ObjectiveTo investigate the clinical application value of thromboelastographic parameters in assessing coagulation function by analyzing the thromboelastographic features of patients with primary liver cancer （PLC）， and to provide a basis for coagulation management and prognostic evaluation in liver cancer patients. MethodsA retrospective analysis was performed for 1 253 PLC patients who were admitted to The First Affiliated Hospital of Xi’an Jiaotong University from May 2015 to December 2022. According to the presence or absence of cirrhosis， the patients were divided into non-cirrhosis group with 262 patients and cirrhosis group with 991 patients， and according to the presence or absence of HBV infection， they were divided into HBV infection group with 1 055 patients and non-HBV infection group with 198 patients. The patients were stratified based on the severity of liver cirrhosis （Child-Pugh class and MELD score） and liver reserve function （indocyanine green retention rate at 15 minutes ［ICGR15］）， and thromboelastography was used to measure thromboelastographic parameters （reaction time ［R］， coagulation formation time ［K］， α-angle， maximum thrombosis amplitude ［MA］， and coagulation composite index ［CI］） and conventional coagulation markers. The t-test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the Kruskal-Wallis H test was used for comparison between multiple groups， and the Bonferroni correction method was used for further comparison between two groups. The chi-square test was used for comparison of categorical data between grouips， and the Spearman test was used for correlation analysis. ResultsAmong the 991 patients in the cirrhosis group， 826 had Child-Pugh class A （5 — 6 points）， and 165 had Child-Pugh class B （7 — 9 points）； 812 had an MELD score of <10， and 179 had an MELD score of ≥10； 679 had an ICGR15 of <10%， and 294 had an ICGR15 of ≥10%. Compared with the patients with Child-Pugh class A， the patients with Child-Pugh class B had a significantly longer K time and significant reductions in α-angle， MA， and CI （all P <0.001）； compared with the MELD score <10 group， the MELD score ≥10 group had a significantly longer K time and significant reductions in α-angle， MA， and CI （all P<0.001）； compared with the ICGR15 <10% group， the ICGR15 ≥10% group had a significantly longer K time and a significant reduction in MA （both P <0.001）. Among the 1 253 patients， MA was strongly positively correlated with fibrinogen and platelet count （r=0.675 and 0.667， both P<0.001）； The MA had a weak correlation with Child-Pugh score， MELD score， and ICGR15 （r=-0.112， -0.250， and -0.117， all P<0.001）， while the K time，α-angle and CI were weakly correlated with the MELD score （r=0.222， -0.184， and -0.183， all P<0.001），R time was negatively correlated with ICGR15 （r=-0.080， P=0.005）. The HBV infection group had significantly higher MA and CI than the non-HBV infection group （P<0.05）. ConclusionThromboelastography can sensitively identify the hypocoagulable state associated with the progression of liver cirrhosis and the hypercoagulable tendency in HBV-related liver cancer， which provides an important reference for individualized anticoagulant therapy in clinical practice.

Obesity is a worldwide health problem. An imbalance in energy metabolism is an important cause of obesity and related metabolic diseases. Our previous studies showed that inhibition of miR-429 increased the protein level of uncoupling protein 1 (UCP1) in beige adipocytes; however, whether local inhibition of miR-429 in subcutaneous adipose tissue affects diet-induced obesity and related metabolic disorders remains unclear. The aim of this study was to investigate the effect of local overexpression of miR-429 sponge in subcutaneous adipose tissue on obesity and related metabolic disorders. The control adeno-associated virus (AAV) or AAV expressing the miR-429 sponge was injected into mouse inguinal white adipose tissue. Seven days later, the mice were fed a high-fat diet for 10 weeks to induce obesity. The effects of the miR-429 sponge on body weight, adipose tissue weight, plasma glucose and lipid levels, and hepatic lipid content were explored. The results showed that the overexpression of miR-429 sponge in subcutaneous white adipose tissue reduced body weight and fat mass, decreased fasting blood glucose and plasma cholesterol levels, improved glucose tolerance, and alleviated hepatic lipid deposition in mice. Mechanistic investigation showed that the inhibition of miR-429 significantly upregulated the expression of UCP1 in adipocytes and adipose tissue. These results suggest that local inhibition of miR-429 in subcutaneous white adipose tissue ameliorates obesity and related metabolic disorders potentially by upregulating UCP1, and miR-429 is a potential therapeutic target for the treatment of obesity and related metabolic disorders.
