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.

SOCS3, a feedback inhibitor of the JAK/STAT signal pathway, negatively regulates axonal regrowth and inflammation in the central nervous system (CNS). Here, we demonstrated a distinct role of SOCS3 in the injured spinal cord of the gecko following tail amputation. Severing the gecko spinal cord did not evoke an inflammatory cascade except for an injury-stimulated elevation of the granulocyte/macrophage colony-stimulating factor (GM-CSF) and interferon gamma (IFN-γ) cytokines. Simultaneously, the expression of SOCS3 was upregulated in microglia, and unexpectedly not in neurons. Enforced expression of SOCS3 was sufficient to suppress the GM-CSF/IFN-γ-driven inflammatory responses through its KIR domain by attenuating the activities of JAK1 and JAK2. SOCS3 was also linked to GM-CSF/IFN-γ-induced cross-tolerance. Transfection of adenovirus overexpressing SOCS3 in the injured cord resulted in a significant decrease of inflammatory cytokines. These results reveal a distinct role of SOCS3 in the regenerating spinal cord, and provide new hints for CNS repair in mammals.

Objective: To analyze the significance of serum free light chain (sFLC) for the prognosis of the patients with newly diagnosed multiple myeloma (NDMM). Methods: The clinical data of 621 NDMM patients in Changzheng Hospital from June 2010 to December 2016 was retrospectively analyzed. The serum free light chain levels were measured and the ratios of κ/λ chains were calculated. The significance of serum free light chain ratio (sFLCR) for the prognosis of NDMM patients was analyzed. Results: Among the 621 NDMM patients, 42 patients (6.8%) were in the normal free light chain ratio group (0.26≤sFLCR≤1.65), 247 patients (39.8%) were in the low free light chain ratio group (0.01＜sFLCR＜0.26 or 1.65＜sFLCR＜100), and 332 patients (53.5%) were in the high free light chain ratio group (sFLCR≤0.01 or sFLCR≥100). Compared with normal sFLCR group, the abnormal sFLCR group showed low level of hemoglobin; elevated levels of bone marrow plasma cells, serum creatinine and β 2 -MG, and more patients were in DS stage Ⅲ and ISS stage Ⅲ with high risks of cytogenetics(all P＜0.05). The overall survival (OS) in the normal sFLCR group was significantly better than the abnormol sFLCR groups (not reached vs 58.7 months, P=0.043). Compared with the patients with both high sFLCR and low risks of cytogenetics, the patients with high sFLCR and high risks of cytogenetics showed shorter overall survival time (median OS time was 41.6 months vs 61.4 months, P=0.015). Conclusion The NDMM patients with significantly abnormal sFLCR may indicate more tumor load and higher aggressive progression. sFLCR should be an independent prognostic indicator for the outcome of multiple myeloma. The patients with high sFLCR and cytogenetic abnormalities, have worse prognosis than the others.

Objective To investigate the resection of chest wall tumor and the reconstruction of it.Methods Retrospectively summarize the diagnosis and treatment of 91 cases of chest wall tumors in our hospital from January 2008 to November 2017.There are 55 males and 36 females and the ages ranged from 7 to 78 years,with a median age of 43 years.82 cases were operated for the first time,and 9 cases were reoperated.The postoperative pathology showed that the benign were 52 cases and malignant were 39 cases.The largest benign tumor was 15 cm × 10 cm × 3 cm and the largest malignant tumor was 30 cm × 20 cm × 15 cm.Local excision was performed in 66 cases and extended resection in 25 cases.After the resection,ilium,titanium mesh,Dacron mesh and Matrix reconstruction system were selected for reconstruction of chest wall respectivly.Results All the operation was successful and without death.Local resection was performed in all of benign tumor and in 15 cases of malignant tumor,extended resection was performed in the other 24 malignant tumor cases.After the local resection,the soft tissue was sutured directly to reconstruct the chest wall.The enlarged resection of the bone was performed by reconstructing the bony chest with different materials.In the soft tissue reconstruction,1 cases were treated with myocutaneous flap,and the other 23 cases were sutured directly.Postoperative chest wall integrity is stable,no chest wall floating and abnormal breathing.1 patients received ventilator supportion,and 2 patients had wound infection.The chest wall defect caused by benign tumor has good quality of life,no recurrence.After resection of the malignant tumor of the chest wall,2 died,and the rest were still alive.Conclusion Local resection is the main therapeutic method of benign chest wall tumor,and malignant chest wall tumor is mostly enlarged excision.Bone remodeling after extended resection plays an important role in the reconstruction of chest wall.It is necessary to select appropriate materials for reconstruction.Matrix titanium sternal or rib reconstruction system fixed reliably and the follow-up in a short term were also satisfactory.

