Asymmetric Osteopenia in Adolescent Idiopathic Scoliosis Based on Hounsfield Unit of Computed Tomography.

Purpose: To characterize the asymmetrical loss of bone mass and identify the association between scoliosis and osteopenia in patients with adolescent idiopathic scoliosis (AIS). Methods: Demographic information, Cobb angle, and Hounsfield unit (HU) of the neutral vertebra (NV) and apical vertebra (apex) of the major curve were collected retrospectively in 54 AIS patients. For 84 control subjects, HU values were measured at T12 and L5. Propensity score matching was performed to balance the interference of age and BMI. Results: In the AIS group, the concave and convex lateral HU of the NV and the convex lateral HU of the apex were negatively correlated with the Cobb angle. The AIS patients had lower bilateral HU. The mean HU and the apex-convex HU were also lower in the AIS group, while the apex-concave HU was slightly higher. After matching, the apex-convex HU of the AIS group remained lower, while the apex-concave HU was higher. Conclusion: Patients with AIS exhibit osteopenia, particularly on the convex side. The severity of scoliosis was found to be directly proportional to the severity of bone loss and the degree of bilateral osteopenia asymmetry. Appropriate intervention for bone loss may be able to curb the progression of scoliosis.

ECCT: Efficient Contrastive Clustering via Pseudo-Siamese Vision Transformer and Multi-view Augmentation.

Image clustering aims to divide a set of unlabeled images into multiple clusters. Recently, clustering methods based on contrastive learning have attracted much attention due to their ability to learn discriminative feature representations. Nevertheless, existing clustering algorithms face challenges in capturing global information and preserving semantic continuity. Additionally, these methods often exhibit relatively singular feature distributions, limiting the full potential of contrastive learning in clustering. These problems can have a negative impact on the performance of image clustering. To address the above problems, we propose a deep clustering framework termed Efficient Contrastive Clustering via Pseudo-Siamese Vision Transformer and Multi-view Augmentation (ECCT). The core idea is to introduce Vision Transformer (ViT) to provide the global view, and improve it with Hilbert Patch Embedding (HPE) module to construct a new ViT branch. Finally, we fuse the features extracted from the two ViT branches to obtain both global view and semantic coherence. In addition, we employ multi-view random aggressive augmentation to broaden the feature distribution, enabling the model to learn more comprehensive and richer contrastive features. Our results on five datasets demonstrate that ECCT outperforms previous clustering methods. In particular, the ARI metric of ECCT on the STL-10 (ImageNet-Dogs) dataset is 0.852 (0.424), which is 10.3% (4.8%) higher than the best baseline.

Revealing the optimal traditional processing methods and its protective effects against febrile seizures of Arisaema cum bile.

Arisaema cum bile (known as Dan Nanxing in Chinese, DNX) is a herbal medicine used for treating febrile seizure (FS), which commonly prepared by using Arisaematis Rhizoma and animal bile. This study was designed to explore the optimal processing time of DNX and its potential mechanism on the anti-FS effect. A total of 17 volatile organic compounds (VOCs) were the characteristic ones to distinguish different fermentation stages of DNX by using gas chromatography-ion mobility spectrometry (GC-IMS), such as 2-heptanone monomer, and heptanal monomer. DNX with fermentation for 3 months had an obvious pattern of VOCs with others, which could be regarded as the optimal fermentation time. The Enterococcus and Staphylococcus might be the core bacteria on the production of VOCs. Additionally, DNX (2.8 g/kg, p.o.) reversed hot water bath-induced FSs of rats, as indicated by increased seizure latency and decreased seizure duration time. It also prevented hippocampal neuronal loss, increased GABAAR, and decreased GRIA1 expression. At the genus level, relative abundance of Enterococcus and Akkermansia were enriched after DNX treatment. These findings suggested that fermentation for 3 months might be the optimal process time for DNX, and DNX possess an anti-FS effect through regulating neurotransmitter disorder and gut microbiota.

Complement C3d enables protective immunity capable of distinguishing spontaneously transformed from non-transformed cells.

