVD for vertebrobasilar-associated TN is effective and safe.

Fully neuroendoscopic resection of cerebellopontine angle tumors through a retrosigmoid approach: a retrospective single-center study.

The objective of this study is to preliminarily investigate the surgical safety, efficacy, techniques, and clinical value of fully neuroendoscopic surgery for the resection of cerebellopontine angle (CPA) tumors via a retrosigmoid approach. The clinical data of 47 cerebellopontine angle area (CPA) tumors that were treated by full neuroendoscopic surgery from June 2014 to June 2023 were retrospectively analyzed. The efficacy and advantages of the surgical techniques were evaluated based on indicators such as duration of the surgery, neuroendoscopic techniques, intraoperative integrity of nerves and blood vessels, extent of tumor resection, outcomes or postoperative symptoms, and incidence of complications. The 47 cases of cerebellopontine angle tumors include 34 cases of epidermoid cysts, 7 cases of vestibular schwannomas, and 6 cases of meningiomas. All patients underwent fully neuroendoscopic surgery. Twenty tumors were removed using the one-surgeon two-hands technique, and 27 tumors were removed using the two-surgeons four-hands technique. The anatomical integrity of the affected cranial nerves was preserved in all 47 cases. None of the patients suffered a postoperative hemorrhage, cerebrospinal fluid leak, and aseptic or septic meningitis, or died. The rate of total tumor resection was 72.3% (34/47), and the symptom improvement rate was 89.4% (42/47). All patients were followed up for 2 to 12 months, and none died nor showed any signs of tumor recurrence. By analyzing 47 fully neuroendoscopic resections of CPA tumors using the posterior sigmoid sinus approach in our center, we believe that such method allows complete, safe, and effective resection of CPA tumors and is thereby worthy of clinical promotion.

Inhibition of extracellular vesicle-derived miR-146a-5p decreases progression of melanoma brain metastasis via Notch pathway dysregulation in astrocytes.

Melanoma has the highest propensity of all cancers to metastasize to the brain with a large percentage of late-stage patients developing metastases in the central nervous system (CNS). It is well known that metastasis establishment, cell survival, and progression are affected by tumour-host cell interactions where changes in the host cellular compartments likely play an important role. In this context, miRNAs transferred by tumour derived extracellular vesicles (EVs) have previously been shown to create a favourable tumour microenvironment. Here, we show that miR-146a-5p is highly expressed in human melanoma brain metastasis (MBM) EVs, both in MBM cell lines as well as in biopsies, thereby modulating the brain metastatic niche. Mechanistically, miR-146a-5p was transferred to astrocytes via EV delivery and inhibited NUMB in the Notch signalling pathway. This resulted in activation of tumour-promoting cytokines (IL-6, IL-8, MCP-1 and CXCL1). Brain metastases were significantly reduced following miR-146a-5p knockdown. Corroborating these findings, miR-146a-5p inhibition led to a reduction of IL-6, IL-8, MCP-1 and CXCL1 in astrocytes. Following molecular docking analysis, deserpidine was identified as a functional miR-146a-5p inhibitor, both in vitro and in vivo. Our results highlight the pro-metastatic function of miR-146a-5p in EVs and identifies deserpidine for targeted adjuvant treatment.

BCL2L13 promotes mitophagy through DNM1L-mediated mitochondrial fission in glioblastoma.

There is an urgent need for novel diagnostic and therapeutic strategies for patients with Glioblastoma multiforme (GBM). Previous studies have shown that BCL2 like 13 (BCL2L13) is a member of the BCL2 family regulating cell growth and apoptosis in different types of tumors. However, the clinical significance, biological role, and potential mechanism in GBM remain unexplored. In this study, we showed that BCL2L13 expression is significantly upregulated in GBM cell lines and clinical GBM tissue samples. Mechanistically, BCL2L13 targeted DNM1L at the Ser616 site, leading to mitochondrial fission and high mitophagy flux. Functionally, these alterations significantly promoted the proliferation and invasion of GBM cells both in vitro and in vivo. Overall, our findings demonstrated that BCL2L13 plays a significant role in promoting mitophagy via DNM1L-mediated mitochondrial fission in GBM. Therefore, the regulation and biological function of BCL2L13 render it a candidate molecular target for treating GBM.

