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Early exercise training is safe and feasible in acute and healing phase after myocardial infarction. Early exercise training could attenuate LV remodeling and improve cardiopulmonary capacity in patients with myocardial infarction after hospital discharge (around one week post-MI). Exercise training has favorable effects on LV remodeling and cardiopulmonary capacity rehabilitation. Exercise training should be treated to have the same roles with drugs in secondary prevention of myocardial infarction.

The aim of this study was to determine the prevalence of Staphylococcus aureus enterotoxins (SEs) in the serum from patients with chronic rhinosinusitis (CRS) and its involvement in the condition. Thirty CRS patients without nasal polyps (CRSsNP), 40 CRS patients with nasal polyps (CRSwNP), and 30 healthy controls were enrolled in this study. Peripheral blood was obtained and analyzed to measure the serum levels of total IgE, specific IgE to SEA, SEB and SEC, and eosinophil cationic protein (ECP) using ImmunoCAP assays. The positive rate and level of serum specific IgE to SEB, but not to SEA or SEC, were significantly higher in CRSwNP patients compared with the controls (P=0.027 and P=0.021, respectively). No significant differences were found between CRSsNP patients and controls, or between CRSsNP and CRSwNP patients. Serum total IgE was significantly elevated and positively correlated with SEB-specific IgE in the CRSsNP (P<0.001; r=0.393, P=0.032) and CRSwNP (P<0.001; r=0.581, P<0.001) groups. ECP was also significantly increased in the CRSsNP (P=0.002) and CRSwNP (P<0.001) groups, but not correlated with specific IgE to SEs in either CRS group. The results suggest that SEB may play a role in the pathogenesis of CRSwNP.

Background: Astragaloside IV (As-IV) exerts beneficial effects on hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury, possibly through normalization of sarcoplasmic reticulum Ca²⁺ ATPase (SERCA2a) function. The exact mechanisms remain unknown. This study was designed to investigate the role of protein kinase A (PKA) in the protective effect of As-IV on SERCA2a function. Methods: Cultured cardiomyocytes from neonatal rats were exposed to 6 h of hypoxia followed by 3 h of reoxygenation (H/R) with or without As-IV treatment. Myocyte injury was determined by the creatine kinase (CK)-MB fraction in supernatant. Myocardial SERCA2a activity and PKA kinase activity were assessed. PKA subunit mRNA expression and Ser¹⁶ phosphorylated phospholamban (Ser¹⁶-PLN) protein expression were detected by real-time PCR and Western blot, respectively. Results: The administration of As-IV significantly decreased CK-MB release and restored SERCA2a activity in H/R cardiomyocytes. The mRNAs of PKA subunits, PKA-RIα, PKA-RIIα, PKA-RIIβ, PKA-Cα and PKA-Cβ, were downregulated in H/R cardiomyocytes. However, PKA-Cα mRNA expression was significantly increased after As-IV treatment. Meanwhile, there was a tendency to recovery of the H/R-induced PKA kinase activity decrease after As-IV treatment. The expression of Ser¹⁶-PLN protein, which is specifically phosphorylated by PKA, was upregulated in As-IV-treated H/R cardiomyocytes. Conclusions: These results suggest that the cardioprotection of As-IV may be through the upregulation of PKA and Ser¹⁶-PLN, thereby restoring SERCA2a function in H/R injury.

Background: To: (i) explore the effect of diterpene ginkgolides meglumine injection (DGMI) on neurological deficit symptoms in acute atherosclerotic cerebral infarction (AACI) patients; (ii) measure the level of plasma plasminogen activator inhibitor (PAI)-1 and tissue plasminogen activator (t-PA).Methods: Eighty AACI patients were divided equally and randomly into the DGMI group and control group. In addition to basic treatment, the DGMI group was treated with DGMI (25 mg/d) for 14 days. The control group had basic treatment without DGMI. Before and after treatment, the degree of neurological deficit was assessed, thromboelastography undertaken, and plasma levels of PAI-1 and t-PA measured. Results:The National Institutes of Health Stroke Scale score of patients in the DGMI group after treatment was lower than that in the control group, and the Barthel Index was higher than that in the control group (P < 0.05). Thromboelastography revealed that, in the DGMI group, the R value and K value after treatment were higher than before treatment, the angle and maximum amplitude value were lower than before treatment, and both were significant (P < 0.05). Compared with the control group, the plasma PAI-1 level of patients in the DGMI group was lower than that in the control group, and the t-PA level was higher than that in the control group (P < 0.05) after 14 days of treatment.Conclusions: DGMI may affect the activity of the blood coagulation and fibrinolysis system by regulating the plasma level of PAI-1 and t-PA, and improving neurological deficit symptoms. DGMI is important for improving the prognosis of patients with AACI.