Animals ; MicroRNAs/physiology* ; Obesity/metabolism* ; Mice ; Adipose Tissue, White/metabolism* ; Metabolic Diseases ; Subcutaneous Fat/metabolism* ; Male ; Uncoupling Protein 1/metabolism* ; Diet, High-Fat ; Mice, Inbred C57BL

OBJECTIVES: To investigate the clinical characteristics and prognosis of acute erythroleukemia (AEL) in children. METHODS: A retrospective analysis was conducted on the clinical data, treatment, and prognosis of 8 children with AEL treated at the First Affiliated Hospital of Zhengzhou University from January 2013 to December 2023. RESULTS: Among the 7 patients with complete bone marrow morphological analysis, 4 exhibited trilineage dysplasia, with a 100% incidence of erythroid dysplasia (7/7), a 71% incidence of myeloid dysplasia (5/7), and a 57% incidence of megakaryocytic dysplasia (4/7). Immunophenotyping revealed that myeloid antigens were primarily expressed as CD13, CD33, CD117, CD38, and CD123, with 4 cases expressing erythroid antigens CD71 and 2 cases expressing CD235a. Chromosomal analysis indicated that 2 cases presented with abnormal karyotypes, including +8 in one case and +4 accompanied by +6 in another; no complex karyotypes were observed. Genetic abnormalities were detected in 4 cases, with fusion genes including one case each of dup MLL positive and EVI1 positive, as well as mutations involving KRAS, NRAS, WT1, and UBTF. Seven patients received chemotherapy, with 6 achieving remission after one course of treatment; 2 underwent hematopoietic stem cell transplantation, and all had disease-free survival. Follow-up (median follow-up time of 6 months) showed that only 3 patients survived (2 cases after hematopoietic stem cell transplantation and 1 case during treatment). CONCLUSIONS Children with AEL have unique clinical and biological characteristics, exhibit poor treatment response, and have a poor prognosis; however, hematopoietic stem cell transplantation may improve overall survival rates.
Humans ; Male ; Female ; Prognosis ; Child, Preschool ; Retrospective Studies ; Child ; Leukemia, Erythroblastic, Acute/diagnosis* ; Infant ; Adolescent

OBJECTIVES: To investigate the clinical features and prognosis of children with non-Down-syndrome-related acute megakaryoblastic leukemia (non-DS-AMKL). METHODS: A retrospective analysis was conducted on the medical data of 17 children with non-DS-AMKL who were admitted to Children's Hospital of The First Affiliated Hospital of Zhengzhou University from January 2013 to December 2023, and their clinical features, treatment, and prognosis were summarized. RESULTS: Among the 17 children with non-DS-AMKL, there were 8 boys and 9 girls. Fourteen patients had an onset age of less than 36 months, with a median age of 21 months (range:13-145 months). Immunophenotyping results showed that 16 children were positive for CD61 and 13 were positive for CD41. The karyotype analysis was performed on 16 children, with normal karyotype in 6 children and abnormal karyotype in 9 children, among whom 5 had complex karyotype and 1 had no mitotic figure. Detected fusion genes included EVI1, NUP98-KDM5A, KDM5A-MIS18BP1, C22orf34-BRD1, WT1, and MLL-AF9. Genetic alterations included TET2, D7S486 deletion (suggesting 7q-), CSF1R deletion, and PIM1. All 17 children received chemotherapy, among whom 16 (94%) achieved complete remission after one course of induction therapy, and 1 child underwent hematopoietic stem cell transplantation (HSCT) and remained alive and disease-free. Of all children, 7 experienced recurrence, among whom 1 child received HSCT and died of graft-versus-host disease. At the last follow-up, six patients remained alive and disease-free. CONCLUSIONS Non-DS-AMKL primarily occurs in children between 1 and 3 years of age. The patients with this disorder have a high incidence rate of chromosomal abnormalities, with complex karyotypes in most patients. Some patients harbor fusion genes or gene mutations. Although the initial remission rate is high, the long-term survival rate remains low.
