Objective:To investigate the clinical, laboratory, and prognostic features of myelodysplastic neoplasm (MDS) patients harboring acute myeloid leukemia (AML) -like mutations.Methods:We retrospectively analyzed clinical, molecular, and outcome data from 1 464 adults with primary MDS diagnosed at the Institute of Hematology and Blood Diseases Hospital from August 2016 to June 2024.Results:AML-like mutations were detected in 64 patients (4.4% ). Compared with patients without AML-like mutations, those with AML-like mutations were younger [median 50 ( IQR 39–60) vs 56 (45, 65) years; P=0.001], more often female (51.6% vs 35.4% ; P=0.009), had higher bone marrow blast percentage [6.5% (3.0%, 10.5% ) vs 2.5% (1.0%, 7.0% ) ; P<0.001], a higher rate of normal karyotype (75.0% vs 48.1% ; P<0.001), and lower hemoglobin levels [73 (67, 82) g/L vs 80 (66, 98) g/L; P=0.006]. The AML-like group had a higher number of gene mutations than the non-AML-like group [3 ( IQR 2–4) vs 2 (1, 3) ; P<0.001). It was enriched for mutations in NPM1, DNMT3A, WT1, PTPN11, NRAS, BCOR, FLT3, CEBPA, and MYC (all P<0.05) and had lower rates of U2AF1, ASXL1, and TP53 mutations (all P<0.05). Overall survival (OS) did not differ between groups ( P=0.730) ; however, the AML-like group had significantly shorter leukemia-free survival (LFS) [19 months (95% CI: 13–25) vs 46 months (95% CI: 38–54) ; P=0.012] and a higher 2-year cumulative incidence of AML transformation [ (41.7±9.1) % vs (10.4±1.1) % ; P<0.001]. Within the AML-like group, OS, LFS, and cumulative incidence of AML transformation did not differ between patients with low blasts and those with excess blasts (IB). Multivariable Cox regression identified age ≥60 years and PTPN11 mutations as independent adverse prognostic factors for OS, while DNMT3A, PTPN11, and FLT3 mutations independently predicted leukemic transformation. Conclusions:MDS patients harboring AML-like mutations exhibit distinct clinical and molecular features and a higher risk of progression to AML.

Objective:To explore the effects of IFN-γ on IL-8 secretion by human liver cancer cells and the impact on their malignant biological functions in vitro. Methods:HuH7 and Hep3B cells were treated with different concentrations of IFN-γ for 24 or 48 h. Changes in the cellular activity, IL-8 secretion, and the proportion of CD133 + liver cancer stem cells were evaluated using CCK8 kit and flow cytometry. Western blot was used to detect the effects of IFN-γ on the expression of several molecules such as phosphorylated protein kinase B (p-Akt), phosphorylated c-Jun N-terminal kinase (p-JNK), vimentin, and E-cadherin in the liver cancer cells. Effects of IFN-γ with or without IL-8 on the migration of liver cancer cells were detected by transwell assay. Additionally, effects of IFN-γ combined with IL-8 or IL-8 receptor inhibitor repertaxin on the differentiation of liver cancer stem cells were detected by flow cytometry. One-way analysis of variance and Tukey-Kramer test were used for statistical analysis. Results:HuH7 and Hep3B cells secreted significantly higher levels of IL-8 than normal hepatocytes LO2 ( P<0.01) and high expression level of IL-8 gene ( CXCL8) was closely correlated with the expression levels of vimentin gene ( VIMENTIN), CD133 gene ( PRCM1), PD-L1 gene ( CD274), PD-1 gene ( PDCD1), and CD163 gene ( CD163), as well as the poor prognosis of liver cancer patients ( P<0.01). IFN-γ (1-100 ng/ml) had no significant effect on the proliferative activity of HuH7 and Hep3B cells ( P>0.05), but could significantly inhibit IL-8 secretion, cell migration, CD133 + liver cancer stem cell differentiation and suspension tumor sphere formation through the Akt and JNK pathways ( P<0.01). IFN-γ combined with IL-8 could significantly reversed the inhibitory effects of IFN-γ on liver cancer cell migration, stem cell differentiation, and suspension tumor sphere formation ( P<0.01). IFN-γ in combination with repertaxin could synergistically inhibited the differentiation of CD133 + liver cancer stem cells ( P<0.01). Conclusion:IFN-γ inhibits the differentiation and migration of human liver cancer cells through the Akt/JNK-IL-8 signaling pathway, providing a new strategy for future clinical immunotherapy of liver cancer.

