Efferocytosis refers to the process of phagocytes engulfing and clearing the cells after programmed cell death. In recent years, an increasing number of studies have shown that the mechanisms of efferocytosis are closely related to drug-induced liver injury, hepatic ischemia-reperfusion injury, viral hepatitis, cholestatic liver diseases, metabolic-associated fatty liver disease, alcoholic liver disease, and other liver disorders. This review summarized the research progress on the role of efferocytosis in liver diseases, with the hope of providing new targets for the prevention and treatment of liver diseases.
Humans ; Liver Diseases/metabolism* ; Animals ; Phagocytosis/physiology* ; Phagocytes ; Efferocytosis

Objective Based on 25 indicators including immune factors, cell count classification, and smear results of the knee joint fluid, machine learning models were established to distinguish between osteoarthritis (OA) and rheumatoid arthritis (RA). Methods 100 OA and 40 RA patients scheduled for total knee arthroplasty were enrolled respectively. Each patient's knee joint fluid was collected preoperatively. Nucleated cells were counted and classified. The expression levels of immune factors, including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, IL-8, IL-15, matrix metalloproteinase 3 (MMP3), MMP9, MMP13, rheumatoid factor (RF), serum amyloid A (SAA), C-reactive protein (CRP), and others were measured. Smears and microscopic classification of all the immune factors were performed. Independent influencing factors for OA or RA were identified using univariate binary logistic regression, Lasso regression, and multivariate binary logistic regression. Based on the independent influencing factors, three machine learning models were constructed which are logistic regression, random forest, and support vector machine. Receiver operating characteristic curve (ROC), calibration curve and decision curve analysis (DCA) were used to evaluate and compare the models. Results A total of 5 indicators in the knee joint fluid were screened out to distinguish OA and RA, which were IL-1β(odds ratio(OR)=10.512, 95× confidence interval (95×CI) was 1.048-105.42, P=0.045), IL-6 (OR=1.007, 95×CI was 1.001-1.014, P=0.022), MMP9 (OR=3.202, 95×CI was 1.235-8.305, P=0.017), MMP13 (OR=1.002, 95× CI was 1-1.004, P=0.049), and RF (OR=1.091, 95×CI was 1.01-1.179, P=0.026). According to the results of ROC, calibration curve and DCA, the accuracy (0.979), sensitivity (0.98) and area under the curve (AUC, 0.996, 95×CI was 0.991-1) of the random forest model were the highest. It has good validity and feasibility, and its distinguishing ability is better than the other two models. Conclusion The machine learning model based on immune factors in the knee joint fluid holds significant value in distinguishing OA and RA. It provides an important reference for the clinical early differential diagnosis, prevention and treatment of OA and RA.
Humans ; Arthritis, Rheumatoid/metabolism* ; Machine Learning ; Male ; Female ; Middle Aged ; Aged ; Synovial Fluid/immunology* ; Osteoarthritis, Knee/metabolism* ; Knee Joint/metabolism* ; ROC Curve ; Diagnosis, Differential

Objective To evaluate the clinical efficacy of a novel sleep-aid decoction in treating elderly insomnia patients with different traditional Chinese medicine (TCM) constitutional types, and its effects on neurotransmitter and inflammatory factor levels. Methods A total of 200 patients with four different TCM constitutions-peaceful, Qi-deficient, Yin-deficient, and Yang-deficient-were recruited. Peripheral blood neurotransmitter and inflammatory factor levels were measured for variations among insomnia patients across different constitutions. These patients were treated using the novel sleep-aid decoction, the effects of which were evaluated based on changes in neurotransmitters and inflammatory factors. Results Compared to the peaceful constitution group, insomnia patients with Qi-deficient, Yin-deficient, and Yang-deficient constitutions exhibited significantly elevated baseline levels of neurotransmitters (5-HT, GABA) and inflammatory factors (IL-6, TNF-α, IL-1β, CRP). Following the treatment, the Qi-deficient and Yin-deficient groups showed a marked increase in 5-HT levels, restored balance of Glu, GABA, and melatonin, and significant reductions in IL-6 and TNF-α levels. The overall effective rate was 83.5%, with optimal efficacy observed in the Qi-deficient (97.72%) and Yin-deficient (95.34%) groups. Conclusion The novel sleep-aid decoction is effective in treating insomnia in elderly patients, with the best results observed in the Qi-deficient and Yin-deficient constitution groups.
Humans ; Sleep Initiation and Maintenance Disorders/blood* ; Aged ; Male ; Female ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Middle Aged ; Tumor Necrosis Factor-alpha/blood* ; Sleep Aids, Pharmaceutical/therapeutic use* ; Anti-Inflammatory Agents/therapeutic use* ; Interleukin-6/blood* ; Interleukin-1beta/blood* ; Neurotransmitter Agents/blood* ; Aged, 80 and over ; C-Reactive Protein/metabolism*

