Exosomes derived from vMIP-II-Lamp2b gene-modified M2 cells provide neuroprotection by targeting the injured spinal cord, inhibiting chemokine signals and modulating microglia/macrophage polarization in mice.

Inflammation is one of the key injury factors for spinal cord injury (SCI). Exosomes (Exos) derived from M2 macrophages have been shown to inhibit inflammation and be beneficial in SCI animal models. However, lacking targetability restricts their application prospects. Considering that chemokine receptors increase dramatically after SCI, viral macrophage inflammatory protein II (vMIP-II) is a broad-spectrum chemokine receptor binding peptide, and lysosomal associated membrane protein 2b (Lamp2b) is the key membrane component of Exos, we speculated that vMIP-II-Lamp2b gene-modified M2 macrophage-derived Exos (vMIP-II-Lamp2b-M2-Exo) not only have anti-inflammatory properties, but also can target the injured area by vMIP-II. In this study, using a murine contusive SCI model, we revealed that vMIP-II-Lamp2b-M2-Exo could target the chemokine receptors which highly expressed in the injured spinal cords, inhibit some key chemokine receptor signaling pathways (such as MAPK and Akt), further inhibit proinflammatory factors (such as IL-1ß, IL-6, IL-17, IL-18, TNF-α, and iNOS), and promote anti-inflammatory factors (such as IL-4 and Arg1) productions, and the transformation of microglia/macrophages from M1 into M2. Moreover, the improved histological and functional recoveries were also found. Collectively, our results suggest that vMIP-II-Lamp2b-M2-Exo may provide neuroprotection by targeting the injured spinal cord, inhibiting some chemokine signals, reducing proinflammatory factor production and modulating microglia/macrophage polarization.

The beneficial effect of α-lipoic acid on spinal cord injury repair in rats is mediated through inhibition of oxidative stress: A transcriptomic analysis.

BACKGROUND: Oxidative stress is a crucial factor contributing to the occurrence and development of secondary damage in spinal cord injuries (SCI), ultimately impacting the recovery process. α-lipoic acid (ALA) exhibits potent antioxidant properties, effectively reducing secondary damage and providing neuroprotective benefits. However, the precise mechanism by which ALA plays its antioxidant role remains unknown. METHODS: We established a model of moderate spinal cord contusion in rats. Experimental rats were randomly divided into 3 distinct groups: the sham group, the model control group (SCI_Veh), and the ALA treatment group (SCI_ALA). The sham group rats were exposed only to the SC without contusion injury. Rats belonging to SCI_Veh group were not administered any treatment after SCI. Rats of SCI_ALA group were intraperitoneally injected with the corresponding volume of ALA according to body weight for three consecutive days after the surgery. Subsequently, three days after SCI, spinal cord samples were obtained from three groups of rats: the sham group, model control group, and administration group. Thereafter, total RNA was extracted from the samples and the expression of three sets of differential genes was analyzed by transcriptome sequencing technology. Real-time PCR was used to verify the sequencing results. The impact of ALA on oxidative stress in rats following SCI was assessed by measuring their total antioxidant capacity and hydrogen peroxide (H2O2) content. The effects of ALA on rat recovery following SCI was investigated through Beattie and Bresnahan (BBB) score and footprint analysis. RESULTS: The findings from the transcriptome sequencing analysis revealed that the model control group had 2975 genes with altered expression levels when compared to the ALA treatment group. Among these genes, 1583 were found to be upregulated while 1392 were down-regulated. Gene ontology (GO) displayed significant enrichment in terms of functionality, specifically in oxidative phosphorylation, oxidoreductase activity, and signaling receptor activity. The Kyoto encyclopedia of genes and genomes (KEGG) pathway was enriched in oxidative phosphorylation, glutathione metabolism and cell cycle. ALA was found to have multiple benefits for rats after SCI, including increasing their antioxidant capacity and reducing H2O2 levels. Additionally, it was effective in improving motor function (such as 7 days after SCI, the BBB score for SCI_ALA was 8.400 ± 0.937 compared to 7.050 ± 1.141 for SCI_Veh) and promoting histological recovery after SCI (The results of HE demonstrated that the percentage of damage area in was 44.002 ± 6.680 in the SCI_ALA and 57.215 ± 3.964 in the SCI_Veh at the center of injury.). The sequence data from this study has been deposited into Sequence Read Archive (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE242507). CONCLUSION: Overall, the findings of this study confirmed the beneficial effects of ALA on recovery in SCI rats through transcriptome sequencing, behavioral, as well histology analyses.

