Lower HBV DNA level is associated with more severe liver fibrosis in HBeAg-positive chronic hepatitis B with normal alanine transaminase.

BACKGROUND: The association of hepatitis B virus (HBV) DNA levels and liver fibrosis in chronic hepatitis B (CHB) patients with immune-tolerant phase remains unclear. We explored the association between liver fibrosis and HBV DNA levels in HBeAg-positive CHB patients with normal alanine transaminase (ALT) with relatively high HBV DNA. METHODS: Six hundred and twenty-two HBeAg-positive CHB patients with normal ALT were included. Patients were divided into three categories: low (6 log10 IU/mL ≤ HBV DNA < 7 log10 IU/mL), moderate (7 log10 IU/mL ≤ HBV DNA < 8 log10 IU/mL), and high (HBV DNA ≥ 8 log10 IU/mL). APRI, FIB-4, transient elastography, or liver biopsy were used to assess liver fibrosis. RESULTS: The median age of patients was 33.0 years and 57.9% patients were male. 18.8%, 52.1%, and 29.1% of patients had low, moderate, and high HBV DNA levels, respectively. The APRI (0.33 vs. 0.26 vs. 0.26, P < 0.001), FIB-4 (1.03 vs. 0.71 vs. 0.68, P < 0.001), and LSM values (7.6 kPa vs. 5.6 kPa vs. 5.5 kPa, P = 0.086) were higher in low HBV DNA group than other two groups. Low HBV DNA group had higher proportions of significant fibrosis (24.8% vs. 9.9% vs. 3.3%, P < 0.001) and cirrhosis (7.7% vs. 2.5% vs. 1.1%, P = 0.004) than moderate and high HBV DNA groups. Moderate (OR 3.095, P = 0.023) and low (OR 4.968, P = 0.003) HBV DNA were independent risk factors of significant fibrosis. CONCLUSION: Lower HBV DNA level was associated with more severe liver fibrosis in HBeAg-positive CHB patients with ALT.

A facile nanozyme-based colorimetric method to realize the quantitative and specific detection of casein phosphopeptides in food samples.

As a popular nutritional enhancer, casein phosphopeptides (CPPs) have attracted growing attention in food industry. However, conventional methods for CPPs detection are usually less precise or requires expensive instruments. Herein, a nanozyme-based colorimetric method was developed to achieve the quantitative detection of CPPs in food samples. This method is based on a facilely fabricated peroxidase-like nanozyme (Fe@UiO-66), which combines the specific binding of CPPs, as well as the nanozyme-catalyzed colorimetric sensing that can be easily detected by spectrometer. The method displayed good quantitative ability toward CPPs with the linear range of 2-30 µg/mL, the low limit of detection of 0.267 µg/mL and limit of quantification of 1.335 µg/mL. We highlighted the specificity, anti-interference and practicability of this method, by investigating the performances toward food samples. Besides, a smartphone-based colorimetric sensing platform was also established, which is conducive to the portable detection. The developed nanozyme-based colorimetric sensing method provides a promising strategy for CPPs detection in food samples.

A Food Poisoning Caused by Salmonella Enterica (S. Enteritidis) ST11 Carrying Multi-Antimicrobial Resistance Genes in 2019, China.

