Physical and chemical signals in the central nervous system yield crucial information that is clinically relevant under both physiological and pathological conditions. The emerging field of bioelectronics focuses on the monitoring and manipulation of neurophysiological signals with high spatiotemporal resolution and minimal invasiveness. Significant advances have been realized through innovations in materials and structural design, which have markedly enhanced mechanical and electrical properties, biocompatibility, and overall device performance. The diagnostic and therapeutic potential of soft bioelectronics has been corroborated across a diverse array of pre-clinical settings. This review summarizes recent studies that underscore the developments and applications of soft bioelectronics in neurological disorders, including neuromonitoring, neuromodulation, tumor treatment, and biosensing. Limitations and outlooks of soft devices are also discussed in terms of power supply, wireless control, biocompatibility, and the integration of artificial intelligence. This review highlights the potential of soft bioelectronics as a future platform to promote deciphering brain functions and clinical outcomes of neurological diseases.
Facial palsy (FP) profoundly influences interpersonal communication and emotional expression, necessitating precise diagnostic and monitoring tools for optimal care. However, current electromyography (EMG) systems are limited by their bulky nature, complex setups, and dependence on skilled technicians. Here we report an innovative biosensing approach that utilizes a PEDOT:PSS-modified flexible microneedle electrode array (P-FMNEA) to overcome the limitations of existing EMG devices. Supple system-level mechanics ensure excellent conformality to the facial curvilinear regions, enabling the detection of targeted muscular ensemble movements for facial paralysis assessment. Moreover, our apparatus adeptly captures each electrical impulse in response to real-time direct nerve stimulation during neurosurgical procedures. The wireless conveyance of EMG signals to medical facilities via a server augments access to patient follow-up evaluation data, fostering prompt treatment suggestions and enabling the access of multiple facial EMG datasets during typical 6-month follow-ups. Furthermore, the device's soft mechanics alleviate issues of spatial intricacy, diminish pain, and minimize soft tissue hematomas associated with traditional needle electrode positioning. This groundbreaking biosensing strategy has the potential to transform FP management by providing an efficient, user-friendly, and less invasive alternative to the prevailing EMG devices. This pioneering technology enables more informed decision-making in FP-management and therapeutic intervention.
Purpose: Lower-grade gliomas (LGGs) are a group of infiltrative growing glial brain tumors characterized by intricate intratumoral heterogeneity and subtle visual appearance differences from non-tumor tissue, which can lead to errors in pathologic tissue sampling. Although 5-ALA fluorescence has been an essential method for visualizing gliomas during surgery, its effectiveness is limited in the case of LGGs due to low sensitivity. Therefore, we developed a novel PET/NIR dual-modality image probe targeting gastrin-releasing peptide receptor (GRPR) in glioma cells to enhance tumor visualization and improve the accuracy of sampling. Methods: A prospective, non-randomized, single-center feasibility clinical trial (NCT03407781) was conducted in the referral center from October 21, 2016, to August 17, 2018. Consecutive enrollment included patients suspected of having LGGs and considered suitable candidates for surgical removal. Group 1 comprised ten patients who underwent preoperative 68Ga-IRDye800CW-BBN PET/MRI assessment followed by intraoperative fluorescence-guided surgery. Group 2 included 42 patients who underwent IRDye800CW-BBN fluorescence-guided surgery. The primary endpoints were the predictive value of preoperative PET imaging for intraoperative fluorescence and the sensitivity and specificity of fluorescence-guided sampling. Results: Thirty-nine patients were included in the in-depth analysis of endpoints, with 25 (64.1%) exhibiting visible fluorescence, while 14 (35.9%) did not. The preoperative positive PET uptake exhibited a greater accuracy in predicting intraoperative fluorescence compared to MRI enhancement (100% [10/10] vs. 87.2% [34/39]). A total of 125 samples were harvested during surgery. Compared with pathology, subjective fluorescence intensity showed a sensitivity of 88.6% and a specificity of 88.2% in identifying WHO grade III samples. For WHO grade II samples, the sensitivity and specificity of fluorescence were 54.7% and 88.2%, respectively. Conclusion: This study has demonstrated the feasibility of the novel dual-modality imaging technique for integrated pre- and intraoperative targeted imaging via the same molecular receptor in surgeries for LGGs. The PET/NIR dual-modality probe exhibits promise for preoperative surgical planning in fluorescence-guided surgery and provides greater accuracy in guiding tumor sampling compared to 5-ALA in patients with LGGs.
