Serum ApoB/ApoA1 ratio in patients with CHB and the occurrence of HBV related cirrhosis and HBV related hepatocellular carcinoma.

Clinical research has suggested that chronic HBV infection exerts a certain effect on the occurrence of cardiovascular disease by regulating cholesterol metabolism in liver cells. High serum apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio plays a certain role in the above regulation, and it serves as a risk factor for cardiovascular disease. However, whether the ApoB/ApoA1 ratio is correlated with chronic HBV infection and its disease progression remains unclear. In accordance with the inclusion and exclusion criteria, all 378 participants administrated at Renmin Hospital of Wuhan University from March 2021 to March 2022, fell into Healthy Control (HC) group (50 participants), Hepatocellular carcinoma (HCC) group (107 patients), liver cirrhosis (LC) group (64 patients), chronic hepatitis B (CHB) group (62 patients), chronic hepatitis C (CHC) group (46 patients) and Hepatitis E Virus (HEV) group (49 patients). Serum ApoA1 and ApoB concentrations were measured at admission, and the ApoB/ApoA1 ratio was determined. The levels of laboratory parameters in the respective group were compared and ApoB/ApoA1 ratios in HCC patients and LC patients with different severity were further analyzed. ROC curves were plotted to analyze the early diagnostic ability of ApoB/ApoA1 ratio for HBV-associated HCC. Logistic regression and restricted cubic spline analysis were used to explore the correlation between ApoB/ApoA1 ratio and LC and HCC risk. A comparison was drawn in terms of ApoB/ApoA1 ratio between the groups, and the result was expressed in descending sequence: HEV group > CHB group > LC group > HCC group > CHC group > HC group, early-stage HCC < middle-stage HCC < advanced-stage HCC, Class A LC < Class B LC < Class C LC. Serum ApoB/ApoA1 ratio combined diagnosis with AFP exhibited the capability of increasing the detection efficacy and specificity of AFP for HCC and AFP-negative HCC. The incidence of LC and HCC in the respective logistic regression model showed a negative correlation with the serum ApoB/ApoA1 ratio in CHB patients (P < 0.05). After all confounding factors covered in this study were regulated, the result of the restricted cubic spline analysis suggested that in a certain range, serum ApoB/ApoA1 ratio showed an inverse correlation with the prevalence of LC or HCC in CHB patients. Serum ApoB/ApoA1 ratio in CHB patients may be conducive to identifying high-risk patients for HCC or LC, such that LC and HCC can be early diagnosed and treated.

Diagnostic and Prognostic Value of C1q in Sepsis-Induced Coagulopathy.

Early identification of biomarkers that can predict the onset of sepsis-induced coagulopathy (SIC) in septic patients is clinically important. This study endeavors to examine the diagnostic and prognostic utility of serum C1q in the context of SIC. Clinical data from 279 patients diagnosed with sepsis at the Departments of Intensive Care, Respiratory Intensive Care, and Infectious Diseases at the Renmin Hospital of Wuhan University were gathered spanning from January 2022 to January 2024. These patients were categorized into two groups: the SIC group comprising 108 cases and the non-SIC group consisting of 171 cases, based on the presence of SIC. Within the SIC group, patients were further subdivided into a survival group (43 cases) and non-survival group (65 cases). The concentration of serum C1q in the SIC group was significantly lower than that in the non-SIC group. Furthermore, A significant correlation was observed between serum C1q levels and both SIC score and coagulation indices. C1q demonstrated superior diagnostic and prognostic performance for SIC patients, as indicated by a higher area under the curve (AUC). Notably, when combined with CRP, PCT, and SOFA score, C1q displayed the most robust diagnostic efficacy for SIC. Moreover, the combination of C1q with the SOFA score heightened predictive value concerning the 28-day mortality of SIC patients.

Analysis of Serum Anti-HBs Levels and HBsAg/HBeAg Markers in Children and Adolescents: A Cross-Sectional Study.