Purpose: This study was to identify and analyze the pathogen responsible for food poisoning in a tourist group traveling from Macao to Zhuhai. Patients and Methods: Samples were obtained from 27 patients of 96 cases, as well as samples of contaminated food in Macau. The collected samples were subjected to serological identification, drug sensitivity analysis, drug resistance gene identification, virulence factor analysis, and tracing. Results: Twenty-six isolates and the salad isolate were S. enteritidis ST11. Isolates from patients were exhibited significant resistance to Penicillin AMP (Ampicillin) and quinolones NAL (Nalidixic acid). Among these isolates, 21 strains were resistant to two or more antibiotics, indicating the multi-drug resistance (MDR). Genomic characteristics and phylogenetic analysis were performed on 9 of the isolates using whole genome sequencing (WGS). The analysis revealed that the resistance to AMP and NAL was primarily caused by a gryA mutation D87Y (9/9, 100%), and the presence of beta-lactam resistance genes blaOXA-1 (1/9, 11.11%), blaTEM-141 (1/9, 11.11%), and blaTEM-1B (8/9, 88.89%). It was also found a strains isolated from patients had two resistance genes to quinolones or beta-lactam drugs (1/8, 12.5%), respectively. The strains were found to possess 165 virulence genes, one adherence class virulence factor, one invasion class virulence factor and various pathogenicity islands, including SPI-1, SPI-2, SPI-3, SPI-4, SPI-5, SPI-9, SPI-10, SPI-13, SPI-14, SPI-15, SGI 1, CS54_island, and C63PI-1. Additionally, the virulence plasmids were detected, including IncFIB(s)-IncFII(s)-IncX1 (55.56%), IncFIB(s)-IncFII(s) (33.33%), and IncFIB(s)-IncFII(s)-IncHI2-IncHI2A (11.11%). PFGE (Pulsed Field Gel Electrophoresis) and phylogenetic tree analysis revealed a high degree of similarity between Salmonella isolates from patients and food samples from Macao. Conclusion: This study identified Salmonella enterica ST11 as the cause of the food poisoning outbreak. The findings highlight the importance of phenotypic characterization and next-generation sequencing (NGS) tools in epidemiological studies and emphasize the potential risk of a new emerging multi-antibiotic ST11 clone for S. enteritidis.

Corrigendum: Genetic overlap and causality between COVID-19 and multi-site chronic pain: the importance of immunity.

[This corrects the article DOI: 10.3389/fimmu.2024.1277720.].

Interaction of ubiquitin-like protein SILENCING DEFECTIVE 2 with LIKE HETEROCHROMATIN PROTEIN 1 is required for regulation of anthocyanin biosynthesis in Arabidopsis thaliana in response to sucrose.

The regulatory mechanisms of anthocyanin biosynthesis have been well documented at the transcriptional and translational levels. By contrast, how anthocyanin biosynthesis is epigenetically regulated remains largely unknown. In this study, we employed genetic, molecular biology, and chromatin immunoprecipitation-quantitative polymerase chain reaction assays to identify a regulatory module essential for repressing the expression of genes involved in anthocyanin biosynthesis through chromatin remodeling. We found that SILENCING DEFECTIVE 2 (SDE2), which was previously identified as a negative regulator for sucrose-induced anthocyanin accumulation in Arabidopsis, is cleaved into N-terminal SDE2-UBL and C-terminal SDE2-C fragments at the first diglycine motif, and the cleaved SDE2-C, which can fully complement the sde2 mutant, is localized in the nucleus and physically interacts with LIKE HETEROCHROMATIN PROTEIN 1 (LHP1) in vitro and in vivo. Genetic analyses showed that both SDE2 and LHP1 act as negative factors for anthocyanin biosynthesis. Consistently, immunoblot analysis revealed that the level of LHP1-bound histone H3 lysine 27 trimethylation (H3K27me3) significantly decreases in sde2 and lhp1 mutants, compared to wild-type (WT). In addition, we found that sugar can induce expression of SDE2 and LHP1, and enhance the level of the nucleus-localized SDE2-C. Taken together, our data suggest that the SDE2-C-LHP1 module is required for repression of gene expression through H3K27me3 modification during sugar-induced anthocyanin biosynthesis in Arabidopsis thaliana.

Thermogalvanic hydrogel-based e-skin for self-powered on-body dual-modal temperature and strain sensing.

Sensing of both temperature and strain is crucial for various diagnostic and therapeutic purposes. Here, we present a novel hydrogel-based electronic skin (e-skin) capable of dual-mode sensing of temperature and strain. The thermocouple ion selected for this study is the iodine/triiodide (I-/I3-) redox couple, which is a common component in everyday disinfectants. By leveraging the thermoelectric conversion in conjunction with the inherent piezoresistive effect of a gel electrolyte, self-powered sensing is achieved by utilizing the temperature difference between the human body and the external environment. The composite hydrogels synthesized from polyvinyl alcohol (PVA) monomers using a simple freeze‒thaw method exhibit remarkable flexibility, extensibility, and adaptability to human tissue. The incorporation of zwitterions further augments the resistance of the hydrogel to dehydration and low temperatures, allowing maintenance of more than 90% of its weight after 48 h in the air. Given its robust thermal current response, the hydrogel was encapsulated and then integrated onto various areas of the human body, including the cheeks, fingers, and elbows. Furthermore, the detection of the head-down state and the monitoring of foot movements demonstrate the promising application of the hydrogel in supervising the neck posture of sedentary office workers and the activity status. The successful demonstration of self-powered on-body temperature and strain sensing opens up new possibilities for wearable intelligent electronics and robotics.