Intestinal microbiota via NLRP3 inflammasome dependent neuronal pyroptosis mediates anxiety-like behaviour in mice exposed to 3.5 GHz radiofrequency radiation.

The rapid development of 5G communication technology has increased public concern about the potential adverse effects on human health. Till now, the impacts of radiofrequency radiation (RFR) from 5G communication on the central nervous system and gut-brain axis are still unclear. Therefore, we investigated the effects of 3.5 GHz (a frequency commonly used in 5G communication) RFR on neurobehavior, gut microbiota, and gut-brain axis metabolites in mice. The results showed that exposure to 3.5 GHz RFR at 50 W/m2 for 1 h over 35 d induced anxiety-like behaviour in mice, accompanied by NLRP3-dependent neuronal pyroptosis in CA3 region of the dorsal hippocampus. In addition, the microbial composition was widely divergent between the sham and RFR groups. 3.5 GHz RFR also caused changes in metabolites of feces, serum, and brain. The differential metabolites were mainly enriched in glycerophospholipid metabolism, tryptophan metabolism, and arginine biosynthesis. Further correlation analysis showed that gut microbiota dysbiosis was associated with differential metabolites. Based on the above results, we speculate that dysfunctional intestinal flora and metabolites may be involved in RFR-induced anxiety-like behaviour in mice through neuronal pyroptosis in the brain. The findings provide novel insights into the mechanism of 5G RFR-induced neurotoxicity.

A revision of the genus Eurymesosa Breuning, 1938 (Cerambycidae, Lamiinae, Mesosini).

A taxonomic revision and redescription of the genus Eurymesosa Breuning, 1938 are presented, including a key to species. Three of the five currently accepted species are considered valid: Eurymesosaventralis (Pascoe, 1865), Eurymesosaallapsa (Pascoe, 1866) and Eurymesosaziranzhiyi Yamasako & Lin, 2016. Three junior synonyms are proposed for E.ventralis: Eurymesosaalbostictica Breuning, 1962, syn. nov., Eurymesosaaffinis Breuning, 1970, syn. nov., and Eurymesosamultinigromaculata Breuning, 1974, syn. nov. Additionally, E.allapsa (Pascoe, 1866) is resurrected from synonyms of E.ventralis. Females of E.allapsa and E.ziranzhiyi Yamasako & Lin, 2016 are described for the first time.

Application of noninvasive sampling technique in mitochondrial genome intraspecific phylogeny of the endangered butterfly, Teinopalpus aureus (Lepidoptera: Papilionidae).

The butterfly genus of Teinopalpus, endemic to Asia, embodies a distinct species of mountain-dwelling butterflies with specific habitat requirements. These species are rare in the wild and hold high conservation and research value. Similar to other protected species, the genetic analysis of the rare Teinopalpus aureus poses challenges due to the complexity of sampling. In this study, we successfully extracted DNA and amplified mitochondrial genomic DNA from various noninvasive sources such as larval feces, larval exuviae, larval head capsules, pupal exuviaes, and filamentous gland secretions, all integral parts of butterfly metamorphosis. This was conducted as part of a research initiative focused on the artificial conservation of T. aureus population in Jinggang Shan Nature Reserve. Our findings illustrated the successful extraction of DNA from multiple noninvasive sources, achieved through modified DNA extraction methodologies. Although the DNA concentration obtained from noninvasive samples was lower than that from muscle tissues of newly dead larvae during rearing, all samples met the requirements for PCR amplification and sequencing, yielding complete circular sequences. These sequences are pivotal for both interspecific and intraspecific genetic relationship analysis. Our methods can be extended to other insects, especially scarce species.