Hepatitis B virus (HBV) is a global public health concern, and China continues to face a high burden of HBV cases. Vaccination plays a critical role in controlling and eradicating HBV. However, studies have shown that some individuals may experience waning immunity over time, highlighting the importance of enhanced immunization strategies. This study aimed to investigate the relationship between age, gender, and anti-HBs antibody levels, as well as the prevalence of serum hepatitis B surface antigen (HBsAg)/HBV e antigen (HBeAg) positivity. This retrospective study included 43,609 pediatric patients who visited the outpatient department between January 2013 and December 2022. Serum biomarkers (HBsAg, anti-HBs, HBeAg, anti-HBe, and anti-HBc) were measured using Roche Cobas 8000. There is a significant difference in anti-HBs titer between genders and across different age groups (p < 0.05). The serological markers HBsAg/HBeAg exhibited the highest positivity rate in the age group of 15-18 years. The findings demonstrate a gradual decrease in anti-HBs levels following HBV vaccination. The prevalence of serum markers HBsAg/HBeAg is higher among adolescents aged 15-18 years, which should be a matter of concern and attention.

Analysis of Key Genes and miRNA-mRNA Networks Associated with Glucocorticoids Treatment in Chronic Obstructive Pulmonary Disease.

Background: Some patients with chronic obstructive pulmonary disease (COPD) benefit from glucocorticoid (GC) treatment, but its mechanism is unclear. Objective: With the help of the Gene Expression Omnibus (GEO) database, the key genes and miRNA-mRNA related to the treatment of COPD by GCs were discussed, and the potential mechanism was explained. Methods: The miRNA microarray dataset (GSE76774) and mRNA microarray dataset (GSE36221) were downloaded, and differential expression analysis were performed. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the differentially expressed genes (DEGs). The protein interaction network of the DEGs in the regulatory network was constructed with the STRING database, and the key genes were screened through Cytoscape. Potential downstream target genes regulated by differentially expressed miRNAs (DEMs) were predicted by the miRWalk3.0 database, and miRNA-mRNA regulatory networks were constructed. Finally, some research results were validated. Results: ① Four DEMs and 83 DEGs were screened; ② GO and KEGG enrichment analysis mainly focused on the PI3K/Akt signalling pathway, ECM receptor interaction, etc.; ③ CD2, SLAMF7, etc. may be the key targets of GC in the treatment of COPD; ④ 18 intersection genes were predicted by the mirwalk 3.0 database, and 9 pairs of miRNA-mRNA regulatory networks were identified; ⑤ The expression of miR-320d-2 and TFCP2L1 were upregulated by dexamethasone in the COPD cell model, while the expression of miR-181a-2-3p and SLAMF7 were downregulated. Conclusion: In COPD, GC may mediate the expression of the PI3K/Akt signalling pathway through miR-181a-2-3p, miR-320d-2, miR-650, and miR-155-5p, targeting its downstream signal factors. The research results provide new ideas for RNA therapy strategies of COPD, and also lay a foundation for further research.

Application of a nomogram from coagulation-related biomarkers and C1q and total bile acids in distinguishing advanced and early-stage lung cancer.

BACKGROUND: This study aimed to establish a nomogram to distinguish advanced- and early-stage lung cancer based on coagulation-related biomarkers and liver-related biomarkers. METHODS: A total of 306 patients with lung cancer and 172 patients with benign pulmonary disease were enrolled. Subgroup analyses based on histologic type, clinical stage, and neoplasm metastasis status were carried out and multivariable logistic regression analysis was applied. Furthermore, a nomogram model was developed and validated with bootstrap resampling. RESULTS: The concentrations of complement C1q, fibrinogen, and D-dimers, fibronectin, inorganic phosphate, and prealbumin were significantly changed in lung cancer patients compared to benign pulmonary disease patients. Multiple regression analysis based on subgroup analysis of clinical stage showed that compared with early-stage lung cancer, female (P < 0.001), asymptomatic admission (P = 0.001), and total bile acids (P = 0.011) were negatively related to advanced lung cancer, while C1q (P = 0.038), fibrinogen (P < 0.001), and D-dimers (P = 0.001) were positively related. A nomogram model based on gender, symptom, and the levels of total bile acids, C1q, fibrinogen, and D-dimers was constructed for distinguishing advanced lung cancer and early-stage lung cancer, with an area under the receiver operating characteristic curve of 0.919. The calibration curve for this nomogram revealed good predictive accuracy (P-Hosmer-Lemeshow = 0.697) between the predicted probability and the actual probability. CONCLUSIONS: We developed a nomogram based on gender, symptom, and the levels of fibrinogen, D-dimers, total bile acids, and C1q that can individually distinguish early- and advanced-stage lung cancer.

