STOmicsDB: a comprehensive database for spatial transcriptomics data sharing, analysis and visualization.

Recent technological developments in spatial transcriptomics allow researchers to measure gene expression of cells and their spatial locations at the single-cell level, generating detailed biological insight into biological processes. A comprehensive database could facilitate the sharing of spatial transcriptomic data and streamline the data acquisition process for researchers. Here, we present the Spatial TranscriptOmics DataBase (STOmicsDB), a database that serves as a one-stop hub for spatial transcriptomics. STOmicsDB integrates 218 manually curated datasets representing 17 species. We annotated cell types, identified spatial regions and genes, and performed cell-cell interaction analysis for these datasets. STOmicsDB features a user-friendly interface for the rapid visualization of millions of cells. To further facilitate the reusability and interoperability of spatial transcriptomic data, we developed standards for spatial transcriptomic data archiving and constructed a spatial transcriptomic data archiving system. Additionally, we offer a distinctive capability of customizing dedicated sub-databases in STOmicsDB for researchers, assisting them in visualizing their spatial transcriptomic analyses. We believe that STOmicsDB could contribute to research insights in the spatial transcriptomics field, including data archiving, sharing, visualization and analysis. STOmicsDB is freely accessible at https://db.cngb.org/stomics/.

Stratifying ICIs-responsive tumor microenvironment in HCC: from parsing out immune-hypoxic crosstalk to clinically applicable MRI-radiomics models.

BACKGROUND: We aimed to redefine Immune checkpoint inhibitors (ICIs)-responsive "hot" TME and develop a corresponding stratification model to maximize ICIs-efficacy in Hepatocellular Carcinoma (HCC). METHODS: Hypoxic scores were designed, and the relevance to immunotherapy responses were validated in pan-cancers through single cell analysis. Multi-omics analysis using the hypoxic scores and immune infiltrate abundance was performed to redefine the ICIs-responsive TME subtype in HCC patients from TCGA (n = 363) and HCCDB database (n = 228). The immune hypoxic stress index (IHSI) was constructed to stratify the ICIs-responsive TME subtype, with exploring biological mechanism in vitro and in vivo. MRI-radiomics models were built for clinical applicability. RESULTS: The hypoxic scores were lower in the dominant cell-subclusters of responders in pan-cancers. The higher immune infiltrate-normoxic (HIN) subtype was redefined as the ICIs-responsive TME. Stratification of the HIN subtype using IHSI effectively identified ICIs-responders in Melanoma (n = 122) and urological cancer (n = 22). TRAF3IP3, the constituent gene of IHSI, was implicated in ICIs-relevant "immune-hypoxic" crosstalk by stimulating MAVS/IFN-I pathway under normoxic condition. MRI-radiomics models assessing TRAF3IP3 with HIF1A expression (AUC > 0.80) screened ICIs-Responders in HCC cohort (n = 75). CONCLUSION: The hypoxic-immune stratification redefined ICIs-responsive TME and provided MRI-Radiomics models for initial ICIs-responders screening, with IHSI facilitating further identification.

Sparse Generalized Canonical Correlation Analysis: Distributed Alternating Iteration-Based Approach.

Sparse canonical correlation analysis (CCA) is a useful statistical tool to detect latent information with sparse structures. However, sparse CCA, where the sparsity could be considered as a Laplace prior on the canonical variates, works only for two data sets, that is, there are only two views or two distinct objects. To overcome this limitation, we propose a sparse generalized canonical correlation analysis (GCCA), which could detect the latent relations of multiview data with sparse structures. Specifically, we convert the GCCA into a linear system of equations and impose ℓ1 minimization penalty to pursue sparsity. This results in a nonconvex problem on the Stiefel manifold. Based on consensus optimization, a distributed alternating iteration approach is developed, and consistency is investigated elaborately under mild conditions. Experiments on several synthetic and real-world data sets demonstrate the effectiveness of the proposed algorithm.

A CD6 homolog of Nile tilapia (Oreochromis niloticus) conserved binding bacteria involved in the regulation of Streptococcus agalactiae induced inflammation.

