ABSTRACT Background Ultrasound is a promising tool for diagnosing sarcopenia, yet standardized cut‐off points and criteria are currently lacking. This study aimed to identify the optimal muscle sites and reference values for diagnosing low muscle mass in older Chinese adults using ultrasound, with dual‐energy X‐ray absorptiometry (DXA) as the reference standard, and to compare its diagnostic performance with bioelectrical impedance analysis (BIA). Methods We included 1011 participants aged over 60 years. Fat thickness (FT), muscle thickness (MT) and muscle cross‐section area (CSA) at various sites, including biceps brachii, rectus abdominis, rectus femoris, vastus intermedius, vastus lateralis, vastus medialis and tibialis anterior, were assessed for participants. DXA measurements were used as the standard for defining low muscle mass. Receiver operating characteristic (ROC) curve analysis and 10‐fold cross‐validation were conducted to evaluate the prediction performance of ultrasound parameters for low muscle mass. The Youden index was employed to determine optimal cut‐offs, while sensitivity, specificity and accuracy were calculated to assess diagnostic performance. Intra‐class correlation coefficients (ICC) were used to evaluate inter‐rater reliability between two examiners. Results In males, the biceps brachii CSA (AUC = 0.832, 95% CI: 0.793–0.870) and in females, the tibialis anterior MT (0.833, 95% CI: 0.789–0.877) demonstrated superior predictive power for low muscle mass compared with other ultrasound parameters. A biceps brachii CSA < 7.1 cm2 in males and tibialis anterior MT < 2.3 cm in females were identified as effective indicators for diagnosing low muscle mass, with good sensitivities (73.9% in males, 73.6% in females), specificities (78.6% in males, 76.8% in females) and accuracies (75.7% in males, 75.8% in females). These values were comparable with those obtained using BIA (sensitivity: 62.6%, specificity: 80.2% and accuracy: 71.5%). Low muscle mass as defined by ultrasound was significantly associated with poor performance on the Short Physical Performance Battery, Activities of Daily Living and frailty indices, with effect sizes higher than DXA or BIA defined low muscle mass. The inter‐rater reliability was excellent for biceps brachii CSA (ICC = 0.869, 95% CI: 0.650–0.937) and good for tibialis anterior MT (ICC = 0.730, 95% CI: 0.622–0.810). Conclusions Muscle ultrasound demonstrated excellent inter‐rater reliability and stronger associations with adverse health outcomes compared with DXA and BIA, making ultrasound a preferable tool for assessing low muscle mass. This study provides valuable reference values for ultrasound‐based diagnosis of sarcopenia in older Chinese adults.
Immunotherapy with Immune Checkpoint Inhibitors (ICIs) has shown promising therapeutic effects in the treatment of lung cancer, the overall efficacy of PD-1/PD-L1 inhibitors is only 20%-30%. Thus, more effective combination therapies are needed. This study finds that cystine and cysteine levels in tumor tissues of lung cancer patients are significantly higher than adjacent non-tumor tissues. Cystine deficiency polarizes macrophages toward an M1 phenotype, secreting more TNF-α, CXCL9, and CXCL10. However, using a cystine-free diet marginally reduces the development of lung cancer in vivo. A cystine-free diet slightly reduces lung cancer progression in vivo. Further studies show that cystine deprivation or erastin-mediated transport inhibition increased PD-L1 expression in macrophages both in vitro and in vivo. Combining a cystine-free diet or IKE injection with PD-L1 antibody treatment significantly inhibited subcutaneous tumor growth in mice. Mechanistic studies indicat that cystine deficiency-induced GSH depletion activates NF-κB in macrophages by reducing its glutathionylation. This effect can be reversed by replenishing GSH or using an NF-κB inhibitor. At the same time, lung cancer patients with better responses to immunotherapy are found to have lower serum GSH levels. These findings suggest that targeting cystine metabolism combined with PD-L1 inhibition is a promising therapeutic strategy.
