Background. Radiofrequency of the Gasserian ganglion can be used for ophthalmic herpetic neuralgia (OHN), but it is associated with complications. This study aimed to use the supraorbital nerve for ...computed tomography- (CT-) guided radiofrequency thermocoagulation to treat refractory OHN. Methods. This was a retrospective case series study of patients with simple or combined OHN treated at our hospital between 06/2012 and 06/2018. The numerical rating score (NRS), spontaneous pain, allodynia, gabapentin dosage, paracetamol/oxycodone dosage, patient global impression of change (PGIC) score, Barrow numbness score, postoperative 360-day recurrence rate, and complications were recorded before the operation and at 1, 30, 90, 180, and 360 days after the operation. Results. Compared with baseline, the NRS was decreased, and PGIC was increased at postoperative 1, 30, 90, 180, and 360 days, and the gabapentin and paracetamol oxycodone doses at postoperative 30, 90, 180, and 360 days were decreased (all P<0.001). Compared with 1 day after the operation, numbness was decreased at 30, 90, 180, and 360 days after the operation (P<0.001). Compared with baseline, the number of patients with allodynia at each time point after the operation was decreased (P<0.001), but without a difference for spontaneous pain (P=0.407). No subjects showed drooping eyelid, corneal ulcers, eyeball damage, decreased vision, and other severe complications. Conclusion. CT-guided supraorbital nerve radiofrequency thermocoagulation for the treatment of OHN can effectively relieve pain and reduce the dose of analgesics, without any serious complication. This study suggests that this technique is feasible and applicable to clinical practice.
Abstract
Whole-genome recoding has been shown to enable nonstandard amino acids, biocontainment and viral resistance in bacteria. Here we take the first steps to extend this to human cells ...demonstrating exceptional base editing to convert TAG to TAA for 33 essential genes via a single transfection, and examine base-editing genome-wide (observing ~40 C-to-T off-target events in essential gene exons). We also introduce GRIT, a computational tool for recoding. This demonstrates the feasibility of recoding, and highly multiplex editing in mammalian cells.
Background. Primary V1 trigeminal neuralgia is a common refractory neuralgia in clinical practice, lacking effective treatments. Radiofrequency therapy has certain treatment efficacy, but its ...long-term efficacy remained poor and the disease might relapse. Objective. To compare the effects of different types of supraorbital foramen variations on the treatment efficacy of radiofrequency therapy for V1 trigeminal neuralgia. Methods. Data of 54 patients with V1 trigeminal neuralgia who underwent treatment in the First Hospital of Jiaxing, Zhejiang, were retrospectively analyzed. All these patients received CT-guided radiofrequency thermocoagulation of supraorbital nerve. According to the CT images, the supraorbital foramen of the patients was categorized as holes (hole group) or notches (notch group). The patient characteristics, including Numerical Rating Scale (NRS) score and effective treatment rates before and 1 d, 0.5 y, 1 y, and 2 y after operation, and numbness degree at day 1 and 2 y after the operation were compared. The short- and long-term complications during postoperative follow-up period were also recorded. Results. Among the 54 patients, 25 patients were grouped into the hole group and 29 into the notch group. The NRS scores before and at 1 d, 0.5 y, 1 y, and 2 y after operation showed no significant differences between the two groups. However, the NRS scores at the remaining time points after operation were significantly decreased when compared with scores before operation (P<0.05). The numbness and numbness degree after operation showed no significant differences between the two groups. The numbness degree at 2 y after operation was significantly lower than 1 d after operation (P<0.05). The effective rate at 1 d, 0.5 y, and 1 y after operation showed no significant differences between the hole and notch groups. However, the effective rate at 2 y after operation was significantly lower in the notch group than hole group (P<0.05). No severe short- or long-term complications were found in either group. Conclusion. The short- and long-term effective rates of radiofrequency therapy during V1 trigeminal neuralgia treatment are relatively high in patients with different types of supraorbital foramen variations. However, the effective rate is even higher in patients with hole-type supraorbital foramen. No other severe complications, except numbness, were found, and the acceptability rate remained high in patients.
The generation of organoids and tissues with programmable cellular complexity, architecture and function would benefit from the simultaneous differentiation of human induced pluripotent stem cells ...(hiPSCs) into divergent cell types. Yet differentiation protocols for the overexpression of specific transcription factors typically produce a single cell type. Here we show that patterned organoids and bioprinted tissues with controlled composition and organization can be generated by simultaneously co-differentiating hiPSCs into distinct cell types via the forced overexpression of transcription factors, independently of culture-media composition. Specifically, we used such orthogonally induced differentiation to generate endothelial cells and neurons from hiPSCs in a one-pot system containing either neural or endothelial stem-cell-specifying media, and to produce vascularized and patterned cortical organoids within days by aggregating inducible-transcription-factor and wild-type hiPSCs into randomly pooled or multicore-shell embryoid bodies. Moreover, by leveraging multimaterial bioprinting of hiPSC inks without extracellular matrix, we generated patterned neural tissues with layered regions composed of neural stem cells, endothelium and neurons. Orthogonally induced differentiation of stem cells may facilitate the fabrication of engineered tissues for biomedical applications.