As a lymphocyte-specific surface receptor belonging to the cysteine-rich superfamily of scavenger receptors, CD6 acts as a pattern recognition receptor for microbial components and is involved in the regulation of inflammatory responses. However, the characteristics and functions of CD6 molecules in lower vertebrates represented by teleost fish are unknown. In this study, a CD6 homolog (designated OnCD6) was characterized from Nile tilapia (Oreochromis niloticus), and establishing its role as a PRRs that participates in immune recognition. OnCD6 contains an open reading frame of 1872 bp that encodes a peptide of 623 amino acids, and contains two conserved SR domain. Multiple sequence alignment revealed that OnCD6 shares a relatively high level of identity with those of other species. Transcriptional expression analysis revealed that OnCD6 was constitutively expressed in immunes tissues such as head kidney and thymus. The expression level of OnCD6 in mainly immune tissues were found significantly upregulated after the injection of Streptococcus agalactiae (S. agalactiae). Moreover, OnCD6 protein was located in the head kidney and brain, mainly over the plasma membrane of lymphocytes in these immune tissues. In vitro experiments showed that CD6 extracellular protein bound to and aggregated several Gram-positive and -negative bacterial strains through the recognition of bacterial surface conserved components LPS and LTA etc. In vivo experiments demonstrated that overexpression OnCD6 before S. agalactiae challenge significantly improved tilapia survival, and this was concomitant with reduced bacterial load and pro-inflammatory cytokines (IL-1ß and TNF-α). Taken together, our results illustrated the function of CD6 molecular pattern recognition receptors (PRRs) is conserved and plays an important role in antibacterial infection.

Functional properties of ATPIF1 in the orange-spotted grouper (Epinephelus coioides) in response to viral infection.

ATP synthase inhibitory factor 1 (ATPIF1) can activate mitochondrial autophagic pathway and mediates immune response by regulating ATP synthase activity. However, the role of fish ATPIF1 on viral infection is still unknown. In this study, we identified an ATPIF1 homolog (Ec-ATPIF1) from orange-spotted grouper (Epinephelus coioides). Ec-ATPIF1 is mainly expressed in the kidney and liver. The expression of Ec-ATPIF1 was significantly up-regulated after RGNNV stimulation in vitro. Further experiments showed that overexpression of Ec-ATPIF1 inhibited the expression of viral genes (CP and RdRp) and intracellular ATP synthesis. Ec-ATPIF1 overexpression also promoted the expression of mitophagy related genes (PINK1, Parkin, BNIP3, NIX, FUNDC1, LC3), inflammation-related factors (IL-1ß, IL-6, IL-8, IL-10, TNF-α, TLR2) and interferon pathway factors (IRF1, IRF3, IRF7, MX1, ISG15, ISG56, MDA5, TRIF). While the knockdown of Ec-ATPIF1 exhibited the opposite effects on the expression of viral genes and immune-related factors above. These data suggest that Ec-ATPIF1 can impact viral infection by regulating mitophagy, ATP synthesis, the expression of inflammatory factors and interferon pathway factors. These findings will be beneficial to better explore the immune regulatory mechanisms of fish respond to viral infection.

Novel C-type lectin mediated non-specific cytotoxic cells killing activity through NCCRP-1 in nile tilapia (Oreochromis niloticus).

Non-specific cytotoxic cells (NCCs) are vital immune cells involved in teleost's non-specific immunity. As a receptor molecule on the NCCs' surface, the non-specific cytotoxic cell receptor protein 1 (NCCRP-1) is known to play a crucial role in mediating their activity. Nevertheless, there have been limited studies on the signal molecule that transmits signals via NCCRP-1. In this study, a yeast two-hybrid (Y2H) library of tilapia liver and head kidney was constructed and subsequently screened with the bait vector NCCRP-1 of Oreochromis niloticus (On-NCCRP-1) to obtain a C-type lectin (On-CTL) with an interacting protein sequence. Consequently, the full-length sequence of On-CTL was cloned and analyzed. The expression analysis revealed that On-CTL is highly expressed in the liver and is widely distributed in other tissues. Furthermore, On-CTL expression was significantly up-regulated in the brain, intestine, and head kidney following a challenge with Streptococcus agalactiae. A point-to-point Y2H method was also used to confirm the binding between On-NCCRP-1 and On-CTL. The recombinant On-CTL (rOn-CTL) protein was purified. In vitro experiments demonstrated that rOn-CTL can up-regulate the expression of killer effector molecules in NCCs via its interaction with On-NCCRP-1. Moreover, activation of NCCs by rOn-CTL resulted in a remarkable enhancement in their ability to eliminate fathead minnow cells, indicating that rOn-CTL effectively modulates the killing activity of NCCs through the NCC receptor molecule On-NCCRP-1. These findings significantly contribute to our comprehension of the regulatory mechanisms governing NCC activity, paving the way for future research in this field.