Magnetically Assisted Immobilization-Free Detection of microRNAs Based on the Signal Amplification of Duplex-Specific Nuclease.

The double specific nuclease (DSN)-based methods for microRNAs (miRNAs) detection usually require the immobilization of DNA probes on a solid surface. However, such strategies have the drawbacks of low hybridization and cleavage efficiency caused by steric hindrance effect and high salt concentration on the solid surface. Herein, we proposed an immobilization-free method for miRNA detection on the basic of DSN-assisted signal amplification. The biotin- and fluorophore-labeled probes were captured by streptavidin-modified magnetic beads through streptavidin-biotin interactions, thus producing a poor fluorescence signal. Once the DNA probes were hybridized with target miRNA in solution to form DNA-miRNA duplexes, DNA stands in the duplexes would be selectively digested by DSN. The released target miRNA could initiate the next hybridization/cleavage recycling in the homogeneous solution, finally resulting in the release of numerous fluorophore-labeled fragments. The released fluorophores remained in solution and emitted strong fluorescence after treatment by the streptavidin-modified magnetic beads. The immobilization-free method achieved the assays of miRNA-21 with a detection limit down to 0.01 pM. It was employed to evaluate the expression levels of miRNA-21 in different cancer cells with satisfactory results.

[Effects of hydrogen gas on NOD-like receptor protein 3 inflammasomes in the cerebral cortex of rats with traumatic brain injury].

OBJECTIVE: To investigate the effect of hydrogen gas on NOD-like receptor protein 3 (NLRP3) inflammasomes in the cerebral cortex of rats with traumatic brain injury (TBI). METHODS: 120 adult male Sprague-Dawley (SD) rates were randomly divided into 5 groups (n = 24): sham operation group (S group), TBI model group (T group), TBI+NLRP3 inhibitor MCC950 group (T+M group), TBI+hydrogen gas group (T+H group), TBI+hydrogen gas+MCC950 group (T+H+M group). TBI model was established by controlled cortical impact. NLRP3 inhibitor MCC950 (10 mg/kg) was intraperitoneally injected for 14 consecutive days before TBI operation in T+M and T+H+M groups. 2% hydrogen inhalation was given for 1 hour at 1 hour and 3 hours after TBI operation in T+H and T+H+M groups. At 6 hours after TBI operation, the pericontusional cortex tissues were obtained, the content of Evans blue (EB) was detected to evaluate the permeability of the blood-brain barrier. Water content in brain tissue was detected. The cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL) and the neuronal apoptosis index was calculated. The expressions of Bcl-2, Bax, NLRP3, apoptosis-associated speck-like protein containing CARD (ASC) and caspase-1 p20 were detected by Western blotting. The levels of interleukins (IL-1ß, IL-18) were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the S group, the content of EB in cerebral cortex, water content in brain tissue, apoptosis index and the expressions of Bax, NLRP3, ASC, caspase-1 p20 in T group were significantly increased, the expression of Bcl-2 was down-regulated, the levels of IL-1ß and IL-18 were increased [the content of EB (µg/g): 87.57±6.89 vs. 10.54±1.15, water content in brain tissues: (83.79±2.74)% vs. (74.50±1.19)%, apoptotic index: (62.66±5.33)% vs. (4.61±0.96)%, Bax/ß-actin: 4.20±0.44 vs. 1, NLRP3/ß-actin: 3.55±0.31 vs. 1, ASC/ß-actin: 3.10±0.26 vs. 1, caspase-1 p20/ß-actin: 3.28±0.24 vs. 1, Bcl-2/ß-actin: 0.23±0.03 vs. 1, IL-1ß (ng/g): 221.58±19.15 vs. 27.15±3.27, IL-18 (ng/g): 87.26±7.17 vs. 12.10±1.85, all P < 0.05]. Compared with the T group, the T+M, T+H and T+H+M groups had significant reductions in the content of EB and water content in brain tissue, apoptotic index of the cerebral cortex, the expressions of Bax, NLRP3, and caspase-1 p20 in the brain tissue and the levels of IL-1ß and IL-18, significant increases in the expression of Bcl-2. However, there was no significant difference in ASC expression. Compared with the T+H group, the content of EB in the cerebral cortex, water content in brain tissue, and apoptotic index, and the expressions of Bax, NLRP3 and caspase-1 p20 were further down-regulated in T+H+M group, the expression of Bcl-2 was further up-regulated, the levels of IL-1ß and IL-18 were further decreased [the content of EB (µg/g): 40.49±3.15 vs. 51.96±4.69, water content in brain tissue: (76.58±1.04)% vs. (78.76±1.16)%, apoptotic index: (32.22±3.44)% vs. (38.54±3.89)%, Bax/ß-actin: 1.92±0.16 vs. 2.56±0.21, NLRP3/ß-actin: 1.94±0.14 vs. 2.37±0.24, caspase-1 p20/ß-actin: 1.97±0.17 vs. 2.31±0.19, Bcl-2/ß-actin: 0.82±0.07 vs. 0.52±0.04, IL-1ß (ng/g): 86.23±7.09 vs. 110.44±10.48, IL-18 (ng/g): 40.18±3.22 vs. 46.23±4.02, all P < 0.05], but there were no statistical significance in all the indicators between T+M group and T+H group. CONCLUSIONS: The mechanism by which hydrogen gas alleviates TBI may be related to inhibiting NLRP3 inflammasomes in the cerebral cortex of rats.