Humans ; Male ; Female ; Leukemia, Megakaryoblastic, Acute/etiology* ; Child, Preschool ; Infant ; Child ; Retrospective Studies ; Prognosis ; Down Syndrome/complications*

OBJECTIVE: To study the effects and mechanisms of juglone on the proliferation and apoptosis of acute myeloid leukemia (AML) cells. METHODS: Juglone and AML targets were collected from public databases, and the intersecting target clusters were taken for functional enrichment analysis to explore the potential mechanism of juglone in the treatment of AML. Then wet experiments were performed to verify. AML cell lines including KG-1a, MV-411, THP-1 and MOLM-13 were treated with different concentrations of juglone for 24 h. MTT assay was used to detect cell viability and determine the IC₅₀, and the most sensitive cell line was screened for subsequent experiments. Flow cytometry was used to detect the apoptosis of cells treated with different concentrations of juglone. Western blot was performed to check the expression of relevant proteins. RESULTS: Eleven targets were obtained as potential targets for juglone in the treatment of AML, and the top ten significantly enriched pathways were intrinsic pathway of apoptosis, programmed cell death, cytochrome c-mediated apoptotic response, apoptosis, apoptotic factor-mediated response, regulated necrosis, cytokine signaling in immune system, signaling by interleukins, oncogene induced senescence, and signal transduction. The cell viability of KG-1a, MV-411, THP-1 and MOLM-13 was decreased with increasing juglone concentration after 24 h of juglone treatment (r =-0.992, -0.886, -0.956, -0.910). Among them, MOLM-13 was the most sensitive to juglone. The results of flow cytometry showed that the apoptosis rate of MOLM-13 tended to significantly increase with the increasing concentration of juglone (r =0.99). At the same time point, p-RIPK1/RIPK1, p-RIPK3/RIPK3, and p-MLKL/MLK were decreased in each juglone concentration group compared with control group. CONCLUSION Juglone inhibits the viability of KG-1a, MV-411, THP-1 and MOLM-13 cells, and induces apoptosis of MOLM-13 cells, the mechanism of which may be related to the inhibition of RIPK1/RIPK3/MLKL signaling pathway.