Overcoming immunosuppression in the tumor microenvironment (TME) is crucial for developing novel cancer immunotherapies. Here, we report that IL-16 administration enhances the polarization of T helper 1 (Th1) cells by inhibiting glutamine catabolism through the downregulation of glutaminase in CD4+ T cells and increases the production of Th1 effector cytokine IFN-γ, thus improving anti-tumor immune responses. Moreover, we find that establishing an IL-16-dependent, Th1-dominant TME relies on mast cell-produced histamine and results in the increased expression of the CXCR3 ligands in tumor-associated macrophages (TAM), thereby improving the therapeutic effectiveness of immune checkpoint blockade (ICB). Cancer patients exhibit impaired production of IL-16, which correlates with poorer prognosis. Additionally, low IL-16 production is associated with unresponsiveness to immunotherapy in cancer patients. Collectively, our findings provided new insights into the biological function of IL-16, emphasizing its potential clinical significance as a therapeutic approach to augment anti-tumor immunity and sensitize ICB-based cancer immunotherapy.
Ultrasound is a promising tool for sarcopenia diagnosis, yet standardized criteria are lacking. We aimed to identify the optimal muscle sites and reference values for diagnosing low muscle mass in Chinese older adults using ultrasound. The study included 1011 participants aged ≥60 years. Dual-energy X-ray absorptiometry (DXA) served as the reference standard for assessing muscle mass. Seven muscle sites were evaluated via ultrasound for muscle thickness (MT) and cross-sectional area (CSA). Our results showed that the biceps brachii CSA (AUC=0.832, 95%CI: 0.793-0.870) in males and tibialis anterior MT (AUC=0.833, 95%CI: 0.789-0.877) in females demonstrated superior predictive power for low muscle mass compared to other assessed parameters. Diagnostic thresholds were < 7.1 cm² for male biceps brachii CSA and < 2.3 cm for female tibialis anterior MT. Ultrasound achieved sensitivities, specificities, and accuracies of 73.9%, 78.6%, and 75.7% in males, and 73.6%, 76.8%, and 75.8% in females, respectively, comparable to bioelectrical impedance analysis (BIA) at 62.6%, 80.2%, and 71.5%. The inter-rater reliability was excellent for biceps brachii CSA (ICC =0.877, 95%CI: 0.677-0.941) and good for tibialis anterior MT (ICC =0.731, 95%CI: 0.610-0.817). Low muscle mass defined by ultrasound correlated significantly with poorer physical performance outcomes, with the effect size higher than DXA or BIA diagnosed low mass, suggesting better prediction power of ultrasound than DXA or BIA. In conclusion, ultrasound could be a preferable method for sarcopenia assessment, demonstrating good inter-rater reliability and significant correlation with physical performance.
Alzheimer’s disease (AD) is the most common cause of dementia characterized by amyloid-β (Aβ) deposition, tau hyperphosphorylation, and neuroinflammation. Naringenin (NRG), a natural flavonoid widely present in citrus fruits, has been reported can penetrate the blood-brain barrier and exert anti-inflammatory effects in the central nervous system. Here, we investigate the protective effects of long-term NRG treatment on AD. The novel object recognition test and Morris water maze test reveal that NRG treatment can improve the learning and memory ability of APP/PS1 mice. Besides, we find that NRG can significantly reduce Aβ deposition, microglial and astrocytic activation, and pro-inflammatory cytokine levels in APP/PS1 mice. Results further show that NRG effectively decreases pro-inflammatory cytokines in LPS/Aβ-stimulated BV2 cells. Lastly, the molecular mechanistic study reveals that NRG attenuates neuroinflammatory responses via inhibition of the MAPK signaling pathway in vivo and in vitro. Overall, NRG may emerge as a promising compound for the prevention and treatment of AD. A study reveals the protective effects of long-term naringenin treatment on Alzheimer’s disease, including reducing Aβ deposition, decreasing neuroinflammatory responses, and improving cognitive function
Background: CD93 reportedly facilitates tumor angiogenesis. However, whether CD93 regulates antitumor immunity remains undeciphered. Methods: Lung tumor tissues, malignant pleural effusions (MPEs) were obtained from lung cancer patients. Blood was obtained from healthy volunteers and lung cancer patients with anti-PD-1 therapy. Furthermore, p53fl/flLSL-KrasG12D, Ccr7-/-, Cd93-/- mice and CD11c-DTR mice were generated. Specifically, EM, NTA and western blotting were utilized to identify Tumor extracellular vesicles (TEVs). EV labeling, detection of EV uptake in vitro and in vivo, degradation of EV proteins and RNAs were performed to detect the role of TEVs in tumor progression. Pleural mesothelial cells (pMCs) were isolated to investigate related signaling pathways. Recombinant proteins and antibodies were generated to test which antibody was the most effective one to increase CCL21a in p-pMCs. RNA-Seq, MiRNA array, luciferase reporter assay, endothelial tube formation assay, protein labeling and detection, transfection of siRNAs and the miRNA mimic and inhibitor, chemotaxis assay, immunohistochemical staining, flow cytometry, Real-time PCR, and ELISA experiments were performed. Results: We show that CD93 of pMCs reduced lung tumor migration of dendritic cells by preventing pMCs from secreting CCL21, thereby suppressing systemic anti-lung tumor T-cell responses. TEV-derived miR-5110 promotes CCL21 secretion by downregulating pMC CD93, whereas C1q, increasing in tumor individuals, suppresses CD93-mediated CCL21 secretion. CD93-blocking antibodies (anti-CD93) inhibit lung tumor growth better than VEGF receptor-blocking antibodies because anti-CD93 inhibit tumor angiogenesis and promote CCL21 secretion from pMCs. Anti-CD93 also overcome lung tumor resistance to anti-PD-1 therapy. Furthermore, lung cancer patients with higher serum EV-derived miR-5193 (human miR-5110 homolog) are more sensitive to anti-PD-1 therapy, while patients with higher serum C1q are less sensitive, consistent with their regulatory functions on CD93. Conclusions: Our study identifies a crucial role of CD93 in controlling anti-lung tumor immunity and suggests a promising approach for lung tumor therapy.
