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.

The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes much milder changes in far fewer genes. The abnormal gene expression is cardiomyocyte-autonomous and can be rescued by an enzyme-dead HDAC3 mutant but not by an HDAC3 mutant (Δ33-70) that lacks interaction with the nuclear-envelope protein lamina-associated polypeptide 2β (LAP2β). Tethering LAP2β to the HDAC3 Δ33-70 mutant restored its ability to rescue gene expression. Finally, HDAC3 depletion, not loss of HDAC3 enzymatic activity, exacerbates cardiac contractile functions upon aortic constriction. These results suggest that the cardiac function of HDAC3 in adults is not attributable to its enzyme activity, which has implications for understanding the cardioprotective effects of HDIs.

Left atrial appendage closure(LAAC)is an important intervention method for preventing thromboembolic events in patients with non-valvular atrial fibrillation(NVAF).However,incomplete endothelialization following the procedure can impact its long-term efficacy and safety.This article proposes the view of qi flourishment promoting tissue regeneration based on the traditional Chinese medicine(TCM)theory of qi and blood,and explores diagnostic and therapeutic strategies for post-LAAC incomplete endothelialization by examining the theoretical connotation of qi flourishment promoting tissue regeneration and the relationship between qi and vascular endothelial cells.It is proposed that the primary pathogenesis in patients after LAAC is due to qi deficiency.Guided by the view of qi flourishment promoting tissue regeneration,therapeutic approaches such as tonifying qi to promote granulation,supplementing qi to activate blood circulation,and harmonizing the viscera can be employed to address incomplete endothelialization in NVAF patients following LAAC.Clinically,the qi-supplementing and blood-activating classic formula Neituo Shengji San,mainly composed of Astragali Radix,Glycyrrhizae Radix et Rhizoma,Olibanum,Myrrha,Paeoniae Radix Alb,Trichosanthis Radix,Salviae Miltiorrhizae Radix et Rhizoma,etc.,is usually utilized for modified use.Depending on the specific symptom patterns or pathogenesis characteristics of patients with incomplete endothelialization,this basic formula may be used by combining with Shengmai San or augmented with qi-supplementing and blood-activating herbs such as Chuanxiong Rhizoma,Fici Simplicissimae Radix,and Notoginseng Radix et Rhizoma to promote endothelialization.Diagnosing and treating post-LAAC incomplete endothelialization in NVAF patients following the view of qi flourishment promoting tissue regeneration,it is expected to offer a novel TCM perspective and therapeutic strategy to enhance post-LAAC outcomes and address the challenge of incomplete endothelialization.This approach can further serve as a reference for TCM clinicians to manage endothelialization issues following implantation procedures.

Prolactin, a peptide hormone primarily synthesized and secreted by lactotrophs in the anterior pituitary gland, plays key roles in lactation, reproduction, and immune regulation. Recent research has highlighted its critical involvement in maintaining metabolic homeostasis, with both elevated and deficient levels disrupting metabolic functions such as glucose and lipid metabolism, as well as energy regulation. This study reviews recent advancements in prolactin and its receptors′ role in metabolic regulation, emphasizing its pivotal contribution to metabolic homeostasis.

Prolactin, a peptide hormone primarily synthesized and secreted by lactotrophs in the anterior pituitary gland, plays key roles in lactation, reproduction, and immune regulation. Recent research has highlighted its critical involvement in maintaining metabolic homeostasis, with both elevated and deficient levels disrupting metabolic functions such as glucose and lipid metabolism, as well as energy regulation. This study reviews recent advancements in prolactin and its receptors′ role in metabolic regulation, emphasizing its pivotal contribution to metabolic homeostasis.

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.