Analysis of the diagnostic and prognostic value of serum PAD2 in patients with sepsis in the intensive care unit.

BACKGROUND: Sepsis is a common disease in the intensive care unit (ICU). In recent years, the incidence rate and mortality rate remain high. Early diagnosis of sepsis is crucial for treatment and can effectively reduce mortality. So far, the ability of serum peptidylarginine deaminase 2 (PAD2) in the diagnosis and prognosis of sepsis patients is still unclear. We conducted this study to reveal the clinical value of PAD2 as a biomarker for sepsis patients. METHODS: A prospective study method was used to select 207 patients in the ICU of Renmin Hospital of Wuhan University from May 2022 to May 2023. They were divided into the sepsis group (n = 135) and control group (n = 72), and data were collected within 24 h of hospitalization. Sepsis patients were divided into a survival group (n = 80) and a non-survival group (n = 55) based on their 28-day survival status. Using statistical methods to evaluate the diagnostic and prognostic value of PAD2 in sepsis. RESULTS: The serum PAD2 concentrations in the sepsis group were significantly higher than in the control group (median 16.70 vs 35.32 ng/ml, P < 0.001). Multivariate logistic regression analysis showed that the Quick Sequential Organ Failure Assessment (qSOFA), C-reactive protein (CRP), procalcitonin (PCT), and PAD2 were independent risk factors for sepsis. The Receiver operating characteristic (ROC) curve showed that the combined diagnostic value of qSOFA, CRP, PCT, and PAD2 was the highest. The serum PAD2 concentrations in the non-survival group of patients with sepsis were significantly higher than those in the survival group (median 29.26 vs 50.08 ng/ml, P < 0.05). The COX regression analysis showed that PAD2, sequential organ failure score Assessment (SOFA) score, and Acute Physiology and Chronic Health Evaluation (APACHE II) score were independent factors affecting the prognosis of sepsis patients. The ROC analysis showed that the combined prognostic value of PAD2, SOFA, and APACHE II scores was significantly higher than any single indicator. The Kaplan-Meier survival analysis showed that patients with PAD2 ≤ 48.62 ng/ml had a better prognosis. CONCLUSION: The significant increase in serum PAD2 concentrations in patients is an independent risk factor affecting the occurrence of sepsis and 28-day mortality. The combination of PAD2 and other indicators can further improve the diagnostic and prognostic value for ICU sepsis patients.

Changes of Serum Pyruvate Kinase M2 Level in Patients with Sepsis and Its Clinical Value.

Purpose: The glucose metabolic reprogramming is an important pathological mechanism in sepsis, which involves a series of enzymes including Pyruvate kinase M2 (PKM2). The purpose of this study is to explore the diagnostic and prognostic value of serum PKM2 in sepsis patients. Patients and Methods: This study recruited 143 sepsis patients, 91 non-sepsis patients, and 65 physical examiners, divided into sepsis group, non-sepsis group, and control group. Measure the serum PKM2 concentration of subjects, collect and analyze clinical and laboratory indicators of all subjects. Independent risk factors were selected by Logistic regression analysis. The area under curve (AUC) was calculated by plotting the receiver operating characteristic (ROC) curve to determine the diagnostic and prognostic value of biomarkers. Results: Compared with non-sepsis and control groups, the serum PKM2 levels in the sepsis group were significantly increased (both P<0.001). PKM2 was an independent risk factor for sepsis and had the best diagnostic efficacy when combined with procalcitonin, with the AUC value of 0.9352. Patients with high levels of PKM2 were more likely to experience organ damage and had a higher incidence of septic shock. On the 1st and 3rd days of admission, the serum PKM2 levels in the septic shock group were higher than those in the sepsis group (both P<0.05), with AUC values of 0.7296 and 0.6247, respectively. On the 3rd and 7th days of admission, the serum PKM2 levels in the non-survival group were significantly higher than those in the survival group (both P<0.001), with AUC values of 0.7033 and 0.8732, respectively. Conclusion: The serum PKM2 levels in sepsis patients are significantly increased and correlated with disease severity and clinical outcomes. PKM2 may be a new diagnostic and prognostic biomarker for sepsis.

