Search

Introduction: Chronic spontaneous urticaria (CSU) with autoreactivity is often resistant to antihistamines. Autologous whole blood injection (AWBI) has shown potential efficacy in the treatment of this disease, but it is controversial. It is necessary to screen patients who are suitable for this therapy in advance. This study aimed to identify biomarkers that predict the efficacy of AWBI treatment in CSU patients with autoreactivity. Methods: A total of 30 patients with autologous serum skin test-positive CSU treated with AWBI were included in this study; urticaria activity score (UAS7) was recorded and the treatment response was judged based on it. Levels of total serum IgE, anti-high-affinity IgE receptor (FcεRI) IgG, and basophils CD63 and FcεRI expressions, and D-dimer of all patients were determined and analyzed. Results: Baseline levels of total IgE, D-dimer, basophil FcεRI and CD63 expressions showed good correlations with UAS7 variations. D-dimer, basophil FcεRI and CD63 expressions changed significantly before and after AWBI treatment in AWBI responders, and the basophil FcεRI and CD63 expressions consistently and dynamically decreased in AWBI responders during the treatment. Baseline levels of total IgE, D-dimer, basophil FcεRI and CD63 expressions showed certain predictive values for AWBI response. Conclusions: Baseline levels of total IgE, D-dimer, basophil FcεRI and CD63 expressions could be biomarkers of predicting AWBI efficacy in patients with CSU with autoreactivity. [ABSTRACT FROM AUTHOR]

Interleukin (IL)‐38 is a newly discovered cytokine of the IL‐1 family, which binds various receptors (i.e., IL‐36R, IL‐1 receptor accessory protein‐like 1, and IL‐1R1) in the central nervous system (CNS). The hallmark physiological function of IL‐38 is competitive binding to IL‐36R, as does the IL‐36R antagonist. Emerging research has shown that IL‐38 is abnormally expressed in the serum and brain tissue of patients with ischemic stroke (IS) and autism spectrum disorder (ASD), suggesting that IL‐38 may play an important role in neurological diseases. Important advances include that IL‐38 alleviates neuromyelitis optica disorder (NMOD) by inhibiting Th17 expression, improves IS by protecting against atherosclerosis via regulating immune cells and inflammation, and reduces IL‐1β and CXCL8 release through inhibiting human microglial activity post‐ASD. In contrast, IL‐38 mRNA is markedly increased and is mainly expressed in phagocytes in spinal cord injury (SCI). IL‐38 ablation attenuated SCI by reducing immune cell infiltration. However, the effect and underlying mechanism of IL‐38 in CNS diseases remain inadequately characterized. In this review, we summarize the biological characteristics, pathophysiological role, and potential mechanisms of IL‐38 in CNS diseases (e.g., NMOD, Alzheimer's disease, ASD, IS, TBI, and SCI), aiming to explore the therapeutic potential of IL‐38 in the prevention and treatment of CNS diseases. [ABSTRACT FROM AUTHOR]

Liver diseases and their related complications endanger the health of millions of people worldwide. The prevention and treatment of liver diseases are still serious challenges both in China and globally. With the improvement of living standards, the prevalence of metabolic liver diseases, including non-alcoholic fatty liver disease and alcoholic liver disease, has increased at an alarming rate, resulting in more cases of end-stage liver disease. Therefore, the discovery of novel therapeutic drugs for the treatment of liver diseases is urgently needed. Glycyrrhizin (GL), a triterpene glycoside from the roots of licorice plants, possesses a wide range of pharmacological and biological activities. Currently, GL preparations (GLPs) have certain advantages in the treatment of liver diseases, with good clinical effects and fewer adverse reactions, and have shown broad application prospects through multitargeting therapeutic mechanisms, including antisteatotic, anti-oxidative stress, anti-inflammatory, immunoregulatory, antifibrotic, anticancer, and drug interaction activities. This review summarizes the currently known biological activities of GLPs and their medical applications in the treatment of liver diseases, and highlights the potential of these preparations as promising therapeutic options and their alluring prospects for the treatment of liver diseases. [ABSTRACT FROM AUTHOR]

Background: Functional gastrointestinal disorders (FGIDs) are closely related to disorders of brain-gut interaction. FGIDs are the dominant disease of acupuncture treatment, which can improve the symptoms and emotional state. Aim: To evaluate the results and quality of the available clinical evidence and to summarize the central mechanism and effect of acupuncture on FGIDs. Methods: PubMed, EMBASE, Web of science, Cochrane Library, China National Knowledge Infrastructure (CNKI) were searched by computer to collect the randomized controlled trials (RCTs), which contained central mechanisms via fMRI research of acupuncture in the treatment of FGIDs patients. The search time limit was from the establishment of the database to June 22, 2022. Two researchers independently screened the literature, extracted data, and evaluated the quality. Results: Ten RCTs involving fMRI data were included in this study, including 4 Functional dyspepsia (FD) studies, 3 irritable bowel syndrome (IBS) studies, and 3 functional constipation (FC) studies. The score of improvements in both gastrointestinal symptoms and psychological symptoms showed that acupuncture could significantly improve the clinical symptoms of FGIDs patients, including abdominal pain, abdominal distension, frequency of defecation, and stool characteristics, and could relieve anxiety and depression symptoms of patients. Acupuncture could regulate brain functional connections and functional activity in FGIDs patients, mainly including insula, anterior cingulate cortex, prefrontal cortex, thalamus, hippocampus, amygdala and other brain regions. Conclusion: Acupuncture can improve gastrointestinal symptoms and psychological status in FGIDs patients, and regulate functional connectivity and activity of brain regions such as insula, ACC, PFC, thalamus, HIPP, amygdala, etc. These changes in brain activity may related to visceral sensation, pain regulation, emotion, but further studies of high quality are still necessary. [ABSTRACT FROM AUTHOR]

Therapeutic options for advanced prostate cancer have vastly expanded over the last decade and will continue to expand in the future. Drugs targeting the androgen receptor (AR) signaling pathway, i.e., androgen receptor targeting agents (ARTAs), remain the mainstream treatments that are increasingly transforming the disease into one that can be controlled for an extended period of time. Prostate cancer is inherently addicted to AR. Under the treatment pressure of ARTA, molecular alterations occur, leading to the clonal expansion of resistant cells in a disease state broadly categorized as castration-resistant prostate cancer (CRPC). One castration resistance mechanism involves AR splice variants (AR-Vs) lacking the ligand-binding domain. Some AR-Vs have been identified as constitutively active, capable of activating AR signaling pathways without androgenic ligands. Among these variants, AR-V7 is the most extensively studied and may be measured non-invasively using validated circulating tumor cell (CTC) tests. In the context of the evolving prostate cancer treatment landscape, novel agents are developed and evaluated for their efficacy in targeting AR-V7. In patients with metastatic CRPC (mCRPC), the availability of the AR-V7 tests will make it possible to determine whether the treatments are effective for CTC AR-V7-positive disease, even though the treatments may not be specifically designed to target AR-V7. In this review, we will first outline the current prostate cancer treatment landscape, followed by an in-depth review of relatively newer prostate cancer therapeutics, focusing on AR-targeting agents under clinical development. These drugs are categorized from the standpoint of their activities against AR-V7 through direct or indirect mechanisms. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) with high morbidity and mortality all over the world is characterized by decreased kidney function, a condition which can result from numerous risk factors, including diabetes, hypertension and obesity. Despite significant advances in our understanding of the pathogenesis of CKD, there are still no treatments that can effectively combat CKD, which underscores the urgent need for further study into the pathological mechanisms underlying this condition. In this regard, animal models of CKD are indispensable. This article reviews a widely used animal model of CKD, which is induced by adenine. While a physiologic dose of adenine is beneficial in terms of biological activity, a high dose of adenine is known to induce renal disease in the organism. Following a brief description of the procedure for disease induction by adenine, major mechanisms of adenine-induced CKD are then reviewed, including inflammation, oxidative stress, programmed cell death, metabolic disorders, and fibrillation. Finally, the application and future perspective of this adenine-induced CKD model as a platform for testing the efficacy of a variety of therapeutic approaches is also discussed. Given the simplicity and reproducibility of this animal model, it remains a valuable tool for studying the pathological mechanisms of CKD and identifying therapeutic targets to fight CKD. [ABSTRACT FROM AUTHOR]

