Antiresistin Neutralizing Antibody Alleviates Doxorubicin-Induced Cardiac Injury in Mice.

Background: Resistin is closely related to cardiovascular diseases, and this study is aimed at examining the role of resistin in doxorubicin- (DOX-) induced cardiac injury. Methods: First, 48 mice were divided into 2 groups and treated with saline or DOX, and the expression of resistin at different time points was examined (N = 24). A total of 40 mice were pretreated with the antiresistin neutralizing antibody (nAb) or isotype IgG for 1 hour and further administered DOX or saline for 5 days. The mice were divided into 4 groups: saline-IgG, saline-nAb, DOX-IgG, and DOX-nAb (N = 10). Cardiac injury, cardiomyocyte apoptosis, inflammatory factors, and the biomarkers of M1 and M2 macrophages in each group were analyzed. Result: DOX administration increased the expression of resistin. DOX treatment exacerbated the loss of body and heart weight and cardiac vacuolation in mice. The antiresistin nAb reversed these conditions, downregulated the expression of myocardial injury markers, and decreased apoptosis. In addition, the antiresistin nAb decreased p65 pathway activation, decreased M1 macrophage differentiation and the expression of related inflammatory factors, and increased M2 macrophage differentiation and the expression of related inflammatory factors. Conclusion: The antiresistin nAb protected against DOX-induced cardiac injury by reducing cardiac inflammation and may be a promising target to relieve DOX-related cardiac injury.

Visfatin Amplifies Cardiac Inflammation and Aggravates Cardiac Injury via the NF-κB p65 Signaling Pathway in LPS-Treated Mice.

Background: Visfatin is an adipocytokine that has been demonstrated to be involved in cardiovascular diseases. This study aims at determining the role of visfatin in sepsis-induced cardiac injury and identify its possible mechanisms. Methods: Dynamic changes in visfatin expression in mice with lipopolysaccharide- (LPS-) induced septicemia were measured. Additionally, mice were pretreated with visfatin and further administered LPS to observe the effects of visfatin on cardiac injury. Finally, septic mice were also pretreated with JSH-23 to investigate whether visfatin regulates cardiac injury via the NF-κB p65 pathway. Results: Visfatin expression levels in both the heart and serum were increased in LPS-treated mice and peaked at 6 hours, and visfatin was derived from cardiac macrophages. In septic mice, pretreatment with visfatin reduced the survival rate, worsened cardiac dysfunction, and increased the expression of cardiac injury markers, including creatine kinase myocardial bound (CK-MB) and lactate dehydrogenase (LDH). Treatment with visfatin also increased the infiltration of CD3+ cells and F4/80+ cells, amplified the cardiac inflammatory response, and elevated myocardial cell apoptosis. Treatment with JSH-23 reversed the effects of visfatin in septic mice. Conclusions: This study showed that visfatin amplifies the cardiac inflammatory response and aggravates cardiac injury through the p65 signaling pathway. Visfatin may be a clinical target for preventing cardiac injury in sepsis.

[Clinical Efficacy of Haplo-HSCT of ATG Combined with PTCy for Children with Myelodysplastic Syndrome].

OBJECTIVE: To investigate the efficacy and safety of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in combination of ATG and post-transplant cyclophosphamide (PTCy) -induced immune tolerance after transplantation in treatment of childhood myelodysplastic syndromes(MDS）. METHODS: From July 2016 to November 2020, a total of 8 children with MDS receiving the haploidentical allo-HSCT combined with ATG and PTCy-induced immune tolerance after transplantation in our hospital were enrolled, whose clinical data were retrospected and analyzed. RESULTS: Median age at diagnosis of the 8 children (1 male and 7 females) was 6.4 (range, 10 months to 15 years) years old. The median medical history of MDS was 2.7 years (range, 3 months to 8 years). Among the 8 patients, 7 cases were diagnosed with refractory cytopenia of childhood and one with refractory anemia with excess of blasts. The HSC donors were father, mother or brother of patients and HLA matching in 6-9/12 loci were identical. All the donors were healthy and didn't carry the same pathogenic genes as the recipients. The median age of donors was 36.4 (range, 25 to 49) years old. The median mononuclear cell (MNC) number of the graft was 19.8, ranging in (13.2-47.3)×108/kg, and the median CD34+ cell number was 11.8×106/kg, ranging in (5.0-18.3)×106/kg. Graft-versus-host disease prophylactic regimen was started on day 3 and 4 after transplantation, in which cyclophosphamide (50 mg/kg·d) was administered by intravenous infusion. From day 5 after transplantation, low-dose tacrolimus was administered by intravenous infusion and mycophenolate mofetil was administered orally. The median time of neutrophil and platelet engraftment was 12.6 (rang, 11 to 15) days and 13.3 (rang, 11 to 18) days, respectively. All the patients achieved full donor chimerism on neutrophil engraftment after transplantation. The median follow-up time was 1 032 (rang, 747 to 1 536) days. Both overall survival rate and disease-free survival rate were 100%. CONCLUSION: Haplo-HSCT combined with ATG and PTCy-induced immune tolerance after transplantation is a safe and effective treatment for children with MDS.