Prevalence of acute infection in adults with asthma exacerbation: A systematic review and meta-analysis.

BACKGROUND: Acute respiratory infections are a major trigger of asthma exacerbations. This study sought to estimate the overall proportion of viruses, atypical pathogens, and bacteria detected in adults with asthma exacerbations. METHODS: PubMed, EMBASE, and Cochrane Library databases and all related studies from the reviews and references were searched from inception to February 13, 2020. Two authors independently performed study selection, data extraction, as well as quality evaluation. Subsequently, meta-analysis, between-study heterogeneity, and publication bias assessment were conducted on RStudio. RESULTS: Forty-three eligible studies comprising 3511 adults were included, of which 21 publications mentioned multiple infections during acute asthma attacks. Meta-analysis showed an acute infection prevalence of 40.19% (95% confidence interval [CI] 34.53%-45.99%). Viruses, atypical pathogens, and bacteria were detected in 38.76% (95% CI 32.02%-45.71%), 8.29% (95% CI 2.64%-16.27%), and 7.05% (95% CI 3.34%-11.81%) of asthmatics during exacerbations, respectively. Rhinovirus infections are always the dominant trigger for exacerbations with a proportion of 20.02% (95% CI 14.84%-25.73%). Substantial heterogeneity across studies (Cochran Q test: 479.43, P < 0.0001, I2 = 91.2%) was explained by subgroup analysis, indicating that year, region, population, respiratory secretion, detection method, pathogen, and study quality were all influencing factors. CONCLUSION: This meta-analysis provided the first quantitative epidemiological data for adults, and in the future, more research and health-care supports are necessary in this area.

T2T-YAO: A Telomere-to-telomere Assembled Diploid Reference Genome for Han Chinese.

Since its initial release in 2001, the human reference genome has undergone continuous improvement in quality, and the recently released telomere-to-telomere (T2T) version - T2T-CHM13 - reaches its highest level of continuity and accuracy after 20 years of effort by working on a simplified, nearly homozygous genome of a hydatidiform mole cell line. Here, to provide an authentic complete diploid human genome reference for the Han Chinese, the largest population in the world, we assembled the genome of a male Han Chinese individual, T2T-YAO, which includes T2T assemblies of all the 22 + X + M and 22 + Y chromosomes in both haploid. The quality of T2T-YAO is much better than all currently available diploid assemblies, and its haploid version, T2T-YAO-hp, generated by selecting the better assembly for each autosome, reaches the top quality of fewer than one error per 29.5 Mb, even higher than that of T2T-CHM13. Derived from an individual living in the aboriginal region of the Han population, T2T-YAO shows clear ancestry and potential genetic continuity from the ancient ancestors. Each haplotype of T2T-YAO possesses ∼ 330-Mb exclusive sequences, ∼ 3100 unique genes, and tens of thousands of nucleotide and structural variations as compared with CHM13, highlighting the necessity of a population-stratified reference genome. The construction of T2T-YAO, a truly accurate and authentic representative of the Chinese population, would enable precise delineation of genomic variations and advance our understandings in the hereditability of diseases and phenotypes, especially within the context of the unique variations of the Chinese population.

IL-30 protects against sepsis-induced myocardial dysfunction by inhibiting pro-inflammatory macrophage polarization and pyroptosis.