Objective:To investigate risk factors for adverse pregnancy outcomes(APO) in women with hypertriglyceridemia(HTG) during late pregnancy despite normal thyroid function, focusing on thyroid-stimulating hormone receptor(TSHR) levels.Methods:A total of 242 pregnant women with normal thyroid function who delivered in General Hospital of Central Theater Command from October 2023 to June 2024 were divided into HTG( n=111) and non-HTG groups( n=131). Clinical data, lipid profiles, thyroid function, TSHR levels, and APO were compared, and the influencing factors of APO were analyzed. Results:Compared with non-HTG group, APO, adverse maternal outcomes, and gestational diabetes mellitus(GDM) were significantly more frequent in the HTG group( P<0.05). The HTG group also had higher triglyceride(TG), fasting plasma glucose(FPG), triglyceride glucose index(TyG), triglyceride/high density lipoprotein cholesterol(TG/HDL-C), thyroid stimulating hormone(TSH) and TSHR, with lower free triiodothyronine (FT 3)( P<0.05). TSHR was an independent risk factor for APO, maternal adverse outcomes, and GDM in all pregnant women( OR=1.112, 95% CI 1.007-1.229; OR=1.126, 95% CI 1.020-1.243; OR=1.133, 95% CI 1.025-1.253) and was also an independent risk factor for APO in the HTG group( OR=1.165, 95% CI 1.005-1.351). Conclusion:Pregnant women with normal thyroid function and HTG in late pregnancy are more likely to have APO, manifested as maternal adverse outcomes and GDM. TSHR is an independent risk factor for APO.

Objective To establish a 103-plex InDel-SNP composite marker amplification system based on Ion Torrent PGM/S5 sequencing platform targeting fragment length less than 175bp,providing an efficient analytical tool for forensic individual identification and paternity identification.Methods Using the human genome GRCh38 as the reference sequence,InDel-SNP composite marker loci suitable for Chinese population were screened from 22 pairs of autosomes and sex chromosomes by using dbSNP database with East Asian population as the target population.Population genetic data of 267 unrelated individuals of Han nationality in Shandong province were investigated,and genetic relationship was verified using 16 real triplet families.Results The 103-plex InDel-SNP composite marker detection system developed in this study,based on the second-generation sequencing platform,exhibits notable features including high sensitivity,excellent stability,strong specificity,and wide applicability to conventional test materials.It effectively enables the determination of typing results for degraded and mixed samples.Conclusion All 16 parent triplet pairs demonstrated adherence to Mendelian inheritance law without any observed allelic dropout or mutation.This detection system holds significant value for forensic individual identification and paternity testing.

Gliomas, especially high-grade gliomas such as glioblastoma multiforme (GBM), are primary malignant tumors of the central nervous system, characterized by high proliferative capacity, invasiveness, and therapeutic resistance. The development of GBM relies heavily on continuous metabolic reprogramming to adapt to the unique intracranial microenvironment, with nicotinamide adenine dinucleotide (NAD⁺) metabolic remodeling playing a pivotal role. Dysregulation of NAD⁺ and its associated metabolic pathways sustains increased intracellular NAD⁺ levels, which drive the malignant proliferation and invasive potential of GBM, correlating with worsened patient prognosis. This review systematically summarizes the current research landscape of NAD⁺ metabolic remodeling in GBM, elucidates the mechanisms by which NAD⁺ contributes to GBM pathogenesis and progression, and explores the clinical potential of NAD⁺-targeted diagnostic and therapeutic strategies to provide novel insights and directions for the clinical management of GBM.