Immune-surveillance depends in part on the recognition of peptide variants by T cell antigen receptors. Given that both normal B cells and malignant B cells accumulate mutations we chose a murine model of multiple myeloma to test conditions to induce cell-mediated immunity targeting malignant plasma cell (PC) clones but sparing of normal PCs. Revealing a novel function for intracellular C3d, we discovered that C3d engaged T cell responses against malignant plasma cells in the bone marrow of mice that had developed multiple myeloma spontaneously. Our results show that C3d internalized by cells augments immune surveillance by several mechanisms. In one, C3d induces a master transcription regulator, E2f1, to increase the expression of long non-coding (lnc) RNAs, to generate peptides for MHC-I presentation and increase MHC-I expression. In another, C3d increases expression of RNAs encoding ribosomal proteins linked to processing of defective ribosomal products (DRiPs) that arise from non-canonical translation and known to promote immunosurveillance. Cancer cells are uniquely susceptible to increased expression and presentation of mutant peptides given the extent of protein misfolding and accumulation of somatic mutations. Accordingly, although C3d can be internalized by any cell, C3d preferentially targets malignant clones by evoking specific T cell mediated immunity (CMI) and sparing most non-transformed polyclonal B cells and plasma cells with lower mutation loads. Malignant plasma cell deletion was blocked by cyclosporin or by CD8 depletion confirming that endogenous T cells mediated malignant clone clearance. Besides the potential for therapeutic application our results highlight how intracellular C3d modifies cellular metabolism to augment immune surveillance. One Sentence Summary: We show that intracellular soluble fragment 3d of complement (C3d) induces regression of spontaneous multiple myeloma in mice reducing tumor burden by 10 fold, after 8 weeks. C3d enables cell-mediated immunity to target multiple myeloma clones sparing non-transformed polyclonal B cells and plasma cells with lower mutation loads. We show that C3d increases the expression of ribosomal subunits associated with the translation of defective ribosomal products (DRiPs). C3d also decreases expression of protein arginine methyl transferase (PRMT) 5 which in turn relieves E2f1 repression increasing the expression of Lnc RNAs and derived peptides that evoke anti-tumor cellular immunity. The approach increases MHC-I expression by tumor cells and generates a CMI response that overcomes tumor immune-evasion strategies. Significance: Tumors are immunogenic in part because of somatic mutations that originate novel peptides that once presented on MHC engage cell-mediated immunity (CMI). However, in spite of the higher mutation load most tumors evade immunity. We discovered that a component of the complement system (C3d) overcomes tumor immune evasion by augmenting expression of ribosomal proteins and lncRNAs linked to the presentation of novel peptides by tumor cells. C3d induced CMI targets cancer cells sparing non transformed cells uncovering a novel function for complement in immune surveillance.

Global Tendencies and Frontier Topics in Cervical Laminoplasty: A Bibliometric Analysis from 1982 to 2023.

BACKGROUND: This bibliometric analysis aimed to map the knowledge network of laminoplasty research. METHODS: Studies on laminoplasty published from 1982 to 2023 were retrieved from the Web of Science Core Collection (WoSCC). The contributions of countries, institutions, authors, and journals were identified using VOSviewer, Scimago Graphica, and Microsoft Excel. Tendencies, hotspots, and knowledge networks were analyzed and visualized using VOSviewer and CiteSpace. RESULTS: We identified 2577 publications on laminoplasty. The annual number of publications exhibited an overall increasing trend since 2004. Among these, Japan, China, and the United States were the 3 major contributing countries. Keio University, Nagoya University, and Tokyo Medical & Dental University were the 3 most productive institutions. Shiro Imagama ranked first among authors regarding the number of articles, while K Hirabayashi was first among co-cited authors. Spine was the top journal in terms of the number of publications, citations, and co-citations. In addition, the research topics can be divided into 3 clusters: (1) Comparison between laminoplasty and other surgery in outcomes and complications; (2) Axial symptoms in laminoplasty; (3) Sagittal alignment and sagittal balance in laminoplasty. Emerging topics sagittal alignment and sagittal balance in degenerative cervical spondylosis are identified as current research frontiers. CONCLUSIONS: This study drew a knowledge map of the top countries, institutions, authors, publications, and journals on laminoplasty over the past 4 decades. The current and future hotspots of laminoplasty focus on sagittal balance, comparison between other surgery in outcomes and complication, and axial symptoms in laminoplasty.

