Comparison of radiotherapy versus surgical resection following neoadjuvant chemoimmunotherapy in potentially resectable stage III non-small-cell lung cancer: A propensity score matching analysis.

BACKGROUND: Neoadjuvant chemoimmunotherapy followed by surgery is recommended for resectable non-small-cell lung cancer (NSCLC). However, a considerable proportion of patients do not undergo surgery and opt for alternative treatments such as radiotherapy. The efficacy of radiotherapy in this context remains unclear. METHODS: This retrospective study analyzed data from patients with stage III NSCLC who received neoadjuvant chemoimmunotherapy followed by either surgery or radiotherapy. Propensity score matching (PSM) was used to balance the heterogeneity between the groups. Efficacy outcomes, safety profiles, and disease recurrence patterns were assessed. RESULTS: In total, 175 patients were included; 50 underwent radiotherapy, and 125 underwent surgery. Prior to matching, radiotherapy was inferior to surgery in terms of progression-free survival (PFS; Hazard ratio [HR], 2.23; P = 0.008). Following a 1:1 PSM adjustment, each group consisted of 40 patients. The median PFS was 30.8 months in the radiotherapy group and not reached in the surgery group (HR, 1.46; P = 0.390). The 12- and 24-month PFS rates were 90.4 % and 69.0 % for the radiotherapy group compared to 94.1 % and 73.9 % for the surgery group, respectively. Subgroup analyses after PSM showed that patients with stage IIIA disease tend to benefit more from surgery than those with stage IIIB disease (HR, 3.00; P = 0.074). Grade 3-4 treatment-related adverse events (TRAEs) occurred in 62.5 % of patients in the radiotherapy group and 55.0 % in the surgery group, with no grade 5 TRAEs reported. The incidence of grade 3-4 treatment-related pneumonitis or pneumonia was 7.5 % and 2.5 % in the radiotherapy and surgery groups, respectively. CONCLUSION: Radiotherapy may be a viable alternative to surgery in patients with resectable NSCLC who do not undergo surgical resection after initial neoadjuvant chemoimmunotherapy, offering comparable efficacy and a manageable safety profile. Larger prospective studies are needed to validate these findings and optimize the treatment strategies for this patient population.

MRD-YOLO: A Multispectral Object Detection Algorithm for Complex Road Scenes.

Object detection is one of the core technologies for autonomous driving. Current road object detection mainly relies on visible light, which is prone to missed detections and false alarms in rainy, night-time, and foggy scenes. Multispectral object detection based on the fusion of RGB and infrared images can effectively address the challenges of complex and changing road scenes, improving the detection performance of current algorithms in complex scenarios. However, previous multispectral detection algorithms suffer from issues such as poor fusion of dual-mode information, poor detection performance for multi-scale objects, and inadequate utilization of semantic information. To address these challenges and enhance the detection performance in complex road scenes, this paper proposes a novel multispectral object detection algorithm called MRD-YOLO. In MRD-YOLO, we utilize interaction-based feature extraction to effectively fuse information and introduce the BIC-Fusion module with attention guidance to fuse different modal information. We also incorporate the SAConv module to improve the model's detection performance for multi-scale objects and utilize the AIFI structure to enhance the utilization of semantic information. Finally, we conduct experiments on two major public datasets, FLIR_Aligned and M3FD. The experimental results demonstrate that compared to other algorithms, the proposed algorithm achieves superior detection performance in complex road scenes.

Compression Therapy after Thermal Ablation of Varicose Veins: A Meta-Analysis.

