Malignant proliferating liver cancer cells possess the ability to detect and respond to various body signals, thereby facilitating tumor growth, invasion, and metastasis. One crucial mechanism through which hepatocellular carcinoma (HCC) cells interpret these signals is crosstalk. Within liver cancer tissues, cancer cells engage in communication with hepatic stellate cells (HSCs), tumor-associated macrophages (TAMs), and immune cells. This interaction plays a pivotal role in regulating the proliferation, invasion, and metastasis of HCC cells. Crosstalk occurs in multiple ways, each characterized by distinct functions. Its molecular mechanisms primarily involve regulating immune cell functions through the expression of specific receptors, such as CD24 and CD47, modulating cell functions by secreting cytokines like transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF), and mediating cell growth and proliferation by activating pathways such as Wnt/β-catenin and Hedgehog. A comprehensive understanding of the mechanisms and interactions within crosstalk is essential for unraveling the pathogenesis of HCC. It also opens up new avenues for the development of innovative therapeutic strategies. This article reviews the relationship between crosstalk and the progression of HCC, offering insights and inspiration for future research.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Hepatic Stellate Cells/physiology* ; Disease Progression ; Signal Transduction/physiology* ; Transforming Growth Factor beta/metabolism* ; Cell Proliferation ; Hedgehog Proteins/metabolism* ; Tumor-Associated Macrophages ; Platelet-Derived Growth Factor/metabolism* ; Cell Communication/physiology*

OBJECTIVE: This study aimed to determine the expression levels and prognostic significance of MYCN in bone marrow of adult patients with newly diagnosed acute myeloid leukemia (AML). METHODS: A total of 62 newly diagnosed patients with non-M3 AML were enrolled as the study group, and 20 healthy donors as the control group. Real-time quantitative reverse transcription-polymerase chain reaction (PCR) was performed to detect the expression level of MYCN, and the relationship between MYCN expression and prognosis of AML patients was analyzed. RESULTS: MYCN was up-regulated in newly diagnosed AML patients compared with normal controls (P < 0.001). Receiver operating characteristic (ROC) curve analysis revealed that MYCN could serve as a diagnostic biomarker for AML. Kaplan-Meier survival analysis showed that the patients with high MYCN expression had a shorter overall survival (OS) time than the patients with low MYCN expression (P =0.016). The expression level of MYCN was lower during the complete ressimion (CR) phase of AML compared to the initial diagnosis, but it returned to the initial diagnostic level or even higher during relapse phase. Multivariate Cox regression analysis showed that high expression of MYCN was an independent risk factor for OS of AML patients (P =0.021). CONCLUSION MYCN is highly expressed and associated with poor prognosis in de novo AML, which might be serve as a novel diagnostic and prognostic biomarker for adult AML.
Humans ; Leukemia, Myeloid, Acute/metabolism* ; Prognosis ; N-Myc Proto-Oncogene Protein ; Adult ; Female ; Male ; Middle Aged

OBJECTIVE: To investigate the predictive value of morphology, immunology, and cytogenetics for isocitrate dehydrogenase 1 and 2 (IDH1/2) gene mutation in newly diagnosed acute myeloid leukemia (AML) patients. METHODS: The clinical data of 186 newly diagnosed AML patients (except M3 subtype) in the First People's Hospital of Changzhou were retrospectively analyzed, and the variables associated with IDH1/2 mutation in patients were screened using LASSO regression to construct a multivariate logistic regression analysis model. The Bootstrap method was used for internal validation of the model and nomograms were used to visualize the model, and receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of the model. RESULTS: A total of 60 AML patients had IDH1/2 mutation at initial diagnosis. LASSO regression screened 9 predictive variables associated with IDH1/2 mutation, including CD7, CD56, CD11b, CD15, CD64, HLA-DR, platelet count≥50×10⁹/L, isolated +8 and normal karyotype. The nomogram and ROC curve were plotted based on the above 9 variables. The area under the ROC curve (AUC) of the training set and the validation set were 0.871 and 0.806, respectively. Internal validation showed that the nomogram had good predictive ability. CONCLUSION The prediction model based on MIC typing constructed in this study has a good predictive ability for the presence of IDH1/2 mutations in newly diagnosed AML patients and has important clinical application value when the gene mutation detection results are unavailable.
Humans ; Isocitrate Dehydrogenase/genetics* ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Retrospective Studies ; Nomograms ; Female ; Male ; ROC Curve ; Middle Aged