Association of liver function and prognosis in patients with severe fever with thrombocytopenia syndrome.

OBJECTIVES: Severe fever with thrombocytopenia syndrome (SFTS) is an epidemic emerging infectious disease with high mortality rate. We investigated the association between liver injury and clinical outcomes in patients with SFTS. METHODS: A total of 291 hospitalized SFTS patients were retrospectively included. Cox proportional hazards model was adopted to identify risk factors of fatal outcome and Kaplan-Meier curves were used to estimate cumulative risks. RESULTS: 60.1% of patients had liver injury at admission, and the median alanine transaminase, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil) levels were 76.4 U/L, 152.3 U/L, 69.8 U/L and 9.9 µmol/L, respectively. Compared to survivors, non-survivors had higher levels of AST (253.0 U/L vs. 131.1 U/L, P < 0.001) and ALP (86.2 U/L vs. 67.9 U/L, P = 0.006), higher proportion of elevated ALP (20.0% vs. 4.4%, P < 0.001) and liver injury (78.5% vs. 54.9%, P = 0.001) at admission. The presence of liver injury (HR 2.049, P = 0.033) at admission was an independent risk factor of fatal outcome. CONCLUSIONS: Liver injury was a common complication and was strongly associated with poor prognosis in SFTS patients. Liver function indicators should be closely monitored for SFTS patients.

Genetic overlap and causality between COVID-19 and multi-site chronic pain: the importance of immunity.

Background: The existence of chronic pain increases susceptibility to virus and is now widely acknowledged as a prominent feature recognized as a major manifestation of long-term coronavirus disease 2019 (COVID-19) infection. Given the ongoing COVID-19 pandemic, it is imperative to explore the genetic associations between chronic pain and predisposition to COVID-19. Methods: We conducted genetic analysis at the single nucleotide polymorphism (SNP), gene, and molecular levels using summary statistics of genome-wide association study (GWAS) and analyzed the drug targets by summary data-based Mendelian randomization analysis (SMR) to alleviate the multi-site chronic pain in COVID-19. Additionally, we performed a latent causal variable (LCV) method to investigate the causal relationship between chronic pain and susceptibility to COVID-19. Results: The cross-trait meta-analysis identified 19 significant SNPs shared between COVID-19 and chronic pain. Coloc analysis indicated that the posterior probability of association (PPH4) for three loci was above 70% in both critical COVID-19 and COVID-19, with the corresponding top three SNPs being rs13135092, rs7588831, and rs13135092. A total of 482 significant overlapped genes were detected from MAGMA and CPASSOC results. Additionally, the gene ANAPC4 was identified as a potential drug target for treating chronic pain (P=7.66E-05) in COVID-19 (P=8.23E-03). Tissue enrichment analysis highlighted that the amygdala (P=7.81E-04) and prefrontal cortex (P=8.19E-05) as pivotal in regulating chronic pain of critical COVID-19. KEGG pathway enrichment further revealed the enrichment of pleiotropic genes in both COVID-19 (P=3.20E-03,Padjust=4.77E-02,hsa05171) and neurotrophic pathways (P=9.03E-04,Padjust =2.55E-02,hsa04621). Finally, the latent causal variable (LCV) model was applied to find the genetic component of critical COVID-19 was causal for multi-site chronic pain (P=0.015), with a genetic causality proportion (GCP) of was 0.60. Conclusions: In this study, we identified several functional genes and underscored the pivotal role of the inflammatory system in the correlation between the paired traits. Notably, heat shock proteins emerged as potential objective biomarkers for chronic pain symptoms in individuals with COVID-19. Additionally, the ubiquitin system might play a role in mediating the impact of COVID-19 on chronic pain. These findings contribute to a more comprehensive understanding of the pleiotropy between COVID-19 and chronic pain, offering insights for therapeutic trials.

Straw Addition Enhances Crop Yield, Soil Aggregation, and Soil Microorganisms in a 14-Year Wheat-Rice Rotation System in Central China.