A revision of some species of Souvanna Breuning, 1963, Mispila Pascoe, 1864, and Athylia Pascoe, 1864 (Coleoptera, Cerambycidae, Lamiinae).

Alidussignatus Pic, 1926 is transferred from Mispila to Souvanna, and Souvannasignata (Pic, 1926), comb. nov. is proposed. The lectotype of Alidussignatus is designated. The following synonyms are proposed: Souvannasignata = Athylia (s. str.) quadristigma (Gressitt, 1940), syn. nov. = Souvannaphoumai Breuning, 1963, syn. nov. = Mispila (Dryusa) coomani Breuning, 1968, syn. nov., Mispila (s. str.) tenuevittata (Pic, 1930) = Mispila (s. str.) assamensis Breuning, 1938, syn. nov. The gender of the holotype of Alidusmultilineatus Pic, 1925 is determined. New distributional records for Souvannasignata, Mispilacurvilinea Pascoe, 1869, M.subtonkinea Breuning, 1968 and M.tenuevittata are provided.

Clinical analysis of bacterial infection characteristics in lymphoma patients with high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation-a single-centered retrospective study.

BACKGROUND: High-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (HDT/AHSCT) is used to treat lymphoma. Although AHSCT has made considerable strides and become safer, HDT-AHSCT infection continues to be a leading cause of morbidity and mortality associated with transplantation. OBJECTIVE: To characterise pathogenic bacterial infections in HDT/AHSCT-treated lymphoma patients. The prevalence of pathogenic microorganisms and the timing of foci after transplantation, along with bloodstream infection (BSI) risk factors, can help determine the need for empirical antibiotics after AHSCT. METHODS: We retrospectively analyzed 133 lymphoma patients treated by HDT/AHSCT from April 2017 to October 2021 at Peking University International Hospital, Beijing, China. We analyzed their clinical characteristics, microbiological distribution characteristics, and BSI risk factors in detail. RESULTS: In order, intestinal infection (56 cases), BSI (17 cases), pulmonary (12 cases), upper respiratory tract (5 cases), and perianal (4 cases) were the most common locations of infection after HDT/AHSCT. The infection sites yielded 92 putative pathogenic pathogens, with bacteria predominating (61.96%), fungi (28.26%), viruses (5.43%), and mycoplasma (4.35%). Gram-negative bacteria (GNB) strains outnumbered gram-positive bacteria (GPB) strains (73.68%). Two strains of Escherichia coli produced extended-spectrum ß-lactamase (ESBL) and one strain of carbapenem-resistant enterobacteriaceae (CRE). Methicillin-resistant Staphylococcus epidermidis (MRSE) had one strain. BSI was caused by Escherichia coli (82.35%), Intestinal mucositis (23.52%), and catheter-associated infections (11.76%). Age, CD34, pretreatment regimen, antibiotic regimen, and past chemotherapeutic agent lung damage were BSI risk variables in univariate analysis. CD34 and past chemotherapeutic drug lung damage were the primary causes of BSI after HDT/AHSCT for lymphoma. CONCLUSION: High-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (HDT/AHSCT) is used to treat lymphoma. Although AHSCT has made considerable strides and become safer, HDT-AHSCT infection continues to be a leading cause of morbidity and mortality associated with transplantation.

Factors associated with persistent positive in HBV DNA level in patients with chronic Hepatitis B receiving entecavir treatment.