Exploring the diagnostic potential of immunoglobulin A-microbiota interplay in liver cirrhosis and spontaneous bacterial peritonitis.

The human gut microbiota significantly impacts health, including liver conditions like liver cirrhosis (LC) and spontaneous bacterial peritonitis (SBP). Immunoglobulin A (IgA) plays a central role in maintaining gut microbial balance. Understanding IgA's interplay with gut microbiota and liver health is crucial. This study explores the relationship between fecal IgA levels, gut microbiota, and liver injury severity. A total of 69 LC patients and 30 healthy controls were studied. Fecal IgA levels were measured using ELISA, and IgA-coated bacteria were quantified via flow cytometry. Microbiota diversity and composition were assessed through 16S rRNA sequencing. Liver injury severity was graded using the Child-Pugh score. Statistical analyses determined correlations. LC patients had higher fecal IgA levels than controls, correlating positively with liver injury severity. Microbiota diversity decreased with severity, accompanied by shifts in composition favoring pro-inflammatory species. Ralstonia abundance positively correlated with liver injury, whereas Faecalibacterium showed a negative correlation. Specific microbial markers for SBP were identified. Functional profiling revealed altered microbial functionalities in LC and SBP. Elevated fecal IgA levels, coupled with microbiota alterations, correlate with liver injury severity in LC patients. Modulating gut microbiota could be a promising strategy for managing liver-related conditions. Further research is needed to understand underlying mechanisms and translate findings into clinical practice, potentially improving patient outcomes.

Research Progress on Starfish Outbreaks and Their Prevention and Utilization: Lessons from Northern China.

Starfish are keystone species as predators in benthic ecosystems, but when population outbreaks occur, this can have devastating consequences ecologically. Furthermore, starfish outbreaks and invasions can have adverse impact economically by impacting shellfish aquaculture. For example, an infestation of starfish in Qingdao led to a 50% reduction in sea cucumber production and an 80% reduction in scallop production, resulting in an economic loss of approximately RMB 100 million to oyster and other shellfish industries. Addressing the imperative need to proactively mitigate starfish invasions requires comprehensive research on their behavior and the underlying mechanisms of outbreaks. This review scrutinizes the historical patterns of outbreaks among diverse starfish species across various regions, delineates the factors contributing to the proliferation of Asterias amurensis in Chinese waters, articulates preventive and remedial strategies, and outlines the potential for the sustainable utilization of starfish.

Association between indoor environmental risk factors and pneumonia among preschool children in Urumqi：A case-control study.

Background: Pediatric pneumonia presents a significant global health challenge, particularly in low- and middle-income countries. This study aimed to investigate the incidence of pneumonia in preschool children in Urumqi and its association with indoor environmental factors. Methods: This case-control study collected data from December 2018 to December 2019 on 1522 preschool children in Urumqi (779 boys and 743 girls) who were diagnosed with pneumonia by a physician. A control group of children who had never had pneumonia was matched in a 1:1 ratio based on gender, age, and ethnicity. Using questionnaires, data were collected on children's general characteristics, passive smoking, types of housing, flooring materials, and indoor dampness, analyzing potential factors associated with the incidence of pediatric pneumonia. Results: Multivariate analysis revealed that cesarean birth (odds ratio [OR] = 1.27; 95 % confidence interval [95%CI] = 1.08-1.48), being an only child (OR = 1.32; 95%CI = 1.13-1.55), antibiotic treatment during the first year of life (OR = 2.51; 95%CI = 1.98-3.19), passive smoking during the mother's pregnancy (OR = 1.62; 95%CI = 1.24-2.13), living in multi-family apartment housing (OR = 1.64; 95%CI = 1.28-2.10) and other types of housing (OR = 1.47; 95%CI = 1.09-1.99), laminate flooring (OR = 1.31; 95%CI = 1.01-1.72), and tile/stone/cement flooring flooring (OR = 1.31; 95%CI = 1.06-1.61), and dampness in dwelling (during first year of mother's pregnancy) (OR = 1.30; 95%CI = 1.04-1.63) were risk factors for pediatric pneumonia. The use of fresh air filtration systems in children's residences (OR = 0.66; 95%CI = 0.50-0.86) was identified as a protective factor. Conclusion: This study underscores the importance of indoor environmental factors in the prevention of pediatric pneumonia. Public health strategies should consider these factors to reduce the incidence of pneumonia in children. Future research needs to be conducted over a broader geographical range and consider a more comprehensive range of factors influencing pediatric pneumonia.