Cyclophilin A (CypA), the first member of cyclophilins, is distributed extensively in eukaryotic and prokaryotic cells, primarily localized in the cytoplasm. In addition to acting as an intracellular receptor for cyclosporin A (CSA), CypA plays a crucial role in diseases such as aging and tumorigenesis. Apoptosis, a form of programmed cell death, is able to balance the rate of cell viability and death. In this review, we focus on the effects of CypA on apoptosis and the relationship between specific mechanisms of CypA promoting or inhibiting apoptosis and diseases, including tumorigenesis, cardiovascular diseases, organ injury, and microbial infections. Notably, the process of CypA promoting or inhibiting apoptosis is closely related to disease development. Finally, future prospects for the association of CypA and apoptosis are discussed, and a comprehensive understanding of the effects of CypA on apoptosis in relation to diseases is expected to provide new insights into the design of CypA as a therapeutic target for diseases. Key points: • Understand the effect of CypA on apoptosis. • CypA affects apoptosis through specific pathways. • The effect of CypA on apoptosis is associated with a variety of disease processes. [ABSTRACT FROM AUTHOR]

Metal–organic frameworks (MOFs) have been broadly applied in biomedical and other fields. MOFs have high porosity, a large comparative area, and good biostability and have attracted significant attention, especially in cancer therapies. This paper presents the latest applications of MOFs in chemodynamic therapy (CDT), sonodynamic therapy (SDT), photodynamic therapy (PDT), photothermal therapy (PTT), immunotherapy (IT), and combination therapy for breast cancer. A combination therapy is the combination of two different treatment modalities, such as CDT and PDT combination therapy, and is considered more effective than separate therapies. Herein, we have also discussed the advantages and disadvantages of combination therapy in the treatment of breast cancer. This paper aims to illustrate the potential of MOFs in new cancer therapeutic approaches, discuss their potential advantages, and provide some reflections on the latest research results. [ABSTRACT FROM AUTHOR]

Amblyopia affects development of children's monocular vision and binocular function and becomes a largely intractable problem with increasing aging. This study is to investigate the binocular function and evaluate efficacy of digital therapy in children 8–13 years of age with anisometropic amblyopia. The patients in the digital therapy group performed the training with the digital amblyopia therapeutic software. The visual acuity and binocular function (perceptual eye position [PEP], suppression, and stereopsis) were examined at the first visit and 3-month post-treatment. Twenty-three cases in the control group and 25 cases in the digital therapy group were enrolled. The results revealed that 3-month digital therapy can effectively improve corrected distance visual acuity (CDVA) and improve the binocular function, including PEP, suppression, and second-order stereopsis in children with anisometropic amblyopia, 8–13 years of age. Digital therapy for amblyopia can effectively improve monocular CDVA of amblyopic eyes and binocular function in older children with anisometropic amblyopia. [ABSTRACT FROM AUTHOR]

NRP1/CD304 is a typical membrane-bound co-receptor for the vascular endothelial cell growth factor (VEGF), semaphorin family members, and viral SARS-CoV-2. Cordycepin (CD) is a natural product or active gradient from traditional Chinese medicine (TCM) from Cordyceps militaris Link and Ophiocordyceps sinensis (Berk.). However, NRP1 expression regulation via CD in cancers and the potential roles and mechanisms of SARS-CoV-2 infection are not clear. In this study, online databases were analyzed, Western blotting and quantitative RT-PCR were used for NRP1 expression change via CD, molecular docking was used for NRP/CD interaction, and a syncytial formation assay was used for CD inhibition using a pseudovirus SARS-CoV-2 entry. As a result, we revealed that CD inhibits NRP1 expressed in cancer cells and prevents viral syncytial formation in 293T-hACE2 cells, implying the therapeutic potential for both anti-cancer and anti-viruses, including anti-SARS-CoV-2. We further found significant associations between NRP1 expressions and the tumor–immune response in immune lymphocytes, chemokines, receptors, immunostimulators, immune inhibitors, and major histocompatibility complexes in most cancer types, implying NRP1's roles in both anti-cancer and anti-SARS-CoV-2 entry likely via immunotherapy. Importantly, CD also downregulated the expression of NRP1 from lymphocytes in mice and downregulated the expression of A2AR from the lung cancer cell line H1975 when treated with CD, implying the NRP1 mechanism probably through immuno-response pathways. Thus, CD may be a therapeutic component for anti-cancer and anti-viral diseases, including COVID-19, by targeting NRP1 at least. [ABSTRACT FROM AUTHOR]

ABSTRACTThe Zika virus (ZIKV) outbreak and its link to microcephaly triggered a public health concern. To examine antibody response in a patient infected with ZIKV, we used single-cell PCR to clone 31 heavy and light chain-paired monoclonal antibodies (mAbs) that bind to ZIKV envelope (E) proteins isolated from memory B cells of a ZIKV-infected patient. Three mAbs (7B3, 1C11, and 6A6) that showed the most potent and broad neutralization activities against the African, Asian, and American strains were selected for further analysis. mAb 7B3 showed an IC50 value of 11.6 ng/mL against the circulating American strain GZ02. Epitope mapping revealed that mAbs 7B3 and 1C11 targeted residue K394 of the lateral ridge (LR) epitope of the EDIII domain, but 7B3 has a broader LR epitope footprint and recognizes residues T335, G337, E370, and N371 as well. mAb 6A6 recognized residues D67, K118, and K251 of the EDII domain. Interestingly, although the patient was seronegative for DENV infection, mAb 1C11, originating from the VH3-23 and VK1-5 germline pair, neutralized both ZIKV and DENV1. Administration of the mAbs 7B3, 1C11, and 6A6 protected neonatal SCID mice infected with a lethal dose of ZIKV. This study provides potential therapeutic antibody candidates and insights into the antibody response after ZIKV infection.

Stroke is a major public health problem worldwide with a high burden of neurological disability and mortality. Long noncoding RNAs (lncRNAs) have attracted much attention in the past decades because of their newly discovered roles in pathophysiological processes in many diseases. The abundance of lncRNAs in the nervous system indicates that they may be part of a complex regulatory network governing physiology and pathology of the brain. In particular, lncRNAs have been shown to play pivotal roles in the pathogenesis of stroke. In this article, we provide a review of the multifaceted functions of lncRNAs in the pathogenesis of ischemic stroke and intracerebral hemorrhage, highlighting their promising use as stroke diagnostic biomarkers and therapeutics. To this end, we discuss the potential of stem cells in aiding lncRNA applications in stroke.

