Transcriptomic analysis of differentially alternative splicing patterns in mice with inflammatory and neuropathic pain.

Although the molecular mechanisms of chronic pain have been extensively studied, a global picture of alternatively spliced genes and events in the peripheral and central nervous systems of chronic pain is poorly understood. The current study analyzed the changing pattern of alternative splicing (AS) in mouse brain, dorsal root ganglion, and spinal cord tissue under inflammatory and neuropathic pain. In total, we identified 6495 differentially alternatively spliced (DAS) genes. The molecular functions of shared DAS genes between these two models are mainly enriched in calcium signaling pathways, synapse organization, axon regeneration, and neurodegeneration disease. Additionally, we identified 509 DAS in differentially expressed genes (DEGs) shared by these two models, accounting for a small proportion of total DEGs. Our findings supported the hypothesis that the AS has an independent regulation pattern different from transcriptional regulation. Taken together, these findings indicate that AS is one of the important molecular mechanisms of chronic pain in mammals. This study presents a global description of AS profile changes in the full path of neuropathic and inflammatory pain models, providing new insights into the underlying mechanisms of chronic pain and guiding genomic clinical diagnosis methods and rational medication.

Mechanisms of adverse mammary effect induced by olanzapine and therapeutic interventions in rat model.

BACKGROUND: Olanzapine antagonizes dopamine receptors and is prescribed to treat multiple psychiatric conditions. The main side effect of concern for olanzapine is weight gain and metabolic syndrome. Olanzapine induces hyperprolactinemia, however its effect on the mammary gland is poorly documented. METHODS: Rats received olanzapine by gavage or in drinking water at 1, 3, and 6 mg/kg/day for 5-40 days or 100 days, with and without coadministration of bromocriptine or aripiprazole and using once daily or continuous administration strategies. Histomorphology of the mammary gland, concentrations of prolactin, estradiol, progesterone, and olanzapine in serum, mammary gland and adipose tissue, and mRNA and protein expressions of prolactin receptors were analyzed. RESULTS: In adult and prepubescent female rats and male rats, olanzapine induced significant development of mammary glands in dose- and time-dependent manners, with histopathological hyperplasia of mammary ducts and alveoli with lumen dilation and secretion, marked increase of mammary prolactin receptor expression, a marker of breast tissue, and with mild increase of circulating prolactin. This side effect can be reversed after medication withdrawal, but long-term olanzapine treatment for 100 days implicated tumorigenic potentials indicated by usual ductal epithelial hyperplasia. Olanzapine induced mammary development was prevented with the coaddition of the dopamine agonist bromocriptine or partial agonist aripiprazole, or by continuous administration of medication instead of a once daily regimen. CONCLUSIONS: These results shed light on the previously overlooked effect of olanzapine on mammary development and present experimental evidence to support current clinical management strategies of antipsychotic induced side effects in the breast.

Lanatoside C inhibits herpes simplex virus 1 replication by regulating NRF2 distribution within cells.

BACKGROUND: In the past decades, extensive research has been conducted to identify new drug targets for the treatment of Herpes simplex virus type 1 (HSV-1) infections. However, the emergence of drug-resistant HSV-1 strains remains a major challenge. This necessitates the identification of new drugs with novel mechanisms of action. Lanatoside C (LanC), a cardiac glycoside (CG) approved by the US Food and Drug Administration (FDA), has demonstrated anticancer and antiviral properties. Nevertheless, its potential as an agent against HSV-1 infections and the underlying mechanism of action are currently unknown. PURPOSE: This study aimed to investigate the antiviral activity of LanC against HSV-1 and elucidate its molecular mechanisms. METHODS: The in vitro antiviral activity of LanC was assessed by examining the levels of viral genes, proteins, and virus titers in HSV-1-infected ARPE-19 and Vero cells. Immunofluorescence (IF) analysis was performed to determine the intracellular distribution of NRF2. Additionally, an in vivo mouse model of HSV-1 infection was developed to evaluate the antiviral activity of LanC, using indicators such as intraepidermal nerve fibers (IENFs) loss and viral gene inhibition. RESULTS: Our findings demonstrate that LanC significantly inhibits HSV-1 replication both in vitro and in vivo. The antiviral effect of LanC is mediated by the perinuclear translocation of NRF2. CONCLUSIONS: LanC exhibits anti-HSV-1 effects in viral infections, which are associated with the intracellular translocation of NRF2. These findings suggest that LanC has the potential to serve as a novel NRF2 modulator in the treatment of viral diseases.