Haemolysis index conundrum in a COVID-19 patient.

In this study, we report a preanalytical challenge noted in our laboratory on plasma samples from a critically ill COVID-19 patient treated with hydroxychloroquine. This is significant because, in critically ill COVID-19 patients on hydroxychloroquine, plasma samples can have a high measured haemolysis index in the absence of haemolysis, with the impact on reporting the results for potassium and other analytes.

An Evaluation of the Corrosion Inhibition Performance of Chitosan Modified by Quaternary Ammonium Salt for Carbon Steel in Stone Processing Wastewater.

Chitosan was used as the raw material. A quaternization reaction was carried out between 2,3-epoxypropyltrimethylammonium chloride and water-soluble chitosan to prepare quaternary ammonium salt water-soluble chitosan (QWSC), and its corrosion inhibition performance against the corrosion of carbon steel in stone processing wastewater was evaluated. The corrosion inhibition efficiencies of QWSC on carbon steel in stone processing wastewater were investigated through weight loss, as well as electrochemical and surface morphology characterization techniques. The results show that QWSC has superior corrosion inhibition performance for A3 carbon steel. When an amount of 60 mL·L-1 is added, the corrosion inhibition efficiency can reach 59.51%. Electrochemical research has shown that a QWSC inhibitor is a mixed-type corrosion inhibitor. The inhibition mechanisms of the QWSC inhibitor revealed that the positive charge on the surface of carbon steel in stone wastewater was conducive to the adsorption of Cl- in the medium, which produced an excessive negative charge on the metal's surface. At the same time, the quaternary ammonium cation and amino cation formed in QWSC in stone processing wastewater can be physically absorbed on the surface of A3 carbon steel, forming a thin-film inhibitor to prevent metal corrosion.

Mechanism of immune activation mediated by genomic instability and its implication in radiotherapy combined with immune checkpoint inhibitors.

Various genetic and epigenetic changes associated with genomic instability (GI), including DNA damage repair defects, chromosomal instability, and mitochondrial GI, contribute to development and progression of cancer. These alterations not only result in DNA leakage into the cytoplasm, either directly or through micronuclei, but also trigger downstream inflammatory signals, such as the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. Apart from directly inducing DNA damage to eliminate cancer cells, radiotherapy (RT) exerts its antitumor effects through intracellular DNA damage sensing mechanisms, leading to the activation of downstream inflammatory signaling pathways. This not only enables local tumor control but also reshapes the immune microenvironment, triggering systemic immune responses. The combination of RT and immunotherapy has emerged as a promising approach to increase the probability of abscopal effects, where distant tumors respond to treatment due to the systemic immunomodulatory effects. This review emphasizes the importance of GI in cancer biology and elucidates the mechanisms by which RT induces GI remodeling of the immune microenvironment. By elucidating the mechanisms of GI and RT-induced immune responses, we aim to emphasize the crucial importance of this approach in modern oncology. Understanding the impact of GI on tumor biological behavior and therapeutic response, as well as the possibility of activating systemic anti-tumor immunity through RT, will pave the way for the development of new treatment strategies and improve prognosis for patients.

Clonal evolution of hematopoietic stem cells after cancer chemotherapy.

Normal hematopoietic stem and progenitor cells (HSPCs) inherently accumulate somatic mutations and lose clonal diversity with age, processes implicated in the development of myeloid malignancies 1 . The impact of exogenous stressors, such as cancer chemotherapies, on the genomic integrity and clonal dynamics of normal HSPCs is not well defined. We conducted whole-genome sequencing on 1,032 single-cell-derived HSPC colonies from 10 patients with multiple myeloma (MM), who had undergone various chemotherapy regimens. Our findings reveal that melphalan treatment distinctly increases mutational burden with a unique mutation signature, whereas other MM chemotherapies do not significantly affect the normal mutation rate of HSPCs. Among these therapy-induced mutations were several oncogenic drivers such as TET2 and PPM1D . Phylogenetic analysis showed a clonal architecture in post-treatment HSPCs characterized by extensive convergent evolution of mutations in genes such as TP53 and PPM1D . Consequently, the clonal diversity and structure of post-treatment HSPCs mirror those observed in normal elderly individuals, suggesting an accelerated clonal aging due to chemotherapy. Furthermore, analysis of matched therapy-related myeloid neoplasm (t-MN) samples, which occurred 1-8 years later, enabled us to trace the clonal origin of t-MNs to a single HSPC clone among a group of clones with competing malignant potential, indicating the critical role of secondary mutations in dictating clonal dominance and malignant transformation. Our findings suggest that cancer chemotherapy promotes an oligoclonal architecture with multiple HSPC clones possessing competing leukemic potentials, setting the stage for the selective emergence of a singular clone that evolves into t-MNs after acquiring secondary mutations. These results underscore the importance of further systematic research to elucidate the long-term hematological consequences of cancer chemotherapy.