Straw return utilizes waste resources to reduce the use of chemical fertilizers worldwide. However, information is still lacking on the relative impact of straw return on soil fertility, the nutrient composition of different soil aggregates, and soil microbial communities. Therefore, this study aimed to understand the effects of different management practices on the crop yield, soil fertility, and soil community composition in a 14-year wheat-rice rotation system. The treatments included a control (without fertilizer and straw addition), chemical fertilization (NPK), straw return without fertilizer (S), and straw addition with chemical fertilizer (NPKS). The results showed that NPKS improved the wheat and rice yield by 185.12% and 88.02%, respectively, compared to the CK treatment. Additionally, compared to the CK treatment, the N, P, and K contents of the wheat stem were increased by 39.02%, 125%, and 20.23% under the NPKS treatment. Compared to the CK treatment, SOM, TN, TP, AN, AP, AK, CEC, AFe, AMn, ACu, and AZn were increased by 49.12%, 32.62%, 35.06%, 22.89%, 129.36%, 48.34%, 13.40%, 133.95%, 58.98%, 18.26% and 33.33% under the NPKS treatment, respectively. Moreover, straw addition promoted the creation and stabilization of macro-aggregates in crop soils. The relative abundance of macro-aggregates (0.25-2 mm) increased from 37.49% to 52.97%. Straw addition was associated with a higher proportion of aromatic and carbonyl carbon groups in the soil, which, in turn, promoted the formation of macro-aggregates. Redundancy analysis showed that straw return significantly increased the microbial community diversity. These findings demonstrate that straw addition together with chemical fertilizer could increase the crop yield by improving soil fertility, soil aggregate stability, and the diversity of fungi.

Clinical outcomes of treatment-naïve HBeAg-negative patients with chronic hepatitis B virus infection with low serum HBsAg and undetectable HBV DNA.

Serum hepatitis B surface antigen (HBsAg) level < 100 IU/ml and undetectable hepatitis B virus (HBV) DNA have been recently proposed as an alternate endpoint of "partial cure" in chronic hepatitis B (CHB). We investigated clinical outcomes of hepatitis B e antigen (HBeAg)-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA. Treatment-naïve HBeAg-negative CHB patients with undetectable HBV DNA and normal alanine aminotransferase were retrospectively included from three institutions. Patients were classified into the low HBsAg group (<100 IU/ml) and the high HBsAg group (≥100 IU/ml). Liver fibrosis was evaluated by noninvasive tests (NITs). A total of 1218 patients were included and the median age was 41.5 years. Patients with low HBsAg were older (45.0 vs. 40.0 years, P < 0.001) than those in the high HBsAg group, while the NIT parameters were comparable between groups. During a median follow-up of 25.7 months, patients with low HBsAg achieved a higher HBsAg clearance rate (13.0% vs. 0%, P < 0.001) and a lower rate of significant fibrosis development (2.2% vs. 7.0%, P = 0.049) compared to patients with high HBsAg. No patient developed HCC in either group. HBsAg level was negatively associated with HBsAg clearance (HR 0.213, P < 0.001) and patients with HBsAg < 100 IU/ml had a low risk of significant fibrosis development (HR 0.010, P = 0.002). The optimal cutoff value of HBsAg for predicting HBsAg clearance was 1.1 Log10 IU/ml. Treatment-naïve HBeAg-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA had favourable outcomes with a high rate of HBsAg clearance and a low risk of fibrosis progression.

Kalium channelrhodopsins effectively inhibit neurons.

The analysis of neural circuits has been revolutionized by optogenetic methods. Light-gated chloride-conducting anion channelrhodopsins (ACRs)-recently emerged as powerful neuron inhibitors. For cells or sub-neuronal compartments with high intracellular chloride concentrations, however, a chloride conductance can have instead an activating effect. The recently discovered light-gated, potassium-conducting, kalium channelrhodopsins (KCRs) might serve as an alternative in these situations, with potentially broad application. As yet, KCRs have not been shown to confer potent inhibitory effects in small genetically tractable animals. Here, we evaluated the utility of KCRs to suppress behavior and inhibit neural activity in Drosophila, Caenorhabditis elegans, and zebrafish. In direct comparisons with ACR1, a KCR1 variant with enhanced plasma-membrane trafficking displayed comparable potency, but with improved properties that include reduced toxicity and superior efficacy in putative high-chloride cells. This comparative analysis of behavioral inhibition between chloride- and potassium-selective silencing tools establishes KCRs as next-generation optogenetic inhibitors for in vivo circuit analysis in behaving animals.