This article explores the potential of immunotherapy in treating cancer, specifically focusing on "cold tumors" that are resistant to traditional treatments. Immunotherapy offers high specificity and minimal side effects by stimulating the body's immune response against tumors. The article discusses innovative approaches to enhance the effectiveness and safety of immunotherapy, such as discovering new biomarkers, reshaping the tumor microenvironment, and exploring combination therapies. It also highlights emerging therapies like DNA/RNA vaccines. However, there are still challenges in translating these strategies into clinical practice, emphasizing the need for further research and the discovery of new targets to advance tumor immunotherapy. [Extracted from the article]

Traditional Chinese medicine (TCM) is increasingly used to manage type 2 diabetes and its nonpharmacological interventions are showing potential for preventing type 2 diabetes. This study mainly reviews relevant research. The most mentioned non-drug treatments for preventing type 2 diabetes in TCM are healthy diet, physical activity, emotional therapy, and acupuncture. In most studies, blood glucose status in patients with prediabetes and type 2 diabetes was significantly improved after TCM non-drug interventions, and there was no significant difference between the adverse effect of TCM and control groups or other intervention groups, while the methodological quality of the clinical trials involving TCM generally kept a low level. The effectiveness of TCM in preventing type 2 diabetes has yet to be validated in large randomized controlled trials and the underlying mechanism also needs further exploration. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PCa), a globally prevalent malignancy, displays intricate heterogeneity within its epithelial cells, closely linked with disease progression and immune modulation. However, the clinical significance of genes and biomarkers associated with these cells remains inadequately explored. To address this gap, this study aimed to comprehensively investigate the roles and clinical value of epithelial cell-related genes in PCa. Methods: Leveraging single-cell sequencing data from GSE176031, we conducted an extensive analysis to identify epithelial cell marker genes (ECMGs). Employing consensus clustering analysis, we evaluated the correlations between ECMGs, prognosis, and immune responses in PCa. Subsequently, we developed and validated an optimal prognostic signature, termed the epithelial cell marker gene prognostic signature (ECMGPS), through synergistic analysis from 101 models employing 10 machine learning algorithms across five independent cohorts. Additionally, we collected clinical features and previously published signatures from the literature for comparative analysis. Furthermore, we explored the clinical utility of ECMGPS in immunotherapy and drug selection using multi-omics analysis and the IMvigor cohort. Finally, we investigated the biological functions of the hub gene, transmembrane p24 trafficking protein 3 (TMED3), in PCa using public databases and experiments. Results: We identified a comprehensive set of 543 ECMGs and established a strong correlation between ECMGs and both the prognostic evaluation and immune classification in PCa. Notably, ECMGPS exhibited robust predictive capability, surpassing traditional clinical features and 80 published signatures in terms of both independence and accuracy across five cohorts. Significantly, ECMGPS demonstrated significant promise in identifying potential PCa patients who might benefit from immunotherapy and personalized medicine, thereby moving us nearer to tailored therapeutic approaches for individuals. Moreover, the role of TMED3 in promoting malignant proliferation of PCa cells was validated. Conclusions: Our findings highlight ECMGPS as a powerful tool for improving PCa patient outcomes and supply a robust conceptual framework for in-depth examination of PCa complexities. Simultaneously, our study has the potential to develop a novel alternative for PCa diagnosis and prognostication. [ABSTRACT FROM AUTHOR]

The composition of the gut microbiome is profoundly influenced by the accumulation of toxins in end-stage renal disease (ESRD) and specific medical treatments during kidney transplantation (KT). However, variations in results may arise due to factors such as genetics, dietary habits, and the strategy of anti-rejection therapy. Therefore, we conducted a 16S rRNA sequencing study to characterize intestinal microbiomes by using 75 fecal specimens obtained from 25 paired Chinese living donors (LDs) of kidneys and recipients before and after KT. Surprisingly, similar enterotypes were observed between healthy LDs and ESRD recipients. Nonetheless, following KT, the fecal communities of recipients exhibited distinct clustering, which was primarily characterized by Escherichia–Shigella and Streptococcus at the genus level, along with a reduction in the diversity of microbiota. To further explore the characteristics of gut microorganisms in early rejection episodes, two recipients with biopsy-proven borderline changes during follow-up were enrolled in a preliminary sub-cohort study. Our findings reveal a comparable construction of gut microbiota between ESRD patients and their healthy relatives while also highlighting the significant impact of KT on gut microbial composition. [ABSTRACT FROM AUTHOR]

Congenital heart disease (CHD), birth defect with the highest incidence rates worldwide, and is mainly characterized by the abnormal internal structure of the heart or/and the anatomical structure of great vessels. In the past few decades, CHD repair surgery through standard median sternotomy incision combined with cardiopulmonary bypass (CPB) technology has been considered the gold standard for surgical correction of heart and great vessels. With the promotion and clinical application of interventional catheterization technology, transcatheter closure of CHD under radioactive radiation has gradually been recognized and applied. However, its radiation exposure and potential complications related to arteriovenous vessels still face challenges. In recent years, an increasing number of surgeons have explored new surgical procedures, for the safe and effective treatment of CHD, as far as possible to reduce surgical trauma, avoid radiation exposure, and improve the cosmetic effect. Therefore, on the premise of satisfactory exposure or guidance, how to integrate ultrasound and percutaneous interventional technology remained the focus of the exploration. This mini-review highlights and summarizes the signs of progress of ultrasound intervention in the last decade that have proven the effectiveness and operability of a well-established procedure for percutaneous closure of congenital heart diseases under echocardiographic guidance only. We discuss potential diseases that will benefit from this emerging procedure based on this progress. Owing to the crucial advantages played by this strategy in the treatment of CHD, better understanding and promotion of this less exploited field may contribute to the development of therapeutics targeting CHD, improve medical utilization rate, promote the optimization of medical resources, and ultimately achieve precise and efficient medical treatment. [ABSTRACT FROM AUTHOR]

The latest evidence suggested that the onset of dilated cardiomyopathy (DCM) is closely associated with immune microenvironment disturbance. Since N6‐methyladenosine (m6A) RNA methylation impacts on immunocyte function and antitumor immunity, it is predictable that m6A RNA methylation may result in immune microenvironment disorder. Here, we attempted to verify this hypothesis. We used single‐sample gene set enrichment analysis (ssGSEA) to investigate the infiltration abundance of immunocytes, single‐cell RNA‐Seq to identify key m6A regulator, and a doxorubicin (Dox)‐induced DCM mouse model to confirm our findings. ssGSEA revealed a higher infiltration abundance of CD8+ T lymphocytes, NK cells, monocytes, and B+ lymphocytes in DCM myocardium tissue. Single‐cell RNA‐Seq indicated a critical role of IGFBP2 in DCM. Cross‐checking analysis hinted an interaction between IGFBP2 and NSUN5, ALYREF, RRP8, and ALKBH3. Mechanically, IGFBP2‐mediated RNA methylation deteriorated the immune microenvironment and thus increased the risk of DCM by enhancing CD8+ T lymphocyte, NK cell, monocyte, B+ lymphocyte infiltration and activating check‐point, MHC‐I, and T cell co‐stimulation signaling pathways. In the DCM mouse model, echocardiography indicated a significant reduction in ejection fraction (EF) and fractional shortening (FS) and an increase in left ventricular internal dimensions at systole (LVIDs) and diastole (LVIDd). MASSON staining indicated an increased fibrosis in myocardium tissue. qPCR and immunofluorescence staining indicated a significant increase in mRNA and protein levels of IGFBP2. The present study indicated that IGFBP2‐mediated RNA methylation remodeled the immune microenvironment and increased the risk of DCM. IGFBP2 may serve as potential therapeutic target for DCM. [ABSTRACT FROM AUTHOR]

