Objective: To analyze the association of cytogenetic abnormalities with the prognosis of chronic myeloid leukemia (CML) patients in tyrosine kinase inhibitors (TKI) era. Methods: Karyotype analysis of chromosome G-banding was carried out in 387 newly diagnosed CML patients by short-term culture of bone marrow cells. The correlation of cytogenetic abnormalities and CML progression was explored in combination with ABL tyrosine point mutations. Result: Of 387 patients with positive BCR-ABL fusion gene assayed by fluorescence in situ hybridization (FISH) technique, 94.1% (364/387) patients were Ph positive and 5.9% (23/387) Ph negative; 320 patients (87.9%) had a translocation t (9;22) (q34;q11) and 5 (1.4%) a variant translocation t (v;22) . Additional cytogenetic aberrations (ACA) at diagnosis were found in 10.7% (39/387) Ph⁺ patients, major route ACA in 22 (56.4%) cases and minor route ACA in 15 (38.5%) cases and 2 patients (5.1%) lacked the Y chromosome (−Y) ; 23.4% (71/303) patients occurred ACA during TKI treatment and the most frequent abnormalities were abnormal chromosome numbersd, which were likely associated with high proportion of disease progression (χ²=168.21, P<0.001) and ABL tyrosine point mutations (χ²=29.04, P<0.001) . Newly diagnosed CML-CP patients with t (9;22) (q34;q11) had a longer event-free survival (EFS) and disease-free survival (DFS) rates than that of patients with ACA (P=0.037; P=0.003) , while the overall survival (OS) had no significant differences (P=0.209) . As for CML-CP patients that occurred ACA during TKI therapy would have a marked low OS, EFS and DFS (all P<0.001) compared with no ACA occurred patients. Survival of advanced patients that occurred ACA were dramatically reduced. Conclusion ACA often emerged during the disease progress in CML patients, regular and timely detection of chromosomes karyotype and ABL tyrosine point mutations during TKI treatment was important for therapeutic evaluation, progress and prognosis of CML.

Objective: To investigate the clinical implications of p16 gene deletion in adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph⁺ ALL) . Methods: Retrospective analysis of clinical, immunophenotypic, cytogenetics, molecular characteristics and prognosis of 80 newly diagnosed Ph⁺ ALL patients with p16 deletion. Results: Of 80 adult Ph⁺ ALL, the prevalence of p16 gene deletion was 31.3%. p16 gene deletion carriers frequently accompanied with high WBC counts (WBC≥30×10⁹/L) and CD20 expression. The incidence of complex chromosome abnormality in p16 gene deletion group was higher than that in non-deletion group, with alternations in chromosome 7, 8, 19 and der (22) more frequently observed. There was no difference occurred between patients with or without p16 gene deletion in complete remission (CR) rate following induction chemotherapy combined with tyrosine kinase inhibitors (TKIs) . However, after three cycles of chemotherapy, the MMR and CMR rate in the p16 gene deletion group was lower than patients with wild-type p16 gene (P=0.034, P=0.036) . The p16 gene deletion patients showed no significant differences in MMR, CMR and relapse rate between Imatinib or Dasatinib plus chemotherapy (P>0.05) . Deletion of p16 gene was significantly associated with poor outcomes including worse overall survival (OS) (37.1% vs 54.1%, P=0.037) , lower disease free-survival (DFS) (12.4% vs 45.9%, P=0.026) , and increased cumulative incidence of relapse (P=0.033) . Among the 25 patients with p16 deletion, 14 underwent allo-HSCT and the median survival was 21 months, better than that of patients received chemotherapy alone (12 months) (P=0.030) . Conclusion This study indicated that deletion of p16 was associated with poor prognosis in adult Ph⁺ ALL, and the utility of second-generation TKI (Dasatinib) does not necessarily have an edge on efficacy over Imatinib, but allo-HSCT has the potential of elongating life expectancy. It is an important significance to define the status of p16 in Ph⁺ ALL for predicting prognosis and guiding therapy decision-making.

Objective:To investigate the mechanism of curcumin in the treatment of diabetic retinopathy (DR) by network pharmacology and molecular docking.Methods:The compounds targets of curcumin were predicted by SEA and SwissTargetPrediction databases, and the DR target genes were obtained by CTD database.The different genes were mapped and matched by Venny database to screen their intersections.The intersecting genes were submitted to GeneMANIA database to construct a protein-protein interaction network.WebGestalt database was used to conduct enrichment analysis and AutoDock Vina was used to perform molecular docking of the core targets.Results:A total of 52 targets of curcumin, 1 599 targets of DR and 48 intersecting targets were detected.The core targets were serine/threonine-protein kinase 1 (AKT1), tumor necrosis factor-α (TNF-α), epidermal growth factor receptor (EGFR), signal transduction and activator of transcription 3 (STAT3) and heat shock protein 90 alpha family class A member 1 (HSP90AA1). Enrichment analysis suggested that these targets were mainly associated with signaling pathways, including the EGFR tyrosine kinase inhibitor resistance signaling pathway, hypoxia-inducible factor-1 (HIF-1) signaling pathway, interleukin (IL)-17 signaling pathway and advanced glycosylation end product-the receptor of advanced glycosylation end product (AGE-RAGE) signaling pathway.Conclusions:Curcumin may play an important role in the treatment of DR by regulating multiple signaling pathways to inhibit the inflammatory response and combat oxidative stress.