OBJECTIVE: To investigate whether compression therapy after thermal ablation of varicose veins can improve the prognosis of patients. METHODS: Systematic research were applied for Chinese and English electronic databases(PubMed, Web of Science, Cochrane Library, CNKI, Wanfang, VIP Databases). Eligible prospective studies that comparing the efficacy of compression therapy and non-compression therapy on patients after thermal ablation of varicose veins were included. The interest outcome such as pain, quality of life (QOL), venous clinical severity score (VCSS), time to return to work and complications were analyzed. RESULTS: 10 studies were of high quality, and randomized controlled trials involving 1,545 patients met the inclusion criteria for this study. At the same time, the meta-analysis showed that the application of compression therapy improved pain (SMD: -0.51, 95% CI: -0.95, -0.07) but exhibited no statistically significant effect on QOL (SMD: 0.04, 95% CI: -0.08, 0.16), VCSS (MD: -0.05, 95% CI: -1.19, 1.09), time to return to work (MD: -0.43, 95% CI: -0.90, 0.03), total complications (RR: 0.54, 95% CI: 0.27, 1.09), and thrombosis (RR: 0.71, 95% CI: 0.31, 1.62). CONCLUSION: Compression therapy after thermal ablation of varicose veins can slightly relieve pain, but it has not been found to be associated with improvement in other outcomes.

High-Order Neighbors Aware Representation Learning for Knowledge Graph Completion.

As a building block of knowledge acquisition, knowledge graph completion (KGC) aims at inferring missing facts in knowledge graphs (KGs) automatically. Previous studies mainly focus on graph convolutional network (GCN)-based KG embedding (KGE) to determine the representations of entities and relations, accordingly predicting missing triplets. However, most existing KGE methods suffer from limitations in predicting tail entities that are far away or even unreachable in KGs. This limitation can be attributed to the related high-order information being largely ignored. In this work, we focus on learning the information from the related high-order neighbors in KGs to improve the performance of prediction. Specifically, we first introduce a set of new nodes called pedal nodes to augment the KGs for facilitating message passing between related high-order entities, effectively injecting the information of high-order neighbors into entity representation. Additionally, we propose strength-guided graph neural networks to aggregate neighboring entity representations. To address the issue of transmitting irrelevant higher order information to entities through pedal nodes, which can potentially hurt entity representation, we further propose to dynamically integrate the aggregated representation of each node with its corresponding self-representation. Extensive experiments have been conducted on three benchmark datasets and the results demonstrate the superiority of our method compared to strong baseline models.

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.

Adaptive class augmented prototype network for few-shot relation extraction.

Relation extraction is one of the most essential tasks of knowledge construction, but it depends on a large amount of annotated data corpus. Few-shot relation extraction is proposed as a new paradigm, which is designed to learn new relationships between entities with merely a small number of annotated instances, effectively mitigating the cost of large-scale annotation and long-tail problems. To generalize to novel classes not included in the training set, existing approaches mainly focus on tuning pre-trained language models with relation instructions and developing class prototypes based on metric learning to extract relations. However, the learned representations are extremely sensitive to discrepancies in intra-class and inter-class relationships and hard to adaptively classify the relations due to biased class features and spurious correlations, such as similar relation classes having closer inter-class prototype representation. In this paper, we introduce an adaptive class augmented prototype network with instance-level and representation-level augmented mechanisms to strengthen the representation space. Specifically, we design the adaptive class augmentation mechanism to expand the representation of classes in instance-level augmentation, and class augmented representation learning with Bernoulli perturbation context attention to enhance the representation of class features in representation-level augmentation and explore adaptive debiased contrastive learning to train the model. Experimental results have been demonstrated on FewRel and NYT-25 under various few-shot settings, and the proposed model has improved accuracy and generalization, especially for cross-domain and different hard tasks.

PIWI-interacting RNA expression regulates pathogenesis in a Caenorhabditis elegans model of Lewy body disease.