Senescence of vascular endothelial cells is the major risk of vascular dysfunction and disease among elderly people. Parishin, which is a phenolic glucoside derived from Gastrodia elata, significantly prolonged yeast lifespan. However, the action of parishin in vascular ageing remains poorly understood. Here, we treated human coronary artery endothelial cells (HCAEC) and naturally aged mice by parishin. Parishin alleviated HCAEC senescence and general age-related features in vascular tissue in naturally aged mice. Network pharmacology approach was applied to determine the compound-target networks of parishin. Our analysis indicated that parishin had a strong binding affinity for Klotho. Expression of Klotho, a protein of age-related declines, was upregulated by parishin in serum and vascular tissue in naturally aged mice. Furthermore, FoxO1, on Klotho/FoxO1 signalling pathway, was increased in the parishin-intervened group, accompanied by the downregulated phosphorylated FoxO1. Taken together, parishin can increase Klotho expression to alleviate vascular endothelial cell senescence and vascular ageing.
Disruption of the intestinal barrier is both the cause and result of sepsis. The proliferation and differentiation of intestinal stem cells (ISCs) promote the regenerative nature of intestinal epithelial cells, repairing the injured intestinal mucosal barrier; however, it is uncertain whether the recovery effects mediated by the ISCs are related to the gut microbiota. This research found that the survival rate of septic mice was improved with a Lactobacillus rhamnosus GG (LGG) treatment. Furthermore, an increased proliferation and decreased apoptosis in colon epithelial cells were observed in the LGG-treated septic mice. In vitro, we found that a LGG supernatant was effective in maintaining the colonoid morphology and proliferation under the damage of TNF-α. Both in the mice colon and the colonoid, the LGG-induced barrier repair process was accompanied by an increased expression of Lgr5+ and lysozyme+ cells. This may be attributed to the upregulation of the IL-17, retinol metabolism, NF-kappa B and the MAPK signaling pathways, among which, Tnfaip3 and Nfkbia could be used as two potential biomarkers for LGG in intestinal inflammation therapy. In conclusion, our finding suggests that LGG protects a sepsis-injured intestinal barrier by promoting ISCs regeneration, highlighting the protective mechanism of oral probiotic consumption in sepsis.
Background: Cardiac aging progressively decreases physiological function and drives chronic/degenerative aging-related heart diseases. Therefore, it is crucial to postpone the aging process of heart and create products that combat aging. Aims & methods: The objective of this study is to examine the effects of parishin, a phenolic glucoside isolated from traditional Chinese medicine Gastrodia elata, on anti-aging and its underlying mechanism. To assess the senescent biomarkers, cardiac function, cardiac weight/body weight ratio, cardiac transcriptomic changes, and cardiac histopathological features, heart tissue samples were obtained from young mice (12 weeks), aged mice (19 months) treated with parishin, and aged mice that were not treated. Results: Parishin treatment improved cardiac function, ameliorated aging-induced cardiac injury, hypertrophy, and fibrosis, decreased cardiac senescence biomarkers p16Ink4a, p21Cip1, and IL-6, and increased the “longevity factor” SIRT1 expression in heart tissue. Furthermore, the transcriptomic analysis demonstrated that parishin treatment alleviated the cardiac aging-related Gja1 downregulation and Cyp2e1, Ccna2, Cdca3, and Fgf12 upregulation in the heart tissues. The correlation analysis suggested a strong connection between the anti-aging effect of parishin and its regulation of gut microbiota and metabolism in the aged intestine. Conclusion: The present study demonstrates the protective role and underlying mechanism of parishin against cardiac aging in naturally aged mice.