Introduction: The clinical significance of persistent positive in Hepatitis B Virus (HBV) DNA level in patients receiving antiviral therapy is not well known. We investigated factors associated with persistent viremia (PV) in patients with chronic hepatitis B (CHB) given 78-week entecavir. Methods: A total of 394 treatment-naïve CHB patients who had undergone liver biopsy at baseline and week 78 of treatment were analyzed in this prospective multicentre study. We identified patients with PV (above the lower limit of quantification, 20 IU/ml) after 78 weeks of entecavir therapy. Stepwise, forward, multivariate regression analyses of specified baseline parameters were apllied to identify factors associated with PV. Futhermore, we assessed the incidence of hepatocellular carcinoma (HCC) in all patients using models of the risk of HCC development. Results: Of the 394 patients, 90 (22.8%) still with PV after 78-week antiviral treatment. Factors associated significantly with PV (vs complete virological response, CVR) were HBV DNA level ≥8 log10 IU/mL (OR, 3.727; 95% CI, 1.851-7.505; P < 0.001), Anti-HBc level < 3 log10 IU/mL (OR, 2.384; 95% CI, 1.223-4.645; P=0.011), and HBeAg seropositivity (OR, 2.871; 95% CI, 1.563-5.272; P < 0.001). Patients with PV were less likely to have fibrosis progression and HCC development than those with the CVR. Of the 11 HBeAg-positive patients with HBV DNA level ≥8 log10 IU/mL and Anti-HBc level < 3 log10 IU/mL at baseline, 9 (81.8%) had persistent positivity in HBV DNA level and 0 had fibrosis progression at week 78 of treatment. Discussion: In conclusion, HBV DNA level ≥8 log10 IU/mL, Anti-HBc level < 3 log10 IU/mL and HBeAg seropositivity at baseline contribute to PV in patients with CHB receiving 78-week antiviral treatment. In addition, the rate of fibrosis progression and the risk of HCC development in patients with PV were kept low. The complete protocol for the clinical trial has been registered at clinicaltrials.gov (NCT01962155 and NCT03568578).

Flexible multichannel electrodes for acute recording in nonhuman primates.

Flexible electrodes have demonstrated better biocompatibility than rigid electrodes in relieving tissue encapsulation and long-term recording. Nonhuman primates are closer to humans in their brains' structural and functional properties, thus making them more suitable than rodents as animal models for potential clinical usage. However, the application of flexible electrodes on nonhuman primates has rarely been reported. In the present study, a flexible multichannel electrode array for nonhuman primates was developed and implemented for extracellular recording in behaving monkeys. To minimize the window of durotomy for reducing possible risks, a guide-tube-compatible implantation solution was designed to deliver the flexible electrodes through the dura into the cortex. The proposed structure for inserting flexible electrodes was characterized ex vivo and validated in vivo. Furthermore, acute recording of multichannel flexible electrodes for the primates was performed. The results showed that the flexible electrodes and implantation method used in this study meet the needs of extracellular recording in nonhuman primates. Task-related neuronal activities with a high signal-to-noise ratio of spikes demonstrated that our whole device is currently a minimally invasive and clinically viable approach for extracellular recording.

Development and validation of an immune infiltration/tumor proliferation-related Notch3 nomogram for predicting survival in patients with primary glioblastoma.

Background: Notch receptors (Notch 1/2/3/4), the critical effectors of the Notch pathway, participate in the tumorigenesis and progression of many malignancies. However, the clinical roles of Notch receptors in primary glioblastoma (GBM) have not been fully elucidated. Methods: The genetic alteration-related prognostic values of Notch receptors were determined in the GBM dataset from The Cancer Genome Atlas (TCGA). Two GBM datasets from TCGA and Chinese Glioma Genome Atlas (CGGA) were used to explore the differential expression between Notch receptors and IDH mutation status, and GBM subtypes. The biological functions of Notch Receptors were explored by Gene Ontology and KEGG analysis. The expression and prognostic significance of Notch receptors were determined in the TCGA and CGGA datasets and further validated in a clinical GBM cohort by immunostaining. A Notch3-based nomogram/predictive risk model was constructed in the TCGA dataset and validated in the CGGA dataset. The model performance was evaluated by receiver operating curves, calibration curves, and decision curve analyses. The Notch3-related phenotypes were analyzed via CancerSEA and TIMER. The proliferative role of Notch3 in GBM was validated in U251/U87 glioma cells by Western blot and immunostaining. Results: Notch receptors with genetic alterations were associated with poor survival of GBM patients. Notch receptors were all upregulated in GBM of TCGA and CGGA databases and closely related to the regulation of transcription, protein-lysine N-methyltransferase activity, lysine N-methyltransferase activity, and focal adhesion. Notch receptors were associated with Classical, Mesenchymal, and Proneural subtypes. Notch1 and Notch3 were closely correlated with IDH mutation status and G-CIMP subtype. Notch receptors displayed the differential expression at the protein level and Notch3 showed a prognostic significance in a clinical GBM cohort. Notch3 presented an independent prognostic role for primary GBM (IDH1 mutant/wildtype). A Notch3-based predictive risk model presented favorable accuracy, reliability, and net benefits for predicting the survival of GBM patients (IDH1 mutant/wildtype and IDH1 wildtype). Notch3 was closely related to immune infiltration (macrophages, CD4+ T cells, and dendritic cells) and tumor proliferation. Conclusion: Notch3-based nomogram served as a practical tool for anticipating the survival of GBM patients, which was related to immune-cell infiltration and tumor proliferation.

