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 investigate the role of microRNA-18a (miR-18a) in the pathogenesis of allergic rhinitis in mice. Methods Twenty-two BALB/c mice were randomly divided into a blank group, a model group and a miR-18a group. Mice in the model group and the miR-18a group were injected intraperitoneally with obumin (OVA) suspension to prepare allergic rhinitis models, and mice in the miR-18a group were simultaneously given lentiviral vector plasmid for overexpression of miR-18a. Allergy symptoms were evaluated by the behavioral score and HE staining. The plasma levels of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor α (TNF-α) were measured by ELISA. The distribution of CD45⁺ cells in nasal mucosa was measured by immunofluorescence histochemistry, and CD45⁺ cells in nasal lavage fluid were measured by flow cytometry. The mRNA expression levels of IL-1β, IL-6 and TNF-α in nasal mucosa tissues were measured by fluorescence quantitative PCR, and the protein expressions of Toll like receptor 4 (TLR4), nuclear factor κB p65 (NF-κB p65), inhibitor of NF-κB α (IκBα) and phosphorylated IκBα (p-IκBα) in nasal mucosa were measured by Western blot analysis. Results Compared with the blank group, the plasma levels of IL-1β, IL-6, and TNF-α in the model group increased significantly. The number of CD45⁺ cells in both nasal mucosa tissue and nasal irrigation fluid increased, and the mRNA levels of IL-1β, IL-6 and TNF-α and the protein expression levels of TLR4, NF-κB p65 and p-IκBα in nasal mucosa increased. Compared with the model group, the plasma levels of IL-1β, IL-6 and TNF-α in the miR-18a group decreased significantly. The number of CD45⁺ cells in both nasal mucosa tissue and nasal lavage fluid decreased, and the mRNA levels of IL-1β, IL-6 and TNF-α and the exprotein expression levels of TLR4, NF-κB p65 and p-IκBα in nasal mucosa decreased. Conclusion miR-18a can inhibit the occurrence and development of allergic rhinitis, and its molecular mechanism is related to the inhibition of TLR4/NF-κB pathway activation.
Animals ; Mice ; Disease Models, Animal ; Inflammation ; Interleukin-6/genetics* ; MicroRNAs/genetics* ; NF-kappa B/metabolism* ; NF-KappaB Inhibitor alpha ; Rhinitis, Allergic ; RNA, Messenger ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha/genetics*

OBJECTIVE: To investigate a family with congenital dysfibrinogenemia, and analyze the risk of hemorrhage and thrombosis and blood transfusion strategies. METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of the proband and her family members were detected by automatic coagulometer, fibrinogen (Fg) activity and antigen were detected by Clauss method and PT algorithm respectively. Meanwhile, thromboelastometry was analyzed for proband and her family members. Then, peripheral blood samples of the proband and her family members were collected, and all exons of FGA, FGB and FGG and their flanks were amplified by PCR and sequenced to search for gene mutations. RESULTS: The proband had normal APTT and PT, slightly prolonged TT, reduced level of Fg activity (Clauss method). The Fg of the proband's aunt, son and daughter all decreased to varying degrees. The results of thromboelastogram indicated that Fg function of the proband and her family members (except her son) was basically normal. Gene analysis showed that there were 6233 G/A (p.AαArg35His) heterozygous mutations in exon 2 of FGA gene in the proband, her children and aunt. In addition, 2 polymorphic loci were found in the family, they were FGA gene g.9308A/G (p.AαThr331Ala) and FGB gene g.12628G/A (p.BβArg478Iys) polymorphism, respectively. The proband was injected with 10 units of cryoprecipitate 2 hours before delivery to prevent bleeding, and no obvious bleeding occurred during and after delivery. CONCLUSION Heterozygous mutation of 6233G/A (p.AαArg35His) of FGA gene is the biogenetic basis of the disease in this family with congenital dysfibrinogenemia.
Humans ; Child ; Female ; Fibrinogen/genetics* ; Pedigree ; Afibrinogenemia/genetics* ; Mutation ; Blood Transfusion