Myocardial fibrosis and prognosis in heart failure with preserved ejection fraction: a pooled analysis of 12 cohort studies.

OBJECTIVES: Heart failure with preserved ejection fraction (HFpEF) is a syndrome with significant clinical heterogeneity. Myocardial fibrosis has been considered a common pathological process in the development and progress of HFpEF. This study aimed to consolidate data on the prognostic effect of myocardial fibrosis, evaluated by cardiovascular magnetic resonance (CMR) imaging in patients with HFpEF. METHODS: Three medical databases were searched for potentially related articles up to February 28, 2023. Cohort studies reporting associations between myocardial fibrosis and risk of all-cause mortality or composite major adverse cardiac outcomes (MACE) were included. Cardiac fibrosis was evaluated by CMR metrics, including late gadolinium enhancement (LGE) or myocardial extracellular volume (ECV). The hazard ratios (HRs) and 95% confidence intervals (CI) of the outcomes for higher myocardial fibrosis were calculated. RESULTS: Twelve studies with 2787 patients with HFpEF were included for analysis. After a median follow-up duration of 31.2 months, a higher level of cardiac fibrosis was associated with a significant increase in the risk of MACE (HR = 1.34, 95% CI = 1.14-1.57) and all-cause mortality (HR = 1.74, 95% CI = 1.27-2.39), respectively. Furthermore, the increased risk of outcomes was both observed when cardiac fibrosis was defined according to LGE or ECV, respectively. CONCLUSIONS: Higher burden of myocardial fibrosis evaluated by CMR can predict a poor prognosis in patients with HFpEF. Evaluation of LGE or ECV based on CMR could be recommended in these patients for risk stratification and guiding further treatment. CLINICAL RELEVANCE STATEMENT: Inclusion of cardiovascular magnetic resonance examination in the diagnostic and risk-evaluation algorithms in patients with heart failure with preserved ejection fraction should be considered in clinical practice and future studies. KEY POINTS: • Myocardial fibrosis is a common pathological process in heart failure with preserved ejection fraction. • A higher myocardial fibrosis burden on cardiac magnetic resonance predicts a poor prognosis in patients with heart failure with preserved ejection fraction. • Evaluation of myocardial fibrosis may be useful in patients with heart failure with preserved ejection fraction for risk stratification and treatment guidance.

Predicting the pathological invasiveness in patients with a solitary pulmonary nodule via Shapley additive explanations interpretation of a tree-based machine learning radiomics model: a multicenter study.

Background: Radiomics models could help assess the benign and malignant invasiveness and prognosis of pulmonary nodules. However, the lack of interpretability limits application of these models. We thus aimed to construct and validate an interpretable and generalized computed tomography (CT) radiomics model to evaluate the pathological invasiveness in patients with a solitary pulmonary nodule in order to improve the management of these patients. Methods: We retrospectively enrolled 248 patients with CT-diagnosed solitary pulmonary nodules. Radiomic features were extracted from nodular region and perinodular regions of 3 and 5 mm. After coarse-to-fine feature selection, the radiomics score (radscore) was calculated using the least absolute shrinkage and selection operator logistic method. Univariate and multivariate logistic regression analyses were performed to determine the invasiveness-related clinicoradiological factors. The clinical-radiomics model was then constructed using the logistic and extreme gradient boosting (XGBoost) algorithms. The Shapley additive explanations (SHAP) method was then used to explain the contributions of the features. After removing batch effects with the ComBat algorithm, we assessed the generalization of the explainable clinical-radiomics model in two independent external validation cohorts (n=147 and n=149). Results: The clinical-radiomic XGBoost model integrating the radscore, CT value, nodule length, and crescent sign demonstrated better predictive performance than did the clinical-radiomics logistic model in assessing pulmonary nodule invasiveness, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.889 [95% confidence interval (CI), 0.848-0.927] in the training cohort. The SHAP algorithm illustrates the contribution of each feature in the final model. The specific model decision process was visualized using a tree-based decision heatmap. Satisfactory generalization performance was shown with AUCs of 0.889 (95% CI, 0.823-0.942) and 0.915 (95% CI, 0.851-0.963) in the two external validation cohorts. Conclusions: An interpretable and generalized clinical-radiomics model for predicting pulmonary nodule invasibility was constructed to help clinicians determine the invasiveness of pulmonary nodules and devise assessment strategies in an easily understandable manner.