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X‐ray repair cross‐complementing group 1 (Xrcc1), a key DNA repair gene, plays a vital role in maintaining genomic stability and is highly expressed in the early stages of spermatogenesis, but the exact functions remain elusive. Here we generated primordial germ cell–specific Xrcc1 knockout (cXrcc1−/−) mice to elucidate the effects of Xrcc1 on spermatogenesis. We demonstrated that Xrcc1 deficiency results in infertility in male mice due to impaired spermatogenesis. We found that cXrcc1−/− mice exhibited smaller size of testes as well as lower sperm concentration and motility than the wild‐type mice. Mechanistically, we demonstrated that Xrcc1 deficiency in primordial germ cells induced elevated levels of reactive oxygen species, mitochondria dysfunction, apoptosis, and loss of stemness of spermatogonial stem cells (SSCs) in testes. In Xrcc1‐deficienct SSCs, elevated oxidative stress and mitochondrial dysfunction could be partially reversed by treatment with the antioxidant N‐acetylcysteine (NAC), whereas NAC treatment did not restore the fertility or ameliorate the apoptosis caused by loss of Xrcc1. Overall, our findings provided new insights into understanding the crucial role of Xrcc1 during spermatogenesis.—Xu, C., Xu, J., Ji, G., Liu, Q., Shao, W., Chen, Y., Gu, J., Weng, Z., Zhang, X., Wang, Y., Gu, A. Deficiency of X‐ray repair cross‐complementing group 1 in primordial germ cells contributes to male infertility. FASEB J. 33, 7427–7436 (2019). http://www.fasebj.org

Rheumatoid arthritis (RA) is a common autoimmune disease worldwide. Neutrophils play critical roles in the onset and development of RA and are the promising target for RA treatment. Tetrandrine is a bis-benzyl isoquinoline alkaloid derived from the traditional Chinese herbal Stephania tetrandra S. Moore. Tetrandrine is effective in alleviating RA by inhibiting macrophage inflammatory response, fibroblast overproliferation, and pannus formation. However, whether tetrandrine regulates the activities of neutrophils in RA is largely unknown. In this study, we adopted adjuvant-induced arthritis (AA) murine model to explore the effect of tetrandrine on RA and neutrophils. Twenty-eight mice were divided into four groups. The control group was injected with PBS in the limbs and treated with PBS by intraperitoneal injection (i.p.) from Day 10 to Day 37. The arthritis murine model was induced by injecting FCA into the ankle joints of hind limbs. The AA group, the AA + TET group, and the AA + DEX group mice were treated with PBS, tetrandrine (6 mg/kg), or dexamethasone (1 mg/kg) i.p. daily, respectively. Arthritic scores were evaluated, and the joint diameter was measured every three days. A cytometric bead assay was performed to measure the concentrations of IFN-γ, TNF-α, and IL-6 in the serum. H&E staining and Safranin O-fast staining were adopted to monitor the tissue changes in the joint. Immunohistochemistry assays were applied to detect the MPO, NE, CitH3, and PAD4 expression levels. To assess the effect of tetrandrine on neutrophil activities in vitro, CCK8 tests were applied to determine cell viability. The qPCR and ELISA were performed to determine IL-1β and IL-6 expression levels. Immunofluorescence assays were performed to measure the formation of NETs. The results indicated that tetrandrine significantly alleviated the symptoms of RA in terms of the ankle diameter (from 4.629 ± 2.729 to 3.957 ± 0.257; P < 0.01 ) and ankle score (from 4.000 ± 0.000 to 3.286 ± 0.756; P < 0.05 ). Tetrandrine treatment significantly increased the cartilage areas and decreased serum IL-6 significantly (from 5.954 ± 2.127 to 2.882 ± 2.013; P < 0.01 ). The immunohistochemistry assays also showed decreased expression levels of NE, MPO, PAD4, and CitH3 induced by tetrandrine in comparison with the AA group ( P < 0.01 ). The qPCR assays and ELISAs showed that tetrandrine had an anti-inflammatory effect in vitro by significantly inhibiting IL-6 ( P < 0.01 ). The immunofluorescence assays showed that NET formation induced by PMA could be reduced by tetrandrine ( P < 0.01 ). In conclusion, tetrandrine has good efficacy in treating RA by regulating neutrophil-involved inflammation and NET formation.