Objective To determine the prevalence and risk factors of Epstein-Barr virus (EBV) infection after pediatric liver transplantation for patients with biliary atresia. Methods Clinical data of 65 pediatric patients with biliary atresia, who underwent liver transplantation, were retrospectively analyzed. Patients were divided into EBV infection group
(n=30) and non-EBV infection group (n=35). The univariate analysis was used to analyse the preoperative, intraoperative and postoperative data of patients included. The variables with a P <0.1 were included in the multivariate Logistic regression analysis of EBV infections after pediatric liver transplantation for patients with biliary atresia. Results A total of 30 cases (46.15%) of pediatric recipients showed EBV infection in 65 cases, of which 23 cases (76.67%) occurred within 3 months after operation. The univariate analysis showed that there were significant differences in the ratio of patients younger than 1 year preoperation, EBV serology D+/R-, acute rejection, the usage of mycophenolate mofetil and supratheraputic tacrolimus level between two groups (P<0.05) . The type of graft (P=0.060), input quantity of red blood cell intraoperation (P=0.063) and factors mentioned above were included in the multivariate Logistic regression analysis. It revealed that donor EBV serology positive but recipient negative, acute rejection and supratheraputic tacrolimus level were risk factors of EBV infection for pediatric liver transplantation recipients with biliary atresia. Conclusion Donor EBV serology positive but recipient negative, acute rejection, supratheraputic tacrolimus level are closely related to EBV infection in pediatric recipients with biliary atresia after liver transplantation. Appropriate antiviral drugs should be adopted to prevent EBV infection in high risk patients.

Objective To investigate the clinical features and treatment of chronic invasive fungal rhinosinusitis(CIFRS).Methods From June 2006 to August 2011,seven patients were pathologically diagnosed as CIFRS in otorhinolaryngology department of Peking university first hospital and included in this study.The clinical records were reviewed.The clinical features,clinical course,symptoms,clinical signs,CT/MRI scan of the sinuses,surgical approach,postoperative pathology and medications were analyzed retrospectively.These 7 patients received both surgical and systemic anti-fungal treatment.Among them,2 cases with characteristically clinical features were addressed into further analyses to explore the clinical feature and treatment of CIFRS.Results Among the 7 patients,5 were female and 2 were male.The course of diseases were from 2 months to 8 years.All patients had no systemic immune diseases and history of diabetes mellitus,while 1 case had a history of facial trauma,and another 1 case had received antibiotics for long-stay in bed after a car accident.The onset lesions of 6 cases were in unilateral maxillary sinus and 1 in unilateral ethmoid sinus.Aspergillus fungi were detected in 6 cases and mold fungi were detected in 1 case by pathology or fungal culture.After follow-up for 1-5 years,6 patients were cured,and 1 was died.Conclusions CIFRS are often diagnosed in patients with normal immune function.Lesions alwasys occur in single sinus,and maxillary sinus is the most commonly involved.Aspergillus is the most common pathogens.Early clinical manifestation and sinus CT images are lack of specificity.Surgery associated with adequate antifungal treatment might be the best treatment strategy.

Objective To investigate the effects of lanthanum(La)subchronic exposure on the metabolism of calcium(Ca),magnesium(Mg)and iron(Fe)in the liver tissue and serum in rats.Methods 36 Wistar rats were treated with lanthanum chloride(LaCl3)through oral exposure at 0.1,2 and 40 mg/kg respectively.After 90 days of treatment,the rats were sacrificed and the La,Ca,Mg and Fe in the liver tissue were determined,the serum was collected for analysis of Ca,phosphorus(P),Mg,Fe,unsaturated iron-binding capacity(UIBC)and total iron binding capacity(TIBC).Results The La levels in the liver tissue in all LaCl3 exposed dose groups rats were higher obviously than those in the control group(P0.05).Conclusion The result suggests that La subchronic exposure may have some effects on the level and distribution of Ca,Mg and Fe in the liver tissue and serum,which may be a part of its biological effects.