PIWI-interacting RNAs (piRNAs) are small noncoding RNAs that regulate gene expression, yet their molecular functions in neurobiology are unclear. While investigating neurodegeneration mechanisms using human α-syn(A53T)Tg and AßTg;α-syn(A53T)Tg pan-neuronal overexpressing strains, we unexpectedly observed dysregulation of piRNAs. RNAi screening revealed that knock down of piRNA biogenesis genes improved thrashing behavior; further, a tofu-1 gene deletion ameliorated phenotypic deficits in α-syn(A53T)Tg and AßTg;α-syn(A53T)Tg transgenic strains. piRNA expression was extensively downregulated and H3K9me3 marks were decreased after tofu-1 deletion in α-syn(A53T)Tg and AßTg;α-syn(A53T)Tg strains. Dysregulated piRNAs targeted protein degradation genes suggesting that a decrease of piRNA expression leads to an increase of degradation ability in C. elegans. Finally, we interrogated piRNA expression in brain samples from PD patients. piRNAs were observed to be widely overexpressed at late motor stage. In this work, our results provide evidence that piRNAs are mediators in pathogenesis of Lewy body diseases and suggest a molecular mechanism for neurodegeneration in these and related disorders.

YOLOv5s-DSD: An Improved Aerial Image Detection Algorithm Based on YOLOv5s.

Due to the challenges of small detection targets, dense target distribution, and complex backgrounds in aerial images, existing object detection algorithms perform poorly in aerial image detection tasks. To address these issues, this paper proposes an improved algorithm called YOLOv5s-DSD based on YOLOv5s. Specifically, the SPDA-C3 structure is proposed and used to reduce information loss while focusing on useful features, effectively tackling the challenges of small detection targets and complex backgrounds. The novel decoupled head structure, Res-DHead, is introduced, along with an additional small object detection head, further improving the network's performance in detecting small objects. The original NMS is replaced by Soft-NMS-CIOU to address the issue of neighboring box suppression caused by dense object distribution. Finally, extensive ablation experiments and comparative tests are conducted on the VisDrone2019 dataset, and the results demonstrate that YOLOv5s-DSD outperforms current state-of-the-art object detection models in aerial image detection tasks. The proposed improved algorithm achieves a significant improvement compared with the original algorithm, with an increase of 17.4% in mAP@0.5 and 16.4% in mAP@0.5:0.95, validating the superiority of the proposed improvements.

Antimicrobial Resistance Profiling and Genome Analysis of the penA-60.001 Neisseria gonorrhoeae Clinical Isolates in China in 2021.

BACKGROUND: Neisseria gonorrhoeae antimicrobial resistance (AMR) is an urgent public health threat. With dissemination of FC428-related clones, the efficacy of ceftriaxone has become controversial. METHODS: Agar dilution and whole genome sequencing were used to analyze AMR. RESULTS: High resistance to penicillin (75.2%), tetracycline (87.9%), ciprofloxacin (98.3%), ceftriaxone (8.9%), cefixime (14.3%), and azithromycin (8.6%) was observed among 463 isolates first collected in China in 2021. All penA-60.001 clones exhibited resistance to ceftriaxone or cefixime, and 1 of the 12 cases was resistant to azithromycin. ngMAST and ngSTAR of penA-60.001 isolates showed that single-nucleotide polymorphisms in the porB, tbpB, ponA, gyrA, and parC genes were the major causes of different sequence types. MLST-7365 (n = 5) and MLST-1903 (n = 3) were main genotypes, and the other 4 strains featured MLST-10314, MLST-13871, MLST-7827 and MLST-1600. Furthermore, resistance markers (eg, penA, blaTEM-1, blaTEM-135) and virus factors were detected. Most penA-60.001 strains were fully mixed with global FC428-related clones; 2021-A2 and F89 had the same origin; and 2021-A1 exhibited a unique evolutionary trajectory. CONCLUSIONS: Results provide the first demonstration of extremely severe AMR rates of N gonorrhoeae in China in 2021, particularly strains with ceftriaxone decreased susceptibility. The sustained transmission of penA-60.001 subclones might further threaten treatment effectiveness.

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.

Comparative Transcriptome of Dorsal Root Ganglia Reveals Distinct Etiologies of Paclitaxel- and Oxaliplatin-induced Peripheral Neuropathy in Rats.