Brain Neoplasms , Glioma , Humans , Receptors, Bombesin , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/surgery , Brain Neoplasms/pathology , Prospective Studies , Glioma/diagnostic imaging , Glioma/surgery , Glioma/pathology , Aminolevulinic Acid , Positron-Emission Tomography/methods
Medical devices are commonly implanted underneath the skin, but how to real-time noninvasively monitor their migration, integrity, and biodegradation in human body is still a formidable challenge. Here, the study demonstrates that benzyl violet 4B (BV-4B), a main component in the FDA-approved surgical suture, is found to produce fluorescence signal in the first near-infrared window (NIR-I, 700-900 nm) in polar solutions, whereas BV-4B self-assembles into highly crystalline aggregates upon a formation of ultrasmall nanodots and can emit strong fluorescence in the second near-infrared window (NIR-II, 1000-1700 nm) with a dramatic bathochromic shift in the absorption spectrum of ≈200 nm. Intriguingly, BV-4B-involved suture knots underneath the skin can be facilely monitored during the whole degradation process in vivo, and the rupture of the customized BV-4B-coated silicone catheter is noninvasively diagnosed by NIR-II imaging. Furthermore, BV-4B suspended in embolization glue achieves hybrid fluorescence-guided surgery (hybrid FGS) for arteriovenous malformation. As a proof-of-concept study, the solid-state BV-4B is successfully used for NIR-II imaging of surgical sutures in operations of patients. Overall, as a clinically translatable solid-state dye, BV-4B can be applied for in vivo monitoring the fate of medical devices by NIR-II imaging.
Coloring Agents , Optical Imaging , Humans , Optical Imaging/methods , Spectroscopy, Near-Infrared
In microneurosurgery, it is crucial to maintain the structural and functional integrity of the nerve through continuous intraoperative identification of neural anatomy. To this end, here we report the development of a translatable system leveraging soft and stretchable organic-electronic materials for continuous intraoperative neurophysiological monitoring. The system uses conducting polymer electrodes with low impedance and low modulus to record near-field action potentials continuously during microsurgeries, offers higher signal-to-noise ratios and reduced invasiveness when compared with handheld clinical probes for intraoperative neurophysiological monitoring and can be multiplexed, allowing for the precise localization of the target nerve in the absence of anatomical landmarks. Compared with commercial metal electrodes, the neurophysiological monitoring system allowed for enhanced post-operative prognoses after tumour-resection surgeries in rats. Continuous recording of near-field action potentials during microsurgeries may allow for the precise identification of neural anatomy through the entire procedure.