OBJECTIVE: To investigate the clinical features and outcomes of infants (<1 year old) with acute lymphoblastic leukemia (IALL). METHODS: The clinical manifestations, laboratory examination results, treatment and prognosis of 18 infants diagnosed with ALL at our department between January 1, 2014 and August 31, 2022 were retrospectively analyzed. RESULTS: Among the 18 cases of IALL, there were 10 males and 8 females. The median age of patients was 6.5 months old (3 months-11 months old). The median white blood cell count (WBC) was 33.63×10⁹/L ［(3.92-470)×10⁹/L］ at initial diagnosis, including 2 patients with WBC≥300×10⁹/L. Flow cytometric immunophenotyping showed a B-lineage infant ALL in all the 18 patients. Eight of the 18 children had abnormal chromosome karyotype analysis. Fusion gene detection showed 12 KMT2A-rearrangement of 18 patients. 15 patients underwent leukemia related mutation gene screening, among which KRAS, NRAS and FLT3 were the most common mutation genes. 4 patients underwent allogeneic hematopoietic stem cell transplantation and two survived. 14 patients received chemotherapy only and ten survived. The 3-year OS rate was (65.5±11.5)%, while the EFS rate was (46.9±12.3)%. CONCLUSION B-cell ALL and KMT2A rearrangement are prevalent in IALL. The therapeutic effect of IALL with standard childhood ALL protocal is similer to international infant specific protocal.
Male ; Child ; Infant ; Female ; Humans ; Retrospective Studies ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Prognosis ; Hematopoietic Stem Cell Transplantation ; Mutation

OBJECTIVE: To investigate the expression level and the diagnostic value of serum free light chain in B-cell non-Hodgkin's lymphoma (B-NHL). METHODS: We retrospectively analyzed the results of serum free light chain (sFLC) of 394 newly treated B-NHL patients in our hospital from January 2014 to December 2021 and compared the secretion levels of sFLC among different subtypes of B-NHL. The value of sFLC secretion levels in the diagnosis of WM was evaluated using ROC. RESULTS: Increased proportion of sFLC, abnormal ratio of sFLC (κ / λ) and the secretion levels of sFLC (κ+λ) were different in different B-NHL subtypes, Waldenstrom's macroglobulinemia (WM) had the highest proportion of elevated sFLC(82.68%) and abnormal sFLC(κ/ λ)(87.0%), the proportion of FL(18.0%) and DLBCL patients(12.8%) with elevated sFLC was lower (P<0.05). The expression levels of sFLC can helpful in the diagnosis of WM (AUC=0.874，P<0.001， 95% CI: 0.779-0.970). At the same time, higher sFLC levels and sFLC cloning patterns predicted the possibility of bone marrow infiltration of lymphoma. CONCLUSION The serum free light chains is common in patients with B-NHL. The elevated level and type of free light chain are associated with the type of lymphoma, and the patients with bone marrow infiltration have higher sFLC（κ+ λ） expression level.
Humans ; Retrospective Studies ; Immunoglobulin Light Chains ; Lymphoma, B-Cell/diagnosis*

OBJECTIVE: To explore the value of multiple detection methods based on histopathology and supplemented by bone marrow or peripheral blood sample detections in the comprehensive diagnosis of mantle cell lymphoma (MCL). METHODS: The clinical, immunophenotypic, pathologic, cytogenetic and molecular features of 153 newly diagnosed MCL patients admitted to the hematology department of our hospital from May 2009 to September 2022 were analyzed. RESULTS: 144 (96.6%) of the 149 MCL patients who underwent marrow or peripheral blood IGH/CCND1 FISH detection at initial diagnosis were positive, of which 36 cases (24.2%) had a low proportion positive. The immunophenotypes in 115 patients were analyzed by flow cytometry (FCM), 89 cases (77.4%) conformed to MCL while 23 cases (20.0%) were initially diagnosed as B-cell lymphoproliferative disorders (B-LPD). Of the 75 cases who performed bone marrow biopsy, 50 cases (66.7%) had morphological and immunophenotypic characteristics consistent with MCL, 15 cases (20.0%) were classified as B-LPD, and 10 cases with no obvious abnormality. 77 patients underwent histopathology examination, of which 73 cases (94.8%) had typical clinicopathological features of MCL, including 2 CCND1 negative MCL, 2 pleomorphic variants, 5 pleomorphic variants and 4 cases diagnosed as other leukemia or lymphoma. Among 153 cases of MCL, 128 cases were classic MCL(cMCL), and another 25 cases (16.3%) were diagnosed as leukemic non-lymph node MCL (lnnMCL). The incidence of IGHV mutation, TP53 mutation and CD23 expression positive were significantly different between cMCL and lnnMCL. CONCLUSION Histopathology is still the main standard for the diagnosis of cMCL, and detection based on bone marrow or peripheral blood samples is an important means for the diagnosis of lnnMCL. Single marker or examination can cause a certain proportion of misdiagnosis. The accurate diagnosis of MCL depends on a combination of multiple detection methods.
Adult ; Humans ; Lymphoma, Mantle-Cell/genetics* ; Bone Marrow/pathology* ; Leukemia/pathology* ; Mutation ; Immunophenotyping