Bone cancer pain (BCP) is an intractable clinical problem, and lacked effective drugs for treating it. Recent research showed that several chemokines in the spinal cord are involved in the ...pathogenesis of BCP. In this study, the antinociceptive effects of liquiritin, which is an active component extracted from Glycyrrhizae Radix, were tested and the underlying mechanisms targeting spinal dorsal horn (SDH) were investigated. The BCP group displayed a significant decrease in the mechanical withdrawal threshold on days 6, 12, and 18 when compared with sham groups. Intrathecal administration of different doses of liquiritin alleviated mechanical allodynia in BCP rats. The results of immunofluorescent staining and western blotting showed that liquiritin inhibited BCP-induced activation of astrocytes in the spinal cord. Moreover, intrathecal administration of liquiritin effectively inhibited the activation of CXCL1/CXCR2 signaling pathway and production of IL-1β and IL-17 in BCP rats. In astroglial-enriched cultures, Lipopolysaccharides (LPS) elicited the release of chemokine CXCL1, and the release was decreased in a dose-dependent manner by liquiritin. In primary neurons, liquiritin indirectly reduced the increase of CXCR2 by astroglial-enriched-conditioned medium but not directly on the CXCR2 target site. These results suggested that liquiritin effectively attenuated BCP in rats by inhibiting the activation of spinal astrocytic CXCL1 and neuronal CXCR2 pathway. These findings provided evidence regarding the the antinociceptive effect of liquiritin on BCP.
Cerebral organoids can be used to gain insights into cell type specific processes perturbed by genetic variants associated with neuropsychiatric disorders. However, robust and scalable phenotyping of ...organoids remains challenging. Here, we perform RNA sequencing on 71 samples comprising 1,420 cerebral organoids from 25 donors, and describe a framework (Orgo-Seq) to integrate bulk RNA and single-cell RNA sequence data. We apply Orgo-Seq to 16p11.2 deletions and 15q11-13 duplications, two loci associated with autism spectrum disorder, to identify immature neurons and intermediate progenitor cells as critical cell types for 16p11.2 deletions. We further applied Orgo-Seq to identify cell type-specific driver genes. Our work presents a quantitative phenotyping framework to integrate multi-transcriptomic datasets for the identification of cell types and cell type-specific co-expressed driver genes associated with neuropsychiatric disorders.
Coronavirus disease 2019 (COVID-19) continues to burden society worldwide. Despite most patients having a mild course, severe presentations have limited treatment options. COVID-19 manifestations ...extend beyond the lungs and may affect the cardiovascular, nervous, and other organ systems. Current treatments are nonspecific and do not address potential long-term consequences such as pulmonary fibrosis, demyelination, and ischemic organ damage. Cell therapies offer great potential in treating severe COVID-19 presentations due to their customizability and regenerative function. This review summarizes COVID-19 pathogenesis, respective areas where cell therapies have potential, and the ongoing 89 cell therapy trials in COVID-19 as of 1 January 2021.
Gene activation with the CRISPR-Cas system has great implications in studying gene function, controlling cellular behavior, and modulating disease progression. In this review, we survey recent ...studies on targeted gene activation and multiplexed screening for inducing neuronal differentiation using CRISPR-Cas transcriptional activation (CRISPRa) and open reading frame (ORF) expression. Critical technical parameters of CRISPRa and ORF-based strategies for neuronal programming are presented and discussed. In addition, recent progress on
applications of CRISPRa to the nervous system are highlighted. Overall, CRISPRa represents a valuable addition to the experimental toolbox for neuronal cell-type programming.
Whole-genome recoding has been shown to enable nonstandard amino acids, biocontainment and viral resistance in bacteria. Here we take the first steps to extend this to human cells demonstrating ...exceptional base editing to convert TAG to TAA for 33 essential genes via a single transfection, and examine base-editing genome-wide (observing ~40 C-to-T off-target events in essential gene exons). We also introduce GRIT, a computational tool for recoding. This demonstrates the feasibility of recoding, and highly multiplex editing in mammalian cells.
Having complete spatial and temporal information about biological systems will provide the ultimate guidebook about how complex systems like the human body function. In the meantime, the ...understanding of how the complex human body work will inevitably lead to strategies to perturb, restore, or even optimize how it performs. While the human genome is the underlying blueprint that instructs how the system should work, the transcriptome is the functional manifestation that carries the genetically encoded information into action. Reading the transcriptome could offer valuable insight into cellular function, tissue/organ development, and disease progression. Technologies for reading the transcriptome have evolved tremendously over the past two decades, from microarray to next-generation sequencing (NGS), to single-cell sequencing, and, recently, to spatial transcriptomics. As the methods for reading the transcriptome evolve, so does the methods for writing the transcriptome. From siRNA to transcription factors, from zinc-finger proteins to CRISPR/Cas9, the arsenal to precisely influence and control cellular behaviors has expanded rapidly.In this thesis, work on both fronts will be presented. Chapter One reviews previous developments in technologies for reading and writing of the transcriptome. Chapter Two describes the first major project about developing a highly multiplexed method for targeted in situ RNA detection, Barcoded oligonucleotides ligated on RNA amplified for multiplexed and parallel in situ analyses (BOLORAMIS). Chapter Three describes the second major project about iterative single-cell transcription factor library screens for hiPSCs differentiation, with a particular focus on microglia. Also included in this chapter is an exploratory analysis of using single-cell atlas data to guide cell fate engineering. Finally, in Chapter Four, conclusions from the work presented in previous chapters and future directions are discussed.
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