Characterization and functional analysis of SOCS9 from orange-spotted grouper (Epinephelus coioides) during virus infection.

The suppressor of cytokine signaling (SOCS) proteins family have twelve members including eight known mammalian SOCS members (CISH, SOCS1-7) and four new discovery members (SOCS3b, SOCS5b, SOCS8 and SOCS9) that is regarded as a classic feedback inhibitor of cytokine signaling. Although the function of the mammalian SOCS proteins have been well studied, little is known about the roles of SOCS in fish during viral infection. In this study, the molecular characteristics of SOCS9 from orange-spotted grouper (Epinephelus coioides, EcSOCS9) is investigated. The EcSOCS9 protein encoded 543 amino acids with typical SH2 (389-475aa) and SOCS_box (491-527aa), sharing high identities with reported fish SOCS9. EcSOCS9 was expressed in all detected tissues and highly expressed in kidney. After red-spotted grouper nervous necrosis virus (RGNNV) infection, the expression of EcSOCS9 was significantly induced in vitro. Furthermore, EcSOCS9 overexpression enhanced RGNNV replication, promoted virus-induced mitophagy that evidenced by the increased level of LC3-Ⅱ, BCL2, PGAM5 and decreased level of BNIP3 and FUNDC1. Besides, EcSOCS9 overexpression suppressed the expression levels of ATP6, CYB, ND4, ATP level and induced ROS level. The expression levels of interferon (IFN) related factors (IRF1, IRF3, IRF7, P53), inflammatory factors (IL1-ß, IL8, TLR2, TNF-α) and IFN-3, ISRE, NF-κB, AP1 activities were also reduced by overexpressing EcSOCS9. These date suggests that EcSOCS9 impacts RGNNV infection through modulating mitophagy, regulating the expression levels of IFN- related and inflammatory factors, which will expand our understanding of fish immune responses during viral infection.

Immune response and protective efficacy of Streptococcus agalactiae vaccine coated with chitosan oligosaccharide for different immunization strategy in nile tilapia (Oreochromis niloticus).

In the past decade, the outbreak of Streptococcus agalactiae has caused significant economic losses in tilapia farming. Vaccine immunization methods and strategies have gradually evolved from single-mode to multi-mode overall prevention and control strategies. In this study, an inactivated vaccine of S. agalactiae with a chitosan oligosaccharide (COS) adjuvant was constructed using different administration methods: intraperitoneal injection (Ip), immersion combined with intraperitoneal injection (Im + Ip), immersion combined with oral administration (Im + Or), and oral administration (Or). Safety analysis revealed no adverse effects on tilapia, and the vaccine significantly promoted fish growth and development when administered through Im + Or or Or immunization. Following vaccination, innate immunity parameters including SOD, ACP and CAT activities were all significantly enhanced. Additionally, specific serum IgM antibodies reached their highest level at the 6th week post vaccination. Skin and intestinal mucus IgT antibodies reached peaked at the 6th and 7th week post vaccination, respectively. The relative peak expression values for IL-8, IL-12, MHC-I, MHC-II, IgM, IgT, CD4, CD8, TNFα, IFNγ from Im + Ip group were significantly higher than those in Ip group, Im + Or group and Or group in most cases (p < 0.05). Importantly, the relative protection survival of Im + Ip group was the highest (78.6%), followed by the Ip group (71.4%), the Or group (64.3%) and the Im + Or group (57.1%). In summary, this study encourages further research on multi-channel immunization strategies of other kinds of vaccines in other aquatic economic animals to improve their disease resistance.

A novel study of brain microvascular endothelial cells induced by astrocyte conditioned medium for constructing blood brain barrier model in vitro: A promising tool for meningitis of teleost.