We aimed to develop a new biocompatible gastrin-releasing peptide receptor (GRPR) targeted optical probe, IRDye800-RM26, for fluorescence image-guided surgery (FGS) of brain malignancies in near-infrared window II (NIR-II) imaging. We developed a novel GRPR targeting probe using a nine-amino-acid bombesin antagonist analog RM26 combined with IRDye800CW, and explored the fluorescent probe according to optical properties. Fluorescence imaging characterization in NIR-I/II region was performed in vitro and in vivo. Following simulated NIR-II image-guided surgery, we obtained time-fluorescent intensity curves and time-signal and background ratio curves. Further, we used histological sections of brain from tumor-beating mice model to compare imaging specificity between 5-aminolevulinic acid (5-ALA) and IRDye800-RM26, and evaluated biodistribution and biocompatibility. IRDye800-RM26 had broad emission ranging from 800 to 1200 nm, showing considerable fluorescent intensity in NIR-II region. High-resolution NIR-II imaging of IRDye800-RM26 can enhance the advantages of NIR-I imaging. Dynamic and real time fluorescence imaging in NIR-II region showed that the probe can be used to treat brain malignancies in mice between 12 and 24 h post injection. Its specificity in targeting glioblastoma was superior to 5-ALA. Biodistribution analysis indicated IRDye800-RM26 excretion in the kidney and liver. Histological and blood test analyses did not reveal acute severe toxicities in mice treated with effective dose (40 µg) of the probe for NIR-II imaging. Because of the considerable fluorescent intensity in NIR-II region and high spatial resolution, biocompatible and excretable IRDye800-RM26 holds great potentials for FGS, and is essential for translation into human use.
As an eco-friendly material, PLA was a desirable alternative to polyethylene and polypropylene films due to its biodegradability. The preferable melt strength of PLA-based materials was a key factor in ensuring its processing using extrusion blow. This paper focuses on the influence of interchain force and/or chain entanglement on the melt strength and ductility of PLA-based materials in recent years. In addition, the preparation of PLA-based materials via physical blending or reactive processing was also summarized. The blending of PLA with a flexible heteropolymer, driven by the interchain force and/or chain entanglements, were characterized as a practicable method for toughening PLA-based materials. Also, the restructuring of PLA chains, by branching based on chain entanglement, was suitable for increasing chain entanglements in PLA matrix, yielding satisfactory melt strength and ductility. This review aims to elucidate the relationship between interchain forces and/or entanglement with the melt strength and ductility of PLA-based materials. An essential and systematic understanding of the tailoring melt strength and rheological properties of PLA by interchain forces and/or entanglement was apt to improve and perfect the processing technology of the extrusion blow, and consequently improve the tensile strength and toughness of PLA films.
Background: The lack of a well-designed brain tumour registry with standardized pathological diagnoses in underdeveloped countries hinders the ability to compare epidemiologic data across the globe. The National Brain Tumour Registry of China (NBTRC), created in January 2018, is the first multi-hospital-based brain tumour registry in China. Patient data reported to the NBTRC in years 2019-2020 were assessed. Methods: Tumour pathology was based on the 2016 World Health Organization (WHO) classification of tumours of the central nervous system and ICD-O-3. The anatomical site was coded per the Surveillance, Epidemiology, and End Results (SEER) solid tumour module (version of July 2019). The cases were tabulated by histology and anatomical site. Categorical variables were reported as numbers (percentages). The distribution of tumours by age (0-14, 15-19, 20-39, 40-64, and 65+ years) was analysed. Findings: There were a total of 25,537 brain tumours, foremost among them meningioma (23.63%), followed by tumours of the pituitary (23.42%), and nerve sheath tumours (9.09%). Glioblastoma, the most common and lethal form of primary brain cancer in adults, represented 8.56% of all cases. Of note, 6.48% of the malignant tumours were located in the brain stem. The percentage of malignant brain tumours decreased with increasing age, 24.08% in adults (40+ years), 30.25% in young adults (20-39 years), 35.27% in adolescents (15-19 years), and 49.83% in children (0-14 years). Among the 2107 paediatric patients, the most common sites were ventricle (17.19%), brainstem (14.03%), pituitary and craniopharyngeal duct (13.4%), and cerebellum (12.3%), a distribution that differed from that of the entire cohort. The histology distribution was also unique in children, with glioblastoma much less incident compared to the whole cohort (3% vs. 8.47%, p < 0.01). 58.80% of all patients chose higher-level neurosurgical hospitals outside of their province of residence. The median in-hospital length of stay (LOS) for the various pathologies ranged from 11 to 19 days. Interpretation: The histological and anatomical site distribution of brain tumours in the NBTRC was statistically different in the subgroup of children (0-14 years). Patient choice of pursuing trans-provincial treatment was common and the in-hospital LOS was longer compared to that reported in similar European and American patient populations, which merits further attention. Funding: The National Key Research and Development Program of China (2015BAI12B04, 2013BAI09B03, 2014BAI04B01, and 2021YFF1201104) and Chinese National Natural Science Foundation of China (81971668).