Cardiac dysfunction is a well-recognized complication of sepsis and seriously affects the prognosis of sepsis patients. IL-30 has been reported to exert anti-inflammatory effects in various diseases. However, the role of IL-30 in sepsis-induced myocardial dysfunction (SIMD) remains unclear. Here, we explored the protective role of IL-30 in cecum ligation and puncture (CLP)-induced SIMD mice. IL-30 expression increased in the cardiac tissues of septic mice and was mainly derived from macrophages. IL-30 deletion or neutralization aggravated sepsis-induced cardiac dysfunction and injury, whereas recombinant IL-30 treatment significantly ameliorated it. Mechanistically, IL-30 deficiency exerts pro-inflammatory effects by promoting Ly6Chigh macrophage polarization and pyroptosis. Inhibiting NLRP3 with MCC950 significantly reversed cardiac dysfunction, macrophage polarization and pyroptosis aggravated by IL-30 deficiency. Recombinant IL-30 inhibited pro-inflammatory macrophage polarization and pyroptosis in vivo and vitro. Taken together, these results suggest that IL-30 protects against SIMD by inhibiting pro-inflammatory macrophage polarization and pyroptosis.

Kilogram-scale fabrication of TiO2 nanoparticles modified with carbon dots with enhanced visible-light photocatalytic activity.

Incorrect discharge of dye wastewater will cause environment pollution and be very harmful to human health. Visible-light photocatalysis over large-scale synthesized semiconductor materials can become one of the feasible solutions for the practical application of purifying dye wastewater. As a new candidate, carbon dots (CDs) with unique fluorescence were fabricated on a tens of grams scale and then further applied to the kilogram-scale synthesis of a CDs/TiO2 composite by one-step heat treatment. Compared with single TiO2 nanoparticles (NPs), the CDs/TiO2 composite with a large specific surface area exhibits enhanced photo-degradation performance for methyl orange (MO). This phenomenon can be attributed to the loading of CDs in the TiO2 NPs, which is conducive to broadening the light absorption spectrum and improving absorption intensity, narrowing the band gap, charge carrier trapping, up-converting properties, and charge separation. The kilogram-scale synthesis of the CDs/TiO2 photocatalyst does not affect the morphology, structure, optical properties and photocatalytic performance of the composite, which opens up a new avenue to construct elaborate heterostructures for enhanced photocatalytic performance using visible light as the light source.

ZnO Nanoparticles Modified by Carbon Quantum Dots for the Photocatalytic Removal of Synthetic Pigment Pollutants.

Synthetic pigment pollutants caused by the rapid development of the modern food industry have become a serious threat to people's health and quality of life. Environmentally friendly ZnO-based photocatalytic degradation exhibits satisfactory efficiency, but some shortcomings of large band gap and rapid charge recombination reduce the removal of synthetic pigment pollutants. Here, carbon quantum dots (CQDs) with unique up-conversion luminescence were applied to decorate ZnO nanoparticles to effectively construct the CQDs/ZnO composites via a facile and efficient route. The ZnO nanoparticles with a spherical-like shape obtained from a zinc-based metal organic framework (zeolitic imidazolate framework-8, ZIF-8) were coated by uniformly dispersive quantum dots. Compared with single ZnO particles, the obtained CQDs/ZnO composites exhibit enhanced light absorption capacity, decreased photoluminescence (PL) intensity, and improved visible-light degradation for rhodamine B (RhB) with the large apparent rate constant (k app). The largest k app value in the CQDs/ZnO composite obtained from 75 mg of ZnO nanoparticles and 12.5 mL of the CQDs solution (∼1 mg·mL-1) was 2.6 times that in ZnO nanoparticles. This phenomenon may be attributed to the introduction of CQDs, leading to the narrowed band gap, an extended lifetime, and the charge separation. This work provides an economical and clean strategy to design visible-light-responsive ZnO-based photocatalysts, which is expected to be used for the removal of synthetic pigment pollutants in food industry.

Scutellaria baicalensis in the Treatment of Hepatocellular Carcinoma: Network Pharmacology Analysis and Experimental Validation.