The blood-brain barrier (BBB) is mainly composed of specialized endothelial cells, which can resist harmful substances, transport nutrients, and maintain the stability of the brain environment. In this study, an endothelial cell line from tilapia (Oreochromis niloticus) named TVEC-01 was successfully established. During the earlier establishment phase of the cell line, the TVEC-01 cells were persistently exposed to an astrocyte-conditioned medium (ACM). TVEC-01 cells were identified as an endothelial cell line. TVEC-01 cells retained the multiple functions of endothelial cells and were capable of performing various experiments in vitro. Furthermore, TVEC-01 cells efficiently expressed BBB-related tight junctions and key efflux transporters. From the results of the qRT-PCR, we found that the TVEC-01 cell line did not gradually lose BBB characteristics after persistent and repetitive passages, which was different from the vast majority of immortalized endothelial cells. The results showed that ACM induced up-regulation of the expression levels of multiple BBB-related genes in TVEC-01 cells. We confirmed that Streptococcus agalactiae was capable of invading the TVEC-01 cells and initiating a series of immune responses, which provided a theoretical basis for S. agalactiae to break through the BBB of teleost through the transcellular traversal pathway. In summary, we have successfully constructed an endothelial cell line of teleost, named TVEC-01, which can be used in many experiments in vitro and even for constructing BBB in vitro. Moreover, it was confirmed that S. agalactiae broke through the BBB of teleost through the transcellular traversal pathway and caused meningitis.

Protective effects of curcumin on desipramine-induced islet ß-cell damage via AKAP150/PKA/PP2B complex.

Tricyclic antidepressants (TCAs) are widely used to treat depression and anxiety-related mood disorders. But evidence shows that TCAs elevate blood glucose levels and inhibit insulin secretion, suggesting that TCAs are a risk factor, particularly for individuals with diabetes. Curcumin is a bioactive molecule from the rhizome of the Curcuma longa plant, which has shown both antidepressant and anti-diabetic activities. In the present study, we investigated the protective effect of curcumin against desipramine-induced apoptosis in ß cells and the underlying molecular mechanisms. In the mouse forced swimming test (FST), we found that lower doses of desipramine (5 and 10 mg/kg) or curcumin (2.5 mg/kg) alone did not affect the immobility time, whereas combined treatment with curcumin (2.5 mg/kg) and desipramine (5, 10 mg/kg) significantly decreased the immobility time. Furthermore, desipramine dose-dependently inhibited insulin secretion and elevated blood glucose levels, whereas the combined treatment normalized insulin secretion and blood glucose levels. In RIN-m5F pancreatic ß-cells, desipramine (10 µM) significantly reduced the cell viability, whereas desipramine combined with curcumin dose-dependently prevented the desipramine-induced impairment in glucose-induced insulin release, most effectively with curcumin (1 and 10 µM). We demonstrated that desipramine treatment promoted the cleavage and activation of Caspase 3 in RIN-m5F cells. Curcumin treatment inhibited desipramine-induced apoptosis, increased mitochondrial membrane potential and Bcl-2/Bax ratio. Desipramine increased the generation of reactive oxygen species, which was reversed by curcumin treatment. Curcumin also inhibited the translocation of forkhead box protein O1 (FOXO1) from the cytoplasm to the nucleus and suppressed the binding of A-kinase anchor protein 150 (AKAP150) to protein phosphatase 2B (PP2B, known as calcineurin) that was induced by desipramine. These results suggest that curcumin protects RIN-m5F pancreatic ß-cells against desipramine-induced apoptosis by inhibiting the phosphoinositide 3-kinase/AKT/FOXO1 pathway and the AKAP150/PKA/PP2B interaction. This study suggests that curcumin may have therapeutic potential as an adjunct to antidepressant treatment.

Discovery of a nitroaromatic nannocystin with potent in vivo anticancer activity against colorectal cancer by targeting AKT1.