Background: The aging-induced decrease in intestinal barrier function contributes to many age-related diseases. Studies on preventive measures for "leaky gut" may help improve the quality of life of geriatric patients. The potent anti-aging effect of Gastrodia elata and par-ishin, which is one of its active ingredients, has been reported previously. However, their effects on the gut remain elusive, and the effect of parishin on mammals has not been studied. Methods: We used quantitative RT-PCR, western blotting, immunohistochemical analysis, and 16S rRNA sequencing to investigate the effect of G. elata and parishin on the intestinal barrier function of D-Gal-induced aging mice.Results: G. elata and parishin prevented the decrease in tight junction protein (TJP) expression and morphological changes, modulated the composition of fecal microbiota to a healthier state, and reversed the translocation of microbial toxins and systemic inflam-mation. The correlation analyses showed that TJP expression and systemic inflammation were significantly positively or negatively correlated with the composition of fecal microbiota after G. elata and parishin administration. Additionally, TJP expression was also correlated with systemic inflammation. Moreover, G. elata and parishin administration reversed the decreased or increased expression of aging-related biomarkers, such as FOXO3a, SIRT1, CASPASE3 and P21, in the gut.
Epidemiological and clinical studies have shown that exposure to particulate matter (PM) is associated with an increased incidence of lung cancer and metastasis. However, the underlying mechanism remains unclear. Here, we demonstrated the central role of PM-induced neutrophil recruitment in promoting lung cancer metastasis. We found that reactive oxygen species (ROS)-mediated alveolar epithelial macroautophagy/autophagy was essential for initiating neutrophil chemotaxis and pre-metastatic niche formation in the lungs in response to PM exposure. During PM-induced autophagy, the E3 ubiquitin ligase TRIM37 was degraded and protected TRAF6 from proteasomal degradation in lung epithelial cells, which promoted the NFKB-dependent production of chemokines to recruit neutrophils. Importantly, ROS blockade, autophagy inhibition or TRAF6 knockdown abolished PM-induced neutrophil recruitment and lung metastasis enhancement. Our study indicates that host lung epithelial cells and neutrophils coordinate to promote cancer metastasis to the lungs in response to PM exposure and provides ideal therapeutic targets for metastatic progression.Abbreviations: ACTA2/α-SMA: actin alpha 2, smooth muscle, aorta; ATII: alveolar type II; Cho-Traf6 siRNA: 5'-cholesterol-Traf6 siRNA; EMT: epithelial-mesenchymal transition; HBE: human bronchial epithelial; HCQ: hydroxychloroquine; MAPK: mitogen-activated protein kinase; NAC: N-acetyl-L-cysteine; NFKB: nuclear factor of kappa light polypeptide gene enhancer in B cells; NS: normal saline; PM: particulate matter; ROS: reactive oxygen species; TRAF6: TNF receptor-associated factor 6; TRIM37: tripartite motif-containing 37.
Background:The sarcopenia index (SI, serum creatinine/serum cystatin C × 100) is recently suggested to be a reliable marker for sarcopenia. It has been reported that sarcopenia is associated with poorer cognition. The purpose of this study was to evaluate the correlation between SI and cognitive function among middle-aged and older adults from the China Health and Retirement Longitudinal Study (CHARLS).Materials and methods:A total of 6,442 participants ≥45 years of age were enrolled in this study from CHARLS between 2011 and 2012. Cognitive function was assessed by interview-based measurements, including orientation and attention, episodic memory, visuo-construction, and the total cognitive function. SI was calculated by serum creatinine (mg/dL)/cystatin C (mg/L) × 100. One-way analysis of variance (ANOVA) was used to compare the differences among groups divided according to SI quartiles by gender. Both linear and logistic regression models were applied to investigate the relationship between SI and cognitive function.Results:After adjustment for potential confounders, we found SI was significantly and positively correlated with total cognitive function scores both in males and females [β = 0.014, 95% confidence interval (CI) 0.007 to 0.021, P < 0.001; β = 0.011, 95 CI% 0.003 to 0.018, P = 0.004; respectively]. Similarly, when the total cognitive function score was treated as a categorical variable according to quartiles in males and females, higher SI was related to better total cognitive function scores in both males and females [odds ratio (OR) = 1.147, 95% CI 1.028 to 1.279, P = 0.014; OR = 1.219, 95% CI 1.106 to 1.344, P < 0.001; respectively] following adjustment for confounders.Conclusions:Lower sarcopenia index was correlated with a higher prevalence of cognitive impairment among middle-aged and older adults in China.