SLC25A32 promotes malignant progression of glioblastoma by activating PI3K-AKT signaling pathway.

BACKGROUND: Solute carrier family 25 member 32 (SLC25A32) is an important member of SLC25A family and plays a role in folate transport metabolism. However, the mechanism and function of SLC25A32 in the progression of human glioblastoma (GBM) remain unclear. METHODS: In this study, folate related gene analysis was performed to explore gene expression profiles in low-grade glioma (LGG) and GBM. Western blotting, real-time quantitative PCR (qRT-PCR), and immunohistochemistry (IHC) were used to confirm the expression levels of SLC25A32 in GBM tissues and cell lines. CCK-8 assays, colony formation assays, and Edu assays were performed to assess the role of SLC25A32 on proliferation in GBM in vitro. A 3D sphere invasion assay and an ex vivo co-culture invasion model were performed to assess the effects of SLC25A32 on invasion in GBM. RESULTS: Elevated expression of SLC25A32 was observed in GBM, and high SLC25A32 expression was associated with a high glioma grade and poorer prognosis. Immunohistochemistry performed with anti-SLC25A32 on samples from an independent cohort of patients confirmed these results. Knockdown of SLC25A32 inhibited the proliferation and invasion of GBM cells, but overexpression of SLC25A32 significantly promoted cell growth and invasion. These effects were mainly due to the activation of the PI3K-AKT-mTOR signaling pathway. CONCLUSION: Our study demonstrated that SLC25A32 plays a significant role in promoting the malignant phenotype of GBM. Therefore, SLC25A32 can be used as an independent prognostic factor in patients with GBM, providing a new target for the comprehensive treatment of GBM.

Construction of nano-drug delivery and antitumor system of stimuli-responsive polypeptides.

The size of the nanoparticles is moderate and the dispersion is well, which will not be recognized nonspecifically and clearance by the endothelial reticular system. In this study, stimuli-responsive polypeptides nano-delivery system has been constructed, which can realize the response to various stimuli in the tumor microenvironment. Tertiary amine groups are grafted to the side chain of polypeptides as the point of charge reversal and particle expansion. In addition, a new kind of liquid crystal monomer was prepared by substituting cholesterol-cysteamine, which can promote polymers to realize the transformation of spatial conformation by adjusting the ordered arrangement of macromolecules. The introduction of hydrophobic elements greatly enhanced the self-assembly performance of polypeptides, which could effectively improve the drug loading and encapsulation rate of nanoparticles. Nanoparticles could achieve targeted aggregation in tumor tissues, and there were no toxicity and side effects on normal bodies during treatment, with good safety in vivo.