Purpose: The incidence of linezolid-induced thrombocytopenia (LIT) has been reported to vary widely across studies. We performed a meta-analysis to identify the risk factors for thrombocytopenia among patients who received linezolid treatment. Methods: The PubMed, Embase and Cochrane Library databases were searched from inception to November 2022 to identify eligible studies. Data on the potential predictors of incidence in LIT were pooled using a random effects model. Sensitivity analyses were performed to determine the robustness of the results when significant heterogeneity was observed. Results: Forty observational studies involving 6454 patients treated with linezolid were included in the analysis. LIT was estimated to occur in 37% of patients. The following important factors were associated with the incidence of LIT: advanced age, body mass index, concurrent renal impairment or liver disease, abnormal laboratory parameters (including white blood cell count, serum creatinine, baseline platelet count, albumin, creatinine clearance rate, and estimated glomerular filtration rate), treatment duration and renal replacement therapy. Conclusions: A variety of risk factors related to the occurrence of LIT were revealed in our analysis. Early identification of these factors could help patients improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Patients with inflammatory bowel disease (IBD) always suffer from severe abdominal pain and appear to be at high risk for colorectal cancer. Recently, the co-delivery of targeted drugs and gut microbiota has developed into an attractive strategy. A new strategy using gut microbiota fermentation to overcome the interspace diffuse resistance from the mucus layer to control drug release in inflammatory bowel sites (IBS sites) has not yet been available. Here, we designed an alginate hydrogel microsphere encapsulating bifidobacterium (Bac) and drug-modified nanoscale dietary fibers (NDFs). The hydrogel microsphere is responsible for protecting drugs from acidic and multi-enzymatic environments and delivering drugs to the colorectum. Subsequently, the fermentation of Bac by digesting NDFs and proteins as carbon and nitrogen sources can promote drug release and play a probiotic role in the gut microbiota. In vitro evidence indicated that small-sized NDF (NDF-1) could significantly promote short-chain fatty acid (SCFA) expression. Notably, NDF-1 hydrogel microspheres showed a boost release of 5-ASA in the IBS sites, resulting in the amelioration of gut inflammation and remodeling of gut microbiota in chronic colitis mice. This study developed a controlled release system based on microbial fermentation for the treatment of IBD. [ABSTRACT FROM AUTHOR]

Pulmonary lobe segmentation is an important prerequisite for accurately quantifying pulmonary damage in many pulmonary diseases and planning treatment. However, due to the incomplete lobar structures and morphological changes caused by diseases, the lobe segmentation still encounters great challenges. In this study, a Learnable Interpolation and Extrapolation Network (LIE‐Net) is proposed to form complete and consecutive fissure surfaces by learning to extract information of the fissures from existing fissure points and absent points (unsegmented points belonging to fissures) to predict the z coordinate of the absent fissure points. The completed pulmonary fissures are further used for accurate pulmonary lobe segmentation. Specifically, LIE‐Net takes the coordinate information of existing fissure points (their (x, y, z) coordinates) and absent fissure points (their (x, y) coordinates) as two independent inputs, and predicts the z coordinates of absent points. The proposed LIE‐Net makes voxel‐wise predictions based on the spatial structure characteristics of the lung fissure, and is able to provide a consecutive fissure surface in space. According to the evaluation of radiologists, the lobe segmentation performance was remarkably enhanced in approximately 76% of patients in our additional dataset after the application of LIE‐Net, especially for those cases with large‐scale missing fissures. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by chronic, progressive, and fibrotic lung injury. Although remarkable progress has been made toward understanding the pathogenesis of PF, finding more effective treatments for this fatal disease remains a challenge. In this study, we describe an innovative macrophage‐based approach to deliver anti‐fibrotic protein to the lung and inhibit PF in a mouse model of bleomycin (BLM)‐induced lung injury. We engineered macrophages to continuously secrete three types of proteins: interleukin‐10, which prevents inflammation; TGFRcFc, a soluble truncated TGF‐βR2 that blocks TGF‐β; and CD147, which induces matrix metalloproteinases (MMPs) and causes collagen degradation. Infusing these engineered macrophages into the lungs of BLM‐induced PF mouse models in an optimal pattern significantly ameliorated PF in mice. Specifically, the most effective therapeutic outcome was achieved by infusing IL‐10‐secreting macrophages on day 1, followed by TGFRcFc‐secreting macrophages on day 7 and CD147‐secreting macrophages on day 14 into the same mice after BLM treatment. Our data suggest that macrophage‐based delivery of anti‐fibrotic proteins to the lungs is a promising therapy for fibrotic lung disorders. [ABSTRACT FROM AUTHOR]

Pressure ulcers often become chronic wounds that are difficult to treat and that tend to recur after healing. In China, convincing data from randomised trials have demonstrated that the pharmaceutical preparations of Periplaneta americana (KangFuXin Liquid, KFX) have a significant efficacy for pressure ulcers. To provide more reference to the clinicians and experts, we conducted a meta‐analysis based on the existing randomised controlled trials (RCTs). We searched the RCTs about KFX for the treatment of pressure ulcers published up to July 2022 in major English and Chinese databases with no language restriction, including PubMed, EMBASE, Web of Science (WOS), Cochrane Central Register of Controlled Trials (CENTRAL), China Network Knowledge Infrastructure (CNKI), Chinese Biomedicine (CBM), Chinese Scientific Journals Database (VIP), and WanFang database. Cochrane Handbook guidelines were used to assess the risk of bias and to evaluate the methodological quality of included RCTs. Estimates of the intervention's effects are expressed as the risk ratio (RR) (95% CI) for binary outcomes and mean difference or standardised mean difference (95% CI) for continuous outcomes. We applied fixed or random effects models, and all analyses were performed using Review Manager version 5.4 and Stata/SE version 12.0. We included 22 studies with a total of 1575 participants. Compared with controls, KFX combined with basic wound care or KFX combined with basic wound care and another topical drug or physical treatment significantly increase clinical efficacy (RR: 1.17; 95% CI, 1.06‐1.28; P = 0.001; I2 = 81%) and shorten the complete healing time (MD = −5.11; 95% CI [−8.19, −2.02]; P = 0.001) for pressure ulcers. Subgroup analysis showed a significant difference in the total clinical effect rate between KFX combined with basic wound care and controls. (n = 1018, RR 1.21, 95% CI [1.07, 1.36], I2 = 82%, P = 0.003). No difference was found in the total clinical effective rate between patients using KFX combined with basic wound care and another topical drug or physical treatment with controls (KFX combined with basic wound care and topical physical treatment: n = 267, RR 1.15, 95% CI [0.86, 1.52], I2 = 87%, P = 0.34; KFX combined with basic wound care and topical drug: n = 290, RR 1.05, 95% CI [0.80, 1.37], I2 = 86%, P = 0.71). Based on treatment duration, subgroup analysis indicated that increasing treatment duration increased the total clinical effective rate when treatment duration was not long. (treatment duration: 14 days: n = 158, OR 5.48, 95% CI [1.47, 20.43], I2 = 0%, P = 0.01; 21 days: n = 132, OR 5.93, 95% CI [1.86, 18.91], I2 = 65%, P = 0.003). When treatment duration was 28 days or 30 days, the results showed that there was no significant difference in total clinical effective rate between interventions and controls (treatment duration: 28 days: n = 107, OR 3.04, 95% CI [0.25, 37.32], I2 = 50%, P = 0.38; 30 days: n = 256, OR 0.58, 95% CI [0.11, 3.15], I2 = 65%, P = 0.53). No data on side effects were reported in any of the 22 studies. The conclusion is that the combination of KFX and basic wound care is effective in increasing the total clinical effectiveness and shortening the complete healing time of pressure ulcers. [ABSTRACT FROM AUTHOR]