The physiological and pathological processes that accompany aging can seriously affect the quality of life of the elderly population. Therefore, delaying aging and developing antiaging products have become popular areas of inquiry. Gut microbiota plays an important role in age-related phenotypes. The present study aimed to investigate the antiaging effects and underlying mechanism of parishin, a phenolic glucoside isolated from traditional Chinese medicine Gastrodia elata. Samples from adult (12 weeks), low-dose (10 mg/kg/d) or high-dose (20 mg/kg/d) parishin-treated and untreated aged (19 months) mice were collected to determine blood indicators, gut microbiota and metabolome, and cardiopulmonary histopathological features. The results showed that parishin treatment ameliorates aging-induced cardiopulmonary fibrosis and increase in serum p16 Ink 4 a , GDF15, and IL-6 levels. Furthermore, parishin treatment alleviated dysbiosis in gut microbiota, including altered microbial diversity and the aberrant abundance of opportunistic pathogenic bacteria such as Turicibacter and Erysipelatoclostridium . Gene function prediction and gut metabolome analysis results indicated that the parishin treatment-altered gut microbiota played important roles in sugar, lipid, amino acid and nucleic acid metabolism, and improved gut metabolic disorders in aged mice. In conclusion, the present study provides an experimental basis of potential applications of parishin against aging.
Background: Ultrasound is emerging as an effective method for measuring muscle mass in elderly people. It has been applied in numerous studies to obtain measurement of lower limbs. The study aims to explore the relationship between sarcopenia and ultrasound measurements of biceps brachii. Methods: Participants (n=179) aged over 60 years were enrolled from the first affiliated hospital of Zhejiang University. The muscle thickness (MT), cross-sectional area (CSA) and fat thickness (FT) of these participants were recorded. Spearman test and partial correlation test was used to determine the correlation between indicators. Mann-Whitney U test was performed to compare ultrasonic parameters between sarcopenia group and non-sarcopenia group. The binary logistic regression analysis was employed to detect the potential indicators and prediction equation of sarcopenia. Receiver operating characteristic (ROC) curve analysis was performed for the accuracy of equation. Results: The prevalence of sarcopenia were 16.3% and 10.8% respectively in men and women. CSA was significantly lower in sarcopenia group than non-sarcopenia group in women (P<0.05). CSA was positively correlated with skeletal muscle mass index (SMI) and grip strength (men: r=0.460, 0.433; women: r=0.267, 0.392). After controlling of age and BMI, these correlations disappeared. Binary logistic regression analysis showed that age (OR=1.149, 95%CI: 1.060-1.246; P=0.001) and CSA (OR=0.465, 95%CI: 0.225-0.963; P=0.039) was significant indicators associated with sarcopenia. Area Under Curve was 0.822 (95%CI: 0.725-0.919, P<0.001) for the prediction equation composed of age, gender and CSA for sarcopenia. Conclusion: CSA of the biceps brachii measured with ultrasound is an important indicator associated with sarcopenia.
Immune checkpoint inhibitors (ICIs) have brought impressive clinical benefits in a variety of malignancies over the past years, which dramatically revolutionized the cancer treatment paradigm. Monotherapy or in combination with chemotherapy of ICIs targeting programmed death 1/programmed death ligand 1 (PD-L1) has emerged as an alternative treatment for patients with advanced non-small-cell lung cancer (NSCLC). However, constrained by primary or acquired resistance, most patients obtain limited benefits from ICIs and occasionally suffer from severe immune-related adverse events. Moreover, owing to the complexity of the tumor microenvironment and the technical limitations, clinical application of PD-L1 and tumor mutation burden as biomarkers shows many deficiencies. Thus, additional predictive biomarkers are required to further advance the precision of proper patient selection, avoiding the exposure of potential non-responders to unnecessary immunotoxicity. Nowadays, an increasing number of investigations are focusing on peripheral blood as a noninvasive alternative to tissue biopsy in predicting and monitoring treatment outcomes. Herein, we summarize the emerging blood-based biomarkers that could predict the clinical response to checkpoint immunotherapy, specifically in patients with NSCLC.