Objective:To explore the risk factors affecting the survival and efficacy of patients with acute myeloid leukemia with myelodysplasia-related changes(AML-MRC)transformed from myelodysplastic syndrome(MDS).Methods:The clinical data of 60 patients with AML-MRC transformed from MDS who hospitalized in The Third Affiliated Hospital of Soochow University from January 2010 to December 2021 were retrospectively analyzed.The demographic data and laboratory parameters,cytogenetic karyotypes,target genes of AML detected by next generation sequence,risk stratification,treatment regimen,therapeutic efficacy and survival outcome were documented.Rank sum test and Chi-square test or Fisher exact test were used to compare the survival and efficacy.The effects of clinical parameters,risk stratification and treatment regimens on the survival and efficacy of the AML-MRC patients were analyzed by univariate and multivariate analysis.Results:The median overall survival(OS)of the AML-MRC patients was 4.5 months,the 1-year OS rate was 28.3％,and the complete remission(CR)rate after treatment was 33.3％.The univariate analysis showed that age≥60 years,leukocytosis,severe thrombocytopenia,poor-risk group and only accepted hypomethylating agents(HMAs)or supportive therapy were the risk factors affecting OS.COX multivariate analysis showed that thrombocytopenia(HR=4.46),HMAs therapy(compared to transplantation,HR=10.47),supportive therapy(compared to transplantation,HR=25.80)and poor-risk group(compared to medium-risk group,HR=13.86)were independent hazard factors for median OS of patients with AML-MRC.The univariate analysis showed that the risk factors affecting 1-year OS in patients with AML-MRC were age ≥ 60 years,thrombocytopenia,time of transformation from MDS to AML(TTA)≥3 months,fibrinogen-albumin ratio index(FARI)≥ 0.07,CONUT score≥5,poor-risk group and supportive therapy.Binary logistic regression analysis showed that the independent risk factors for 1-year OS in AML-MRC patients were age ≥ 60 years(HR=11.23),thrombocytopenia(HR=8.71),FARI ≥ 0.07(HR=5.19)and poor-risk group(HR=14.00).The risk factors affecting CR of AML-MRC patients in univariate analysis were age ≥ 60 years,thrombocytopenia,FARI ≥ 0.1,CONUT score ≥ 5,poor-risk group and supportive therapy,while binary logistic regression analysis showed that age ≥ 60 years(HR=7.35),CONUT score ≥ 5(HR=9.60),thrombocytopenia(HR=12.05)and poor-risk group(HR=32.5)were independent risk factors affecting CR of the patients.Conclusion:The OS of AML-MRC patients is poor,old age(≥ 60 years old),supportive therapy,HMA therapy,poor-risk,thrombocytopenia,FARI ≥ 0.07 and CONUT score ≥ 5 may be associated with poor prognosis.