Aorto-ventricular tunnel with three orifices: a unique case report diagnosed by transthoracic echocardiography.

BACKGROUND: Aorto-ventricular tunnel (AVT) is an abnormal communication channel between the ascending aorta and the ventricle. It commonly has two orifices, i.e., one aortic opening and one ventricular opening. In this study, we present a unique case of AVT with three orifices: one aortic opening, one LV opening, and one RV opening. CASE PRESENTATION: A 64-year-old male presented with chest discomfort and dyspnea on exertion lasting the past six months. Physical examination revealed a grade 4/6 continuous biphasic murmur along the left sternal edge and a grade 3/6 systolic murmur at the apex. Transthoracic echocardiography (TTE) demonstrated: (1) an AVT with three orifices, i.e., one aortic opening, one LV opening, and one RV opening. The LV and RV openings were located in the left and right ventricular outflow tracts, respectively. (2) The aortic valve (AV) was calcified with a small aneurysm at the non-coronary cusp. (3)The mitral valve (MV) chordal rupture of the P2 and P3 segments was observed in the posterior leaflet with severe eccentric regurgitation. Subsequent coronary computed tomography angiography (CTA) further confirmed the diagnosis of AVT with three openings, and clarified the coronary arteries normally arose from the aortic sinuses. The patient was then referred for surgical treatment, consisting of closure of three AVT orifices, AV replacement, and MV replacement. Six months following surgery, the patient was asymptomatic. TTE demonstrated normal mechanic AV and MV function, and there was no residual shunt among the ascending aorta, LV and RV. CONCLUSIONS: It is the first case to report an AVT with three orifices. This paper described the entire process from diagnosis to treatment of this unique case, thus providing some novel insights into AVT.

Construction of poly(amino acid)s nano-delivery system and sustained release with redox-responsive.

A series of novel poly(amino acid)s materials were designed to prepare drug-loaded nanoparticles by physical encapsulation and chemical bonding. The side chain of the polymer contains a large number of amino groups, which effectively increases the loading rate of doxorubicin (DOX). The structure contains disulfide bonds that showing a strong response to the redox environment, which can achieve targeted drug release in the tumor microenvironment. Nanoparticles mainly present spherical morphology with the suitable size for participating in systemic circulation. cell experiments demonstrate the non-toxicity and good cellular uptake behavior of polymers. In vivo anti-tumor experiments shows nanoparticles could inhibit tumor growth and effectively reduce the side effects of DOX.

Observation Effectiveness of Dose-Dense Neoadjuvant Anthracycline Sequential Weekly Paclitaxel for Triple-Negative Breast Cancer Patients.