Optimizing ARA and DHA in infant formula: A systematic review of global trends, regional disparities, and considerations for precision nutrition.

In the context of precision nutrition, the addition of ARA and DHA in infant formula needs to consider more factors. This study conducted a comprehensive literature review, including 112 relevant Chinese and English articles, to summarize and analyze the global levels of ARA, DHA, and the ARA/DHA ratio in breast milk. The data were correlated with local aquatic products intake and children's IQ. The results indicated that the average level of DHA in breast milk across regions is lower than that of ARA. Variations in DHA content were identified as a primary factor influencing ARA/DHA ratio fluctuations. Breast milk ARA and DHA levels decrease with prolonged lactation periods but increase over the past 22 years. Correlation analysis revealed a significant positive relationship between aquatic products intake and breast milk DHA levels (r = 0.64, p < 0.05). Breast milk DHA levels also showed a significant positive correlation with children's IQ (r = 0.67, p < 0.01). Stable breast milk ARA content did not exhibit significant correlations with aquatic products intake or children's IQ (r = 0, p > 0.05). Among 22 infant formula products available in China, only 5 had ARA levels within the range of breast milk. Most formula products had higher ARA levels than DHA, resulting in ARA/DHA ratios generally exceeding 1. The temporal and spatial variability in breast milk ARA and DHA levels may lead to diverse health outcomes in infants. Therefore, the addition of ARA and DHA in infant formula should consider this variability, including the molecular forms and positional isomerism of the added ARA and DHA. Additionally, considering the impact of different cognitive development tests and infant's gene expression on formula assessment results, there is a need to establish a more comprehensive infant health assessment system to guide the addition of ARA and DHA in formula.

Microbial fermentation and black soldier fly feeding to enhance maize straw degradation.

This study used an innovative synergistic microbial and insect approach to treat maize straw and kitchen waste substrates, including cyclic microbial fermentation and feeding of black soldier fly larvae (BSFL) using the fermented substrate. Increasing cycle numbers led to significantly increased cellulose, hemicellulose, and lignin degradation rates (DR) in the maize straw, which increased by 68.28%, 81.43% and 99.95%, respectively, compared to those in the blank group without frass addition. Moreover, according to the experimental results, it was revealed that the structure of lignocellulose, the composition and structure of the bacterial community in the BSFL gut and frass changed significantly after the addition of the previous cycle of frass treatment. Moreover, the differences in amplicon sequence variants (ASVs) between the gut and frass further increased. The relative abundances of Enterococcus and Actinobacteria in the gut and Gammaproteobacteria_unclassified and Dysgonomonas in the frass increased significantly, which may play a more positive role in lignocellulose degradation. In conclusion, this study showed that frass fermentation + BSFL feeding to degrade straw is a promising method and that frass fermentation is beneficial for the whole cycle. Furthermore, these findings underscore the beneficial impact of frass fermentation on the entire cycle.

Quantifying Dielectric Material Charge Trapping and De-Trapping Ability Via Ultra-Fast Charge Self-Injection Technique.

Recently, utilizing the air breakdown effect in the charge excitation strategy proves as an efficient charge injection technique to increase the surface charge density of dielectric polymers for triboelectric nanogenerators (TENGs). However, quantitative characterization of the ability of dielectric polymers to trap reverse charges and the effect on the startup time of secondary self-charge excitation (SSCE) are essential for extensive applications. Here, an ultra-fast charge self-injection technique based on a self-charge excitation strategy is proposed, and a standard method to quantify the charge trapping and de-trapping abilities of 23 traditional tribo-materials is introduced. Further, the relationship among the distribution of dielectric intrinsic deep, shallow trap states, and transportation of trapped charges is systematically analyzed in this article. It shows that the de-trapping rate of charges directly determines the reactivation and failure of SSCE. Last, independent of TENG contact efficiency, an ultra-high charge density of 2.67 mC m-2 and an ultra-fast startup time of SSCE are obtained using a 15 µm poly(vinylidene fluoride-trifluoroethylene) film, breaking the historical record for material modification. As a standard for material selection, this work quantifies the charge trapping and de-trapping ability of the triboelectric dielectric series and provides insights for understanding the charge transport in dielectrics.