Crystallization Regulation by Self-Assembling Liquid Crystal Template Enables Efficient and Stable Perovskite Solar Cells.

It is found that the disordered growth of bottom perovskite film deteriorates the buried interface of perovskite solar cells (PSCs), so developing a new material to modify the buried interface for regulating the crystal growth and defect passivation is an effective approach for improving the photovoltaic performance of PSCs. Here, we developed a new ionic liquid crystal (ILC, 1-Dodecyl-3-methylimidazolium tetrafluoroborate) as both crystal regulator and defect passivator to modify the buried interface of PSCs. The high lattice matching between this ILC and perovskite promotes preferential growth of perovskite film along [001] direction, while the oriented ILC with mesomorphic phase has a strong chemical interaction with perovskite to passivate the interface defect, as a result, the modified buried interface exhibits suppressed defects, improved band alignment, reduced nonradiative recombination losses, and enhanced charge extraction. The ILC-modified PSC delivers a power conversion efficiency of 24.92 % and maintains 94 % of the original value after storage in ambient for 3000 h.

A recombination-resistant genome for live attenuated and stable PEDV vaccines by engineering the transcriptional regulatory sequences.

IMPORTANCE: Coronaviruses are important pathogens of humans and animals, and vaccine developments against them are imperative. Due to the ability to induce broad and prolonged protective immunity and the convenient administration routes, live attenuated vaccines (LAVs) are promising arms for controlling the deadly coronavirus infections. However, potential recombination events between vaccine and field strains raise a safety concern for LAVs. The porcine epidemic diarrhea virus (PEDV) remodeled TRS (RMT) mutant generated in this study replicated efficiently in both cell culture and in pigs and retained protective immunogenicity against PEDV challenge in pigs. Furthermore, the RMT PEDV was resistant to recombination and genetically stable. Therefore, RMT PEDV can be further optimized as a backbone for the development of safe LAVs.

Cytomegalovirus-vectored COVID-19 vaccines elicit neutralizing antibodies against the SARS-CoV-2 Omicron variant (BA.2) in mice.

IMPORTANCE: Cytomegalovirus (CMV) has been used as a novel viral vector for vaccine development and gene therapy. Coronavirus disease 2019 is an infectious disease caused by the SARS-CoV-2 virus, which is highly mutable and is still circulating globally. The study showed that the CMV viral vector caused transient systemic infection and induced robust transgene expression in vivo. CMV vectors expressing different SARS-CoV-2 proteins were immunogenic and could elicit neutralizing antibodies against a highly mutated Omicron variant (BA.2). The expression level of receptor-binding domain (RBD) protein was higher than that of full-length S protein using CMV as a vaccine vector, and CMV vector expression RBD protein elicited higher RBD-binding and neutralizing antibodies. Moreover, the study showed that CMV-vectored vaccines would not cause unexpected viral transmission, and pre-existing immunity might impair the immunogenicity of subsequent CMV-vectored vaccines. These works provide meaningful insights for the development of a CMV-based vector vaccine platform and the prevention and control strategies for SARS-CoV-2 infection.

Exploring the Potential of Cytomegalovirus-Based Vectors: A Review.