Objective:To investigate the vaccination status, characteristics and prognosis of patients suffering from a combination of COVID-19 and chronic lymphocytic anemia (CLL) in China.Methods:Clinical data of 328 patients with chronic lymphocytic leukemia (CLL) who were first diagnosed with COVID-19 and treated in the Department of Hematology of Jiangsu Provincial People’s Hospital between November 2022 and February 2023 were retrospectively analyzed. Univariate and multivariate analysis of data of patients with severe/critical COVID-19 were conducted by applying the binary logistic regression model.Results:The median age of the CLL patients was 60 (24-87) years. 23.5% (77/328) of these patients suffered from severe/critical COVID-19 infection. Univariate analysis of the data demonstrated that a combination of factors including age >67 years ( OR=2.15, 95% CI 1.24- 3.73, P=0.006), diabetes ( OR=2.09, 95% CI 1.05-4.20, P=0.037), chronic hepatitis B ( OR=2.91, 95% CI 1.30-6.51, P=0.010), CLL progressive ( OR=3.79, 95% CI 1.57-9.15, P=0.003) and CD20 antibody-based treatments within three months prior to the COVID-19 infection ( OR=2.79, 95% CI 1.35-5.77, P=0.006) were the risk factors for severe/critical COVID-19. According to the multivariate analysis, CLL progressive ( OR=2.98, 95% CI 1.10-8.10, P=0.033) was an independent risk factor for severe/critical COVID-19 and administration of the BTK (Bruton tyrosine kinase) inhibitor monotherapy might exert a protective effect and influence a positive outcome of the COVID-19 infection ( OR=0.38, 95% CI 0.16-0.90, P=0.028). Among the 242 patients who were followed up until October 2023, 9.1% (22/242) had multiple subsequent COVID-19 infections (≥3), and 2.1% (5/242) had persistent COVID-19 infections (patients with persistent positive test for the SARS-CoV-2 antigen testing until missing follow-up for any reason). The peak value of the anti-SARS-CoV-2-IgG titres was observed between three and four months post symptom onset (median: 3.511 S/CO vs 1.047 S/CO, P<0.05). The levels of immunoglobulin A gradually decreased following infection with COVID-19, and its trough levels were attained between two to four weeks post infection (median: 0.30 g/L vs 0.74 g/L, P<0.05). According to this study the mortality of patients suffering from a combination of COVID-19 infection and CLL was 2.7% (9/328), and the main reason for their death was respiratory failure and heart failure. Conclusions:A low rate of COVID-19 vaccination and a high rate of severe/critical COVID-19 infection was observed in the CLL patients. CLL progressive was associated with severe/critical COVID-19. Anti-CD20-based treatments received within the past three months might be a risk factor for exacerbation of COVID-19 infection, whereas a monotherapy with BTK inhibitors exert a protective effect and improve outcome of COVID-19 infection.

Objective Based on intra-set correlation analysis, this paper deconstructs the clinical medical records of traditional Chinese medicine (TCM) Master ZHOU Zhongying in treating thyroid cancer, and analyzes the experience in “mechanism-syndrome-medicine-prescription” for thyroid cancer. Methods Through Medcase data processing platform, based on Frequent Pattern (FP)-Growth enhanced correlation analysis algorithm, the medical records of Professor ZHOU Zhongying for the treatment of thyroid cancer from June 1, 2001 to February 28, 2015 were analyzed within the set. Results This study involved 43 medical records, 43 patients, and 167 visits. After processing intra-set correlations, 28 groups of highly correlated symptoms, 21 groups of highly correlated tongue images, 10 groups of highly correlated pulse conditions, 28 groups of highly correlated pathogenesis, 34 groups of highly correlated herbs, and 26 groups of highly correlated western medicine diagnosis were selected. Professor ZHOU Zhongying treats thyroid cancer according to syndrome differentiation. Symptoms with more association rules included neck swelling, neck pain, cough, and dry mouth; tongue images with more association rules included dark purple tongue, dark red tongue, and fissured tongue; pulse conditions with more association rules were wiry pulse, thready pulse, small pulse, and slippery pulse; the pathogenesis with more association rules was phlegm and blood stasis, damp-heat accumulation, and impairment of both Qi and Yin; herbs with more association rules were Chaihu (Bupleuri Radix), Zeqi (Sun Euphoribiae Herb), and Tiandong (Asparagi Radix); western medicine diagnosis with more association rules included thyroid cancer, insomnia, and chronic gastritis. Conclusion Thyroid cancer mostly presents as deficiency in origin and excess in manifestations. The basic pathogenesis is phlegm and blood stasis, damp-heat accumulation, and impairment of both Qi and Yin, which are closely related to liver, kidney, and spleen. Professor ZHOU Zhongying adopts both attack and supplement approaches as the general treatment principle, with a strong emphasis on regulating Qi and relieving depression, eliminating phlegm and resolving stagnation, eliminating dampness and turbidity, clearing fire and destroying poison, moistening dryness and softening hard mass, invigorating Qi and nourishing Yin, and paying attention to nourishing liver and kidney, invigorating spleen and stomach, while protecting the heart and lungs.