Objective: The aim of the study was to use a network pharmacological method and experimental validation to examine the mechanism of Scutellaria baicalensis (SB) against hepatocellular carcinoma (HCC). Methods: The traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and GeneCards were used for screening of targets of SB for the treatment of HCC. Cytoscape (3.7.2) software was used to construct the "drug-compound-intersection target interaction" interaction network. The STING database was used to analyze the interactions of the previous intersecting targets. The results were visualized and processed by performing GO (Gene Ontology) enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) signaling pathway enrichment analysis at the target sites. The core targets were docked with the active components by AutoDockTools-1.5.6 software. We used cellular experiments to validate the bioinformatics predictions. Results: A total of 92 chemical components and 3258 disease targets including 53 intersecting targets were discovered. The results showed that wogonin and baicalein, the main chemical components of SB, could inhibit the viability and proliferation of hepatocellular carcinoma cells, promote apoptosis through the mitochondrial apoptotic pathway, and effectively act on AKT1, RELA, and JUN targets. Conclusion: SB has multiple components and targets in the treatment of HCC, providing possible potential targets for the treatment of HCC and providing a basis for further research.

Prognostic and immunological role of alpha-L-fucosidase 2 (FUCA2) in hepatocellular carcinoma.

Background: This study investigated the prognostic and immunological significance of alpha-L-fucosidase 2 (FUCA2) in hepatocellular cancer (HCC). Methods: The expression of FUCA2 and its clinical and prognostic values were explored across several databases, namely the University of Alabama Cancer Database, The Cancer Genome Atlas, Gene Expression Profiling Interactive Analysis, and the Human Protein Atlas. The prognostic relevance of FUCA2 was investigated using Kaplan-Meier curves, nomograms, and Cox analysis. The "limma" package in R was used to identify differentially expressed genes between high and low FUCA2 expression. A protein interaction network was established using the Search Tool for the Retrieval of Interacting Genes (STRING), whereas hub genes and clustering modules were identified using Cytoscape. "clusterProfiler", an R package, was used to examine the potential function of FUCA2. Using gene set enrichment analysis, signaling pathways associated with FUCA2 expression were identified. Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT), Tumor Immune Estimation Resource (TIMER) 2.0, and Tumor and Immune System Interaction Database (TISIDB) were used to examine immune infiltration and FUCA2 in HCC. Results: Many datasets indicated that FUCA2 expression is higher in HCC, and that this is related to age and overall survival (OS). With the cutoff value of 50% as the dividing threshold, the patients were divided into a high-FUCA2 expression group (n=167) and a low-FUCA2 expression group (n=168). High levels of FUCA2 expression coincided with decreased OS. FUCA2 expression in HCC was associated with immune infiltrates. The functional mechanisms of FUCA2 depend on signal release, extracellular matrix collagen, and neuroactive ligands and receptors. Conclusions: In HCC, increased FUCA2 expression is associated with a poor prognosis and immune infiltration. FUCA2 may serve as an immunological and predictive biomarker for HCC.

Duration of SARS-CoV-2 Serum-Neutralizing Antibodies Against SARS-CoV-2 Dependent on the Individual.

We investigated the persistence of SARS-CoV-2-specific neutralizing antibodies in serum (CoV-2-SNAb) against the "WH-Human 1" coronavirus in 57 convalescent persons from January 2020 to January 2021. The CoV-2-SNAb response against authentic "WH-Human 1" showed a significant (p < 0.01) neutralizing high effect (≥95%) in the following manner: by 94.7% neutralization for up to 6 months, by 73.1% for up to 8 months, and by 31.7% for up to 10 months in correlation with a significant decrease in the concentration of the virus determined by SARS-CoV-2 spike protein extracellular domain and spike-receptor-binding domain (S-RBD). There was neutralizing effect (<95%) when the S-RBD optical density (OD) value was more than 1.0, showing a suitable threshold of S-RBD = 1.0 (antibody-tittering, OD). However, in some convalescent persons, no neutralizing effect (<95%) was observed although the SARS-CoV-2-specific neutralizing antibodies were bound to the S-RBD (OD >1.0). The neutralization of the virus in these cases may not involve S-RBD, but rather B- and T cell memory responses in overall immunity, using the threshold value (OD = 1.0) of S-RBD as a simple and effective method to determine the neutralization effect of the antibody efficacy and use of vaccination in combination with a standard pseudovirus neutralizing assay. We suggest that convalescent persons should contact their physicians 6-month postinfection to test the function of their serum neutralizing antibodies and determine whether administering a SARS-CoV-2 vaccine is necessary to prevent the development of severe illness in the future.