Viral vectors have emerged as powerful tools for delivering and expressing foreign genes, playing a pivotal role in gene therapy. Among these vectors, cytomegalovirus (CMV) stands out as a promising viral vector due to its distinctive attributes including large packaging capacity, ability to achieve superinfection, broad host range, capacity to induce CD8+ T cell responses, lack of integration into the host genome, and other qualities that make it an appealing vector candidate. Engineered attenuated CMV strains such as Towne and AD169 that have a ~15 kb genomic DNA deletion caused by virus passage guarantee human safety. CMV's large genome enables the efficient incorporation of substantial foreign genes as demonstrated by CMV vector-based therapies for SIV, tuberculosis, cancer, malaria, aging, COVID-19, and more. CMV is capable of reinfecting hosts regardless of prior infection or immunity, making it highly suitable for multiple vector administrations. In addition to its broad cellular tropism and sustained high-level gene expression, CMV triggers robust, virus-specific CD8+ T cell responses, offering a significant advantage as a vaccine vector. To date, successful development and testing of murine CMV (MCMV) and rhesus CMV (RhCMV) vectors in animal models have demonstrated the efficacy of CMV-based vectors. These investigations have explored the potential of CMV vectors for vaccines against HIV, cancer, tuberculosis, malaria, and other infectious pathogens, as well as for other gene therapy applications. Moreover, the generation of single-cycle replication CMV vectors, produced by deleting essential genes, ensures robust safety in an immunocompromised population. The results of these studies emphasize CMV's effectiveness as a gene delivery vehicle and shed light on the future applications of a CMV vector. While challenges such as production complexities and storage limitations need to be addressed, ongoing efforts to bridge the gap between animal models and human translation continue to fuel the optimism surrounding CMV-based vectors. This review will outline the properties of CMV vectors and discuss their future applications as well as possible limitations.

Insights into the Transcriptome of Human Cytomegalovirus: A Comprehensive Review.

Human cytomegalovirus (HCMV) is a widespread pathogen that poses significant risks to immunocompromised individuals. Its genome spans over 230 kbp and potentially encodes over 200 open-reading frames. The HCMV transcriptome consists of various types of RNAs, including messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs), with emerging insights into their biological functions. HCMV mRNAs are involved in crucial viral processes, such as viral replication, transcription, and translation regulation, as well as immune modulation and other effects on host cells. Additionally, four lncRNAs (RNA1.2, RNA2.7, RNA4.9, and RNA5.0) have been identified in HCMV, which play important roles in lytic replication like bypassing acute antiviral responses, promoting cell movement and viral spread, and maintaining HCMV latency. CircRNAs have gained attention for their important and diverse biological functions, including association with different diseases, acting as microRNA sponges, regulating parental gene expression, and serving as translation templates. Remarkably, HCMV encodes miRNAs which play critical roles in silencing human genes and other functions. This review gives an overview of human cytomegalovirus and current research on the HCMV transcriptome during lytic and latent infection.

Functions of Circular RNA in Human Diseases and Illnesses.

Circular RNAs (circRNAs) represent single-stranded RNA species that contain covalently closed 3' and 5' ends that provide them more stability than linear RNA, which has free ends. Emerging evidence indicates that circRNAs perform essential functions in many DNA viruses, including coronaviruses, Epstein-Barr viruses, cytomegalovirus, and Kaposi sarcoma viruses. Recent studies have confirmed that circRNAs are present in viruses, including DNA and RNA viruses, and play various important functions such as evading host immune response, disease pathogenesis, protein translation, miRNA sponges, regulating cell proliferation, and virus replication. Studies have confirmed that circRNAs can be biological signatures or pathological markers for autoimmune diseases, neurological diseases, and cancers. However, our understanding of circRNAs in DNA and RNA viruses is still limited, and functional evaluation of viral and host circRNAs is essential to completely understand their biological functions. In the present review, we describe the metabolism and cellular roles of circRNA, including its roles in various diseases and viral and cellular circRNA functions. Circular RNAs are found to interact with RNA, proteins, and DNA, and thus can modulate cellular processes, including translation, transcription, splicing, and other functions. Circular RNAs interfere with various signaling pathways and take part in vital functions in various biological, physiological, cellular, and pathophysiological processes. We also summarize recent evidence demonstrating cellular and viral circRNA's roles in DNA and RNA viruses in this growing field of research.

The added value of apparent diffusion coefficient and microcalcifications to the Kaiser score in the evaluation of BI-RADS 4 lesions.