Artificial skin that simultaneously mimics sensory feedback and mechanical properties of natural skin holds substantial promise for next-generation robotic and medical devices. However, achieving such a biomimetic system that can seamlessly integrate with the human body remains a challenge. Through rational design and engineering of material properties, device structures, and system architectures, we realized a monolithic soft prosthetic electronic skin (e-skin). It is capable of multimodal perception, neuromorphic pulse-train signal generation, and closed-loop actuation. With a trilayer, high-permittivity elastomeric dielectric, we achieved a low subthreshold swing comparable to that of polycrystalline silicon transistors, a low operation voltage, low power consumption, and medium-scale circuit integration complexity for stretchable organic devices. Our e-skin mimics the biological sensorimotor loop, whereby a solid-state synaptic transistor elicits stronger actuation when a stimulus of increasing pressure is applied.
Feedback, Sensory , Robotics , Skin, Artificial , Wearable Electronic Devices , Humans , Electronics , Skin , Transistors, Electronic
Background: Lung adenocarcinoma (LUAD) is the most common form of lung cancer and is often accompanied by brain metastasis (BM). The heterogeneity of the tumor renders all current conventional treatments less effective. This study aims to dissect tumor cell heterogeneity and identify potential therapeutic targets. Methods: We conducted single-cell RNA-sequencing (scRNA-seq) in 8 patients with treatment-naïve LUAD BM and included scRNA-seq data of 10 primary LUAD samples and their matched adjacent normal tissue from GSE131907 to determine the tumor cell heterogeneity. Results: Our analyses revealed tumor cells derived from brain metastases were more heterogeneous. Tumor cells from BM harbored significantly more copy number variants (CNVs), and cells of magnoid subtype were the critical source of malignant cells both in BM and the primary lung tumor. Pseudo-time trajectory analysis revealed that malignant cells had upregulated genes enriched for cell cycle and cell division. Integrated analysis of tumor cells revealed 2 distinct malignant cell clusters (cluster 4 and cluster 6) and their marker genes. The signatures identified in the single-cell profile had prognostic value in the bulk tumor profiles. Moreover, the signature of cluster 4 had significant prognostic value in predicting patients surviving longer than 3.5 years, while the signature of cluster 6 showed better predictive ability within 1 year. Magnoid-type cells are most likely to develop into the riskiest cell type and potentially promote tumor progression. Conclusions: scRNA profiling that integrates LUAD BM and primary LUAD can provide information on those malignant cells with BM potential, offering additional prognostic information at cellular level, and may serve as a foundational resource for further tumor cell dissection and therapeutic target exploration.
Introduction: Integrin αvß6, which is upregulated in malignancies and remains absent or weak in normal tissue, is a promising target in molecular imaging therapeutics. In vivo imaging of integrin αvß6 could therefore be valuable for early tumor detection and intraoperative guidance. Methods: In this study, integrin αvß6-targeting probe G2-SFLAP3 was labeled with near-infrared (NIR) dye Cy5.5 or radioisotope 68Ga. The resulting probes were evaluated in integrin αvß6-positive A549 and αvß6-negative H1703 xenograft mice models. Results: The cellar uptake of G2-SFLAP3-Cy5.5 was consistent with the expression of integrin αvß6. Both subcutaneous and brain metastatic A549 tumors could be clearly visualized by NIR fluorescent imaging of G2-SFLAP3-Cy5.5. A549 tumors demonstrated the highest G2-SFLAP3-Cy5.5 accumulation at 4h post-injection (p.i.) and remain detectable at 84h p.i. The fluorescent signal of G2-SFLAP3-Cy5.5 was significantly reduced in H1703 and A549-blocking groups. Consistently, small-animal PET imaging showed tumor-specific accumulation of 68Ga-DOTA-G2-SFLAP3. Discussion: G2-SFLAP3 represents a promising agent for noninvasive imaging of non-small cell lung cancer (NSCLC) and brain metastases.