The development of targeted chemotherapeutic agents against colorectal cancer (CRC), one of the most common cancers with a high mortality rate, is in a constant need. Nannocystins are a family of myxobacterial secondary metabolites featuring a 21-membered depsipeptide ring. The in vitro anti-CRC activity of natural and synthetic nannocystins was well documented, but little is known about their in vivo efficacy and if positive, the underlying mechanism of action. In this study we synthesized a nitroaromatic nannocystin through improved preparation of a key fragment, and characterized its in vitro activity and in vivo efficacy against CRC. We first described the total synthesis of compounds 2-4 featuring Heck macrocyclization to forge their 21-membered macrocycle. In a panel of 7 cancer cell lines from different tissues, compound 4 inhibited the cell viability with IC values of 1-6 nM. In particular, compound 4 (1, 2, 4 nM) inhibited the proliferation of CRC cell lines (HCT8, HCT116 and LoVo) in both concentration and time dependent manners. Furthermore, compound 4 concentration-dependently inhibited the colony formation and migration of CRC cell lines. Moreover, compound 4 induced cell cycle arrest at sub-G1 phase, apoptosis and cellular senescence in CRC cell lines. In three patient-derived CRC organoids, compound 4 inhibited the PDO with IC values of 3.68, 28.93 and 11.81 nM, respectively. In a patient-derived xenograft mouse model, injection of compound 4 (4, 8 mg/kg, i.p.) every other day for 12 times dose-dependently inhibited the tumor growth without significant change in body weight. We conducted RNA-sequencing, molecular docking and cellular thermal shift assay to elucidate the anti-CRC mechanisms of compound 4, and revealed that it exerted its anti-CRC effect at least in part by targeting AKT1.

Study on network pharmacology of Ginkgo biloba extract against ischaemic stroke mechanism and establishment of UPLC-MS/MS methods for simultaneous determination of 19 main active components.

INTRODUCTION: Ginkgo biloba extract (GBE) is an effective substance from traditional Chinese medicine (TCM) G. biloba for treating ischaemic stroke (IS). However, its active ingredients and mechanism of action remain unclear. OBJECTIVES: This study aimed to reveal the potential active component group and possible anti-IS mechanism of GBE. MATERIALS AND METHODS: The network pharmacology method was used to reveal the possible anti-IS mechanism of these active ingredients in GBE. An ultra-high-performance liquid chromatography triple quadrupole electrospray tandem mass spectrometry (UPLC-MS/MS) method was established for the simultaneous detection of the active ingredients of GBE. RESULTS: The active components of GBE anti-IS were screened by literature integration. Network pharmacology results showed that the anti-IS effect of GBE is achieved through key active components such as protocatechuic acid, bilobalide, ginkgolide A, and so on. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the possible anti-IS mechanism of GBE is regulating the PI3K-Akt signalling pathway and other signal pathways closely related to inflammatory response and apoptosis regulation combined with AKT1, MAPK, TNF, ALB, CASP3, and other protein targets. Nineteen main constituents in seven batches of GBE were successfully analysed using the established UPLC-MS/MS method, and the results showed that the content of protocatechuic acid, gallic acid, ginkgolide A, and so forth was relatively high, which was consistent with network pharmacology results, indicating that these ingredients may be the key active anti-IS ingredients of GBE. CONCLUSION: This study revealed the key active components and the anti-IS mechanism of GBE. It also provided a simple and sensitive method for the quality control of related preparations.

Borneol-modified docetaxel plus tetrandrine micelles for treatment of drug-resistant brain glioma.

OBJECTIVE: Glioma is the most common and deadly primary malignant tumor in adults. Treatment outcomes are ungratified due to the presence of blood-brain barrier (BBB), glioma stem cells (GSCs) and multidrug resistance (MDR). Docetaxel (DTX) is considered as a potential drug for the treatment of brain tumor, but its effectiveness is limited by its low bioavailability and drug resistance. Tetrandrine (TET) reverses the resistance of tumor cells to chemotherapy drugs. Borneol (BO) modified in micelles has been shown to promote DTX plus TET to cross the BBB, allowing the drug to better act on tumors. Therefore, we constructed BO-modified DTX plus TET micelles to inhibit chemotherapeutic drug resistance. SIGNIFICANCE: Provide a new treatment method for drug-resistant brain gliomas. METHODS: In this study, BO-modified DTX plus TET micelles were prepared by thin film dispersion method, their physicochemical properties were characterized. Its targeting ability was investigated. The therapeutic effect on GSCs was investigated by in vivo and in vitro experiments. RESULTS: The BO-modified DTX plus TET micelles were successfully constructed by thin film dispersion method, and the micelles showed good stability. The results showed that targeting micelles increased bEnd.3 uptake and helped drugs cross the BBB in vitro. And we also found that targeting micelles could inhibit cell proliferation, promote cell apoptosis and inhibit the expression of drug-resistant protein, thus provide a new treatment method for GSCs in vitro and in vivo. CONCLUSIONS: BO-modified DTX plus TET micelles may provide a new treatment method for drug-resistant brain gliomas.