Objective To explore the value of vesical imaging reporting and data system(VI-RADS)combined with absolute tumor-wall contact length(ABTCL)and actual tumor-wall contact length(ACTCL)in diagnosing muscle invasive bladder cancer(MIBC).Methods The MRI data of 113 patients with pathologically confirmed bladder cancer(BCa)were analyzed retrospectively.All patients underwent conventional MRI,diffusion weighted imaging(DWI)and dynamic contrast enhanced(DCE)MRI before sur-gery.Two radiologists independently evaluated MRI images based on VI-RADS score,and measured quantitative parameters,inclu-ding ABTCL and ACTCL.The Chi-square test was used to compare the difference of VI-RADS scores between MIBC and non-mus-cle invasive bladder cancer(NMIBC).Quantitative parameters between MIBC and NMIBC were compared by Mann-Whitney U test.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic value of VI-RADS,quantitative parameters and VI-RADS combined with quantitative parameters in the diagnosis of MIBC.Results VI-RADS,ABTCL and ACTCL had significant differences between MIBC and NMIBC(P＜0.05).The area under the curve(AUC)for VI-RADS,ABTCL and ACTCL in diagno-sing MIBC were 0.89,0.76 and 0.77,respectively.There was no significant difference between the AUC for ABTCL and ACTCL(P＞0.05).The AUC for VI-RADS combined with ABTCL or ACTCL in diagnosing MIBC was 0.93,higher than that of only VI-RADS(P＜0.05).Conclusion The combination of VI-RADS with either ABTCL or ACTCL can effectively improve the diagnostic performance of MIBC.ABTCL obtainedby linear measurement is easier to implement in clinical practice than ACTCL obtained by curved measurement.

Objective To investigate the effect of inhibiting S100A4 expression to enhance the dissociation of mast cells pre-bound by immunoglobulin E(IgE)by omalizumab(OmAb).Methods LAD2 cells were randomly divided into normal group,IgE group(IgE induction),OmAb-L group(0.5 mg·mL-1 OmAb),OmAb-M group(1.0 mg·mL-1 OmAb),OmAb-H group(2.0 mg·mL-1 OmAb),OmAb-h+si-S100A4 group(transfected with si-S100A4+2.0 mg·mL-1 OmAb).IgE levels on cell surface were detected by flow cytometry;degranulation was measured by β-amino-hexosidase release assay;the levels of histamine and leukotriene C4 were detected by enzyme-linked immunosorbent assay(ELISA);the expression of related proteins was detected by Western blot.Results After 6 h treatment,IgE levels in normal group,IgE group,OmAb-H group and OmAb-H+si-S100A4 group were(4.13±0.52)％,(100.00±6.20)％,(60.12±3.41)％and(54.04±5.60)％,respectively;β-amino-hexosidase release rates were(12.59±1.35),(69.27±6.43),(45.39±2.14)and(37.80±2.77)％,respectively;histamine levels were(2.43±0.16),(8.57±0.41),(4.91±0.24),(3.01±0.23)ng·mL-1,respectively;the C4 levels of leukotriene were(198.85±18.91),(423.56±1.25),(273.68±17.11)and(242.79±12.44)pg·mL-1,respectively;relative phosphorylated extracellular signal-regulated kinases(p-ERK)expression levels were 0.31±0.04,0.91±0.12,0.55±0.04 and 0.35±0.02,respectively.The above indexes in IgE group were compared with those in normal group,the above indexes of OmAb-H group were compared with IgE group,the above indexes of OmAb-H+si-S100A4 group were respectively compared with those of OmAb-H group,the differences were statistically significant(all P＜0.05).Conclusion Inhibition of S100A4 can enhance the dissociation effect of OmAb on mast cells and IgE,and further block the release of allergic mediators.