Humans ; Naphthoquinones/pharmacology* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Leukemia, Myeloid, Acute/pathology* ; Cell Line, Tumor ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Protein Kinases/metabolism* ; Signal Transduction ; Cell Survival/drug effects*

Objective To investigate the effect of varying blood pressure stratification on renal function in the diabetic population.Methods A prospective cohort study was conducted,enrolling 9 489 diabetic patients from a total of 101 510 Kailuan Group employees who underwent health examinations between July 2006 and October 2007.The follow-up period was(8.6±4.0)years.Participants were categorized into four groups based on their baseline blood pressure levels:normal blood pressure(systolic blood pressure<120 mmHg and diastolic blood pressure<80 mmHg),elevated blood pressure(systolic blood pressure 120-130 mmHg and diastolic blood pressure<80 mmHg),stage 1 hypertension(systolic blood pressure 130-140 mmHg and/or diastolic blood pressure 80-90 mmHg),and stage 2 hypertension(systolic blood pressure≥140 mmHg and/or diastolic blood pressure≥90 mmHg).The incidence density of chronic kidney disease(CKD)was compared among these groups.A multivariate Cox proportional hazards regression model was employed to assess the effects of different blood pressure levels on renal function in diabetic patients,with the stability of the results confirmed using a multivariate time-dependent Cox proportional hazards model.Sensitivity analysis was conducted after excluding cases of cardiovascular disease(CVD)during follow-up,and cases using antihypertensive and antidiabetic medications at baseline.Results(1)At baseline,stage 1 hypertension patients demonstrated statistically significant higher differences with age and body mass index(BMI)compared to normal blood pressure group(P<0.05).(2)By the end of the follow-up,2 294 cases of CKD were identified,including 1 117 cases of estimated glomerular filtration rate(eGFR)decline and 1 575 cases of urinary protein.The incidences density of CKD,eGFR decline and urinary protein for stage 1 hypertension group were 39.4,16.3 and 25.5 per thousand person-years,respectively,all of which were statistically significant different from normal blood pressure group(log-rank test,P<0.01).(3)Multivariate Cox regression analysis revealed that,compared to the normal blood pressure group,stage 1 hypertension was associated with a 29%increased risk of CKD(HR=1.29,95%CI 1.09-1.52)and a 40%increased risk of eGFR decline(HR=1.40,95%CI 1.08-1.80)in diabetic individuals.Conclusion Stage 1 hypertension significantly increases the risk of CKD and eGFR decline in diabetic individuals,with a particularly notable effect on the risk of eGFR decline.

Objective:To explore the overall survival and prognostic factors of patients over 50 years old with acute myeloid leukemia(AML).Methods:The clinical data of 222 AML patients aged over 50 years in our hospital from January 2016 and June 2021 were retrospectively analyzed.Kaplan-Meier method was used to evaluate the overall survival(OS)rate,and Cox regression model to evaluate the prognostic factors.Results:The 1-year and 3-year OS rates of all patients were 46.8％and 28.8％,respectively.The recurrence rate of patients who achieved remission during follow-up time was 57％.Both univariate and multivariate analysis showed that advanced age,MLL family fusion gene,PHF6 gene mutation,TP53 gene mutation,intolerance to standard chemotherapy,incomplete remission,complex karyotype,+mar karyotype and inv(3)karyotype were significantly correlated with prognosis(all P＜0.05).Negative fusion gene and positive AML-ETO fusion gene had no obvious survival advantage in this population.In patients with complete remission,there was no significant survival advantage in those who achieved minimal residual disease negative.Conclusion:AML patients aged over 50 years have a poor outcome and high recurrence rate.The prognosis is affected by multiple factors and has its own characteristics.

Objective:To study the early predictors of refractory septic shock (RSS) in neonates.Methods:From July 2020 to December 2021, clinical data of neonates with septic shock admitted to the Neonatal Department of our hospital were retrospectively reviewed. According to the maximum septic shock score (SSS) during clinical course, the neonates were assigned into RSS group and non-RSS group. Perinatal data, laboratory results and hemodynamic parameters at diagnosis were compared between the two groups. Multiple logistic regression analysis was used to identify independent risk factors of RSS and septic shock-related death. Receiver operating characteristic (ROC) curve was constructed to evaluate the early predictors of poor prognosis.Results:A total of 130 neonates were enrolled, including 54 in RSS group and 76 in non-RSS group. Compared with the non-RSS group, the RSS group had significantly lower pH, base excess (BE), stroke volume index (SVI), cardiac output (CO) and cardiac index (CI).Meanwhile, the RSS group had significantly higher mean arterial pressure (MAP) to CI ratio (MAP/CI) and SSS [including bedside SSS (bSSS), computed SSS (cSSS) and modified version of cSSS (mcSSS)] (all P<0.05). Multiple logistic regression analysis showed that increased MAP/CI was an independent predictor of RSS. The cut-off value of MAP/CI was 11.6 [sensitivity 62%, specificity 87%, positive predictive value (PPV) 79% and negative predictive value (NPV) 77%], with an area under the curve (AUC) of 0.734. Increased mcSSS was an independent predictor of septic shock-related death. The cut-off value of mcSSS was 5.8 (sensitivity 83%, specificity 72%, PPV 21% and NPV 97%), with an AUC of 0.845. Conclusions:Increased MAP/CI (≥11.6) and mcSSS (≥5.8) may be early predictors of RSS and septic shock-related death in neonates.