Background/AimsThis study investigated the protection provided by gabexate mesylate thermo-sensitive in-situ gel (GMTI) against grade III pancreatic trauma in rats.Methods : A grade III pancreatic trauma model with main pancreatic duct dividing was established, and the pancreas anatomical diagram, ascites, and serum biochemical indices, including amylase, lipase, C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α), were examined. The pancreas was sliced and stained with hematoxylin eosin and subjected to terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining.Results : Ascites, serum amylase, lipase, CRP, IL-6, and TNF-α levels were significantly increased in the pancreas trauma (PT) groups with prolonged trauma time and were significantly decreased after GMTI treatment. The morphological structure of the pancreas was loose, the acinus was significantly damaged, the nuclei were irregular and hyperchromatic, and there was inflammatory cell invasion in the PT group compared to the control. After GMTI treatment, the morphological structure of the pancreas was restored, and the damaged acinus and inflammatory cell invasion were decreased compared to the PT group. Moreover, the cell apoptosis index was significantly increased in the PT group and restored to the same levels as the control group after GMTI treatment.Conclusion : sGMTI, a novel formulation and drug delivery method, exhibited specific effective protection against PT with acute pancreatitis therapy and has potential value as a minimally invasive adjuvant therapy for PT with acute pancreatitis.

Objectives. Traditional Chinese medicine (TCM) is a widely used method for treating dengue fever in China. TCM improves the symptoms of patients with dengue, but there is no standard TCM prescription for dengue fever. This real-world study aimed to evaluate the effects of Chai-Shi-Jie-Du (CSJD) granules for the treatment of dengue fever and the underlying mechanisms. Methods. We implemented a multicenter real-world study, an in vitro assay and network pharmacology analysis. Patients from 5 hospitals in mainland China who received supportive western treatment in the absence or presence of CSJD were assigned to the control and CSJD groups between 1 August and 31 December 2019. Propensity score matching (PSM) was performed to correct for biases between groups. The clinical data were compared and analyzed. The antidengue virus activity of CSJD was tested in Syrian baby hamster kidney (BHK) cells using the DENV2-NGC strain. Network pharmacological approaches along with active compound screening, target prediction, and GO and KEGG enrichment analyses were used to explore the underlying molecular mechanisms. Results. 137 pairs of patients were successfully matched according to age, sex, and the time from onset to presentation. The time to defervescence (1.7 days vs. 2.5 days, P < 0.05) and the disease course (4.1 days vs. 6.1 days, P < 0.05) were significantly shorter in the CSJD group than those in the control group. CSJD showed no anti-DENV2-NGC virus activity in BHK cells. Network pharmacology analysis revealed 108 potential therapeutic targets, and the top GO and KEGG terms were related to immunity, oxidative stress response, and the response to lipopolysaccharide. Conclusions. CSJD granules exhibit high potential for the treatment of dengue fever, and the therapeutic mechanisms involved could be related to regulating immunity, moderating the oxidative stress response, and the response to lipopolysaccharide. [ABSTRACT FROM AUTHOR]

Background: Cerebral palsy (CP), a complex syndrome with multiple etiologies, is characterized by a range of movement disorders within the hypokinetic and hyperkinetic spectrum (dystonia or choreoathetosis). CP is often accompanied by neurological and psychiatric signs, such as spasticity, ataxia, and cognitive disorders. Although current treatment options for CP include pharmacological interventions, rehabilitation programs, and spasticity relief surgery, their effectiveness remains limited. Deep brain stimulation (DBS) has demonstrated significant effectiveness in managing dyskinesia; however, its potential therapeutic effect on CP remains determined. Methods: We present a case of a 44-year-old Asian female who was born as a twin with neonatal ischemic-hypoxic encephalopathy due to prolonged labor and delivery. She was diagnosed with CP at the age of 1 year. The patient exhibited delayed development compared to her peers and presented with various symptoms, including slurred speech, broad-based gait, horseshoe inversion of the right lower extremity, involuntary shaking of the upper extremities bilaterally, and hypotonia and showed no improvement with levodopa therapy. Two years ago, she developed progressive head tremors, which worsened during periods of tension and improved during sleep. As medical treatments proved ineffective and there were no contraindications to surgery, we performed bilateral globus pallidus interna DBS (GPi-DBS) to alleviate her motor dysfunction. Results: Following a 6-month follow-up, the patient demonstrated significant improvements in motor symptoms, including head and limb tremors and dystonia. In addition, significant improvement was observed in her overall psychological well-being, as evidenced by reduced anxiety and depression levels. Conclusion: DBS is an effective treatment for dyskinesia symptoms associated with CP in adults. Moreover, its effectiveness may continue to increase over time. [ABSTRACT FROM AUTHOR]

Frequent use of hormones and drugs may be associated with side-effects. Recent studies have shown that probiotics have effects on the prevention and treatment of immune-related diseases. Limosilactobacillus reuteri (L. reuteri) had regulatory effects on intestinal microbiota, host epithelial cells, immune cells, cytokines, antibodies (Ab), toll-like receptors (TLRs), tryptophan (Try) metabolism, antioxidant enzymes, and expression of related genes, and exhibits antibacterial and anti-inflammatory effects, leading to alleviation of disease symptoms. Although the specific composition of the cell-free supernatant (CFS) of L. reuteri has not been clarified, its efficacy in animal models has drawn increased attention to its potential use. This review summarizes the effects of L. reuteri on intestinal flora and immune regulation, and discusses the feasibility of its application in atopic dermatitis (AD), asthma, necrotizing enterocolitis (NEC), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS), and provides insights for the prevention and treatment of immune-related diseases. [ABSTRACT FROM AUTHOR]

Drugs may undergo costly preclinical studies but still fail to demonstrate their efficacy in clinical trials, which makes it challenging to discover new drugs. Both in vitro and in vivo models are essential for disease research and therapeutic development. However, these models cannot simulate the physiological and pathological environment in the human body, resulting in limited drug detection and inaccurate disease modelling, failing to provide valid guidance for clinical application. Organs-on-chips (OCs) are devices that serve as a micro-physiological system or a tissue-on-a-chip; they provide accurate insights into certain functions and the pathophysiology of organs to precisely predict the safety and efficiency of drugs in the body. OCs are faster, more economical, and more precise. Thus, they are projected to become a crucial addition to, and a long-term replacement for, traditional preclinical cell cultures, animal studies, and even human clinical trials. This paper first outlines the nature of OCs and their significance, and then details their manufacturing-related materials and methodology. It also discusses applications of OCs in drug screening and disease modelling and treatment, and presents the future perspective of OCs. [ABSTRACT FROM AUTHOR]