Objective:To investigate the prognostic significance of DTA(DNMT3A,TET2,ASXL1)gene mutations in patients with non-M3 acute myeloid leukemia(AML).Methods:The clinical data of 180 newly diagnosed AML patients hospitalized in the First People's Hospital of Changzhou from January 2018 to April 2022 were retrospectively analyzed.Next-generation sequencing technology was used to detect 150 gene mutations in the patients,and log-rank tests and Cox regression models were used to analyze the prognostic factors.Results:DTA gene mutations were detected in 83(46.1％)of 180 AML patients.Compared to patients without DTA mutations,patients with DTA mutations were significantly older(P＜0.001).The median overall survival(OS)time and disease-free survival(DFS)time in the DTA mutation group were significantly shorter than those in the group without DTA mutation(both P＜0.05).Multivariate analysis showed that age ≥ 60 years(P＜0.001),with DTA mutation(P=0.018),and intermediate-risk(relative to favorable-risk)(P=0.005)were independent risk factors for OS in AML patients.Conclusion:AML patients with DTA mutations are relatively older,with shorter median OS time and DFS time,and poor prognosis.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective To explore the clinical effect of amniotic membrane transplantation combined with entropion correction for ocular surface and eyelid burns.Methods A total of 80 patients with ocular surface injury and lower eyelid entropion caused by chemical or thermal burns who received surgical treatment in our hospital were selected as the research objects.All patients received amniotic membrane transplantation combined with entropion correction.All patients were examined by slit-lamp microscope and photographed before and 8 weeks after surgery.The visual acuity changes,tear film rupture time and serum levels of vascular endothelial growth factor(VEGF),trans-forming growth factor β1(TGF-β1)and insulin growth factor 1(IGF-1)were compared before and 8 weeks after surgery.Eight weeks after surgery,exfoliated epithelial cells of the central cornea and limbus were collected and analyzed by PAS staining and immunofluorescence staining.Results At 8 weeks after surgery,the patient's ocular surface condition recovered well,eyelid entropion was successfully corrected,postoperative visual acuity was significantly better than that before surgery(P<0.05).Compared with before surgery,the tear film rupture time 8 weeks after surgery was significantly prolonged(P<0.05),and the serum VEGF,TGF-β1 and IGF-1 levels 8 weeks after surgery were significantly increased(P<0.05).PAS staining showed that there was no goblet cell in the central cornea and limbus.Immunofluorescence staining showed that cytokeratin 12(CK12)was highly expressed in the corneal epithelial cells,and low expressed in corneal limbal epithelial cells near the cornea.Conclusion Amniotic membrane transplantation combined with entropion correction has a significant therapeutic effect on patients with ocular burn,which can promote ocular surface repair,correct entropion,improve postoperative visual acuity,and achieve self-amplification of cornea stem cells.It is a safe and effective treatment method.

Renal outer medullary potassium (ROMK) channel is an important K⁺ excretion channel in the body, and K⁺ secreted by the ROMK channels is most or all source of urinary potassium. Previous studies focused on the ROMK channels of thick ascending limb (TAL) and collecting duct (CD), while there were few studies on the involvement of ROMK channels of the late distal convoluted tubule (DCT2) in K⁺ excretion. The purpose of the present study was mainly to record the ROMK channels current in renal DCT2 and observe the effect of high potassium diet on the ROMK channels by using single channel and whole-cell patch-clamp techniques. The results showed that a small conductance channel current with a conductance of 39 pS could be recorded in the apical membrane of renal DCT2, and it could be blocked by Tertiapin-Q (TPNQ), a ROMK channel inhibitor. The high potassium diet significantly increased the probability of ROMK channel current occurrence in the apical membrane of renal DCT2, and enhanced the activity of ROMK channel, compared to normal potassium diet (P < 0.01). Western blot results also demonstrated that the high potassium diet significantly up-regulated the protein expression levels of ROMK channels and epithelial sodium channel (ENaC), and down-regulated the protein expression level of Na⁺-Cl^- cotransporter (NCC). Moreover, the high potassium diet significantly increased urinary potassium excretion. These results suggest that the high potassium diet may activate the ROMK channels in the apical membrane of renal DCT2 and increase the urinary potassium excretion by up-regulating the expression of renal ROMK channels.
Potassium Channels, Inwardly Rectifying/metabolism* ; Kidney Tubules, Distal/metabolism* ; Potassium/metabolism* ; Epithelial Sodium Channels/metabolism* ; Diet

OBJECTIVE: To investigate the biological effects and its relative mechanism of decitabine combined with anlotinib on multiple myeloma cells. METHODS: The human MM cell lines and primary cells were treated with different concentrations of decitabine, anlotinib, and decitabine+anlotinib, respectively. The cell viability was detected and combination effect was calculated by CCK-8 assay. The apoptosis rate was measured by flow cytometry and the level of c-Myc protein was determined by Western blot. RESULTS: Both decitabine and anlotinib could effectively inhibit the proliferation and induce the apoptosis of MM cell lines NCI-H929 and RPMI-8226. The effect of combined treatment on the inhibition of cell proliferation and induction of apoptosis was stronger than that of single-drug treatment. The combination of the two drugs also showed strong cytotoxicity in primary MM cells. Decitabine and anlotinib could down-regulate the level of c-Myc protein in MM cells and the c-Myc level in the combination group was the lowest. CONCLUSION Decitabine combined with anlotinib can effectively inhibit the proliferation and induce apoptosis of MM cells, which provides a certain experimental basis for the treatment of human MM.
Humans ; Multiple Myeloma/metabolism* ; Decitabine ; Cell Line, Tumor ; Apoptosis ; Cell Proliferation