Acute myeloid leukemia (AML) is a malignant clonal disease of hematopoietic stem cells, characterized by the proliferation of abnormal primordial cells of myeloid origin in bone marrow, blood and other tissues. At present, the standard induction therapy for AML mainly includes “3+7” standard treatment(anthracycline combined with cytarabine), allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and targeted drug therapy. However, AML cells usually express high levels of P-glycoprotein, which mediates the efflux of chemotherapeutic drugs, which makes AML cells resistant to chemotherapy, resulting in many patients who are not sensitive to chemotherapy or relapse after complete remission. And some patients can not tolerate intensive therapy or lack of donors and can not use Allo-HSCT therapy. Therefore, it is of great clinical significance to find new drugs to improve the efficacy of AML patients. Epigenetic disorders play a key role in the pathogenesis of many diseases, especially cancer. Studies have shown that most AML patients have epigenetic regulatory gene mutations, such as DNMT3A, IDH and TET2, and these mutations are potentially reversible, which has become one of the therapeutic targets of AML. Histone deacetylase inhibitors (HDACi) can regulate the balance between histone acetylation and deacetylation, change the expression of proto-oncogenes or tumor suppressor genes that control cancer progression from epigenetics, and play an important role in many kinds of tumor therapy. At present, HDACi has shown the ability to induce differentiation, cell cycle arrest and apoptosis of AML cells. The mechanism may be mainly related to HDACi inducing chromatin conformation opening of tumor suppressor gene by inhibiting HDAC activity, promoting oncogene damage and preventing oncogene fusion protein from recruiting HDAC. Although the preclinical outcome of HDACi is promising, it is not as effective as the conventional therapy of AML. However, the combination strategy with various anticancer drugs is in clinical trials, showing significant anti-AML activity, improving efficacy through key targeting pathways in a typical synergistic or additive way, increasing AML sensitivity to chemotherapy, reducing tumor growth and metastasis potential, inhibiting cell mitotic activity, inducing cell apoptosis, regulating bone marrow microenvironment, which provides a good choice for the treatment of AML. Especially for those AML patients who are not suitable for intensive therapy and drug resistance to chemotherapy. This review introduces the relationship between HDAC and cancer; the classification of HDAC and its function in AML; the correlation between HDAC and AML; the clinical application of five types of HDACi; preclinical research results and clinical application progress of six kinds of HDACi in AML, such as Vrinota, Belinostat, Panobinostat, Valproic acid, Entinostat, and Chidamide, the mechanism of HDACi combined with other anticancer drugs in AML indicates that the current HDACi is mainly aimed at various subtypes of pan-HDAC inhibitors, with obvious side effects, such as fatigue, thrombocytopenia, nausea, vomiting, diarrhea. In recent years, the next generation of HDACi is mainly focused on the selectivity of analogues or isomers. Finding the best combination of HDACi and other drugs and the best timing of administration to balance the efficacy and adverse reactions is a major challenge in the treatment of AML, and the continued development of selective HDACi with less side effects and more accurate location is the key point for the development of this drug in the future. It is expected to provide reference for clinical treatment of AML.