There is an increasing interest in non-pharmacological treatments for children with attention-deficit/hyperactivity disorder (AD/HD), especially digital techniques that can be remotely delivered, such as neurofeedback (NFT) and computerized cognitive training (CCT). In this study, a randomized controlled design was used to compare training outcomes between remotely delivered NFT, CCT, and combined NFT/CCT training approaches. A total of 121 children with AD/HD were randomly assigned to the NFT, CCT, or NFT/CCT training groups, with 80 children completing the training program. Pre- and post-training symptoms (primary outcome), executive and daily functions were measured using questionnaires as well as resting EEG during eyes-closed (EC) and eyes-open (EO) conditions. After 3 months of training, the inattentive and hyperactive/impulsive symptoms, inhibition, working memory, learning and life skills of the three groups of children were significantly improved. The objective EEG activity showed a consistent increase in the relative alpha power in the EO condition among the three training groups. Training differences were not observed between groups. There was a positive correlation between pre-training EO relative alpha power and symptom improvement scores of inattention and hyperactivity/impulsivity, as well as a negative correlation between pre-training inattention scores and change in EO relative alpha. This study verified the training effects of NFT, CCT, and combined NFT/CCT training in children with AD/HD and revealed an objective therapeutic role for individual relative alpha activity. The verified feasibility and effectiveness of home-based digital training support promotion and application of digital remote training. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 Omicron led to the most serious outbreak of COVID-19 in Hong Kong in 2022. Under the pressure of a high volume of patients and limited medical resources, Chinese herbal medicine (CHM) has been extensively used. This is a case-control study of the infected patients that aims to evaluate the effectiveness of CHM using data extracted from the Hong Kong Baptist University Telemedicine Chinese Medicine Centre database. Patients with COVID-19 confirmed by either a rapid antigen test or a polymerase chain reaction who had completed two consultations and taken CHM within 10 days of the first positive test were included in the study (CHM group, n = 3 1 1). The matched control cases were those who did not take CHM within 10 days of the first positive test and were based on age (± 3 years), vaccine doses (< 3 doses, or 3 doses), and gender (no-CHM group, n = 3 1 1). The outcomes included the negative conversion time (NCT, primary outcome), total score of individual symptoms, number of the reported symptoms, and individual symptom disappearance rates. The NCT of the CHM group (median days: 7.0, interquartile range: 6.0–8.0) was significantly shorter than that of the no-CHM group (8.0, 7.0–10.5; P = 0. 0 1 6). CHM treatment significantly reduced the total score of individual symptoms (P < 0. 0 0 1) and the number of the reported symptoms (P < 0. 0 0 1) as compared with that of the no-CHM group. Additionally, the symptom disappearance rates of symptoms such as chills, cough, sputum, dry throat, itching throat, headache, chest tightness, abdominal pain, diarrhea, and fatigue were significantly higher in the CHM group than in the no-CHM group. In conclusion, CHM intervention can significantly reduce NCT and COVID-19 symptoms. Chinese medicine can be accurately prescribed based on a telemedical consultation. [ABSTRACT FROM AUTHOR]

Little evidence exists regarding an integrated multidimensional evaluation methodology to analyze the within-patient effects of medical treatment for chronic rhinosinusitis with nasal polyps (CRSwNP). We aimed to use an integrated evaluation model to analyze the effects of short-course oral corticosteroid (OCS) followed by intranasal corticosteroid spray (INCS) therapy in patients with severe CRSwNP. In all, 32 patients with severe CRSwNP received oral methylprednisolone for three weeks followed by intranasal budesonide spray for nine weeks in this prospective single-arm study. An evaluation model integrating the concepts of the core outcome set (COS), clinical control and minimum clinically important difference (MCID) was longitudinally evaluated. All uncontrolled patients at baseline showed similar progressive improvements from baseline and more than 1 MCID response across core outcomes during the OCS period, with severe CRSwNP being partly controlled in 31 (96.9%) patients and uncontrolled in 1 (3.1%) patient at 3 weeks. During the subsequent INCS period, 14 (43.8%) patients gradually deteriorated to an uncontrolled status at 12 weeks, whereas 18 (56.2%) exhibited partly controlled CRSwNP until 12 weeks. In more than half of the patients, severe CRSwNP was partly controlled with the initial OCS followed by INCS therapy. An integrated evaluation model was used to facilitate the comprehensive evaluation of within-patient response, especially in patients with different responses to the same treatment. ChiCTR1900024287. [ABSTRACT FROM AUTHOR]

It is essential to understand the spatial equity of healthcare services to achieve the Sustainable Development Goals. Spatial and non-spatial factors affect access to healthcare, resulting in inequality in the hierarchical medical treatment system. Thus, to provide a comprehensive equity evaluation, it is indispensable to investigate the extent to which spatial accessibility to healthcare services varies due to various factors. This study attempted to analyze the determinants of healthcare accessibility under multi-trip modes and integrate them into Theil index, as a demand index to evaluate spatial equity in the system. The results reveal an inadequate and inequitable distribution of healthcare resources. While access to primary hospitals is limited (47.37% of residential locations cannot access them on foot), 96.58% of residential locations can access general and tertiary hospitals via public transport or driving. Furthermore, inequitable access to the three-tiered medical system was evaluated on a more granular scale, with primary hospitals being closest to achieving equity (inequitable for only 48.83% of residential locations), followed by general and tertiary hospitals (82.01% and 89.20%, respectively). The unequal residential locations brought on by an abundance of medical resources are far from those with a shortage of resources (66.86% > 5.34%). It is thus suggested that services be expanded or resources be transferred to move toward a more equitable system. Our findings provide policymakers with insights into how to increase accessibility to public health. [ABSTRACT FROM AUTHOR]

Dampness is one of the important external pathogens in Chinese medicine, and with the changes in peoples living habits, dampness syndrome is becoming more and more common. Due to the different characteristics and functions of different parts of the body, the pathogenesis of dampness is not the same when it attacks, so it is helpful to examine it before clinical treatment. Dampness forms through inner unbalance or invades through external environment. This paper discusses the clinical manifestations of dampness in various parts of the body and highlights the similarities and differences in the pathogenic mechanisms of dampness, taking into account the pathogenic characteristics of dampness as a clue for the external dampness invasion pathway from the surface to the inside. In addition, this paper also explains the disease mechanism of dampness syndrome in the context of western medical research, so as to provide research evidence for the integration of Chinese and western medicine and to improve medical treatment in clinical practice. [ABSTRACT FROM AUTHOR]

Background and objective: Vascular cognitive impairment with no dementia (VCIND) is considered to be the prodromal stage of vascular dementia, characterized by insidious onset. Although acupuncture and drug therapies are effective, the optimal therapy for VCIND remains to be further determined. Therefore, we conducted a network meta-analysis to compare the effectiveness of acupuncture therapies and current common medicines for VCIND. Methods: We searched eight electronic databases to identify eligible randomized controlled trials of patients with VCIND treated by acupuncture or drug therapies. The primary outcome was Montreal Cognitive Assessment, and the secondary outcome was Mini-Mental State Examination. We conducted the network meta-analysis within a Bayesian framework. Weighted mean difference with 95% confidence intervals were applied as effect sizes to continuous data for all outcomes. Sensitivity analysis was done to assess the robustness of the findings, and we also carried out a subgroup analysis based on age. We assessed the risk of bias using the Risk of Bias 2.0 tool and applied the Grade of Recommendation Assessment, Development and Evaluation (GRADE) to assess the quality of the outcomes. This study was registered with PROSPERO, number CRD42022331718. Results: A total of 33 studies with 14 interventions were included, including 2603 participants. In terms of the primary outcome, manual acupuncture plus herbal decoction was considered to be the most effective intervention (P = 91.41%), followed by electroacupuncture (P = 60.77%) and manual acupuncture plus piracetam (P = 42.58%), whereas donepezil hydrochloride ranked the least efficacious intervention (P = 54.19%). For the secondary outcome, electroacupuncture plus nimodipine was considered to be the most effective intervention (P = 42.70%), followed by manual acupuncture plus nimodipine (P = 30.62%) and manual acupuncture (P = 28.89%), whereas nimodipine ranked the least efficacious intervention (P = 44.56%). Conclusion: Manual acupuncture plus herbal decoction might be the most effective intervention for VCIND. The combination of acupuncture and drug therapy had a tendency to perform better than monotherapy in terms of clinical outcomes. [ABSTRACT FROM AUTHOR]