Development and validation of a predictive model in diagnosis and prognosis of primary glioblastoma patients based on Homeobox A family.

BACKGROUND: Homeobox A (HOXA) family is involved in the development of malignancies as either tumor suppressors or oncogenes. However, their roles in glioblastoma (GBM) and clinical significance have not been fully elucidated. METHODS: HOXA mutation and expressions in pan-cancers were investigated using GSCA and Oncomine, which in GBM were validated by cBioPortal, Chinese Glioma Genome Atlas (CGGA), and The Cancer Genome Atlas (TCGA) datasets. Kaplan-Meier analyses were conducted to determine prognostic values of HOXAs at genetic and mRNA levels. Diagnostic roles of HOXAs in tumor classification were explored by GlioVis and R software. Independent prognostic HOXAs were identified using Cox survival analyses, the least absolute shrinkage and selection operator (LASSO) regression, quantitative real-time PCR, and immunohistochemical staining. A HOXAs-based nomogram survival prediction model was developed and evaluated using Kaplan-Meier analysis, time-dependent Area Under Curve, calibration plots, and Decision Curve Analysis in training and validation cohorts. RESULTS: HOXAs were highly mutated and overexpressed in pan-cancers, especially in CGGA and TCGA GBM datasets. Genetic alteration and mRNA expression of HOXAs were both found to be prognostic. Specific HOXAs could distinguish IDH mutation (HOXA1-7, HOXA9, HOXA13) and molecular GBM subtypes (HOXA1-2, HOXA9-11, HOXA13). HOXA1/2/3/10 were confirmed to be independent prognostic members, with high expressions validated in clinical GBM tissues. The HOXAs-based nomogram model exhibited good prediction performance and net benefits for patients in training and validation cohorts. CONCLUSION: HOXA family has diagnostic values, and the HOXAs-based nomogram model is effective in survival prediction, providing a novel approach to support the treatment of GBM patients.

High-Sucrose Diet Exposure on Larvae Contributes to Adult Fecundity and Insecticide Tolerance in the Oriental Fruit Fly, Bactrocera dorsalis (Hendel).

Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) is one of the broad host ranges and economically-important insect pests in tropical and subtropical areas. A wide range of hosts means they have strong adaptation ability to changes in dietary macronutrients (e.g., sucrose and protein). However, the effects of dietary conditions on the phenotypes and genotypes of B. dorsalis are still unclear. In this study, we aimed to investigate the effects of larval dietary sucrose on the life history traits and stress tolerance of B. dorsalis, and its defense response at the molecular level. The results showed that low-sucrose (LS) induced decreased body size, shortened developmental duration, and enhanced sensitivity to beta-cypermethrin. Otherwise, high-sucrose (HS) diet increased developmental duration, adult fecundity, and tolerance to malathion. Based on transcriptome data, 258 and 904 differentially expressed genes (DEGs) were identified in the NS (control) versus LS groups, and NS versus HS groups, respectively. These yielded DEGs were relevant to multiple specific metabolisms, hormone synthesis and signaling, and immune-related pathways. Our study will provide biological and molecular perspective to understand phenotypic adjustments to diets and the strong host adaptability in oriental fruit flies.

