Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m¹A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m¹A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.

Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.

During the Yan’an period, under the instructions of the CPC Central Committee and the Central Military Commission, the former Eighth Route Army Health School was expanded into China Medical University. As the first medical university founded by the Communist Party of China, this is a great practice of higher medical education in the new revolution. The school adhered to the policy of educating people with both ability and political integrity, the "saving the dying and healing the wounded, implementing revolutionary humanitarianism" has become the ideological guide and goal of the majority of revolutionary medical workers. The school provided a good teaching environment by strengthening teachers, enriching infrastructure and teaching equipment. Teachers and students have overcome difficulties and made great achievements in teaching and learning. At the same time, through the mass production movement and rectification movement, the development of the school was promoted from two aspects of material production and ideological construction. The practice of China Medical University in education policy, teaching curriculum and teaching content has certain enlightenment for today’s medical education.

Objective To explore the effect of arsenic trioxide maintenance therapy on the long-term recur-rence rate in patients with acute promyelocytic leukemia ( APL ) . Methods From December 2011 to December 2013,60 patients with APL in the First People's Hospital of Huzhou were selected and divided into control group and observation group according to random number table, with 30 cases in each group. All patients received the same induction therapy and consolidation therapy. During the maintenance treatment period, all - trans retinoic acid ( ATRA) was given to the control group,and arsenic trioxide was used in the observation group. The serum levels and incidence of adverse reactions in the two groups were detected and compared after two cycles of the maintenance therapy. Three years of follow - up was conducted after treatment to record and compare the recurrence rate and survival rate in the two groups. Results The levels of TC and TG after 1 and 2 cycles of treatment were higher than those before treatment in both two groups(all P<0. 05),but the levels of lipid indicators in the observation group were lower than those in the control group,and the differences were statistically significant (t=2. 044,2. 175,all P<0. 05). The incidence rates of retinoic acid syndrome,elevated intracranial pressure and other adverse reactions in the observation group during the treatment were lower than those in the control group(6. 67％ vs. 26. 67％,6. 67％ vs. 30. 00％,6. 67％ vs. 26. 67％),and the differences were statistically significant(χ2 =0. 043,0. 023,0. 043,all P<0. 05). The survival rates after 2 and 3 years of treatment in the observation group were higher than those in the control group(90. 00％ vs. 66. 67％,83. 33％ vs. 60. 00％),and the differences were statistically significant(χ2 =4. 812,4. 812,all P<0. 05). The recurrence rate after 3 years of treatment in the observation group was lower than that in the control group(10. 00％ vs. 33. 33％),and the difference was statistically significant(χ2 =4. 812,P <0. 05). Conclusion For patients with APL, the application of arsenic trioxide in the maintenance therapy can produce no significant effect on their lipid metabolism, and at a certain extent, can help reduce the incidence of adverse reactions and recurrence rate,and improve the survival rate.

OBJECTIVETo study the histocompatibility of three bio-derived bones.

METHODSAfter treatment with different physical and chemical method, three bio-derived bones, the composite fully deproteinized bone (CFDB), partially deproteinized bone (PDPB) and partially decalcified bone (PDCB) were implanted into rabbits. The toxicity, immune response and subperiosteum osteogenesis of CFDB, PDPB and PDCB were studied through gross observation, serum antibody measurement, evaluation of local cellular immune response and HE staining.

RESULTSThe study showed that CFDB, PDPB and PDCB had no toxicity. They could conduct peripheral tissue to grow into them and had no harmful effect on subperiosteum osteogenesis. They could also promote cartilage and osteoid tissue derived from periosteum to calcify to new bone, and combine with the peripheral bone. The degree of immune response caused by them was in the sequence of PDCB > PDPB > CFDB.

CONCLUSIONSThe three bio-derived bones, CFDB, PDPB and PDCB have good histocompatibility.

Animals ; Antibodies ; blood ; Bone Transplantation ; Bone and Bones ; immunology ; Female ; Histocompatibility ; Histocompatibility Testing ; Male ; Rabbits ; Tissue Engineering

To detect the properties of natural xenogeneic bone derived materials which were processed with different physical and chemical treatments, we made fully deproteinized bone(FDB), partially deproteinized bone (PDPB), partially decalcified bone(PDCB) from pig ribs. Their morphological features, constitute components and mechanical properties were examined by scanning electron microscopy, x-rays diffraction analysis, mechanical assay and so on. The results showed that FDB, PDPB and PDCB maintained natural network pore system. The ratios of calcium to phosphorus were 1.81, 1.74 and 1.50, and the protein contents were 0.01% +/- 0.02%, 22.41% +/- 0.83% and 35.75% +/- 2.12% respectively. The sequence of their mechanic strength was PDCB > PDPB > FDB. These data indicate that FDB, PDPB and PDCB possess natural network pore system. Their organic and inorganic component ratios and contents are different, so their mechanic properties are not alike. Additionally, more investigations will be necessary to detect the biocompatibility of the three different scaffold materials of natural derived bone.
Animals ; Biocompatible Materials ; chemistry ; Biomechanical Phenomena ; Bone and Bones ; chemistry ; Materials Testing ; Swine ; Tissue Engineering