PURPOSE: To explore the added value of combining microcalcifications or apparent diffusion coefficient (ADC) with the Kaiser score (KS) for diagnosing BI-RADS 4 lesions. METHODS: This retrospective study included 194 consecutive patients with 201 histologically verified BI-RADS 4 lesions. Two radiologists assigned the KS value to each lesion. Adding microcalcifications, ADC, or both these criteria to the KS yielded KS1, KS2, and KS3, respectively. The potential of all four scores to avoid unnecessary biopsies was assessed using the sensitivity and specificity. Diagnostic performance was evaluated by the area under the curve (AUC) and compared between KS and KS1. RESULTS: The sensitivity of KS, KS1, KS2, and KS3 ranged from 77.1% to 100.0%.KS1 yielded significantly higher sensitivity than other methods (P < 0.05), except for KS3 (P > 0.05), most of all, when assessing NME lesions. For mass lesions, the sensitivity of these four scores was comparable (p > 0.05). The specificity of KS, KS1, KS2, and KS3 ranged from 56.0% to 69.4%, with no statistically significant differences(P > 0.05), except between KS1 and KS2 (p < 0.05).The AUC of KS1 (0.877) was significantly higher than that of KS (0.837; P = 0.0005), particularly for assessing NME (0.847 vs 0.713; P < 0.0001). CONCLUSION: KS can stratify BI-RADS 4 lesions to avoid unnecessary biopsies. Adding microcalcifications, but not adding ADC, as an adjunct to KS improves diagnostic performance, particularly for NME lesions. ADC provides no additional diagnostic benefit to KS. Thus, only combining microcalcifications with KS is most conducive to clinical practice.

HSV-1 infection-induced herpetic neuralgia involves a CCL5/CCR5-mediated inflammation mechanism.

Herpetic-related neuralgia (HN) caused by varicella-zoster virus (VZV) infection is one of the most typical and common neuropathic pain in the clinic. However, the potential mechanisms and therapeutic approaches for the prevention and treatment of HN are still unclear. This study aims to provide a comprehensive understanding of the molecular mechanisms and potential therapeutic targets of HN. We used an HSV-1 infection-induced HN mouse model and screened the differentially expressed genes (DEGs) in the DRG and spinal cord using an RNAseq technique. Moreover, bioinformatics methods were used to figure out the signaling pathways and expression regulation patterns of the DEGs enriched. In addition, quantitative real-time RT-PCR and western blot were carried out to further confirm the expression of DEGs. HSV-1 inoculation in mice resulted in mechanical allodynia, thermal hyperalgesia, and cold allodynia, following the infection of HSV-1 in both DRG and spinal cord. Besides, HSV-1 inoculation induced an up-regulation of ATF3, CGRP, and GAL in DRG and activation of astrocytes and microglia in the spinal cord. Moreover, 639 genes were upregulated, 249 genes were downregulated in DRG, whereas 534 genes were upregulated and 12 genes were downregulated in the spinal cord of mice 7 days after HSV-1 inoculation. GO and KEGG enrichment analysis suggested that immune responses and cytokine-cytokine receptor interaction are involved in DRG and spinal cord neurons in mice after HSV-1 infection. In addition, CCL5 and its receptor CCR5 were significantly upregulated in DRG and spinal cord upon HSV-1 infection in mice. And blockade of CCR5 exhibited a significant analgesic effect and suppressed the upregulation of inflammatory cytokines in DRG and spinal cord induced by HSV-1 infection in mice. HSV-1 infection-induced allodynia and hyperalgesia in mice through dysregulation of immune response and cytokine-cytokine receptor interaction mechanism. Blockade of CCR5 alleviated allodynia and hyperalgesia probably through the suppression of inflammatory cytokines. Therefore, CCR5 could be a therapeutic target for the alleviation of HSV-1 infection-induced HN.

Rodent models of postherpetic neuralgia: How far have we reached?