Hypoxic-ischemic encephalopathy (HIE) is the leading cause of long-term neurological disability in neonates and adults. Through bibliometric analysis, we analyzed the current research on HIE in various countries, institutions, and authors. At the same time, we extensively summarized the animal HIE models and modeling methods. There are various opinions on the neuroprotective treatment of HIE, and the main therapy in clinical is therapeutic hypothermia, although its efficacy remains to be investigated. Therefore, in this study, we discussed the progress of neural circuits, injured brain tissue, and neural circuits-related technologies, providing new ideas for the treatment and prognosis management of HIE with the combination of neuroendocrine and neuroprotection. [ABSTRACT FROM AUTHOR]

Background: Tianhuang formula (THF) is a Chinese medicine prescription that is patented and clinically approved, and has been shown to improve energy metabolism, but the underlying mechanism remains poorly understood. The purpose of this study is to clarify the potential mechanisms of THF in the treatment of type 2 diabetes mellitus (T2DM). Methods: A murine model of T2DM was induced by high-fat diet (HFD) feeding combined with low-dose streptozocin (STZ) injections, and the diabetic mice were treated with THF by gavaging for consecutive 10 weeks. Fasting blood glucose (FBG), serum insulin, blood lipid, mitochondrial Ca2+ (mCa2+) levels and mitochondrial membrane potential (MMP), as well as ATP production were analyzed. The target genes and proteins expression of visceral adipose tissue (Vat) was tested by RT-PCR and western blot, respectively. The underlying mechanism of the regulating energy metabolism effect of THF was further explored in the insulin resistance model of 3T3-L1 adipocytes cultured with dexamethasone (DXM). Results: THF restored impaired glucose tolerance and insulin resistance in diabetic mice. Serum levels of lipids were significantly decreased, as well as fasting blood glucose and insulin in THF-treated mice. THF regulated mCa2+ uptake, increased MMP and ATP content in VAT. THF increased the mRNA and protein expression of AMPK, phosphorylated AMPK (p-AMPK), MICU1, sirtuin1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). THF could increase the mCa2+ level of 3T3-L1 adipocytes and regulate mitochondrial function. The protein expression of AMPK, p-AMPK, mCa2+ uniporter (MCU) and MICU1 decreased upon adding AMPK inhibitor compound C to 3T3-L1 adipocytes and the protein expression of MCU and MICU1 decreased upon adding the MCU inhibitor ruthenium red. Conclusions: These results demonstrated that THF ameliorated glucose and lipid metabolism disorders in T2DM mice through the improvement of AMPK/MICU1 pathway-dependent mitochondrial function in adipose tissue. Highlights: • AMPK-MCU/MICU1 mediated mCa2+ uptake in adipose tissue played an important role in insulin resistance • THF restored impaired glucose tolerance and insulin resistance in diabetic mice induced by HFD/STZ • THF improved the mitochondrial function of in T2DM mice via AMPK-MICU1 pathway [ABSTRACT FROM AUTHOR]

Background: Depression is a neuropsychiatric disease resulting from deteriorations of molecular networks and synaptic injury induced by stress. Traditional Chinese formula Xiaoyaosan (XYS) exert antidepressant effect, which was demonstrated by a great many of clinical and basic investigation. However, the exact mechanism of XYS has not yet been fully elucidated. Methods: In this study, chronic unpredictable mild stress (CUMS) rats were used as a model of depression. Behavioral test and HE staining were used to detect the anti-depressant effects of XYS. Furthermore, whole transcriptome sequencing was employed to establish the microRNA (miRNA), long non-coding RNA (lncRNA), circular RNA (circRNA), and mRNA profiles. The biological functions and potential mechanisms of XYS for depression were gathered from the GO and KEGG pathway. Then, constructed the competing endogenous RNA (ceRNA) networks to illustrate the regulatory relationship between non-coding RNA (ncRNA) and mRNA. Additionally, longest dendrite length, total length of dendrites, number of intersections, and density of dendritic spines were detected by Golgi staining. MAP2, PSD-95, SYN were detected by immunofluorescence respectively. BDNF, TrkB, p-TrkB, PI3K, Akt, p-Akt were measured by Western Blotting. Results: The results showed that XYS could increase the locomotor activity and sugar preference, decreased swimming immobility time as well as attenuate hippocampal pathological damage. A total of 753 differentially expressed lncRNAs (DElncRNAs), 28 circRNAs (DEcircRNAs), 101 miRNAs (DEmiRNAs), and 477 mRNAs (DEmRNAs) were identified after the treatment of XYS in whole transcriptome sequencing analysis. Enrichment results revealed that XYS could regulate multiple aspects of depression through different synapse or synaptic associated signal, such as neurotrophin signaling and PI3K/Akt signaling pathways. Then, vivo experiments indicated that XYS could promote length, density, intersections of synapses and also increase the expression of MAP2 in hippocampal CA1, CA3 regions. Meanwhile, XYS could increase the expression of PSD-95, SYN in the CA1, CA3 regions of hippocampal by regulating the BDNF/trkB/PI3K signal axis. Conclusion: The possible mechanism on synapse of XYS in depression was successfully predicted. BDNF/trkB/PI3K signal axis were the potential mechanism of XYS on synapse loss for its antidepressant. Collectively, our results provided novel information about the molecular basis of XYS in treating depression. [ABSTRACT FROM AUTHOR]

Chitinase‐3‐like protein 1 (CHI3L1) is a secreted glycoprotein characterized by its ability to regulate multiple biological processes, such as the inflammatory response and gene transcriptional signaling activation. Abnormal CHI3L1 expression has been associated with multiple neurological disorders and serves as a biomarker for the early detection of several neurodegenerative diseases. Aberrant CHI3L1 expression is also reportedly associated with brain tumor migration and metastasis, as well as contributions to immune escape, playing important roles in brain tumor progression. CHI3L1 is synthesized and secreted mainly by reactive astrocytes in the central nervous system. Thus, targeting astrocytic CHI3L1 could be a promising approach for the treatment of neurological diseases, such as traumatic brain injury, ischemic stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and glioma. Based on current knowledge of CHI3L1, we assume that it acts as a molecule mediating several signaling pathways driving the initiation and progression of neurological disorders. This narrative review is the first to introduce the potential roles of astrocytic CHI3L1 in neurological disorders. We also equally explore astrocytic CHI3L1 mRNA expression under physiological and pathological conditions. Inhibiting CHI3L1 and disrupting its interaction with its receptors through multiple mechanisms of action are briefly discussed. These endeavors highlight the pivotal roles of astrocytic CHI3L1 in neurological disorders and could contribute to the development of effective inhibitors based on the strategy of structure‐based drug discovery, which could be an attractive therapeutic approach for neurological disease treatment. [ABSTRACT FROM AUTHOR]

Background: Keloids and hypertrophic scars frustrate patients by the deformity of appearance and organ dysfunction. Many modalities had been tried in clinic practice, but the results are unsatisfied. Objective: We retrospectively analysed the combined application of bleomycin and triamcinolone for the treatment of keloids and hypertrophic scars. Methods: The combination of bleomycin and triamcin acetonide was applied to the treatment of keloids and hypertrophic scars, 86 cases accepted the treatment. Follow‐up 2–5 years after treatment. Results: (1) The pain of scars and itching symptoms have basically subsided through treatment. (2) After drug injection treatment, the keloid began to shrink, some of the keloids disappeared. (3) Small keloids did not recur after treatment. Large keloids had local recurrence after treatment. When further treatment was given, the recurrence disappeared. Conclusion: The combined application of bleomycin and triamcin acetonide can effectively cure keloids and hypertrophic scars. [ABSTRACT FROM AUTHOR]