Resistance of blended alkali-activated fly ash-OPC mortar to mild-concentration sulfuric and acetic acid attack.

The traditional cementitious product is prone to suffer from a high degree of deterioration in the case of exposure to acid solutions because of the decomposition of the binder network. However, the degradation of concrete structures in service by mild concentrations of acid under conditions involving sewage, industrial waters, and acid rain is more common and results in a significant environmental problem. The utilization of alkali-activated materials has been seen to potentially offer an attractive option with regard to acceptable durability and a low carbon footprint. With the aid of visual observation, mass loss, compressive strength tests, X-ray diffraction, Fourier transform infrared spectroscopy, and field-emission scanning electron microscopy with energy-dispersive X-ray spectroscopy, the acid resistance of alkali-activated fly ash mortars in which the precursor was partially replaced (0-30% by mass proportion) with ordinary Portland cement (OPC) was evaluated after 180 days of exposure to mild-concentration sulfuric and acetic solutions (pH = 3). A conventional cement mortar (100% OPC) was used as a reference group. The results demonstrate that the addition of OPC into the alkali-activated system causes a significant increase in compressive strength (around 16.08-36.61%) while showing an opposite influence on durability after acid attack. Based on a linear mean value and nonlinear artificial neural network model simulation, the mass losses of the specimens were evaluated, and the alkali-activated pure-fly ash mortar demonstrated the lowest value (i.e., a maximum of 5.61%) together with the best behavior in the aspect of discreteness at 180 days. The results from microstructure analysis show that the coexistence of the N-A-S-H and C-S-H networks in the blend system occurred by both OPC hydration and FA. However, the formation of the gypsum deposition within the fly ash-OPC blend systems at sulfuric acid was found to impose internal disintegrating stresses, causing a significant area of delamination and cracks. In addition, alkali metal ion leaching, dealumination, as well as the disappearance of some crystalline phases occurred in specimens immersed in both types of acids.

Status of Analgesic Drugs and Quality of Life Results for Diabetic Peripheral Neuropathy in China.

Objective: The purpose of this study is to describe the current clinical situation of patients with painful diabetic peripheral neuropathy (DPN) and related anxiety, depression, and the quality of life of patients in mainland China, and to report the current status of the use of analgesics. Methods: Between June 15, 2021, and October 15, 2021, a total of 401 participants participated in the study. Recruitment was carried out using a multi-level sampling method. Participants' demographics, medical history, analgesic use, Michigan Symptom Score (MNSI), Numerical Rating Scale (NRS) pain score, Patient Health Questionnaire 9 (PHQ-9) score, Generalized Anxiety Disorder 7 (GAD) -7) Score, quality of life score (SF-12) and diabetes treatment status were collected. Results: Among the participants, there were 236 male patients and female patients. Participants were 322 patients over 40 years old. Regarding the use of analgesics: 132 patients reported using analgesics, 221 patients reported not using analgesics, and 48 patients reported having used analgesics. The results of the scale showed that the scores of NRS, GAD-7, PHQ-9 and SF-12 were 5.12 ± 2.15, 6.33 ± 3.67, 8.46 ± 4.07 and 47.84 ± 19.92 for patients who used analgesics, Compared with patients who did not use analgesics (NRS: 1.99 ± 1.7, GAD-7: 1.81 ± 2.81, PHQ-9: 3.13 ± 4.10, SF-12: 78.34 ± 21.66) there are significant differences (p< 0.001). In addition, patients' NRS scores are also closely related to GAD-7, PHQ-9 and SF-12 scores. Conclusion: The severity of symptoms, mental status and quality of life of patients who used analgesics were more severe than those of patients who did not use analgesics. Pregabalin is still the preferred analgesic for patients with painful DPN, and the use of opioids in my country is extremely low, which is consistent with current international guidelines. Age, diabetic duration, DPN duration, PHQ-9 score, GAD-7 score and SF-12 scores are closely related to NRS pain scores. In addition, there are still a considerable number of patients who have not used analgesics due to financial burdens and other reasons, suggesting that China still has insufficient pain management in DPN patients.