Corn starch was plasticized by glycerol suspension in a twin-screw extruder, in which the glycerol suspension was the pre-dispersion mixture of glycerol with nano-SiO2. Polylactide (PLA)/thermoplastic starch/SiO2 composites were obtained through melt-blending of PLA with thermoplastic starch/SiO2 in a twin-screw extruder. The nonisothermal crystallization behavior of PLA in the composites was investigated by differential scanning calorimetry. An interface of PLA with thermoplastic starch was proven to exist in the composites, and its interfacial bonding characteristics were analyzed. The interfacial binding energy stemming from PLA with thermoplastic starch exerts a significant influence on the segmental mobility of PLA at the interface. The segmental mobility of PLA is gradually improved by increasing interfacial binding energy, and consequently, the relative crystallinity on the interface exhibits progressive promotion. The Jeziorny model could well describe the primary crystallization of PLA in the composites. The extracted Avrami exponents based on the Jeziorny model indicate that the primary crystallization of PLA follows heterogeneous nucleation and three-dimensional growth. This study has revealed the intrinsic effect of the interfacial segmental mobility on the nonisothermal crystallization behavior of PLA in composites, which is of technological significance for its blow molding.
BACKGROUND: Laser interstitial thermal therapy (LITT) has been used to treat brain metastases (BMs) in several countries, and its safety and effectiveness have been confirmed. In most cases, magnetic resonance imaging (MRI) reveals an increase in tumor volume with an enhanced margin after LITT. However, little is known about the relationship between this MRI change and tumor recurrence. OBJECTIVE: We report the first case series of BMs treated by LITT in China to evaluate the clinical characteristics and predictive factors of tumor recurrence. MATERIAL AND METHODS: Patients with less than four brain metastatic lesions and a Karnofsky performance status (KPS) > 70 were eligible for study inclusion. Standard LITT procedures were performed, and a follow-up MRI was performed to analyze the radiographic changes, especially the volume ratio of the enhanced margin and the whole lesion on MRI at 30 days postoperatively. All the volume-related data were delineated and calculated using 3D Slicer software. Related predictors were also collected to evaluate the correlation with local tumor control. RESULTS: Eighteen patients with nineteen lesions were enrolled for treatment and follow-up. Primary tumor histology included pulmonary carcinoma (n = 11) and breast cancer (n = 4). On average, the tumor size measured 3.01 cm3 (range, 0.40-7.40 cm3), the total ablation time was 13.58 min (range, 2.88-37.15 min), and the complete ablation rate was 92.4% (range, 29.2-100%). Comparing 3s0-day follow-up MRI results with preoperative MRI findings, 18 lesions showed a 2.28-fold (range, 1.21-4.88) volume increase; all the lesions displayed an enhanced component with a volume ratio of 42.35% (range, 10.14-100%). Five patients experienced tumor recurrence, and the local tumor control rates at 90 days and 180 days of follow-up were 68.4% and 66.7%, respectively. Univariate analysis indicated that the primary tumor, ablation rate, and enhanced volume ratio (EVR) > 40% in the 30-day MRI were associated with tumor recurrence, whereas multivariate analysis showed that only EVR > 40% was a predictive factor of local control. CONCLUSION: LITT is a minimally invasive method used to ablate brain metastases which can be used as the first-line treatment for BM patients under certain indications. After LITT, most tumors showed volume enlargement on the 30-day MRI scan, and EVR > 40% on the 30-day MRI may indicate late tumor recurrence.