Antisense oligonucleotides (ASONs) have proven potential for the treatment of various diseases. However, their limited bioavailability restricts their clinical application. New structures with improved enzyme resistance stability and efficient drug delivery are needed. In this work, we propose a novel category of ASONs bearing anisamide conjugation at phosphorothioate sites for oncotherapy. ASONs can be conjugated with the ligand anisamide very efficiently and flexibly in a solution. The conjugation sites and the ligand amount both influence anti-enzymatic stability and cellular uptake, resulting in changes in antitumor activity that are detectable by cytotoxicity assay. The conjugate with double anisamide (T6) was identified as the optimal conjugate, and its antitumor activity and the underlying mechanism were examined further in vitro and in vivo. This paper presents a new strategy for the design of nucleic acid-based therapeutics with improved drug delivery and biophysical and biological efficacy. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) with high morbidity and mortality all over the world is characterized by decreased kidney function, a condition which can result from numerous risk factors, including diabetes, hypertension and obesity. Despite significant advances in our understanding of the pathogenesis of CKD, there are still no treatments that can effectively combat CKD, which underscores the urgent need for further study into the pathological mechanisms underlying this condition. In this regard, animal models of CKD are indispensable. This article reviews a widely used animal model of CKD, which is induced by adenine. While a physiologic dose of adenine is beneficial in terms of biological activity, a high dose of adenine is known to induce renal disease in the organism. Following a brief description of the procedure for disease induction by adenine, major mechanisms of adenine-induced CKD are then reviewed, including inflammation, oxidative stress, programmed cell death, metabolic disorders, and fibrillation. Finally, the application and future perspective of this adenine-induced CKD model as a platform for testing the efficacy of a variety of therapeutic approaches is also discussed. Given the simplicity and reproducibility of this animal model, it remains a valuable tool for studying the pathological mechanisms of CKD and identifying therapeutic targets to fight CKD. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a gastrointestinal disease that involves chronic mucosal or submucosal lesions that affect tissue integrity. Although IBD is not life-threatening, it sometimes causes severe complications, such as colon cancer. The exact etiology of IBD remains unclear, but several risk factors, such as pathogen infection, stress, diet, age, and genetics, have been involved in the occurrence and aggravation of IBD. Immune system malfunction with the over-production of inflammatory cytokines and associated oxidative stress are the hallmarks of IBD. Dietary intervention and medical treatment suppressing abnormal inflammation and oxidative stress are recommended as potential therapies. Thymol, a natural monoterpene phenol that is mostly found in thyme, exhibits multiple biological functions as a potential adjuvant for IBD. The purpose of this review is to summarize current findings on the protective effect of thymol on intestinal health in the context of specific animal models of IBD, describe the role of thymol in the modulation of inflammation, oxidative stress, and gut microbiota against gastrointestinal disease, and discuss the potential mechanism for its pharmacological activity. [ABSTRACT FROM AUTHOR]

Various bacterial diseases have caused great economic losses to the high-density and intensive aquaculture industry; however, the pathogenic mechanism underlying the large-scale challenged to caused by many bacteria remain unclear, making the prevention and treatment of these diseases difficult. In the present study, we isolated a bacterial strain from Cyprinus carpio having a typical bacterial disease and named it Cc2021. Through subsequent morphological observations, a regression challenge, biochemical identification, and 16S rRNA gene sequence analysis, we determined Cc2021 to be Plesiomonas shigelloides. Subsequently, we comprehensively investigated the pathogenicity of P. shigelloides in C. carpio through a regression challenge and assessed the underlying the pathogenic mechanism. Mortality results revealed that P. shigelloides is highly pathogenic and infects various tissues throughout the body, resulting in edema of the liver, spleen, and body and head kidneys. Histopathological analysis revealed obvious inflammation, bleeding, and necrosis in the intestine, spleen, and head kidney. The body's immune tissues actively produce complement C3, superoxide dismutase, and lysozyme after a challenge to resist bacterial invasion. With regard to the underlying pathogenesis of P. shigelloides , comparative transcriptome analysis revealed 876 upregulated genes and 828 downregulated genes in the intestine of C. carpio after the challenge. Analysis of differentially expressed unigenes revealed the involvement of major immune pathways, particularly the TNF signaling pathway, interleukin (IL)-17 signaling pathway, and Toll-like receptor signaling pathway. The present study provides new valuable information on the immune system and defense mechanisms of P. shigelloides. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy has emerged as an efficient therapeutic approach for cancer management. However, stimulation of host immune system against cancer cells often fails to achieve promising clinical outcomes mainly owing to the immunosuppressive characteristics of the tumor microenvironment (TME). Combination therapeutics that can trigger sustained immunogenic cell death (ICD) have provided new opportunities for cancer treatment. Methods: In this study, we designed and applied an ICD inducer regimen, including a genetically engineered oncolytic virus (miRNA-modified coxsackieviruses B3, miR-CVB3), a pore-forming lytic peptide (melittin, found in bee venom), and a synthetic toll-like receptor 9 ligand (CpG oligodeoxynucleotides), for breast cancer and melanoma treatment. We compared the anti-tumor efficacy of miR-CVB3 and CpG-melittin (CpGMel) alone and in combination (miR-CVB3 + CpGMel) and investigated possible mechanisms involved. Results: We demonstrated that miR-CVB3 + CpGMel had no major impact on viral growth, while enhancing the cellular uptake of CpGMel in vitro. We further showed that combination therapy led to significant increases in tumor cell death and release of damage-associated molecular patterns compared with individual treatment. In vivo studies in 4T1 tumor-bearing Balb/c mice revealed that both primary and distant tumors were significantly suppressed, and the survival rate was significantly prolonged after administration of miR-CVB3 + CpGMel compared with single treatment. This anti-tumor effect was accompanied by increased ICD and immune cell infiltration into the TME. Safety analysis showed no significant pathological abnormalities in Balb/c mice. Furthermore, the developed therapeutic regimen also demonstrated a great anti-tumor activity in B16F10 melanoma tumor-bearing C57BL/6 J mice. Conclusions: Overall, our findings indicate that although single treatment using miR-CVB3 or CpGMel can efficiently delay tumor growth, combining oncolytic virus-based therapy can generate even stronger anti-tumor immunity, leading to a greater reduction in tumor size. [ABSTRACT FROM AUTHOR]

One of the major limitations in the clinical use of existing oxazolidinone antibiotics is their characteristic adverse reactions, in particular thrombocytopenia. In antiinfective treatment, if patients are suspected of having drug-induced thrombocytopenia, the first step is to immediately discontinue the offending drug. Even in patients with severe infections, the antibacterial drug may need to be changed or the antibacterial treatment may need to be discontinued because thrombocytopenia may have a more serious clinical prognosis. In addition, if the patient needs to continue antibacterial treatment after discharge, the lack of conditions for monitoring platelet levels may also pose hidden dangers to the patient. Contezolid is an orally administered oxazolidinone antibacterial agent approved by the National Medical Products Administration of China in 2021. We found that contezolid may have an improved safety profile with a significantly reduced potential for myelosuppression based on the results of our observational clinical study. In this article, we review the advantages of contezolid as a new oxazolidinone antibiotic and describe three typical clinical cases of patients who experienced drug-induced thrombocytopenia after using linezolid. The platelet levels of these different patients were all significantly improved to varying degrees after initiation of contezolid treatment. [ABSTRACT FROM AUTHOR]