Chemotherapy-induced peripheral neuropathy is one of the most common side effects of anticancer therapy. It is anticipated that chemotherapies with different mechanisms of action may affect somatosensory neurons differently. This study aimed to explore similar and differential etiologies of oxaliplatin- and paclitaxel-induced neuropathy by comparing the transcriptomes of dorsal root ganglia (DRGs). We retrieved our previously published transcriptome data of DRGs extracted from vehicle-, oxaliplatin- and paclitaxel-treated rats (GSE160543), to analyze in parallel the differentially expressed genes (DEGs) and Gene ontology (GO) terms enrichment. We found that both oxaliplatin and paclitaxel treatments consistently produced mechanical allodynia, thermal hyperalgesia, and cold hyperalgesia in rats. Compared to vehicle, 320 and 150 DEGs were identified after oxaliplatin and paclitaxel treatment, respectively. Only 17 DEGs were commonly dysregulated by the two reagents. Activating transcription factor 3 (Atf3), a marker of nerve injury, was elevated only after paclitaxel treatment. GO analysis suggested that paclitaxel treatment was associated with neuronal changes characterized by numerous terms that are related to synaptic transmission, while oxaliplatin was more likely to affect dividing cells (e.g., the glia) and neuroinflammation. Notably, 29 biological processes GO terms were commonly enriched in response to both drugs. However, 28 out of 29 terms were oppositely modulated. This study suggests that distinct mechanisms underly paclitaxel- and oxaliplatin-induced neuropathy. Paclitaxel might directly affect somatosensory neurons while oxaliplatin primarily targets dividing cells and immune cells.

Perfluorononanoic Acid Induces Neurotoxicity via Synaptogenesis Signaling in Zebrafish.

Perfluorononanoic acid (PFNA), commonly used as an alternative polyfluorinated compound (PFC) of perfluorooctanoic acid (PFOA), has been widely detected in the aquatic environment. Previous ecotoxicological and epidemiological results suggested that some neurobehavioral effects were associated with PFC exposure; however, the ecological impacts and underlying neurotoxicity mechanisms remain unclear, particularly in aquatic organisms during sensitive, early developmental stages. In this study, zebrafish embryos were exposed to environmentally relevant concentrations of PFNA for 120 h, and the neurological effects of PFNA were comprehensively assessed using transcriptional, biochemical, morphological, and behavioral assays. RNA sequencing and advanced bioinformatics analyses predicted and characterized the key biological processes and pathways affected by PFNA exposure, which included the synaptogenesis signaling pathway, neurotransmitter synapse, and CREB signaling in neurons. Neurotransmitter levels (acetylcholine, glutamate, 5-hydroxytryptamine, γ-aminobutyric acid, dopamine, and noradrenaline) were significantly decreased in zebrafish larvae, and the Tg(gad67:GFP) transgenic line revealed a decreased number of GABAergic neurons in PFNA-treated larvae. Moreover, the swimming distance, rotation frequency, and activity degree were also significantly affected by PFNA, linking molecular-level changes to behavioral consequences.

Biodegradation of Dibutyl Phthalate by the New Strain Acinetobacter baumannii DP-2.

Optimizing the culture conditions of DBP degradation by bacteria and investigating its biodegradation pathways have a great importance to develop effective PAEs pollution control strategies. In this study, we investigated the cultivation condition optimization, degradation kinetics, and degradation pathways of a newly isolated dibutyl phthalate (DBP) degradation strain, which was isolated from activated sludge and identified as Acinetobacter baumannii DP-2 via morphological observation, biochemical identification, and 16S rDNA sequence analysis. The degradation conditions were optimized based on the results of single-factor experiments and response surface optimization experiments. The DBP degradation rate of Acinetobacter baumannii DP-2 reached up to 85.86% when the inoculation amount was 17.14%, the DBP concentration was 9.81 mg·L-1 and the NaCl concentration was 5 g·L-1. The GC-MS analysis results indicated that the intermediate metabolites of Acinetobacter baumannii DP-2 mainly consisted of DMP, MBP, PA, and benzoic acid derivatives, which confirmed the degradation pathway from DBP to PA under aerobic pathway and then to BA under anaerobic pathway. In summary, Acinetobacter baumannii DP-2 shows great potential for the degradation of DBP in contaminated soils.