Background: Induced by varicella zoster virus (VZV), postherpetic neuralgia (PHN) is one of the common complications of herpes zoster (HZ) with refractory pain. Animal models play pivotal roles in disclosing the pain mechanisms and developing effective treatments. However, only a few rodent models focus on the VZV-associated pain and PHN. Objective: To summarize the establishment and characteristics of popular PHN rodent models, thus offer bases for the selection and improvement of PHN models. Design: In this review, we retrospect two promising PHN rodent models, VZV-induced PHN model and HSV1-induced PHN model in terms of pain-related evaluations, their contributions to PHN pathogenesis and pharmacology. Results: Significant difference of two PHN models is the probability of virus proliferation; 2) Most commonly used pain evaluation of PHN model is mechanical allodynia, but pain-induced anxiety and other behaviours are worth noting; 3) From current PHN models, pain mechanisms involve changes in virus gene and host gene expression, neuroimmune-glia interactions and ion channels; 4) antiviral drugs and classical analgesics serve more on the acute stage of herpetic pain. Conclusions: Different PHN models assessed by various pain evaluations combine to fulfil more comprehensive understanding of PHN.

Treatment of spinal rhabdomyosarcoma in adults: A case report and literature review of current evidence.

Spinal rhabdomyosarcoma (RMS) is a rare yet highly malignant tumor in adults. Literature on this entity is lacking and no mature treatment guideline is currently available. The treatment arsenals include surgery, radiotherapy and chemotherapy, being used singly or jointly. However, the prognosis is dismal, with a mean overall survival period of 10 months. Thus, any case of this disease with encouraging outcomes shall be shared. A case of a middle-aged female patient with spinal RMS was presented in the current report. The patient suffered from back pain but was neurologically intact. The patient underwent a total en-bloc spondylectomy of the T11-L2 vertebrae and spinal reconstruction with 3D-printed prosthetic vertebrae. Afterwards, the patient received a rigid schedule of stereotactic body radiotherapy (SBRT) and chemotherapy. To date, the patient has survived for 40 months, with the preservation of neurological function and sustained mitigation of local pain after the operation. The patient suffered subcutaneous colonization of tumor cells and pulmonary metastasis 10 months postoperatively, but obtained a long locoregional control of 19 months. In conclusion, total en-bloc lesion resection is indicated for the treatment of isolated, primary spinal RMS in adults. Some authors reported that the usage of new surgical tools and instruments has facilitated surgery, which was previously invasive and technically challenging. Advanced radiotherapy techniques, such as SBRT, which were proven effective for local lesion control, should be implemented early after the operation. Chemotherapy remains the mainstay of treatment, but further research and evidence for the efficacy of regimens specifically for adults are required.

21.15%-Efficiency and Stable γ -CsPbI3 Perovskite Solar Cells Enabled by an Acyloin Ligand.

Cesium lead triiodide (CsPbI3 ) is a promising light-absorbing material for constructing perovskite solar cells (PSCs) owing to its favorable bandgap and thermal tolerance. However, the high density of defects in the CsPbI3 film not only act as recombination centers, but also facilitate ion migration, leading to lower PCE and inferior stability compared with the state-of-the-art organic-inorganic hybrid PSC counterpart. Theoretical analyses suggest that the effective suppression of defects in CsPbI3 film is helpful for improving the device performance. Herein, the stable and efficient γ -CsPbI3 PSCs are demonstrated by developing an acyloin ligand (1,2-di(thiophen-2-yl)ethane-1,2-dione (DED)) as a phase stabilizer and defect passivator. The experiment and calculation results confirm that carbonyl and thienyl in DED can synergistically interact with CsPbI3 by forming a chelate to effectively passivate Pb-related defects and further suppress ion migration. Consequently, DED-treated CsPbI3 PSCs yield a champion PCE of 21.15%, which is one of the highest PCE among all the reported CsPbI3 PSCs to date. In addition, the unencapsulated DED-CsPbI3 PSC can retain 94.9% of itsinitial PCE when stored under ambient conditions for 1000 h and 92.8% of its initial PCE under constant illumination for 250 h.

20.67%-Efficiency Inorganic CsPbI3 Solar Cells Enabled by Zwitterion Ion Interface Treatment.