A CD36-dependent non-canonical lipid metabolism program promotes immune escape and resistance to hypomethylating agent therapy in AML.

Environmental lipids are essential for fueling tumor energetics, but whether these exogenous lipids transported into cancer cells facilitate immune escape remains unclear. Here, we find that CD36, a transporter for exogenous lipids, promotes acute myeloid leukemia (AML) immune evasion. We show that, separately from its established role in lipid oxidation, CD36 on AML cells senses oxidized low-density lipoprotein (OxLDL) to prime the TLR4-LYN-MYD88-nuclear factor κB (NF-κB) pathway, and exogenous palmitate transfer via CD36 further potentiates this innate immune pathway by supporting ZDHHC6-mediated MYD88 palmitoylation. Subsequently, NF-κB drives the expression of immunosuppressive genes that inhibit anti-tumor T cell responses. Notably, high-fat-diet or hypomethylating agent decitabine treatment boosts the immunosuppressive potential of AML cells by hijacking CD36-dependent innate immune signaling, leading to a dampened therapeutic effect. This work is of translational interest because lipid restriction by US Food and Drug Administration (FDA)-approved lipid-lowering statin drugs improves the efficacy of decitabine therapy by weakening leukemic CD36-mediated immunosuppression.

Seasonal dynamics of the microbiota and nutritional composition in bee bread from Apis cerana and Apis mellifera colonies.

Bee bread is a product of honeybees, which collect and ferment pollen, that contains highly nutritious and easily digestible active substances. However, its nutritional composition varies significantly with fermentation strains and seasonal changes. To unveil the patterns of microbial community and nutritional component changes in bee bread across seasons, we employed high-throughput techniques to assess the diversity of bacteria and fungi in bee bread. The results indicated that the compositions of bacteria and fungi in bee bread undergo significant seasonal variation, with noticeable changes in the microbial diversity of bee bread from different bee species. Subsequently, metabolomic analysis revealed high activity of glycerophospholipid metabolism in bee bread. Furthermore, our analysis identifaied noteworthy differences in nutritional components, including pH values, sugar content, and free amino acid levels, in bee bread across different seasons.

Metal-Organic Framework-Capped Gold Nanorod Hybrids for Combinatorial Cancer Therapy.

Recently, nanomaterials have attracted extensive attention in cancer-targeting therapy and as drug delivery vehicles owing to their unique surface and size properties. Multifunctional combinations of nanomaterials have become a research hotspot as researchers aim to provide a full understanding of their nanomaterial characteristics. In this study, metal-organic framework-capped gold nanorod hybrids were synthesized. Our research explored their ability to kill tumor cells by locally increasing the temperature via photothermal conclusion. The specific peroxidase-like activity endows the hybrids with the ability to disrupt the oxidative balance in vitro. Simultaneously, chemotherapeutic drugs are administered and delivered by loading and transportation for effective combinatorial cancer treatment, thereby enhancing the curative effect and reducing the unpredictable toxicity and side effects of large doses of chemotherapeutic drugs. These studies can improve combinatorial cancer therapy and enhance cancer treatment.

Behavioral signatures of the rapid recruitment of long-term memory to overcome working memory capacity limits.