Objective:To assess the diagnostic efficiency of long-read sequencing (LRS) for the determination of CYP21A1P/ CYP21A2 and TNXA/ TNXB fusion genotypes among children with 21-hydroxylase deficiency (21-OHD) and explore their clinical characteristics. Methods:LRS sequencing was carried out on 30 children diagnosed with 21-OHD at the Department of Endocrinology, Fujian Children′s Hospital between November 2022 and September 2023 by clinical symptoms or conventional Sanger sequencing combined with multiple ligation-dependent probe amplification (MLPA). The results of the two methods were compared. Clinical data of the children were collected and analyzed. This study has been approved by the Medical Ethic Committee of the Fujian Children Hospital(Ethic No. 2022ETKLR10024).Results:Of the 30 children with 21-OHD, 11 (36.7%) were found to carry CYP21A1P/ CYP21A2 and TNXA/ TNXB fusion genes by LRS. The most common type of fused CYP21A1P/ CYP21A2 gene was CH-1 (61.5%), and 1 (3.3%) was found to harbor TNXA/ TNXB CH-1. 11 cases (36.7%) were found to carry large deletions by Sanger sequencing combined with MLPA, with the most common one being CYP21A2 exons 1-3 del (61.5%), which was followed by CYP21A2 exons 1-7 del (23.1%). Follow up of 11 patients carrying a fusion gene revealed that 6 were sale wasting (SW) types, 5 were simple virilizing (SV) types, whilst no non-classical (NC) type was found. Four girls had presented with central precocious puberty (CPP). One child carrying TNXA/ TNXB CH-1 had presented with CAH-X syndrome. Conclusion:Compared with Sanger sequencing combined with MLPA detection method, LRS sequencing was able to differentiate the subtypes of CYP21A1P/ CYP21A2 and TNXA/ TNXB fusion genes, pinpoint the breakpoints of the deletions, and directly determine the cis-trans position without the need to analyze the genotype of the pedigree members, which has provided a reliable method for the typing of 21-OHD. As some fusion genes may retain 21-hydroxylase activity, female carriers may have a higher incidence of CPP.

Objective:To assess the diagnostic efficiency of long-read sequencing (LRS) for the determination of CYP21A1P/ CYP21A2 and TNXA/ TNXB fusion genotypes among children with 21-hydroxylase deficiency (21-OHD) and explore their clinical characteristics. Methods:LRS sequencing was carried out on 30 children diagnosed with 21-OHD at the Department of Endocrinology, Fujian Children′s Hospital between November 2022 and September 2023 by clinical symptoms or conventional Sanger sequencing combined with multiple ligation-dependent probe amplification (MLPA). The results of the two methods were compared. Clinical data of the children were collected and analyzed. This study has been approved by the Medical Ethic Committee of the Fujian Children Hospital(Ethic No. 2022ETKLR10024).Results:Of the 30 children with 21-OHD, 11 (36.7%) were found to carry CYP21A1P/ CYP21A2 and TNXA/ TNXB fusion genes by LRS. The most common type of fused CYP21A1P/ CYP21A2 gene was CH-1 (61.5%), and 1 (3.3%) was found to harbor TNXA/ TNXB CH-1. 11 cases (36.7%) were found to carry large deletions by Sanger sequencing combined with MLPA, with the most common one being CYP21A2 exons 1-3 del (61.5%), which was followed by CYP21A2 exons 1-7 del (23.1%). Follow up of 11 patients carrying a fusion gene revealed that 6 were sale wasting (SW) types, 5 were simple virilizing (SV) types, whilst no non-classical (NC) type was found. Four girls had presented with central precocious puberty (CPP). One child carrying TNXA/ TNXB CH-1 had presented with CAH-X syndrome. Conclusion:Compared with Sanger sequencing combined with MLPA detection method, LRS sequencing was able to differentiate the subtypes of CYP21A1P/ CYP21A2 and TNXA/ TNXB fusion genes, pinpoint the breakpoints of the deletions, and directly determine the cis-trans position without the need to analyze the genotype of the pedigree members, which has provided a reliable method for the typing of 21-OHD. As some fusion genes may retain 21-hydroxylase activity, female carriers may have a higher incidence of CPP.