All-inorganic CsPbI3 perovskite solar cells (PSCs) have been extensively studied due to their high thermal stability and unprecedented rise in power conversion efficiency (PCE). Recently, the champion PCE of CsPbI3 PSCs has reached up to 21%; however, it is still much lower than that of organic-inorganic hybrid PSCs. Interface modification to passivate surface defects and minimize charge recombination and trapping is important to further improve the efficiency of CsPbI3 PSCs. Herein, a new zwitterion ion is deposited at the interface between electron transporting layer (ETL) and perovskite layer to passivate the defects therein. The zwitterion ions can not only passivate oxygen vacancy (VO ) and iodine vacancy (VI ) defects, but also improve the band alignment at the ETL-perovskite interface. After the interface treatment, the PCE of CsPbI3 device reaches up to 20.67%, which is among the highest values of CsPbI3 PSCs so far. Due to the defect passivation and hydrophobicity improvement, the PCE of optimized device remains 94% of its original value after 800 h storing under ambient condition. These results provide an efficient way to improve the quality of ETL-perovskite interface by zwitterion ions for achieving high performance inorganic CsPbI3 PSCs.

Surgical Treatment of Spinal Metastatic Pheochromocytoma and Paraganglioma: A Single Institutional Cohort of 18 Patients.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVES: To describe surgeries and treatment outcomes of metastatic pheochromocytomas and paragangliomas (PPGLs) on the spine. METHODS: We reviewed a cohort of 18 patients with spinal PPGLs who were consecutively treated in our spinal center. Their clinical data was reviewed. The survival period and its relevant factors was then analyzed. RESULTS: The cohort included ten cases of pheochromocytomas and eight paragangliomas. The local pain and neurological deficits were the two most common symptoms. One third of the spinal PPGLs were diagnosed as functional tumors, arousing secondary hypertension. The imaging features were consistent with those of osteolytic lesions. The surgical strategies for the cohort included percutaneous vertebroplasty, neurological decompression and partial tumor resection, and total en-bloc resection. The postoperative courses were uneventful except 1 patient developed heart failure. The adjuvant therapies were implemented in 6 patients with 131I-MIBG, five with radiotherapy, two with chemotherapy, and 1 with target therapy. The median survival period was 39 months, and the overall survival rate of 1 year was 77.8% (14/18). The patients' Karnofsky performance scores were positively correlated with the survival period (P < .05). CONCLUSION: Surgery is indicated for intractable local pain and neurological impairment in the patients with spinal PPGLs. Palliative surgical strategies, including neurological decompression and partial tumor resection, could bring fair outcomes, especially for the patients in poor physical conditions.

Transcriptome analysis reveals dysregulation of inflammatory and neuronal function in dorsal root ganglion of paclitaxel-induced peripheral neuropathy rats.

Chemotherapy-induced peripheral neuropathy (CIPN) is the most common side-effect of anti-cancer therapy. To date, there are no clinically effective analgesics that could prevent and treat CIPN. However, the exact pathogenesis of CIPN is still unclear. In the present study, we use the paclitaxel-induced peripheral neuropathy (PIPN) model, aiming to better understand the transcriptomic level of the Dorsal root ganglia (DRG) neurons in rats with PIPN. mRNA from each DRG sample was reverse transcribed to cDNA and sequenced using next-generation high throughput sequencing technology. Quantitative RT-PCR verification was used to confirm the identified Differentially expressed genes (DEGs) in the DRG of PIPN rats. RNAseq results have identified 384 DEGs (adjusted P-value < 0.05; fold change ≥ 2) in the DRG of rats 14 days after paclitaxel injection in total, including 97 up-regulated genes, and 287 down-regulated genes. GO analysis revealed that these DEGs were majorly involved in neuropeptide activity, chemokine receptor activity, defense response, and inflammatory response. Kyoto Encyclopedia of Gene and Genomes analysis showed that neuroactive ligand-receptor interaction and cytokine-cytokine receptor interaction were involved in sensory neurons of rats with PIPN. Besides, comparison analysis identified that 11 DEGs in the PIPN model are shared with either inflammatory pain (Ces1d, Cfd, Retn, and Fam150b) or neuropathic pain (Atf3, Csrp3, Ecel1, Gal, Sprr1a, Tgm1, and Vip). Quantitative RT-PCR results also confirmed the validation of the RNAseq data. These results suggested that neuroactive ligand-receptor interaction and cytokine-cytokine receptor interaction are majorly involved in sensory neurons of rats with PIPN. Immune, inflammatory responses and neuron functional changes are the major pathogenesis of PIPN. Paclitaxel-induced peripheral neuropathy has shared characteristics with both inflammatory pain and neuropathic pain.