Working- and long-term memory are often studied in isolation. To better understand the specific limitations of working memory, effort is made to reduce the potential influence of long-term memory on performance in working memory tasks (e.g., asking participants to remember artificial, abstract items rather than familiar real-world objects). However, in everyday life we use working- and long-term memory in tandem. Here, our goal was to characterize how long-term memory can be recruited to circumvent capacity limits in a typical visual working memory task (i.e., remembering colored squares). Prior work has shown that incidental repetitions of working memory arrays often do not improve visual working memory performance - even after dozens of incidental repetitions, working memory performance often shows no improvement for repeated arrays. Here, we used a whole-report working memory task with explicit rather than incidental repetitions of arrays. In contrast to prior work with incidental repetitions, in two behavioral experiments we found that explicit repetitions of arrays yielded robust improvement to working memory performance, even after a single repetition. Participants performed above chance at recognizing repeated arrays in a later long-term memory test, consistent with the idea that long-term memory was used to rapidly improve performance across array repetitions. Finally, we analyzed inter-item response times and we found a response time signature of chunk formation that only emerged after the array was repeated (inter-response time slowing after two to three items); thus, inter-item response times may be useful for examining the coordinated interaction of visual working and long-term memory in future work.

Subtype prediction of intrahepatic cholangiocarcinoma using dynamic contrast-enhanced ultrasound.

OBJECTIVE: The study aimed to investigate the predictive value of dynamic contrast-enhanced ultrasound (DCE-US) in differentiating small-duct (SD) and large-duct (LD) types of intrahepatic cholangiocarcinoma (ICC). METHODS: This study retrospectively enrolled 110 patients with pathologically confirmed ICC lesions who were subject to preoperative contrast-enhanced ultrasound (CEUS) examinations between January 2022 and February 2023. Patients were further classified according to the subtype: SD-type and LD-type, and an optimal predictive model was established and validated using the above pilot cohort. The test cohort, consisting of 48 patients prospectively enrolled from March 2023 to September 2023, was evaluated. RESULTS: In the pilot cohort, compared with SD-type ICCs, more LD-type ICCs showed elevated carcinoembryonic antigen (p < 0.001), carbohydrate antigen 19-9 (p = 0.004), ill-defined margin (p = 0.018), intrahepatic bile duct dilation (p < 0.001). Among DCE-US quantitative parameters, the wash-out area under the curve (WoAUC), wash-in and wash-out area under the curve (WiWoAUC), and fall time (FT) at the margin of lesions were higher in the SD-type group (all p < 0.05). Meanwhile, the mean transit time (mTT) and wash-out rate (WoR) at the margin of the lesion were higher in the LD-type group (p = 0.041 and 0.007, respectively). Logistic regression analysis showed that intrahepatic bile duct dilation, mTT, and WoR were significant predictive factors for predicting ICC subtypes, and the AUC of the predictive model achieved 0.833 in the test cohort. CONCLUSIONS: Preoperative DCE-US has the potential to become a novel complementary method for predicting the pathological subtype of ICC. CRITICAL RELEVANCE STATEMENT: DCE-US has the potential to assess the subtypes of ICC lesions quantitatively and preoperatively, which allows for more accurate and objective differential diagnoses, and more appropriate treatments and follow-up or additional examination strategies for the two subtypes. KEY POINTS: Preoperative determination of intrahepatic cholangiocarcinoma (ICC) subtype aids in surgical decision-making. Quantitative parameters from dynamic contrast-enhanced US (DCE-US) allow for the prediction of the ICC subtype. DCE-US-based imaging has the potential to become a novel complementary method for predicting ICC subtypes.

RNA aggregates harness the danger response for potent cancer immunotherapy.

Cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Here, we create "onion-like" multi-lamellar RNA lipid particle aggregates (LPAs) to substantially enhance the payload packaging and immunogenicity of tumor mRNA antigens. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for Toll-like receptor engagement in immune cells, systemically administered RNA-LPAs activate RIG-I in stromal cells, eliciting massive cytokine/chemokine response and dendritic cell/lymphocyte trafficking that provokes cancer immunogenicity and mediates rejection of both early- and late-stage murine tumor models. In client-owned canines with terminal gliomas, RNA-LPAs improved survivorship and reprogrammed the TME, which became "hot" within days of a single infusion. In a first-in-human trial, RNA-LPAs elicited rapid cytokine/chemokine release, immune activation/trafficking, tissue-confirmed pseudoprogression, and glioma-specific immune responses in glioblastoma patients. These data support RNA-LPAs as a new technology that simultaneously reprograms the TME while eliciting rapid and enduring cancer immunotherapy.