A revision of the genus Trichohoplorana Breuning, 1961 (Arthropoda, Insecta, Coleoptera, Cerambycidae, Lamiinae, Acanthocinini).

A taxonomic revision of the genus Trichohoplorana Breuning, 1961 is presented. A junior synonym of Trichohoplorana, Ipochiromima Sama & Sudre, 2009, syn. nov., is proposed. A junior synonym of T.dureli Breuning, 1961, I.sikkimensis (Breuning, 1982), syn. nov., is proposed. Trichohoplorana is newly recorded from Vietnam. A new species, T.nigeralbasp. nov. is described from Vietnam. Trichohoploranaluteomaculata Gouverneur, 2016 is newly recorded from China and Vietnam. Hind wings and male terminalia of T.luteomaculata are described for the first time. Trichohoplorana is redescribed, and a key to Trichohoplorana species is presented.

Experimental Investigation on Shear Capacity of Steel-Fiber-Reinforced High-Strength Concrete Corbels.

As short cantilever members, corbels are mainly used to transfer eccentric loads to columns. Because of the discontinuity of load and geometric structure, corbels cannot be analyzed and designed using the method based on beam theory. Nine steel-fiber-reinforced high-strength concrete (SFRHSC) corbels were tested. The width of the corbels was 200 mm, the cross-section height of the corbel column was 450 mm, and the cantilever end height was 200 mm. The shear span/depth ratios considered were 0.2, 0.3, and 0.4; the longitudinal reinforcement ratios were 0.55%, 0.75%, and 0.98%; the stirrup reinforcement ratios were 0.39%, 0.52%, and 0.785%; and the steel fiber volume ratios were 0, 0.75%, and 1.5%. According to the test results, this paper discusses the failure process and failure mode of corbel specimens with a small shear span/depth ratio and analyzes the effects of variables such as shear span/depth ratio, longitudinal reinforcement ratio, stirrup reinforcement ratio, and steel fiber volume content on the shear capacity of corbels. The shear capacity of corbels is significantly affected by the shear span/depth ratio, followed by the longitudinal reinforcement ratio and the stirrup reinforcement ratio. Moreover, it is shown that steel fibers have little impact on the failure mode and ultimate load of corbels, but can enhance the crack resistance of corbels. In addition, the bearing capacities of these corbels were calculated by Chinese code GB 50010-2010 and further compared with ACI 318-19 code, EN 1992-1-1:2004 code, and CSA A23.3-19 code, which adopt the strut-and-tie model. The results indicate that the calculation results by the empirical formula in the Chinese code are close to the corresponding test results, while the calculation method based on the strut-and-tie model of a clear mechanical concept yields conservative results, and hence the related parameter values must be further modified.

Identification of CCL20 as a Key Biomarker of Inflammatory Responses in the Pathogenesis of Intracerebral Hemorrhage.

Inflammatory responses after intracerebral hemorrhage (ICH) contribute to severe secondary brain injury, leading to poor clinical outcomes. However, the responsible genes for effective anti-inflammation treatment in ICH remain poorly elucidated. The differentially expressed genes (DEGs) of human ICH were explored by online GEO2R. Go and KEGG were used to explore the biological function of DEGs. Protein-protein interactions (PPI) were built in the String database. Critical modules of PPI were identified by a molecular complex detection algorithm (MCODE). Cytohubba was used to determine the hub genes. The mRNA-miRNA interaction network was built in the miRWalk database. The rat ICH model was applied to validate the key genes. A total of 776 DEGs were identified in ICH. Go and KEGG analyses indicated that DEGs were mainly involved in neutrophil activation and the TNF signaling pathway. GSEA analysis presented that DEGs were significantly enriched in TNF signaling and inflammatory response. PPI network was constructed in the 48 differentially expressed inflammatory response-related genes. The critical module of the PPI network was constructed by 7 MCODE genes and functioned as the inflammatory response. The top 10 hub genes with the highest degrees were identified in the inflammatory response after ICH. CCL20 was confirmed as a key gene and mainly expressed in neurons in the rat ICH model. The regulatory network between CCL20 and miR-766 was built, and the miR-766 decrease was confirmed in a human ICH dataset. CCL20 is a key biomarker of inflammatory response after intracerebral hemorrhage, providing a potential target for inflammatory intervention in ICH.