Objective:To compare the therapeutic effects of modified plantar skin grafting and thigh skin grafting on the deep burn wounds of the back and buttocks.Methods:A retrospective cohort study was conducted to analyze the clinical data of 30 patients with deep burn wounds on their back and buttocks who were admitted to the 910th Hospital of Joint Logistic Support Force of PLA from January 2021 to April 2023, including 26 males and 4 females, aged 21-72 years [(49.9±14.0)years]. The total burn size was 50%-97% of the total body surface area (TBSA), with the third-degree burn on the back and buttocks 6%-16% TBSA. The burn wounds on the back and buttocks were repaired using plantar skin grafts alone, thigh skin grafts alone or plantar skin grafts combined with the grafts from other body parts. The patients were grouped according to the skin graft donor sites and the times of harvesting skin grafts: there were 20 patients undergone plantar skin grafting including 10 patient with plantar skin graft harvested once (group of plantar skin graft harvested once) and 10 patients with plantar skin graft harvested twice or three times (group of plantar skin graft harvested more than once), and 10 patients undergone thigh skin grafting harvested once (group of thigh skin graft harvested once). The areas of plantar skin grafts harvested at the last time and the wound areas on the back and butts that could be repaired each time were calculated. After the last harvest, the thickness of the stratum corneum, 7-day survival rate of the skin grafts, proportion of 3-month residual wound area in the skin graft area, healing time of the donor sites, and 6-month Vancouver Scar Scale (VSS) scores of the donor sites in the group of plantar skin graft harvested once were compared with those in the group of thigh skin graft harvested once and the group of plantar skin graft harvested more than once. The appearance and texture of the skin graft, patients′ walking patterns and complications were observed at 6 months after the last skin harvest.Results:All the patients were followed up for 6-18 months [(7.8±1.6)months]. In the 20 patients with plantar skin grafts harvested, the areas of skin grafts harvested at the last time were 2.5%-4.5% TBSA [(3.4±0.6)% TBSA] and the wound areas that could be repaired each time were 3%-8% TBSA [(5.5±1.5)% TBSA]. After the last harvest, the thickness of the stratum corneum in the group of plantar skin graft harvested once was (190.4±8.9)μm, which was significantly thicker than that in the group of thigh skin graft harvested once [(50.0±6.6)μm] and that in the group of plantar skin graft harvested more than once [(166.8±21.9)μm] ( P<0.01); the 7-day survival rate of the skin grafts, proportion of 3-month residual wound area in the skin graft area, healing time of the donor sites, and 6-month VSS scores of the donor sites were (93.6±2.3)%, 2.0 (0.1, 3.5)%, (9.9±1.8)days and (1.7±0.7)points in the group of plantar skin graft harvested once, (78.0±6.6)%, 5.3 (4.0, 5.8)%, (14.0±1.4)days and (4.9±2.3)points in the group of thigh skin graft harvested once, and (93.4±2.6) %, 2.0 (0.1, 3.8)%, (10.0±1.2)days and (1.8±0.8)points in the group of plantar skin graft harvested more than once. The group of plantar skin graft harvested once showed a significant increase in the 7-day survival rate and a significant decrease in the proportion of 3-month residual wound area in the skin graft area, healing time of the donor sites, and 6-month VSS scores of the donor sites in comparison with the group of thigh skin graft harvested once ( P<0.05 or 0.01), while there were no significant differences in above mentioned indices between the group of plantar skin graft harvested once and the group of plantar skin graft harvested more than once ( P>0.05). At 6 months after the last skin harvest, the skin graft areas on the back and buttocks were flat, hard and firm and all the patients in the three groups could walk normally, with no complications such as severe itching, pain or folliculitis in the skin graft area. Conclusions:In the treatment of burn wounds on the back and buttocks, compared with thigh skin grafting, modified plantar skin grafting has advantages of thicker stratum corneum, better wear resistance and pressure resistance in the skin graft areas, a higher survival rate of skin grafts, rapid healing, mild scar, and undisturbed walking pattern after surgery and no common complications. Moreover, skin grafts can be harvested repeatedly from the donor sites, with no impact on the therapeutic effects.