Objective:To investigate the clinical, laboratory, and prognostic features of myelodysplastic neoplasm (MDS) patients harboring acute myeloid leukemia (AML) -like mutations.Methods:We retrospectively analyzed clinical, molecular, and outcome data from 1 464 adults with primary MDS diagnosed at the Institute of Hematology and Blood Diseases Hospital from August 2016 to June 2024.Results:AML-like mutations were detected in 64 patients (4.4% ). Compared with patients without AML-like mutations, those with AML-like mutations were younger [median 50 ( IQR 39–60) vs 56 (45, 65) years; P=0.001], more often female (51.6% vs 35.4% ; P=0.009), had higher bone marrow blast percentage [6.5% (3.0%, 10.5% ) vs 2.5% (1.0%, 7.0% ) ; P<0.001], a higher rate of normal karyotype (75.0% vs 48.1% ; P<0.001), and lower hemoglobin levels [73 (67, 82) g/L vs 80 (66, 98) g/L; P=0.006]. The AML-like group had a higher number of gene mutations than the non-AML-like group [3 ( IQR 2–4) vs 2 (1, 3) ; P<0.001). It was enriched for mutations in NPM1, DNMT3A, WT1, PTPN11, NRAS, BCOR, FLT3, CEBPA, and MYC (all P<0.05) and had lower rates of U2AF1, ASXL1, and TP53 mutations (all P<0.05). Overall survival (OS) did not differ between groups ( P=0.730) ; however, the AML-like group had significantly shorter leukemia-free survival (LFS) [19 months (95% CI: 13–25) vs 46 months (95% CI: 38–54) ; P=0.012] and a higher 2-year cumulative incidence of AML transformation [ (41.7±9.1) % vs (10.4±1.1) % ; P<0.001]. Within the AML-like group, OS, LFS, and cumulative incidence of AML transformation did not differ between patients with low blasts and those with excess blasts (IB). Multivariable Cox regression identified age ≥60 years and PTPN11 mutations as independent adverse prognostic factors for OS, while DNMT3A, PTPN11, and FLT3 mutations independently predicted leukemic transformation. Conclusions:MDS patients harboring AML-like mutations exhibit distinct clinical and molecular features and a higher risk of progression to AML.

Objective:To explore the effects of IFN-γ on IL-8 secretion by human liver cancer cells and the impact on their malignant biological functions in vitro. Methods:HuH7 and Hep3B cells were treated with different concentrations of IFN-γ for 24 or 48 h. Changes in the cellular activity, IL-8 secretion, and the proportion of CD133 + liver cancer stem cells were evaluated using CCK8 kit and flow cytometry. Western blot was used to detect the effects of IFN-γ on the expression of several molecules such as phosphorylated protein kinase B (p-Akt), phosphorylated c-Jun N-terminal kinase (p-JNK), vimentin, and E-cadherin in the liver cancer cells. Effects of IFN-γ with or without IL-8 on the migration of liver cancer cells were detected by transwell assay. Additionally, effects of IFN-γ combined with IL-8 or IL-8 receptor inhibitor repertaxin on the differentiation of liver cancer stem cells were detected by flow cytometry. One-way analysis of variance and Tukey-Kramer test were used for statistical analysis. Results:HuH7 and Hep3B cells secreted significantly higher levels of IL-8 than normal hepatocytes LO2 ( P<0.01) and high expression level of IL-8 gene ( CXCL8) was closely correlated with the expression levels of vimentin gene ( VIMENTIN), CD133 gene ( PRCM1), PD-L1 gene ( CD274), PD-1 gene ( PDCD1), and CD163 gene ( CD163), as well as the poor prognosis of liver cancer patients ( P<0.01). IFN-γ (1-100 ng/ml) had no significant effect on the proliferative activity of HuH7 and Hep3B cells ( P>0.05), but could significantly inhibit IL-8 secretion, cell migration, CD133 + liver cancer stem cell differentiation and suspension tumor sphere formation through the Akt and JNK pathways ( P<0.01). IFN-γ combined with IL-8 could significantly reversed the inhibitory effects of IFN-γ on liver cancer cell migration, stem cell differentiation, and suspension tumor sphere formation ( P<0.01). IFN-γ in combination with repertaxin could synergistically inhibited the differentiation of CD133 + liver cancer stem cells ( P<0.01). Conclusion:IFN-γ inhibits the differentiation and migration of human liver cancer cells through the Akt/JNK-IL-8 signaling pathway, providing a new strategy for future clinical immunotherapy of liver cancer.

Objective:To investigate risk factors for adverse pregnancy outcomes(APO) in women with hypertriglyceridemia(HTG) during late pregnancy despite normal thyroid function, focusing on thyroid-stimulating hormone receptor(TSHR) levels.Methods:A total of 242 pregnant women with normal thyroid function who delivered in General Hospital of Central Theater Command from October 2023 to June 2024 were divided into HTG( n=111) and non-HTG groups( n=131). Clinical data, lipid profiles, thyroid function, TSHR levels, and APO were compared, and the influencing factors of APO were analyzed. Results:Compared with non-HTG group, APO, adverse maternal outcomes, and gestational diabetes mellitus(GDM) were significantly more frequent in the HTG group( P<0.05). The HTG group also had higher triglyceride(TG), fasting plasma glucose(FPG), triglyceride glucose index(TyG), triglyceride/high density lipoprotein cholesterol(TG/HDL-C), thyroid stimulating hormone(TSH) and TSHR, with lower free triiodothyronine (FT 3)( P<0.05). TSHR was an independent risk factor for APO, maternal adverse outcomes, and GDM in all pregnant women( OR=1.112, 95% CI 1.007-1.229; OR=1.126, 95% CI 1.020-1.243; OR=1.133, 95% CI 1.025-1.253) and was also an independent risk factor for APO in the HTG group( OR=1.165, 95% CI 1.005-1.351). Conclusion:Pregnant women with normal thyroid function and HTG in late pregnancy are more likely to have APO, manifested as maternal adverse outcomes and GDM. TSHR is an independent risk factor for APO.