Brain Neoplasms , Laser Therapy , Humans , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/surgery , Neoplasm Recurrence, Local/etiology , Laser Therapy/methods , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/surgery , Magnetic Resonance Imaging/methods , Lasers , Treatment Outcome
PURPOSE: This study aimed to describe 11C-methionine (11C-MET) PET imaging characteristics in patients with paediatric diffuse intrinsic pontine glioma (DIPG) and correlate them with survival and H3 K27M mutation status. METHODS: We retrospectively analysed 98 children newly diagnosed with DIPG who underwent 11C-MET PET. PET imaging characteristics evaluated included uptake intensity, uniformity, metabolic tumour volume (MTV), and total lesion methionine uptake (TLMU). The maximum, mean, and peak of the tumour-to-background ratio (TBR), calculated as the corresponding standardised uptake values (SUV) divided by the mean reference value, were also recorded. The associations between the PET imaging characteristics and clinical outcomes in terms of progression-free survival (PFS) and overall survival (OS) and H3 K27M mutation status were assessed, respectively. RESULTS: In univariate analysis, imaging characteristics significantly associated with shorter PFS and OS included a higher uniformity grade, higher TBRs, larger MTV, and higher TLMU. In multivariate analysis, larger MTV at diagnosis, shorter symptom duration, and no treatment were significantly correlated with shorter PFS and OS. The PET imaging features were not correlated with H3 K27M mutation status. CONCLUSION: Although several imaging features were significantly associated with PFS and OS, only MTV, indicating the size of the active tumour, was identified as a strong independent prognostic factor.
Brain Neoplasms , Diffuse Intrinsic Pontine Glioma , Glioma , Humans , Child , Methionine/genetics , Brain Neoplasms/genetics , Glioma/diagnostic imaging , Glioma/genetics , Glioma/metabolism , Retrospective Studies , Diffuse Intrinsic Pontine Glioma/diagnostic imaging , Diffuse Intrinsic Pontine Glioma/genetics , Racemethionine , Positron-Emission Tomography , Mutation
BACKGROUND: Evidence about the prognostic value of primary tumor surgery (PTS) in patients with brain metastatic malignancies is ambiguous and controversial. This study assessed the survival benefits of primary tumor surgery in patients with brain metastases (BMs). METHODS: Adults patients with BMs that originated from lung, breast, kidney, skin, colon, and liver diagnosed between 2010 and 2018 were derived from the Surveillance, Epidemiology, and End Results database (SEER). Propensity score matching (PSM) was used to balance the bias between patients with or without PTS. Then the prognostic value of PTS was estimated by Kaplan-Meier analysis and Cox proportional hazard regression models. RESULTS: A total of 32,760 patients with BMs secondary to non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), breast cancer, renal cancer, melanoma, colorectal cancer, and liver cancer were identified from the database. After PSM at 1:1 ratio, PTS appeared to significantly prolong cause-specific survival (CSS) time for patients with BMs secondary to NSCLC, breast cancer, renal cancer, and colorectal cancer (hazard ratio [HR] = 0.60 [0.53-0.68], 0.56 [0.43-0.73], 0.47 [0.37-0.60], and 0.59 [0.37-0.95], respectively, all p < 0.05). Patients with earlier T and N classifications, no extracranial metastasis, and cancer-specific subtypes (adenocarcinoma in NSCLC, hormone receptor-negative breast cancer) may derive more survival benefits from PTS when suffering from BMs. CONCLUSION: This population-based study supported PTS could provide survival benefits for patients with BMs secondary to NSCLC, breast cancer, renal cancer, and colorectal cancer. More emphasis should be put on PTS of selected patients with BMs.