The pathological hallmarks of psoriasis involve alterations in T cell genes associated with transcriptional levels, which are determined by chromatin accessibility. However, to what extent these alterations in T cell transcriptional levels recapitulate the epigenetic features of psoriasis remains unknown. Here, we systematically profiled chromatin accessibility on Th1, Th2, Th1-17, Th17, and Treg cells and found that chromatin remodeling contributes significantly to the pathogenesis of the disease. The chromatin remodeling tendency of different subtypes of Th cells were relatively consistent. Next, we profiled chromatin accessibility and transcriptional dynamics on memory Th/Treg cells. In the memory Th cells, 803 increased and 545 decreased chromatin-accessible regions were identified. In the memory Treg cells, 713 increased and 1206 decreased chromatin-accessible regions were identified. A total of 54 and 53 genes were differentially expressed in the peaks associated with the memory Th and Treg cells. FOSL1, SPI1, ATF3, NFKB1, RUNX, ETV4, ERG, FLI1, and ETC1 were identified as regulators in the development of psoriasis. The transcriptional regulatory network showed that NFKB1 and RELA were highly connected and central to the network. NFKB1 regulated the genes of CCL3, CXCL2, and IL1RN. Our results provided candidate transcription factors and a foundational framework of the regulomes of the disease.
Chromatin/genetics* ; Chromatin Assembly and Disassembly ; Gene Regulatory Networks ; Humans ; Psoriasis/genetics* ; T-Lymphocytes, Regulatory

Objective To explore the role and mechanism of RNA demethylase fat mass and obesity-associated protein(FTO)in the ferroptosis in testicular interstitial cells induced by di(2-ethylhexyl)phthalate(DEHP).Methods Forty 3-week-old C57BL/6 male mice were randomly divided into a control group(corn oil)and 3 dosed DEHP treatment groups(5,250 and 500 mg/kg),and received an intragastric infusion of corresponding agents for 35 d,respectively.After mouse testicular interstitial TM3 cells was treated with 0,100,200 and 400 μmol/L mono-2-ethylhexyl phthalate(MEHP)for 24 h,corresponding plasmids were transfected to construct Fto overexpressing TM3 cells.Serum testosterone level was detected by ELISA,expression of testicular proteins was detected with immunohistochemical assay,and contents of Fe2+,malondialdehyde(MDA)and lipid peroxides in the testicle were detected by colorimetry.Methylated RNA immunoprecipitation,RT-PCR,and Western blotting were used to detect the level of N6-methyladenosine(m6A)modification.Results In the mice exposed to 250 and 500 mg/kg DEHP,the serum testosterone level was significantly reduced(P＜0.01),contents of Fe2+,MAD and lipid peroxides in testicular tissue were obviously increased(P＜0.01),and protein levels of RNA demethylase FTO,and ferroptosis related molecules ferritin heavy chain 1(FTH1)and glutathione peroxidase 4(GPX4)were significantly down-regulated(P＜0.05),while those of transferrin receptor(TFRC),ferroportin(FPN),cyclooxygenase-2(COX-2),and acyl-CoA synthetase long-chain family member 4(ACSL4)were notably up-regulated(P＜0.05).MEHP treatment for 24 h resulted in remarkably decreased cell viability in the TM3 cells,increased production of intracellular reactive oxygen species(ROS),reduced mitochondrial membrane potential(MMP)(P＜0.01),down-regulated mRNA and protein levels of Fto(P＜0.01),and the changes in other ferroptosis related proteins were consistent with the trend in testicular tissue,indicating ferroptosis in testicular interstitial cells.Intervention with ferroptosis inhibitor Fer-1 or overexpression of Fto significantly inhibited MEHP-induced toxicity and ferroptosis in TM3 cells(P＜0.05),and overexpression of Fto reduced the m6A modification of Gpx4 and Fth1 mRNA(P＜0.05).Conclusion Abnormal m6A modification of Gpx4 and Fth1 caused by inhibiting FTO expression may be the mechanism of ferroptosis in testicular interstitial cells induced by DEHP.