Fu-Huang ointment ameliorates impaired wound healing associated with diabetes through PI3K-AKT signalling pathway activation.

A diabetic ulcer (DU) is a dreaded and resistant complication of diabetes mellitus with high morbidity. Fu-Huang ointment (FH ointment) is a proven recipe for treating chronic refractory wounds; however, its molecular mechanisms of action are unclear. In this study, we identified 154 bioactive ingredients and their 1127 target genes in FH ointment through the public database. The intersection of these target genes with 151 disease-related targets in DUs resulted in 64 overlapping genes. Overlapping genes were identified in the PPI network and enrichment analyses. The PPI network identified 12 core target genes, whereas Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that upregulation of the PI3K/Akt signalling pathway was involved in the role of FH ointment in treating diabetic wounds. Molecular docking showed that 22 active compounds in FH ointment could enter the active pocket of PIK3CA. Molecular dynamics was used to prove the binding stability of the active ingredients and protein targets. We found that PIK3CA/Isobutyryl shikonin and PIK3CA/Isovaleryl shikonin combinations had strong binding energies. An in vivo experiment was conducted on PIK3CA, which was the most significant gene.This study comprehensively elucidated the active compounds, potential targets, and molecular mechanism of FH ointment application in treating DUs, and believed that PIK3CA is a promising target for accelerated healing.

miR-1306-3p directly activates P2X3 receptors in primary sensory neurons to induce visceral pain in rats.

ABSTRACT: Mounting evidence indicates that microRNAs (miRNAs) play critical roles in various pathophysiological conditions and diseases, but the physiological roles of extracellular miRNAs on the disease-related ion channels remain largely unknown. Here, we showed that miR-1306-3p evoked action potentials and induced inward currents of the acutely isolated rat dorsal root ganglion (DRG) neurons. The miR-1306-3p-induced effects were significantly inhibited by A317491, a potent inhibitor of the P2X3 receptor (P2X3R), or disappeared after the knockdown of P2X3Rs in DRG neurons. We further identified R180, K315, and R52 as the miR-1306-3p interaction sites on the extracellular domain of P2X3Rs, which were distinct from the orthosteric ATP-binding sites. Intrathecal injection of miR-1306-3p produced visceral pain but not somatic pain in normal control rats. Conversely, intrathecal application of a miR-1306-3p antagomir and A317491 significantly alleviated visceral pain in a rat model of chronic visceral pain. Together, our findings suggest that miR-1306-3p might function as an endogenous ligand to activate P2X3Rs, eventually leading to chronic visceral pain.

Evaluation of Serum FGL1 as Diagnostic Markers for HBV-Related Hepatocellular Carcinoma.

OBJECTIVE: Based on the current difficulties in early diagnosis of HBV-related hepatocellular carcinoma (HBV-HCC), we assessed the values of preoperative serum fibrinogen-like protein 1 (FGL1) by itself and in combination with alpha-fetoprotein (AFP) for the diagnosis of HBV-HCC. METHODS: We used ELISA and chemiluminescence assays to detect the serum levels of FGL1 and AFP, respectively. RESULTS: Serum FGL1 level in the HBV-HCC group was significantly higher than in the chronic HBV (CHBV) group, the liver cirrhosis (LC) group, and the healthy control (HC) group. Serum FGL1 had an outstanding performance in distinguishing AFP-negative HBV-HCC from different control conditions. In the patients with AFP-negative HBV-HCC, the sensitivity of serum FGL1 was high. Moreover, serum FGL1 had a stronger performance than AFP in distinguishing early-stage HBV-HCC. CONCLUSIONS: Serum FGL1 is significantly elevated among patients with HBV-HCC, including those with negative AFP and with disease at an early stage. Hence, serum FGL1 may serve as a potential diagnostic marker in the early diagnosis of HBV-HCC.