PIWI-interacting RNAs in human diseases: databases and computational models.

PIWI-interacting RNAs (piRNAs) are short 21-35 nucleotide molecules that comprise the largest class of non-coding RNAs and found in a large diversity of species including yeast, worms, flies, plants and mammals including humans. The most well-understood function of piRNAs is to monitor and protect the genome from transposons particularly in germline cells. Recent data suggest that piRNAs may have additional functions in somatic cells although they are expressed there in far lower abundance. Compared with microRNAs (miRNAs), piRNAs have more limited bioinformatics resources available. This review collates 39 piRNA specific and non-specific databases and bioinformatics resources, describes and compares their utility and attributes and provides an overview of their place in the field. In addition, we review 33 computational models based upon function: piRNA prediction, transposon element and mRNA-related piRNA prediction, cluster prediction, signature detection, target prediction and disease association. Based on the collection of databases and computational models, we identify trends and potential gaps in tool development. We further analyze the breadth and depth of piRNA data available in public sources, their contribution to specific human diseases, particularly in cancer and neurodegenerative conditions, and highlight a few specific piRNAs that appear to be associated with these diseases. This briefing presents the most recent and comprehensive mapping of piRNA bioinformatics resources including databases, models and tools for disease associations to date. Such a mapping should facilitate and stimulate further research on piRNAs.

CircSCAP interacts with SF3A3 to inhibit the malignance of non-small cell lung cancer by activating p53 signaling.

BACKGROUND: Circular RNA (circRNA) has been recently identified as a critical regulator during carcinogenesis. However, the biological function and potential underlying mechanisms of circRNAs in lung cancer remain to be further elucidated. METHODS: Here, we first evaluated the differentially expressed circRNAs between tumor and the matched adjacent nontumor tissues (3 pairs) of lung cancer patients via circRNA microarray. The expression of top five dysregulated circRNAs were tested in lung cancer cell lines and the circSCAP with concordant alteration in microarray data and cell lines was selected for further investigation. Then we validated the expression level of circSCAP in tumor and corresponding adjacent tissues (161 pairs) from a lung cancer cohort by RT-PCR analysis followed by correlation and prognosis analysis between circSCAP and clinical characteristics. Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer diagnosis (about 80% in the cohort used in this study). Therefore, we focused the role of circSCAP in NSCLC in the present study. In vitro and in vivo assays were performed to study the biological function of circSCAP in NSCLC. Biotin-labeled RNA pulldown and RNA immunoprecipitation (RIP) assays were carried out to identify the proteins directly interacting with circSCAP. The molecular mechanism of circSCAP-driven tumor suppression was demonstrated by immunoblotting, immunoprecipitation and luciferase reporter assays. In vitro and in vivo rescue experiments were conducted to verify the role of the circSCAP/SF3A3/p53 signaling axis in NSCLC. RESULTS: We screened the expression profiles of human circRNAs in lung cancer tissues and found that hsa_circ_0065214 (termed as circSCAP) was significantly decreased. Kaplan-Meier analysis showed that patients with low level of circSCAP had a significantly poor prognosis. Gain- and loss-of-function experiments suggested that circSCAP played an important role in NSCLC cell proliferation, cell migration and apoptosis. Mechanistically, circSCAP directly binds to the SF3A3 protein, facilitating the reduction of SF3A3 by promoting its ubiquitin-proteasome-mediated degradation, which enhances the expression of MDM4-S to finally activate its downstream p53 signaling. CONCLUSION: These findings illustrate a novel circSCAP/SF3A3/p53 signaling axis involved in suppressing the malignance of NSCLC and provide a promising target for NSCLC prognosis prediction and treatment.

Comprehensive treatment experience of anal squamous cell carcinoma from a tertiary cancer center in South China.