The polarization of microglia and infiltrated macrophages in the injured mice spinal cords: a dynamic analysis.

Background: Following spinal cord injury (SCI), a large number of peripheral monocytes infiltrate into the lesion area and differentiate into macrophages (Mø). These monocyte-derived Mø are very difficult to distinguish from the local activated microglia (MG). Therefore, the term Mø/MG are often used to define the infiltrated Mø and/or activated MG. It has been recognized that pro-inflammatory M1-type Mø/MG play "bad" roles in the SCI pathology. Our recent research showed that local M1 cells are mainly CD45-/lowCD68+CD11b+ in the subacute stage of SCI. Thus, we speculated that the M1 cells in injured spinal cords mainly derived from MG rather than infiltrating Mø. So far, their dynamics following SCI are not yet entirely clear. Methods: Female C57BL/6 mice were used to establish SCI model, using an Infinite Horizon impactor with a 1.3 mm diameter rod and a 50 Kdynes force. Sham-operated (sham) mice only underwent laminectomy without contusion. Flow cytometry and immunohistofluorescence were combined to analyze the dynamic changes of polarized Mø and MG in the acute (1 day), subacute (3, 7 and 14 days) and chronic (21 and 28 days) phases of SCI. Results: The total Mø/MG gradually increased and peaked at 7 days post-injury (dpi), and maintained at high levels 14, 21 and 28 dpi. Most of the Mø/MG were activated, and the Mø increased significantly at 1 and 3 dpi. However, with the pathological process, activated MG increased nearly to 90% at 7, 14, 21 and 28 dpi. Both M1 and M2 Mø were increased significantly at 1 and 3 dpi. However, they decreased to very low levels from 7 to 28 dpi. On the contrary, the M2-type MG decreased significantly following SCI and maintained at a low level during the pathological process.

High-potency nucleos(t)ide analogues alone or plus immunoglobulin for HBV prophylaxis after liver transplantation: a meta-analysis.

BACKGROUND: The optimum prophylactic regimen against hepatitis B virus (HBV) recurrence after liver transplantation (LT) in HBV-infected patients is uncertain but of great clinical relevance. New evidence suggests that hepatitis B immunoglobulin (HBIG)-free approach would become a reasonable choice in the era of high-potency nucleos(t)ide analogues (HPNAs). We aimed to provide robust estimates for long-term survival and HBV recurrence in patients receiving different HBV-prophylaxis strategies after LT. METHODS: We did a systematic review and meta-analysis using both pseudo-individual patient data recovered from included studies (IPDMA) and conventional trial-level aggregate data meta-analysis (ADMA). Hazard ratios (HRs) were calculated using different Cox proportional hazard models accounting for inter-study heterogeneity. ADMA was conducted to pool outcomes at specific time points. RESULTS: A total of 16 studies involving 7897 patients and 41 studies involving 9435 were eligible for IPDMA and AMDA, respectively. Cumulative HBV recurrence rate and overall survival (OS) at 1, 3, 5 and 10 years post-LT were 0.3%, 0.9%, 1.2%, 1.7% and 95.6%, 89%, 86.4%, 86.4% in the HPNAs (i.e., entecavir and tenofovir) + HBIG combination group vs. 0.6%, 0.6%, 1.2%, 1.7% and 94.5%, 86.8%, 84.8%, 81.2% in the HPNAs monotherapy group (HR 1.20, 95% CI 0.56-2.60, p = 0.64; HR 1.09, 95% CI 0.70-1.69, p = 0.72), respectively. The results were compatible with AMDA. CONCLUSION: A similar HBV recurrence and overall survival were found in patients who used HPNAs (mainly entecavir) monotherapy as in those who received a combination of HPNAs and HBIG. These findings address concerns regarding the safety and effectiveness of HPNAs monotherapy.