ObjectiveTo observe the changes in the expression and distribution of G protein-gated inwardly rectifying potassium channel subunit 2 （GIRK2） in the dorsal root ganglion （DRG） and spinal cord dorsal horn of rats with remifentanil-induced hyperalgesia. MethodsHyperalgesia was induced by intravenous infusion of remifentanil 4 μg/kg/min for 2 h in adult male SD rats. At 6th hour and on days 1， 3 and 5 following remifentanil treatment， we used immunofluorescence to examine the changes in the GIRK2 distribution and expression. Immunoblotting was used to detect GIRK2 expression of the total protein and membrane protein in DRG and spinal dorsal horn of rats. Behavioral testing was applied to evaluate the effect of intrathecal injection of GIRK2-specific agonist ML297 on thermal nociceptive threshold on day 1 after remifentanil infusion. Resultsmmunofluorescence results showed that GIRK2 was mainly co-localized with IB4-positive small neurons in DRG and nerve fibers in spinal dorsal horn. GIRK2 expression was significantly downregulated following remifentanil treatment. Immunoblotting results revealed that on day 1 following intravenous infusion of remifentanil， compared with those in the control group， GIRK2 expression levels of the total protein and membrane protein in DRG （0.47 ± 0.10 vs. 1.01 ± 0.17， P < 0.001； 0.47 ± 0.11 vs. 1.06 ± 0.12， P < 0.001） and spinal dorsal horn （0.52 ± 0.09 vs. 1.10 ± 0.08， P < 0.001； 0.54 ± 0.10 vs. 1.01 ± 0.13， P < 0.001） were all significantly decreased. The behavioral results showed that intrathecal ML297 effect on thermal withdrawal latency was significantly reduced following remifentanil treatment （P < 0.001）. ConclusionsRemifentanil might induce hyperalgesia via down-regulating GIRK2 expression in rat DRG and spinal cord dorsal horn.

Lu Dangshen, a traditional authentic medicinal material of Codonopsis Radix is mainly produced in Shangdang (Changzhi) area of Shanxi Province. Baitiao Dangshen is mainly produced in Gansu Province. Codonopsis Radix contains many kinds of components such as phenylpropanoids, polyalkynes, alkaloids, terpenes, fatty acids, flavonoids, and so on. At present, the effect of producing areas on its chemical compositions has not been systematically studied. This study analyzed the differences of metabolites among Codonopsis pilosula from different producing areas by UPLC-HRMS. PCA, OPLS-DA coupled with Thermo mzcloud online and local databases were used to compare the overall differences of metabolites among Codonopsis pilosula from different producing areas, and the chemical constituents were identified to further screen and find out the different metabolites and analyze the metabolic pathways by information retrieval in HMDB, PubChem, Chemspider and KEGG databases. The results showed that 72 differential metabolites were identified in this study. There were 15 kinds of up-regulated and 57 kinds of down-regulated metabolites of Lu Dangshen compared with Baitiao Dangshen. The top 30 metabolic pathways were analyzed by KEGG enrichment, and the most important metabolic pathways were phenylpropanoid biosynthesis, which was demonstrated that phenylpropanoid biosynthesis pathway and related intermediate metabolites could be used as the characteristics of distinguishing Lu Dangshen from different habitats of Codonopsis pilosula. The present study provided a basis for analyzing the influence of producing areas on the chemical components of Codonopsis pilosula and reasonably evaluating the quality of Codonopsis Radix, and also provided a new idea for expounding the authenticity of Lu Dangshen.

OBJECTIVE: To investigate the correlation between single-nucleotide polymorphism (SNP) of ARID5B gene and resistance to methotrexate (MTX) in children with acute lymphoblastic leukemia (ALL). METHODS: A total of 144 children with ALL who were treated in General Hospital of Ningxia Medical University from January 2015 to November 2021 were enrolled and divided into MTX resistant group and non-MTX resistant group, with 72 cases in each group. Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) technology was used to measure the SNP of ARID5B gene in all children and analyze its correlation with MTX resistant. RESULTS: There were no significant differences in the genotype and gene frequency of rs7923074, rs10821936, rs6479778, and rs2893881 between MTX resistant group and non-MTX resistant group (P>0.05). The frequency of C/C genotype in the MTX resistant group was significantly higher than that in the non-MTX resistant group, while the frequency of T/T genotype was opposite (P<0.05). The frequency of C allele in the MTX resistant group was significantly higher than that in the non-MTX resistant group, while the frequency of T allele was opposite (P<0.05). Multivariate logistic regression analysis showed that ARID5B gene rs4948488 TT genotype and T allele frequency were risk factors for MTX resistant in ALL children (P<0.05). CONCLUSION The SNP of ARID5B gene is associated with MTX resistant in ALL children.
Child ; Humans ; DNA-Binding Proteins/genetics* ; Gene Frequency ; Genotype ; Methotrexate ; Polymorphism, Single Nucleotide ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Transcription Factors/genetics* ; Drug Resistance, Neoplasm