BACKGROUND: Anal squamous cell carcinoma (ASCC) is a rare malignant tumor with increasing incidence. The goal of our study was to analyze the treatment outcome and prognostic factors of ASCC in South China in the past half-century. METHODS: This study retrospectively included 59 patients with ASCC admitted from 1975 to 2018 in Sun Yat-sen University cancer center. The clinical records and follow-up information of all patients were collected. Survival analysis and univariate and multivariate regression analyses were performed using the "survival" and "survminer" packages of R software. RESULTS: In 59 patients, 5 patients had distant metastasis at diagnosis. Among 54 M0 stage patients, 33 patients received chemoradiotherapy (CRT), 19 patients received local surgery, and 2 patients refused curative treatment and received the best supportive treatment (BST). The most common grade 3-4 acute toxicities during treatment were myelosuppression and radiation dermatitis. The median follow-up time was 32 months. For the whole group, the 3-year and 5-year overall survival (OS) rates and disease-free survival (DFS) were 71.1% and 63.6%, and 73.4% and 69.0%, respectively. Multivariate regression analysis showed that the T3-4 stage was an independent prognostic risk factor for OS, progression-free survival (PFS), and DFS. And M1 was an independent prognostic risk factor for PFS and DFS. Patients in stage M0 mainly treated with CRT had better local control than those mainly treated with surgery (p = 0.027). For M0 patients, induction chemotherapy combined with CRT tends to prolong OS compared with CRT alone (p = 0.26). The 3-year colostomy-free survival for the whole group was 81.1%. CONCLUSIONS: CRT is recommended as the first choice for the treatment of M0 stage ASCC. Induction chemotherapy may bring better survival benefits for some patients. Patients with ASCC in China seem to have a better local control rate, which suggested different treatment strategies may be needed in China.

Change in Cav3.2 T-Type Calcium Channel Induced by Varicella-Zoster Virus Participates in the Maintenance of Herpetic Neuralgia.

Pain, as the most prevalent neurological complication of herpes zoster (HZ), may occur before or during the rash onset or even after the rash has recovered. Particularly, postherpetic neuralgia (PHN) is a refractory chronic condition, usually defined as pain persisting for 3 months or longer from the onset of HZ. Pain evoked by HZ impairs the normal physical and emotional functions of the patients, severely reducing their quality of life. However, how zoster-associated pain occurs and develops into PHN are elusive, making PHN difficult to predict. Uncovering the pathogenesis of zoster-associated pain (or HN) helps us to better understand the onset of PHN and supports developing more effective treatments. In this study, we successfully constructed a model for zoster-associated pain through varicella-zoster virus (VZV) infections of mouse footpads and pain behavior assessments. Next, we used the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Gene Ontology (GO) to analyze PHN rodent dorsal root ganglion (DRG) gene microarray data and found that calcium signal disorder might be involved in the onset of PHN. By using reverse transcription real-time fluorescent quantitative PCR (RT-qPCR) and Western blotting, we confirmed that VZV infection could significantly upregulate the expression of T-type calcium channel Cav3.2 in DRG and spinal dorsal horn (SDH). Intrathecal administration of Cav3.2 blocker (2R/S)-6-prenylnaringenin (6-PNG) relieved mechanical and thermal hyperalgesia induced by VZV. Taken together, our data indicated that VZV might participate in the occurrence and development of HN by upregulating the expression of Cav3.2 in DRG and SDH. These findings will help to reveal the underlying mechanisms on long-lasting pain and PHN formation, providing a new insight that Cav3.2 can be the promising drug target for remitting PHN.

Neoadjuvant chemotherapy and radiotherapy followed by resection/ablation in stage IV rectal cancer patients with potentially resectable metastases.