An-Luo-Hua-Xian Pill Improves the Regression of Liver Fibrosis in Chronic Hepatitis B Patients Treated with Entecavir.

Background and Aims: Chronic hepatitis B (CHB) can cause liver fibrosis and lead to cirrhosis and cancer. As the effectiveness of antiviral therapy to reverse liver fibrosis is limited, We aimed to evaluate the effect of An-Luo-Hua-Xian pill (ALHX) on fibrosis regression in CHB patients treated with entecavir (ETV). Methods: Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX (ETV+ALHX) between October 1, 2013 and December 31, 2020. Demographic, laboratory, and liver histology data before and after 78 weeks of treatment were collected. The Ishak fibrosis score (F) was used and fibrosis regression required a decrease in F of ≥1 after treatment. Results: A total of 780 patients were enrolled, and 394 with a second liver biopsy after treatment were included in the per-protocol population, 132 in ETV group and 262 in ETV+ALHX group. After 78 weeks of treatment, the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients: 124/211 (58.8%) vs. 45/98 (45.9%), p=0.035. The percentage of patients with a decreased liver stiffness measurement (LSM) was higher in the ETV+ALHX group: 156/211 (73.9%) vs. 62/98 (63.%), p=0.056. Logistic regression analysis showed that ETV combined with ALHX was associated with fibrosis regression [odds ratio (OR)=1.94, p=0.018], and a family history of hepatocellular carcinoma was on the contrary. (OR=0.41, p=0.031). Conclusions: ETV combined with ALHX increased liver fibrosis regression in CHB patients.

Active kisspeptin DNA vaccines oral immunization disrupt mRNA hormone receptors expression in ram lambs.

To evaluate the efficacy of oral immunization with active kisspeptin DNA vaccine on the expression of hormone receptor mRNA. For this study, ten 56-day-old Hu breed ram lambs were randomly assigned to the treatment and control groups (n = 5). Treatment Experimental group received C500/pKS-asd and the control group received C500/pVAX-asd (aspartate-ß semialdehyde dehydrogenase orally on days 0, 28, and 56, and blood samples were taken at each immunization interval (14-day) and tissues samples were collected at the end of the experimental period (day 98). The collected samples were stored in the refrigerator at -20 °C and liquid nitrogen, respectively, for laboratory examination. Total RNA was extracted from samples using TRIzol reagent and quantitative real-time polymerase chain reaction (QPCR) was used to quantify the levels of KISS1, G protein-coupled receptor-54 (Kiss1r), and gonadotrophin-releasing hormone (GnRH) mRNA in the hypothalamus. Levels of luteinizing hormone receptor (LHR) and luteinizing hormone beta (LHß) mRNA, and follicle-stimulating hormone receptor (FSHR) and follicle-stimulating hormone beta (FSHß) mRNA in the testes and pituitary were analyzed, respectively. Further, gonadotropin-releasing hormone receptor (GnRHR) mRNA expression level in the pituitary was measured. Moreover, the Kiss1r concentration level in the blood was measured using an indirect ELISA. The concentration of Kiss1r in the blood was lower in the treatment group than in the control group (p < 0.05). The levels of testicular FSHR and LHR mRNA were significantly lower in the treatment group (p < 0.05) when compared to the control group. Furthermore, the treatment group's levels of hypothalamic KISS1, Kiss1r, and GnRH mRNA were significantly lower (p < 0.05) than the controls. LH, FSH, and GnRHR mRNA expression in the pituitary were also significantly lower in the treatment group (p < 0.01 and p < 0.05, respectively). These findings imply that oral immunization with active kisspeptin DNA vaccine suppresses hormone receptor mRNA expression in the ram lambs.

Interpretation of the essential updates in guidelines for the prevention and treatment of chronic hepatitis B (Version 2022) / 中华肝脏病杂志

Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association update the guidelines for the prevention and treatment of chronic hepatitis B (version 2022) in 2022. The latest guidelines recommend more extensive screening and more active antiviral treating for hepatitis B virus infection. This article interprets the essential updates in the guidelines to help deepen understanding and better guide the clinical practice.