Abstract BackgroundThe outbreak of the 2019 novel coronavirus since December, 2019, has now causing nearly 75 thousand confirmed cases in China (until paper preparing). This epidemic has posed significant threats to international health and the economy. Zhejiang province, which once had the 2nd most accumulative cases among all provinces, has now dropped to top No.5 (until paper preparing). It had a high discharge rates (43.86%) from hospital and the lowest death rate among all top 5 epidemic provinces, this drew our attention to the epidemiological, clinical characteristics and local government engagement of this region.MethodsIn this study, we included all confirmed cases of COVID-19 pneumonia in Zhejiang province from Jan 21 to Feb 11, 2020. All data come from cases issued by Zhejiang provincial health commission.ResultsUntil Feb 11, 2020, 1143 cases were confirmed in Zhejiang province. We analysed the cases growth information in Zhejiang province and age, gender, severe cases percent, the source of the patients, the time of disease onset to confirm and the clinical symptoms of the patients. We also compared the clinical symptoms of elders and the young.ConclusionsThe patients in Zhejiang province had no age and gender preference, and the average time of disease onset to confirm was 5.9 days. The clinical symptoms were mainly fever, cough and weakness, similarly with before reported. The difference between elders and younger are not significant. Until paper preparing, Zhejiang province has very high discharge rate and low death rate, low cases increase rate in China.
This cross-sectional study aimed to investigate the characteristics and epidemiology of hyperuricemia in older adults in China and evaluate possible associations between hyperuricemia and sarcopenia. Three hundred and eighty-eight study subjects (>60 years old) meeting the inclusion criteria received blood tests and standardized examinations for bone mineral density, muscle mass, muscle strength, and physical performance. Data including demographic and clinical characteristic and comorbidity were also collected. All data were analyzed retrospectively. In the study population, higher uric acid levels were significantly correlated with higher muscle mass, grip strength, and bone density, but were unrelated to physical performance. When uric acid levels were separated into quartiles and the population was divided by sex, the correlation of uric acid to muscle mass was retained in some quartiles for both men and women, and the correlation to handgrip was only retained for one quartile for men. The correlation to bone density was retained in women in all analyses. In the population as a whole, higher uric acid levels were significantly correlated with higher muscle mass, grip strength, and bone density, but had no relationship to physical performance. Differences between men and women in these relationships need to be studied further.
Objectives: The aim of this study was to investigate the protective role of erythropoietin (EPO) against myocardial fibrosis (MF). Methods: Pressure-overloaded rats were established by abdominal aortic constriction, the rats were randomly divided in a double-blind manner into 3 groups (n = 12 for each group): sham-operated rats (sham), operated rats receiving physiological saline (vehicle) and operated rats receiving 4,000 U/kg rhEPO (EPO group). The vehicle and drugs were administered to rats by intraperitoneal injection. In addition, cultured adult rat cardiac fibroblasts (CFs) were utilized to investigate the role of EPO in CF proliferation and collagen secretion. Results: After 4 weeks, besides an increase in blood pressure, myocardial hypertrophy, collagen deposition in the myocardium and decreased cardiac function were observed in the pressure-overloaded rats. The expression of NADPH oxidase (Nox2 and Nox4) and inflammatory cytokines (CD45, F4/80 and MCP-1) was also significantly increased. All these alterations were prevented by EPO. TGF-ß promoted CF proliferation, collagen secretion, ROS production and Nox2/Nox4 expression, which was inhibited by EPO. In addition, the TGF-ß-induced increase of ERK1/2 phosphorylation and NF-κB expression were attenuated by EPO. Conclusion: EPO inhibited rat MF induced by pressure overload and improved myocardial function by decreasing CF proliferation and differentiation via inhibition of the NADPH-ERK-NF-κB pathway.
交际教学法在很大程度上取代了传统教学法,但其在消除学生在大学英语课堂上焦虑、沉默的情绪方面所取得的效果仍不尽如人意。作者基于学界的前期研究成果,通过对部分教师及学生进行实地访谈录音,总结分析了带来这种课堂沉默现象的原因,进而对如何打破课堂的沉默,拉近师生间的心理距离,提出了几点建议,以期给教学工作者的教学工作带来新思考。