Effects of Chinese herbal medicines on growth performance, intestinal flora, immunity and serum metabolites of hybrid grouper (Epinephelus fuscoguttatus♀×Epinephelus lanceolatu♂).

The immunomodulatory roles of Chinese herbal Medicine (CHM) in aquatic animals have been well-recorded. However, how CHM impacts the intestinal microbiota and serum metabolism is not fully understood. In this study, the effects of different additive levels of CHM on the growth performance, immunity, intestinal flora and serum metabolism of hybrid grouper (♀Epinephelus fuscoguttatus × â™‚Epinephelus lanceolatu) were investigated. The addition of 0.5%, 1.0%, 1.5% and 2.0% Chinese herbal medicine compound to feed could significantly improve the weight gain rate (WGR), specific growth rate (SGR) and survival rate (SR) of grouper, reduced feed coefficient, while had no significant difference on morphometric parameter. The most significant improvement for the parameters above was observed in 1.5% group. Different addition levels of CHM could also significantly enhance the activities of ACP, AKP, SOD, CAT and LZM in serum. Accordingly, the supplementation of CHM significantly induced up-regulation of immune genes such as IL-8, IL-1ß, TNF-α, Nrf2, Lzm in the liver, spleen and head kidney of grouper, improved the resistance of grouper to V. harveyi as well. The intestinal flora analysis showed that at the phylum level, the main dominant species of intestinal microorganisms were Firmicutes, Proteobacteria, Bacteroidota, Actinobacteriota, Gemmatimonadota, Desulfobacterota, Fusobacteriota and Myxococcota. At the genus level, the high abundance was Lactobacillus, Streptococcus, Bacteroides, Escherichia, Romboutsia, Sphingomonas and Muribaculaceae. The abundance of probiotics (such as Lachnospiraceae, Lactobacillaceae, Streptococcaceae, etc) in CHM-supplement groups were higher (highest in 1.5% group) compared with control group. Moreover, a total of 11 common differential metabolic pathways were screened by LC-MS metabolism analysis of serum, they were Neuroactive ligand-receptor interaction, Purine metabolism, Linoleic acid, Glycerophospholipid metabolism, Taurine and hypotaurine metabolism, Arginine and proline metabolism, ABC transporters, Aminoacyl-tRNA biosynthesis, Arachidonic acid metabolism, Drug metabolism-cytochrome P450, alpha-Linolenic acid metabolism. Also, three common differential metabolites (PI(20:4(5Z,8Z,11Z,14Z)/18:1(11Z)), PC(20:3(8Z,11Z,14Z)/22:1(13Z)), PC(22:0/20:4(5Z,8Z,11Z,14Z)) associated with intestinal health, growth and disease resistance was found. These data will contributes to a comprehensive understand for the regulatory roles of CHM on fish, which is also beneficial for the disease control and sustainable development of aquaculture.

Immune response and protective efficacy of mannosylated polyethylenimine (PEI) as an antigen delivery vector, administered with a Streptococcus agalactiae DNA vaccine in Nile tilapia (Oreochromis niloticus).

This study examined the effectiveness of a DNA vaccine for S. agalactiae that was delivered by mannose-based polyethyleneimine (Man-PEI). The results showed that Man-PEI/pcDNA-Sip stimulated a higher serum antibody titer compared to control or other vaccine groups (p < 0.05). Additionally, it induced higher expression of immune-related genes, and increased activities of superoxide dismutase (SOD), acid phosphatase (ACP) and alkaline phosphatase (AKP). Furthermore, the Man-PEI/pcDNA-Sip group showed an improved relative percent survival (RPS) of 85.71%. These results demonstrate the potential value of Man-PEI as a vaccine delivery vehicle, and suggest that it can be effective in boosting the immune protective rate induced by pcDNA-Sip vaccines.