Brain Neoplasms , Breast Neoplasms , Carcinoma, Non-Small-Cell Lung , Carcinoma, Renal Cell , Colorectal Neoplasms , Kidney Neoplasms , Lung Neoplasms , Adult , Humans , Female , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Prognosis , Brain Neoplasms/secondary , SEER Program
Silicone rubber (SR)/vinyl-graphene oxide (vinyl-GO) nanocomposites were prepared through the hydrosilylation reaction of silicon hydrogen polydimethylsiloxane (H-PDMS) with vinyl polydimethylsiloxane (vinyl-PDMS), in which vinyl-GO was used as a nano filler. The thermally conductive and antistatic properties of the nanocomposites, and their tensile strength and thermal stability were evaluated. The thermally conductive and antistatic properties increased naturally when the nanocomposites had eight to nine parts of vinyl-GO. The addition of 9 parts of vinyl-GO increased the thermal conductivity to 0.44 from 0.17 W/m-1·K-1 of neat SR and the surface resistance value to 108 from 1014 Ω of neat SR. Vinyl-GO is effective in improving the tensile strength and toughness of the nanocomposites. The tensile strength and elongation at break of the nanocomposites were much higher than that of neat SR, especially for 10 parts of vinyl-GO in the nanocomposite, and the tensile strength was 1.84 MPa and the elongation at break was 314.1%. Additionally, compared with neat SR, the nanocomposites had a much higher thermal stability. For eight parts of vinyl-GO in the nanocomposites, H-PDMS with the selected silicon hydrogen content and vinyl-PDMS with the selected vinyl content could offer an appropriate cross-linking degree that suits the character of GO. When the nanocomposite had eight parts of vinyl-GO, its scanning electron microscope exhibited a monolayer GO with folded, twisted, and local surface folds. However, there was a certain amount of multilayer aggregation of GO for 10 parts of vinyl-GO in the nanocomposite.
Intrinsically stretchable bioelectronic devices based on soft and conducting organic materials have been regarded as the ideal interface for seamless and biocompatible integration with the human body. A remaining challenge is to combine high mechanical robustness with good electrical conduction, especially when patterned at small feature sizes. We develop a molecular engineering strategy based on a topological supramolecular network, which allows for the decoupling of competing effects from multiple molecular building blocks to meet complex requirements. We obtained simultaneously high conductivity and crack-onset strain in a physiological environment, with direct photopatternability down to the cellular scale. We further collected stable electromyography signals on soft and malleable octopus and performed localized neuromodulation down to single-nucleus precision for controlling organ-specific activities through the delicate brainstem.
Introduction: Secretogranin III (SCG3) physiologically participates in neurotransmitter storage/transport and is widely expressed in neuroendocrine tumors. However, there is no report on SCG3 protein expression in gliomas. Methods: The method of immunohistochemical staining on a glioma tissue microarray was utilized to detect SCG3 protein expression and investigate the correlations of its expression with clinicopathological and genetic features in gliomas. The RNA-seq data of SCG3 in The Cancer Genome Atlas database was exploited to explore these correlations at the transcriptional level. Results: There were 57.5% (130/226) glioma cases having SCG3 cytoplasmic staining in the tissue microarray. SCG3 expression inversely correlated with malignancy grade at both transcriptional and protein levels. The highest level was observed in oligodendroglial tumors, especially in oligodendrogliomas (ODs) with IDH-mutation/1p19q-codeletion. The lowest SCG3 expression was observed in glioblastomas (GBMs), especially in the mesenchymal subtype. Nearly a half of GBM cases (44.4%, 64/144) had any discernible SCG3 staining, and were defined as SCG3-positive by the microarray study. SCG3-positive GBM cases exhibited improved overall survival as compared with the SCG3-negative cases (29.3 vs. 14.5 months; Hazard ratio, 0.364; 95% CI, 0.216-0.612; p < 0.001). A multivariate Cox regression analysis also revealed SCG3 positivity as an independent favorable prognosticator in GBM patients. Conclusion: SCG3 protein expression inversely correlates with glioma malignancy and predicts favorable outcomes in GBM patients.