Association of survival with adjuvant chemotherapy in patients with stage IB gastric cancer: a multicentre, observational, cohort study.

Background: Recurrence following radical resection in patients with stage IB gastric cancer (GC) is not uncommon. However, whether postoperative adjuvant chemotherapy could reduce the risk of recurrence in stage IB GC remains contentious. Methods: We collected data on 2110 consecutive patients with pathologic stage IB (T1N1M0 or T2N0M0) GC who were admitted to 8 hospitals in China from 2009 to 2018. The survival of patients who received adjuvant chemotherapy was compared with that of postoperative observation patients using propensity score matching (PSM). Two survival prediction models were constructed to estimate the predicted net survival gain attributable to adjuvant chemotherapy. Findings: Of the 2110 patients, 1344 received adjuvant chemotherapy and 766 received postoperative observation. Following the 1-to-1 matching, PSM yielded 637 matched pairs. Among matched pairs, adjuvant chemotherapy was not associated with improved survival compared with postoperative observation (OS: hazard ratio [HR], 0.72; 95% CI, 0.52-1.00; DFS: HR, 0.91; 95% CI, 0.64-1.29). Interestingly, in the subgroup analysis, reduced mortality after adjuvant chemotherapy was observed in the subgroups with elevated serum CA19-9 (HR, 0.22; 95% CI, 0.08-0.57; P = 0.001 for multiplicative interaction), positive lymphovascular invasion (HR, 0.32; 95% CI, 0.17-0.62; P < 0.001 for multiplicative interaction), or positive lymph nodes (HR, 0.17; 95% CI, 0.07-0.38; P < 0.001 for multiplicative interaction). The survival prediction models mainly based on variables associated with chemotherapy benefits in the subgroup analysis demonstrated good calibration and discrimination, with relatively high C-indexes. The C-indexes for OS were 0.74 for patients treated with adjuvant chemotherapy and 0.70 for patients treated with postoperative observation. Two nomograms were built from the models that can calculate individualized estimates of expected net survival gain attributable to adjuvant chemotherapy. Interpretation: In this cohort study, pathologic stage IB alone was not associated with survival benefits from adjuvant chemotherapy compared with postoperative observation in patients with early-stage GC. High-risk clinicopathologic features should be considered simultaneously when evaluating patients with stage IB GC for adjuvant chemotherapy. Funding: National Natural Science Foundation of China; the National Key R&D Program of China.

Preoperative assessment of fistula-in-ano using SonoVue enhancement during three-dimensional transperineal ultrasound.

Background: Accurate preoperative evaluation of fistula-in-ano can guide the choice of surgical procedure and may improve healing rates. This prospective study aimed to evaluate the accuracy of conventional 3D transperineal ultrasound (3D-TPUS) compared with SonoVue (SVE)-enhanced 3D-TPUS for the detection and classification of anal fistula. Methods: In this prospective study, 3D-TPUS reconstructions were performed before and after SVE enhancement in 60 patients with fistula-in-ano who intended to undergo surgery at the Department of Anorectal Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University (P. R. China) between January 2021 and October 2021. Accuracies of anal fistula classification, complexity classification, detection of anal fistula branches, and detection of internal opening between 3D-TPUS and SVE 3D-TPUS were compared based on a reference standard-intraoperative findings. Results: This study enrolled 60 patients (mean age, 37.1 ± 11.4 years; mean follow-up, 9 ± 3 months). Intraoperative findings showed that the fistula type was intersphincteric in 23 patients (38.3%), trans-sphincteric in 35 (58.3%; 12 high and 23 low), and suprasphincteric in 2 (3.3%). Moreover, 68 internal openings were found. Compared with the accuracy of 3D-TPUS, that of SVE 3D-TPUS was similar in fistula classification [95.0% (57/60) vs 96.7% (58/60), P = 0.392], but significantly higher in internal opening evaluation [80.9% (55/68) vs 97.1% (66/68), P = 0.001], complexity classification [85.0% (51/60) vs 98.3% (59/60), P = 0.018], and detection of fistula branches [70.4% (19/27) vs 92.6% (25/27), P = 0.031]. Conclusions: SVE 3D-TPUS may be a useful examination for patients with perianal fistulae because of its high accuracy and consistency with intraoperative findings, especially in complex fistula-in-ano and difficult cases.