Da-Jian-Zhong decoction alleviates diarrhea-predominant irritable bowel syndrome via modulation of gut microbiota and Th17/Treg balance.

ETHNOPHARMACOLOGICAL RELEVANCE: Da-Jian-Zhong decoction (DJZD) is a herbal formula clinically used for abdominal pain and diarrhea induced by spleen-Yang deficiency syndrome. Recently, treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) with DJZD has received increasing attention, but the underlying mechanism of action remains elusive. AIM OF THE STUDY: We aimed to evaluate the therapeutic effect of DJZD on IBS-D rats and to elucidate the underlying mechanisms. MATERIALS AND METHODS: An IBS-D rats model was constructed using a two-factor superposition method of neonatal maternal separation and Senna folium aqueous extract lavage. Moreover, the effect of DJZD was evaluated based on the body weight, rectal temperature, abdominal withdrawal reflex (AWR), and Bristol stool scale score (BSS). The factors that regulate the DJZD effects on IBS-D were estimated using whole microbial genome, transcriptome sequencing (RNA-Seq), flow cytometry, and quantitative reverse transcription polymerase chain reaction (RT-qPCR) analyses. RESULTS: We found that DJZD alleviated the symptoms of IBS-D rats, with the low-dose (2.4 g/kg) as the better ones, as shown by the higher body weight and lower AWR score and BSS. At the phylum level, the relative abundance of Bacteroidetes was obviously increased, and at the genus level, Lactobacillus and Parabacteroides were increased, while that of Firmicutes_bacterium_424 and Ruminococcus gnavus was decreased in DJZD group. Furthermore, the significantly enriched GO terms after treatment with DJZD mainly included the immune response, positive regulation of activated T cell proliferation, and positive regulation of interleukin-17 (IL-17) production. Importantly, flow cytometry analysis further revealed that the T helper cell type 17/regulatory T cell (Th17/Treg) balance contributed to the DJZD-induced alleviation of IBS-D symptoms, as DJZD downregulated Th17/Treg ratio and Th17 cell-related cytokines IL-17 and IL-6 levels in the colon. CONCLUSIONS: These results demonstrated that DJZD has a good therapeutic effect on IBS-D rats, probably by maintaining the homeostasis of gut microbiota and regulating Th17/Treg balance and its related inflammatory factors.

Serum cytokines profile changes in amyotrophic lateral sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder, characterized by progressive limb weakness, dysphagia, dysphonia, and respiratory failure due to degeneration of upper and lower motor neurons. The pathogenesis of ALS is still unclear. Neuroinflammation has been found to be involved in its development and progression. Cytokines play a significant role in the inflammatory process. This study aims to identify novel biomarkers that may assist in the diagnosis of ALS. Methods: In Fujian Medical University Union Hospital and Huashan Hospital Fudan University, two independent centers, we prospectively recruited 50 ALS patients, and 41 healthy controls (25 ALS and 26 controls in the first stage and 25 ALS and 15 controls in the validation stage). An 18-plex Luminex kit was used to screen the serum cytokines levels in the first stage. Commercial ELISA kits were used to measure the levels of target cytokines in the validation stage. A single-molecule array HD-X platform was applied to assess the levels of serum neurofilament light chain (NFL). Results: The levels of serum IL-18 were markedly increased in patients with ALS in the first stage (p = 0.016). The ROC curve showed an area under the curve at 0.695 (95% CI 0.50-0.84) in distinguishing ALS patients from healthy controls. The IL-21 was decreased in elderly patients when grouped by 55 years old (the medium age). Furthermore, the IL-5, IL-13, IL-18, and NFL had a positive relationship with the disease progression of ALS. We also found that serum IL-18 was markedly increased in ALS patients in the validation stage (167.67 [148.25-175.59] vs 116.44 [102.43-122.19]pg/ml, p < 0.0015). Conclusion: In this study, we identified systemic cytokine profile changes in the serum of ALS patients, especially the elevated IL-18, as well as the decreased IL-21 in elder patients. These changes in serum cytokine profiles may shed new light on an in-depth understanding of the immunopathogenic characteristics of ALS.