Objective To investigate whether prophylactic anticoagulation therapy can reduce the risk of postoperative complications in patients with primary liver cancer(PLC)after hepatectomy,and to explore the influencing factors of postoperative complications.Methods The clinical data of 495 patients undergoing hepatectomy for PLC in The Third Affiliated Hospital of Naval Medical University(Second Military Medical University)from Feb.2019 to May 2021 were collected.The patients were divided into anticoagulation group(n=287,receiving prophylactic low-molecular-weight heparin after surgery)and conventional treatment group(n=208).The postoperative complications were compared between the 2 groups,and the influencing factors were analyzed using logistic regression model.Results The postoperative overall complication incidence of the 495 patients after hepatectomy was 30.7％(152/495),ranking as infection(9.1％,45/495),acute respiratory distress syndrome(ARDS;6.5％,32/495),bleeding(6.3％,31/495),post-hepatectomy liver failure(PHLF;6.1％,30/495),and venous thromboembolism(VTE;2.8％,14/495).The incidence rates of postoperative VTE,ARDS,and PHLF were significantly lower in the anticoagulation group than those in the conventional treatment group(1.4％[4/287]vs 4.8％[10/208],3.8％[11/287]vs 10.1％[21/208],and 3.8％[11/287]vs 9.1％[19/208];all P＜0.05),but there was no significant difference in the incidence of postoperative bleeding between the 2 groups(P＞0.05).Multivariate logistic regression analysis showed that age,portal hypertension,and tumor number were independent risk factors for postoperative VTE;portal hypertension,intraoperative blood loss,intraoperative blood transfusion,and preoperative procalcitonin(PCT)were independent risk factors for PHLF;ascites and preoperative bilirubin were independent risk factors for ARDS;and postoperative prophylactic anticoagulation was an independent protective factor for VTE and ARDS(all P＜0.05).Conclusion Prophylactic anticoagulation can reduce the risks of VTE,PHLF,and ARDS in PLC patients after hepatectomy,without increasing the risk of postoperative bleeding.Age,portal hypertension,number of tumors,intraoperative blood loss,intraoperative blood transfusion,ascites,preoperative PCT,and preoperative bilirubin are risk factors for postoperative complications of PLC patients after hepatectomy.

In recent years, due to the increasing population of ageing and obesity, the incidence rate of hernia is increasing year by year, which has become a social problem that needs to be focused. Although starting late, the hernia and abdominal wall surgery has developed rapidly in recent years in China, and many remarkable achievements have been made. The development of hernia and abdominal wall surgery is inseparable from the progress of medical technology, the continuous innovation of materials, the improvement of perioperative management concept and the improvement of registration and follow-up system. The authors investigate the relevant research at home and abroad in recent years, and summarize and prospect the materials science, the daytime surgery and the registration and follow-up system, in order to provide reference for the future development of hernia and abdominal wall surgery.

Objective:To investigate the clinical result of biological mesh and synthetic mesh in the repair of hiatal hernia.Methods:a prospective cohort study was conducted to collect and analyze the clinical data of 60 patients with hiatal hernia who were treated at Department of Hernia and Abdominal Wall Surgery, Beijing Chaoyang Hospital, Capital Medical University from May 2019 to Jan 2020. Intraoperative blood loss, hospital stay, clinical symptoms (heartburn, acid regurgitation, belching, early satiety, chest pain), VAS score, postoperative recurrence rate and complications were evaluated.Results:There was no significant difference in the overall repair effect between biological mesh group and synthetic mesh group ( P>0.05). All of the 60 patients underwent successful laparoscopic hiatal hernia repair and fundoplication. There were no massive bleeding caused by organ or vascular injury, and no peri-operative death. No recurrence of hiatal hernia, massive hemorrhage, pneumothorax, pleural effusion, gastrointestinal fistula, mediastinal infection or abscess were found during the follow-up of 6 months. Conclusion:There is no significant difference in short-term clinical effect between the use of biological mesh and synthetic mesh after hiatal hernia repair.

Objective To analyze the changes of CD4⁺ T cell numbers at different periods of antiviral therapy in HIV-infected and AIDS patients (HIV/AIDS) in Yichang City. Methods The relevant information was retrieved from the National AIDS Comprehensive Prevention Information System-Antiretroviral Treatment Management Database. Changes in the number of CD4⁺ T cells were analyzed in HIV/AIDS patients who started receiving highly active antiretroviral therapy (HAART) and continued the treatment for 3 years from January 1, 2003 to December 31, 2017 in Yichang. Results The number of CD4⁺T lymphocytes in 550 HIV/AIDS cases increased significantly at various time points within 3 years after treatment, and increased with the increase of treatment time（F=100.20，P<0.001）. The CD4+T cell counts of different baseline level groups were statistically different before and after treatment（F=8.57，P<0.01）. The CD4+ T cell counts of patients who started treatment at age of 15-30 years old increased faster than those who started treatment at age of over 30 years old（F=1.27，P<0.05）. Conclusion HAART has a significant effect on the increase of CD4+T cells, and the early treatment is more effective. Early detection, diagnosis and treatment should be promoted, and anti-viral treatment should be actively carried out.