Objective:To compare the effects of erector spinae plane block at T 2 (T 2-ESPB) and nerve root block at C 5 (C 5-NRB) in patients undergoing arthroscopic shoulder surgery with general anesthesia. Methods:This was a randomized, controlled, non-inferiority study. Sixty American Society of Anesthesiologists Physical Status classification I or Ⅱ patients, aged 45-75 yr, with body mass index ≤35 kg/m 2, scheduled for elective arthroscopic shoulder surgery at Jining No. 1 People′s Hospital from April 2023 to February 2024, were included and divided into 2 groups ( n=30 each) using a random number table method: C 5-NRB group (group C) and T 2-ESPB group (group T). In group C, C 5-NRB was carried out by injecting 0.5% ropivacaine 5 ml. In group T, T 2-ESPB was performed by injecting 0.25% ropivacaine 30 ml. The efficacy of nerve block was assessed using a prick test at 30 min after administration, and then total intravenous anesthesia was performed in both groups. The time to first rescue analgesia (the non-inferiority boundary Δ =2 h), requirement for rescue analgesia within 24 h after operation and intraoperative consumption of anesthetics were recorded. The motor function of the affected limb during shoulder abduction, elbow flexion and elbow extension was assessed and scored using the modified Bromage scale (MBS) at 30 min and 4 and 12 h after nerve block. The diaphragmatic excursion was measured and recorded using M-mode ultrasound before nerve block and at 30 min after nerve block to evaluate the occurrence of diaphragmatic paralysis. Complications such as local anesthetic toxicity, recurrent laryngeal nerve block and pneumothorax were also recorded. Results:The mean difference (95% confidence interval) for the time to first rescue analgesia between the two groups was 5.551 (1.875-9.148) h, with the upper limit exceeding the non-inferiority boundary. Compared with group T, the intraoperative consumption of remifentanil was significantly reduced, the time to first rescue analgesia was prolonged, the consumption of morphine for rescue analgesia was decreased, MBS scores during shoulder abduction, elbow flexion and elbow extension were decreased at 30 min after block, and MBS scores during shoulder abduction and elbow flexion were decreased at 4 and 12 h after block in group C ( P<0.05). There was no significant difference in the diaphragmatic excursion, incidence of diaphragm paralysis and incidence of complications before and after block in the two groups ( P>0.05). Conclusions:C 5-NRB provides superior efficacy compared to T 2-ESPB when used for arthroscopic shoulder surgery under general anesthesia.

Objective To explore the cost effectiveness of osimertinib and gefitinib in the treatment of advanced non-small cell lung cancer （NSCLC） with epidermal growth factor receptor （EGFR） mutation. Methods A total of 52 advanced NSCLC patients with EGFR mutation treated by osimertinib were selected as group A from June 2021 to August 2022 at the Chengde Central Hospital, and 52 patients treated by gefitinib were selected as group B according to the propensity score matching method in 1∶1 ratio. The treatment cost and effect of the two groups of patients were compared, and the cost-effectiveness ratio was calculated, and sensitivity analysis was conducted. Results The total effective rate of group A was higher than that of group B （90.38% vs 71.15%, χ²=6.190, P=0.013）. The drug cost and total treatment cost of group A were higher than those of group B（P<0.05）, and other direct costs were lower than those of group B （P<0.05）. The incremental cost effectiveness ratio of group A was 374.71. After the cost-effectiveness sensitivity analysis on adjusting drug costs to decrease by 10% and the total effective rate to decrease by 10% of the two groups, the sensitivity analysis results were basically consistent with the original results. Conclusion Based on the latest prices and actual case data of osimertinib and gefitinib, osimertinib was better than gefitinib in the treatment of advanced NSCLC patients with EGFR mutation. Although gefitinib had lower treatment costs, osimertinib had more cost effectiveness advantages. These findings could provide important reference for the clinical development of treatment plans for advanced NSCLC patients with EGFR mutations.