INTRODUCTION/BACKGROUND: To investigate the differences in pathological response and survival outcomes between dose-dense and conventional-interval neoadjuvant chemotherapy (NAC) in patients with triple-negative breast cancer (TNBC). PATIENTS AND METHODS: Patients with TNBC who received NAC including epirubicin plus cyclophosphamide followed by weekly paclitaxel were included. A total of 494 patients were divided into either the dose-dense anthracycline (ddEC-wP) group or conventional interval anthracycline (EC-wP) group. RESULTS: The breast pathological complete response (bpCR, ypT0/is) rate was 45.3% (n = 101) in the dose-dense group and 34.3% (n = 93) in the conventionally scheduled group, which was a significant difference (P = .013), and in the 251 pN+ cases, the lymph node pathological complete response (LNpCR, ypN0) rate was 57.9% (n = 62) in the dose-dense group and 43.7% (n = 63) in the conventionally scheduled group, which was a significant difference (P = .026) in the univariate analysis. In the multivariate logistic regression analysis, 3 variables were predictive of bpCR: pathological type, surgical methods and type of chemotherapy, with P values of .012, .001 and .021, respectively. Two variables were predictive of LNpCR: type of chemotherapy and Her-2 expression, with P values of .039 and .020, respectively. After a median follow-up of 54 months, there was no significant difference in survival for disease-free survival (DFS) (hazard ratio [HR], 0.788; 95% confidence interval [CI], 0.508 to 1.223; P = .288), distant disease-free survival (DDFS) (HR, 0. 709; 95% CI, 0.440 to 1.144; P = .159) or overall survival (OS) (HR, 0. 750; 95% CI, 0.420 to 1.338; P = .330) between the 2 groups. CONCLUSION: Our study demonstrated that TNBC achieved a higher bpCR rate and LNpCR rate after dose-dense neoadjuvant chemotherapy than the conventional scheme. The survival benefit of the 2 groups did not reach statistical difference.

Sustained-release behavior and the antitumor effect of charge-convertible poly(amino acid)s drug-loaded nanoparticles.

Enhancing tissue permeability and achieving drug aggregation is the key to targeted tumor therapy. A series triblock copolymers of poly(ethylene glycol)-poly(L-lysine)-poly(L-glutamine) were synthesized by ring-opening polymerization, and charge-convertible nano-delivery system was constructed by loading doxorubicin (DOX) with 2-(hexaethylimide) ethanol on side chain. In normal environment (pH = 7.4), the zeta potential of the drug-loaded nanoparticle solution is negative, which is conducive to avoiding the identification and clearance of nanoparticles by the reticulo-endothelial system, while potential-reversal can be achieved in the tumor microenvironment, which effectively promotes cellular uptake. Nanoparticles could effectively reduce the distribution of DOX in normal tissues and achieve targeted aggregation at tumor sites, which can effectively improve the antitumor effect, while would not causing toxicity and damage to normal body.

Exposure of Tibetan pregnant women to antibiotics in China: A biomonitoring-based study.

Tibetan people are one Chinese ethnic minority living in Qinghai-Tibet Plateau with an average altitude of more than 4500 m. High altitude could cause a different antibiotic exposure, but relevant information is limited in Tibetan people. We investigated 476 Tibetan pregnant women in Lhasa, Tibet in 2021 and measured 30 antibiotics from five categories in urine, including 13 veterinary antibiotics (VAs), five human antibiotics (HAs), and 12 human/veterinary antibiotics (H/VAs). Food consumption was investigated by a brief food frequency questionnaire. Health risk was assessed by hazard quotient (HQ) and hazard index (HI) based on acceptable daily intakes (ADIs). All antibiotics were overall detected in 34.7% of urine samples with the 75th percentile concentration of 0.19 ng/mL (0.35 µg/g creatinine). HAs, VAs, and H/VAs were respectively detected in 5.3%, 13.0%, and 25.0% of urine samples, with the 95th percentiles of 0.01 ng/mL (0.01 µg/g creatinine), 0.50 ng/mL (0.99 µg/g creatinine), and 3.58 ng/mL (5.02 µg/g creatinine), respectively. Maternal age, smoking of family members, and housework time were associated with detection frequencies of HAs, VAs, or sum of all antibiotics. Pregnant women with a more frequent consumption of fresh milk, egg, yoghourt, poultry meat, and fish had a higher detection frequency of VAs or H/VAs. Only ciprofloxacin and tetracycline had a HQ of larger than one based on microbiological effect in 1.26% and 0.21% of pregnant women, respectively and a HI of larger than one was found in 1.47% of pregnant women. The findings suggested that there was an evident antibiotic exposure from various sources in Tibetan pregnant women with some basic characteristics of pregnant women as potential predictors and several animal-derived food items were important sources of exposure to antibiotic with a fraction of pregnant women in the health risk related to microbiological disruption of gut microbiota.