BACKGROUND: The optimal treatment of stage IV rectal cancer remains controversial. The purpose of this study was to assess the treatment outcomes and toxicity of neoadjuvant chemotherapy and radiotherapy followed by local treatment of all tumor sites and subsequent adjuvant chemotherapy in stage IV rectal cancer patients with potentially resectable metastases. METHODS: Adult patients diagnosed with locally advanced rectal adenocarcinoma with potentially resectable metastases, who received neoadjuvant chemotherapy and radiotherapy from July 2013 and September 2019 at Sun Yat-sen University cancer center, were included. Completion of the whole treatment schedule, pathological response, treatment-related toxicity and survival were evaluated. RESULTS: A total of 228 patients were analyzed with a median follow-up of 33 (range 3.3 to 93.4) months. Eventually, 112 (49.1%) patients finished the whole treatment schedule, of which complete response of all tumor sites and pathological downstaging of the rectal tumor were observed in three (2.7%) and 90 (80.4%) patients. The three-year overall survival (OS) and progression-free survival (PFS) of all patients were 56.6% (50.2 to 63.9%) and 38.6% (95% CI 32.5 to 45.8%), respectively. For patients who finished the treatment schedule, 3-year OS (74.4% vs 39.2%, P < 0.001) and 3-year PFS (45.5% vs 30.5%, P = 0.004) were significantly improved compared those who did not finish the treatment. Grade 3-4 chem-radiotherapy treatment toxicities were observed in 51 (22.4%) of all patients and surgical complications occurred in 22 (9.6%) of 142 patients who underwent surgery, respectively. CONCLUSIONS: Neoadjuvant chemotherapy and radiotherapy followed by resection/ablation and subsequent adjuvant chemotherapy offered chances of long-term survival with tolerable toxicities for selected patients with potentially resectable stage IV rectal cancer, and could be considered as an option in clinical practice.

Preparation of Quantum Dot-Embedded Photonic Crystal Hydrogel and Its Application as Fluorescence Sensor for the Detection of Nitrite.

The development of fluorescence sensing platforms with excellent photoluminescence capabilities is of great importance for their further application. In this work, a photonic crystal structure was successfully applied to enhance the luminescence performance of fluorescent hydrogel, and the application of the obtained hydrogel as a fluorescence sensor was explored. A polystyrene photonic crystal template was constructed via vertical deposition self-assembly; then, the precursor solution containing polyethylenimine-capped CdS quantum dots (PEI-CdS QDs) and monomers filled in the gap of the template. After the polymerization process, the desired hydrogel was obtained. PEI-CdS QDs endowed the hydrogel with its fluorescence property, while interestingly, the photonic crystal structure showed a significant enhancement effect on the fluorescence-emission capability. The mechanism of this phenomenon was revealed. Moreover, this hydrogel could be used as a reusable fluorescence sensor for the detection of nitrite in water with good selectivity. The limit of detection was determined to be 0.25 µmol/L, which is much lower than the maximum limit for nitrite in drinking water.

Construction of the gene expression subgroups of patients with coronary artery disease through bioinformatics approach.

Coronary artery disease (CAD) is a heterogeneous disease that has placed a heavy burden on public health due to its considerable morbidity, mortality and high costs. Better understanding of the genetic drivers and gene expression clustering behind CAD will be helpful for the development of genetic diagnosis of CAD patients. The transcriptome of 352 CAD patients and 263 normal controls were obtained from the Gene Expression Omnibus (GEO) database. We performed a modified unsupervised machine learning algorithm to group CAD patients. The relationship between gene modules obtained through weighted gene co-expression network analysis (WGCNA) and clinical features was identified by the Pearson correlation analysis. The annotation of gene modules and subgroups was done by the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Three gene expression subgroups with the clustering score of greater than 0.75 were constructed. Subgroup I may experience coronary artery disease of an in-creased severity, while subgroup III is milder. Subgroup I was found to be closely related to the upregulation of the mitochondrial autophagy pathway, whereas the genes of subgroup II were shown to be related to the upregulation of the ribosome pathway. The high expression of APOE, NOS1 and NOS3 in the subgroup I suggested that the patients had more severe coronary artery disease. The construction of genetic subgroups of CAD patients has enabled clinicians to improve their understanding of CAD pathogenesis and provides potential tools for disease diagnosis, classification and assessment of prognosis.