Dextran Sulfate Sodium Salt (DSS) induced enteritis in Orange-spotted grouper, Epinephelus coioides.

The enteritis is a common disease in fish farming, but the pathogenesis is still not fully understood. The aim of the present study was to investigate the inducement of Dextran Sulfate Sodium Salt (DSS) intestinal inflammation on Orange-spotted grouper (Epinephelus coioides). The fish were challenged with 200 µl 3% DSS via oral irrigation and feeding, an appropriate dose based on the disease activity index of inflammation. The results indicated that the inflammatory responses induced by DSS were closely associated with the expression of pro-inflammatory cytokines including interleukin 1ß (IL-1ß), IL-8, IL16, IL-10 and tumor necrosis factor α (TNF-α), as well as NF-κB and myeloperoxidase (MPO) activity. At day5 after DSS treatment, the highest levels of all parameters were observed. Also, the severe intestinal lesions (intestinal villus fusion and shedding), strong inflammatory cell infiltration and microvillus effacement were seen through histological examination and SEM (scanning electronic microscopy) analysis. During the subsequent 18 days of the experimental period, the injured intestinal villi were gradually recovery. These data is beneficial to further investigate the pathogenesis of enteritis in farmed fish, which is helpful for the control of enteritis in aquaculture.

Perioperative and oncologic outcomes of laparoscopic versus open liver resection for combined hepatocellular-cholangiocarcinoma: a propensity score matching analysis.

BACKGROUND: Laparoscopic liver resection (LLR) has now been established as a safe and minimally invasive technique that is deemed feasible for treating hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). However, the role of LLR in treating combined hepatocellular-cholangiocarcinoma (cHCC-CC) patients has been rarely reported. This study aimed to assess the efficacy of LLR when compared with open liver resection (OLR) procedure for patients with cHCC-CC. METHODS: A total of 229 cHCC-CC patients who underwent hepatic resection (34 LLR and 195 OLR patients) from January 2014 to December 2018 in Zhongshan Hospital, Fudan University were enrolled and underwent a 1:2 propensity score matching (PSM) analysis between the LLR and OLR groups to compare perioperative and oncologic outcomes. Overall survival (OS) and recurrence-free survival (RFS) parameters were assessed by the log-rank test and the sensitivity analysis. RESULTS: A total of 34 LLR and 68 OLR patients were included after PSM analysis. The LLR group displayed a shorter postoperative hospital stay (6.61 vs. 8.26 days; p value < 0.001) when compared with the OLR group. No significant differences were observed in the postoperative complications' incidence or a negative surgical margin rate between the two groups (p value = 0.409 and p value = 1.000, respectively). The aspartate aminotransferase (AST), alanine aminotransferase (ALT), and inflammatory indicators in the LLR group were significantly lower than those in the OLR group on the first and third postoperative days. Additionally, OS and RFS were comparable in both the LLR and OLR groups (p value = 0.700 and p value = 0.780, respectively), and similar results were obtained by conducting a sensitivity analysis. CONCLUSION: LLR can impart less liver function damage, better inflammatory response attenuation contributing to a faster recovery, and parallel oncologic outcomes when compared with OLR. Therefore, LLR can be recommended as a safe and effective therapeutic modality for treating selected cHCC-CC patients, especially for those with small tumors in favorable location.

Application of double-tube negative pressure drainage in repair of refractory wounds.

OBJECTIVE: To observe the application effect of double-tube negative pressure drainage in the repair of refractory wounds. METHODS: From January 2020 to April 2023, 50 patients undergoing refractory wound repair in the Department of Burn and Plastic Surgery of Jingjiang People's Hospital, Jiangsu were selected. According to different treatment methods, they were divided into an observation group and a control group, with 25 patients in each group. The observation group was treated with double-tube negative pressure drainage inside and outside the wound, while the control group was treated with negative pressure drainage inside the wound. By two-week observation, the wound healing status and complication rate after treatment, as well as the wound bacterial clearance rate, wound pain score and patient satisfaction 3, 7 and 14 d after treatment were compared between the two groups. Statistical analysis was carried out to determine the efficacy. RESULTS: After treatment for two weeks, the observation group showed a higher grade A healing rate (92% vs. 60%, X2  = 7.018, P = 0.008), a higher wound bacterial clearance rate (100% vs. 76%, X2  = 6.818, P = 0.03), a lower pain score (1.44 ± 0.51 vs. 2.36 ± 0.49, t = -6.53, P < 0.01), a higher patient satisfaction score (8.48 ± 0.96 vs. 6.64 ± 0.95, t = 6.80, P < 0.01), and a lower complication rate (8% vs. 40%, X2 = 7.018, P = 0.008) compared with the control group. CONCLUSION: Double-tube negative pressure drainage has a significant application effect in the repair of refractory wounds. It can accelerate wound healing, shorten treatment time, effectively eliminate bacteria, relieve wound infection, reduce complications, alleviate pain and improve patient satisfaction. Therefore, the application, promotion and research of double-tube negative pressure drainage should be strengthened in clinical practice.