Biomarkers, Tumor/metabolism , Brain Neoplasms/pathology , Chromogranins/metabolism , Gene Expression Regulation, Neoplastic , Glioma/pathology , Mutation , Biomarkers, Tumor/genetics , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Chromogranins/genetics , Follow-Up Studies , Glioma/genetics , Glioma/metabolism , Humans , Prognosis , Retrospective Studies , Survival Rate
Supra-maximum surgical tumor resection without neurological damage is highly valuable for treatment and prognosis of patients with glioblastoma multiforme (GBM). We developed a GBM-specific fluorescence probe using IRDye800CW (peak absorption/emission, 778/795 nm) and bombesin (BBN), which (IRDye800-BBN) targets the gastrin-releasing peptide receptor, and evaluated the image-guided resection efficiency, sensitivity, specificity, and survivability. Twenty-nine patients with newly diagnosed GBM were enrolled. Sixteen hours preoperatively, IRDye800-BBN (1 mg in 20 ml sterile water) was intravenously administered. A customized fluorescence surgical navigation system was used intraoperatively. Postoperatively, enhanced magnetic resonance images were used to assess the residual tumor volume, calculate the resection extent, and confirm whether complete resection was achieved. Tumor tissues and nonfluorescent brain tissue in adjacent noneloquent boundary areas were harvested and assessed for diagnostic accuracy. Complete resection was achieved in 82.76% of patients. The median extent of resection was 100% (range, 90.6-100%). Eighty-nine samples were harvested, including 70 fluorescence-positive and 19 fluorescence-negative samples. The sensitivity and specificity of IRDye800-BBN were 94.44% (95% CI, 85.65-98.21%) and 88.24% (95% CI, 62.25-97.94%), respectively. Twenty-five patients were followed up (median, 13.5 [3.1-36.0] months), and 14 had died. The mean preoperative and immediate and 6-month postoperative Karnofsky performance scores were 77.9 ± 11.8, 71.3 ± 19.2, and 82.6 ± 14.7, respectively. The median overall and progression-free survival were 23.1 and 14.1 months, respectively. In conclusion, GBM-specific fluorescent IRDye800-BBN can help neurosurgeons identify the tumor boundary with sensitivity and specificity, and may improve survival outcomes.
INTRODUCTION: Brain tumours encompass a complex group of intracranial tumours that mostly affect young adults and children, with a high incidence rate and poor prognosis. It remains impossible to systematically collect data on patients with brain tumours in China and difficult to perform in-depth analysis on the status of brain tumours, medical outcomes or other important medical issues through a multicentre clinical study. This study describes the first nation-wide data platform including the entire spectrum of brain tumour entities, which will allow better management and more efficient application of patient data in China. METHODS AND ANALYSIS: The National Brain Tumor Registry of China (NBTRC) is a registry of real-word clinical data on brain tumours. It is established and managed by the China National Clinical Research Center for Neurological Diseases and administered by its scientific and executive committees. The 54 participating hospitals of the NBTRC are located in 27 provinces/municipalities, performing more than 40 000 brain tumour surgeries per year. The data consist of in-hospital medical records, images and follow-up information after discharge. Data can be uploaded in three ways: the web portal, remote physical servers and offline software. The data quality control scheme is seven-dimensional. Each participating hospital could focus on a single pathology subtype and public subtypes of brain tumour for which they expect to conduct related multicentre clinical research. The standardised workflow to conduct clinical research is based on the benefit-sharing mechanism. Data collection will be conducted continuously from 1 February 2019 to 31 January 2024. ETHICS AND DISSEMINATION: Informed consent will be obtained from all participants. Consent for the adolescents' participation will be also obtained from their guardians via written consent. The results will be published in professional journals, in both Chinese and English. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR1900021096).
Brain Neoplasms , Data Accuracy , Adolescent , Brain Neoplasms/epidemiology , Child , China/epidemiology , Humans , Incidence , Registries , Young Adult