The diagnostic value of interleukin 35 as a septic biomarker: A meta-analysis.

Background: There is growing evidence that interleukin 35 (IL-35) represents a potential diagnostic biomarker for sepsis. The purpose of this meta-analysis was to evaluate the overall diagnostic accuracy of IL-35 in sepsis. Materials and methods: From October 1998 to May 2022, set retrieval standards were used to search literature Databases. Each included study was assessed diagnostic accuracy study quality assessment tool. Two researchers independently extracted the data and research features. If there are differences, the issue will be resolved by mutual agreement. Meta-disc and Stata software were utilized to calculate combined sensitivity, specificity, and summary diagnostic odds ratio (SDOR), I 2, or Cochrane Q in order to detection for heterogeneity, and meta-regression was performed to figure out the cause of heterogeneity. Utilizing funnel plots, we tested for publication bias. Results: In this meta-analysis, eight publications were included. The combined sensitivity, specificity, and DOR were 0.87 (95% CI, 0.77-0.93), 0.73 (95% CI, 0.60-0.83), and 18.26 (95% CI, 9.70-34.37), respectively. In addition, 0.88 (95% CI, 0.84-0.90) was the area under the summary receiver operating characteristic curve. In the heterogeneity analysis, the sensitivity of comprehensive I 2 statistic was 84.38, and the specificity was 87.82. Deeks' funnel plot showed no publication bias in this meta-analysis (P = 0.17). A meta-analysis revealed that IL-35 has a modest sensitivity (AUC = 0.88) for diagnosing sepsis. We also compared the diagnostic accuracy of IL-35 and procalcitonin (PCT), and our results showed that the diagnostic accuracy parameters for IL-35 were significantly higher than those for PCT. Conclusion: Interleukin 35 is a valuable biomarker for the early detection of sepsis. However, the data should be combined with clinical symptoms, signs, and laboratory and microbiological findings.

Overexpression of GRK6 alleviates chronic visceral hypersensitivity through downregulation of P2Y6 receptors in anterior cingulate cortex of rats with prenatal maternal stress.

AIMS: Visceral hypersensitivity is a major clinic symptom in patients with irritable bowel syndrome (IBS). Anterior cingulate cortex (ACC) is involved in processing the information of pain. Both G protein-coupled receptor kinase 6 (GRK6) and P2Y purinoceptor 6 (P2Y6) are associated with neuroinflammation and pathological pain. The aim of this study was to investigate the interaction between GRK6 and P2Y6 in ACC in the development of visceral hypersensitivity of adult offspring rats with prenatal maternal stress (PMS). METHODS: Visceral hypersensitivity was quantified by abdominal withdrawal reflex threshold to colorectal distension (CRD). The expression and cellular distribution of GRK6 and P2Y6 were determined by Western blotting, qPCR, and fluorescence immunohistochemistry. Co-immunoprecipitation was used to evaluate the interaction between GRK6 and P2Y6. RESULTS: The mRNA and protein levels of GRK6 were significantly decreased in ACC of PMS rats. The injection of GRK6 overexpression virus significantly attenuated visceral hypersensitivity of PMS rats. P2Y6's mRNA level, protein level, and ratio of membrane protein over total protein expression was markedly increased in PMS rats. P2Y6 antagonist MRS2578 microinjection reversed visceral hypersensitivity of PMS rats. GRK6 overexpression significantly reduced P2Y6's expression in membrane proteins and P2Y6's ratio of membrane protein over total protein expression. CONCLUSIONS: These results indicate that decreased GRK6 leads to the accumulation of P2Y6 at neuron membrane in ACC, thereby contributing to visceral hypersensitivity of PMS rats.