Critical window for the association between early electronic screen exposure and hyperactive behaviors in preschool children.

Electronic screens have become an integral part of modern life, accompanied with growing concerns for children's neuropsychological development. This study aimed to evaluate the associations between measures of early life screen exposure and hyperactive behaviors among preschool children. The study also aimed to investigate their cumulative effects and the critical window for these associations. A cross-sectional survey was conducted among 52 625 mother-child dyads at preschools in LongHua District of Shenzhen, China. A self-administered structured questionnaire was used to assess socio-demographic characteristics, duration of children's electronic screen exposure in each of the first 3 years following birth and the presence of current hyperactive behaviors. A series of logistic regression models were used to examine the relationship between previous screen time and current hyperactive behaviors. A crossover analysis was used to explore the critical window for a significant relationship between screen time and hyperactive behaviors. We found that exposure to electronic screens in the first 3 years of life was associated with hyperactive behaviors in preschool children. A cumulative effect was shown in children with an average daily screen time less than 60 min, with adjusted ORs increasing from 1.262 to 1.989 as screen exposure years increased from 1 to 3 years. A critical window was identified in that children in the first 2 years after birth were vulnerable to electronic screen exposure. Exposure to televisions, mobile phones, and computers were all related to elevated risks for hyperactive behaviors. In conclusion, early screen exposure appears to increase the risk for hyperactive behaviors in preschool children with the presence of a cumulative effect, a critical window and different electronic screens having similar effects.

Investigation of Stroke Risk Factors and Prognostic Indicators in NVAF Patients with Low CHA2DS2-VASc Scores.

The prognosis of patients with nonvalvular atrial fibrillation (NVAF) with a low CHA2DS2-VASc score (0-1) following a stroke is not well studied. In this investigation, stroke risk factors and prognostic markers in low-risk NVAF patients who are nonetheless at risk for stroke were examined.From January 2012 to January 2022, we retrospectively assessed atrial fibrillation (AF) patients at Xiamen University's Zhongshan Hospital for ischemic stroke. Along with a control group of patients with CHA2DS2-VASc scores of 0-1 who weren't suffering from a stroke, patients with CHA2DS2-VASc scores of 0-1 at the time of stroke were included in the study. Using multivariate logistic regression, independent risk factors were identified. To assess the cumulative occurrences of in-hospital mortality in patients with NVAF-related stroke, the Kaplan-Meier method was used.The study included 156 out of 3.237 inpatients with AF-related stroke who had CHA2DS2-VASc ratings of 0-1. Left atrial diameter (LAD) (odds ratio [OR]: 1.858, 95% confidence interval (CI) 1.136-3.036, P = 0.013), D-dimer (OR: 2.569, 95% CI 1.274-5.179, P = 0.008), and NT-proBNP (OR: 4.558, 95% CI 2.060-10.087, P = 0.000) were found to be independent risk factors for stroke in NVAF patients with a low CHA2DS2-VASc score. During hospitalization, nine patients with NVAF-related stroke died. In patients with NVAF-related stroke, NT-proBNP (hazard ratio: 3.504, 95% CI 1.079-11.379, P = 0.037) was an indicator of mortality risk.Patients with NVAF and CHA2DS2-VASc scores of 0-1 had independent risk factors for stroke in the form of LAD, D-dimer, and NT-proBNP. Notably, in low-risk NVAF patients with stroke, NT-proBNP was discovered to be a potent predictor of in-hospital death.