Liver inflammation activity in patients with autoimmune hepatitis with normal alanine aminotransferase and immunoglobulin G levels.

Background and aims: Normal serum transaminases and immunoglobulin G (IgG) levels are surrogate markers for hepatic histologic disease activity in autoimmune hepatitis (AIH). This study aimed to evaluate liver inflammation in patients with AIH with normal serum alanine aminotransferase (ALT) and IgG levels. Methods: Two hundred and five AIH patients who underwent liver biopsy in four medical centers were included. Logistic regression analysis was used to identify risk factors associated with advanced inflammation. Results: One hundred and thirty-one (63.9 %) AIH patients had advanced liver inflammation, and 108 (52.7 %) patients had advanced liver fibrosis. 60.0 % of patients with normal ALT and 51.7 % of patients with normal ALT and IgG had advanced inflammation. However, 76.7 % and 35.0 % of patients with or without advanced fibrosis with normal ALT had advanced inflammation, while the corresponding proportions of advanced inflammation were 78.6 % and 26.7 % in patients with normal ALT and IgG, respectively. Moreover, 81.0 % and 44.8 % of patients with and without cirrhosis with normal ALT had advanced inflammation, while the corresponding proportions were 83.3 % and 29.4 % in patients with normal ALT and IgG, respectively. Red cell distribution width (OR = 1.325, 95%CI 1.045-1.681, P = 0.020) and PT (OR = 1.514, 95%CI 1.138-2.014, P = 0.004) were independent factors associated with advanced inflammation. Conclusions: High proportion of advanced inflammation was found in AIH patients with normal ALT and IgG levels despite without advanced fibrosis. Although using non-invasive methods may contribute to rule out liver fibrosis in AIH patients with normal ALT and IgG levels, liver biopsy is encouraged to assess liver inflammation.

Naringin-induced M2 macrophage polarization facilitates osteogenesis of BMSCs and improves cranial bone defect healing in rat.

Osteoimmunology has uncovered the critical role of the immune microenvironment in the bone healing process, with macrophages playing a central part in generating immune responses via chemokine production. Naringin, a flavanone glycoside extracted from various plants, has been shown to promote osteoblast differentiation, thereby enhancing bone formation and mitigating osteoporosis progression. Current research on the osteogenic mechanism primarily focuses on the direct impact of naringin on mesenchymal stem cells, while its indirect immunoregulatory effects remain elusive. In this study, we investigated the bone defect-enhancing effects of varying naringin concentrations in vivo using a cranial bone defect model in Sprague-Dawley rats. We assessed the osteoimmune modulation capacity of naringin by exposing lipopolysaccharide (LPS)-induced RAW 264.7 macrophages to different doses of naringin. To further elucidate the underlying osteogenic enhancement mechanism, Bone Marrow Stromal Cells (BMSCs) derived from mice were treated with conditioned media from naringin-treated macrophages. Our findings indicated that naringin promotes M2 phenotype polarization in macrophages, as evidenced by the downregulation of pro-inflammatory cytokines Inducible Nitric Oxide Synthase (iNOS), interleukin (IL)-1ß, and Tumor Necrosis Factor (TNF)-α, and the upregulation of anti-inflammatory cytokine Transforming growth factor (TGF)-ß. Transcriptome analysis revealed that differentially expressed genes were significantly enriched in osteoblast differentiation and anti-inflammatory response pathways in naringin-pretreated macrophages, with the cytokines signaling pathway being upregulated. The conditioned media from naringin-treated macrophages stimulated the expression of osteogenic-related genes Alkaline phosphatase (Alp), osteocalcin (Ocn), osteopontin (Opn), and Runt-related transcription factor (Runx) 2, as well as protein expression in BMSCs. In conclusion, naringin alleviates macrophage inflammation by promoting M2 phenotype polarization, which in turn enhances the osteogenic differentiation of BMSCs, contributing to its bone healing effects in vivo. These results suggest that naringin holds significant potential for improving bone defect healing through osteoimmune modulation.