Objective: To analyze the clinical characteristics of patients with Mucopolysaccharidosis ⅣA (MPS ⅣA). Methods: A retrospective study was conducted on 111 patients with MPS ⅣA in Xinhua Hospital of Shanghai Jiao Tong University School of Medcine from December 2008 to August 2020, confirmed by enzyme activity and genetic testing. General situation, clinical manifestations and enzyme activity test results were analyzed. According to the clinical manifestations, it can be divided into severe, intermediate and mild group. The independent sample t test was used to compare the birth body length and weight of children with that of normal boys and girls, and group comparisons of enzyme activities were evaluated by median test. Results: One hundred and eleven unrelated patients, 69 males and 42 females, were classified into 3 subtypes: severe (n=85), intermediate (n=14), and mild (n=12). The age at symptom onset were 1.6 (1.0, 3.0) years, and at diagnosis were 4.3 (2.8, 7.8) years. Skeletal manifestations were observed in all patients and consisted mainly of pectus carinatum (96/111, 86.5%), motor dysfunction (78/111, 70.3%), spinal deformity (71/111, 64.0%), growth retardation (64/111, 57.7%), joint laxity (63/111, 56.8%) and genu valgum (62/111, 55.9%). Eighty-eight patients (88/111, 79.3%) with MPS ⅣA were also along with non-skeletal manifestations, mainly including snoring (38/111, 34.2%), coarse faces (34/111, 30.6%), and visual impairment (26/111, 23.4%). The most common skeletal manifestation was pectus carinatum (79 cases), and non-skeletal manifestation was snoring (30 cases) and coarse faces (30 cases) in severe patients, pectus carinatum (13 cases) and snoring (5 cases) in intermediate type, motor dysfunction (11 cases) and snoring (3 cases) and visual impairment (3 cases) in mild patients. The height and weight of severe patients began to fall below -2 s at 2-<5 years and 5-<7 years, respectively. At the age of 10-<15 years, the standard deviation score of the height of severe patients reached (-6.2±1.6) s in males and (-6.4±1.2) s in females, and the score of weight got (-3.0±1.1) s in males and (-3.5±0.5) s in females. The height of intermediate patients began to fall below -2 s at the age of 7-<10 years, and the standard deviation score of height were -4.6 s and -3.6 s in 2 males, and -4.6 s and -3.8 s in 2 females at the age of 10-<15 years. The weight remained within -2 s in 72.0% (18/25) of intermediate patients compared to age-matched healthy children. In the mild patients with MPS ⅣA, the mean standard deviation score of height and weight was within -2 s. The enzyme activities of mild patients (2.02 (1.05, 8.20) nmol/(17 h·mg)) were both significantly higher than that of intermediate (0.57 (0.47, 0.94) nmol/(17 h·mg)) and severe (0.22 (0, 0.59) nmol/(17 h·mg)) patients (Z=9.91, 13.98, P=0.005, 0.001), and the enzyme activity of intermediate patients was significantly higher than that of severe patients (Z=8.56, P=0.010). Conclusions: The clinical manifestations of MPS ⅣA are charactered by pectus carinatum, motor function impairment, spinal deformity and growth retardation. The clinical characteristics, growth rate and enzyme activity differ among the 3 subtypes of MPS ⅣA.
Male ; Child ; Female ; Humans ; Adolescent ; Mucopolysaccharidosis IV ; Pectus Carinatum ; Retrospective Studies ; Snoring ; China ; Mucopolysaccharidoses ; Growth Disorders ; Vision Disorders