Effects of Erastin on depressive- and anxiety-like behavior and the expression of hippocampal ferroptosis-related proteins in rats / 中华行为医学与脑科学杂志

Objective:To explore the effects of intrahippocampal injection of ferroptosis inducer Erastin on depressive- and anxiety-like behavior and the expression of ferroptosis-related proteins in rats.Methods:Forty 6-week-old healthy male Sprague-Dawley rats were randomly divided into five groups ( n=8/group): Control group, Erastin low-dose(200 ng/μL) group, Erastin medium-dose(400 ng/μL) group, Erastin high-dose group(600 ng/μL) and lipopolysaccharide (LPS, 10 μg/L) group.After the intrahippocampal injection of Erastin(2.5 μL per side), body weight, and behavioral tests, including sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), and elevated plus maze (EPM), were performed to evaluate depressive- and anxiety-like phenotypes from the fourth day after injection.The levels of ferroptosis-related proteins and mRNA, including glutathione peroxidase 4 (GPX4), cyclo-oxygenase 2 (COX2), ferritin heavy polypeptide 1 (FTH1), long-chain fatty acyl-CoA synthetase 4 (ACSL4), solute carrier family 7 member 11 (SLC7A11) were measured using real-time quantitative PCR and Western blot analysis.SPSS 22.0 software was used for statistical analysis.One-Way ANOVA was used for multi-group comparison, and LSD was used for further pound-wise comparison. Results:(1)Body weight and behavioral tests: there were no statistically significant differences in baseline body weight and behavioral tests in these groups ( F=0.02-1.15, all P>0.05). After intrahippocampal injection, compared with the control group, medium-dose Erastin induced depression-like behaviors in rats more significantly, as indicated by reduced bodyweight ((245.20±5.24)g, (267.45±13.16)), sucrose preference in SPT ((32.14±8.51)%, (68.17±13.67)%), central time in OFT ((6.01±2.57)s, (16.49±7.21)s), percentage of time in open arm in EPM ((5.00±3.83)%, (19.63±5.91)%) and increased immobility time in FST ((37.00±7.58)s, (12.50±5.51)s) and percentage of time in closed arm in EPM ((89.43±4.77)%, (59.96±9.91)%), and there were statistically significant differences in these groups (all P<0.05). (2)The expression of ferroptosis-related indicators: after intrahippocampal injection, the expression of mRNA ( F=2.23, 8.37, 2.91, 7.60, 3.16, all P<0.05) and protein ( F=3.31, 40.13, 8.52, 3.70, 70.79, all P<0.05) of FTH1, GPX4, SLC7A11, COX2 and ACSL4 in hippocampus were statistically significant differences in the 5 groups.The mRNA and protein levels of FTH1, GPX4 and SLC7A11 in Erastin medium-dose group were lower than those in the control group (all P<0.05), while the mRNA and protein levels of COX2 and ACSL4 were higher than those in the control group (all P<0.05). Conclusion:Intrahippocampal microinjection of Erastin(400 ng/μL) can induce ferroptosis in hippocampus of rats and can also induce depressive-like behaviors in rats.

Preclinical characterization and comparison between CD3/CD19 bispecific and novel CD3/CD19/CD20 trispecific antibodies against B-cell acute lymphoblastic leukemia: targeted immunotherapy for acute lymphoblastic leukemia / 医学前沿

The CD19-targeting bispecific T-cell engager blinatumomab has shown remarkable efficacy in patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. However, several studies showed that blinatumomab has a short plasma half-life due to its low molecular weight, and thus its clinical use is limited. Furthermore, multiple trials have shown that approximately 30% of blinatumomab-relapsed cases are characterized by CD19 negative leukemic cells. Here, we design and characterize two novel antibodies, A-319 and A-2019. Blinatumomab and A-319 are CD3/CD19 bispecific antibodies with different molecular sizes and structures, and A-2019 is a novel CD3/CD19/CD20 trispecific antibody with an additional anti-CD20 function. Our in vitro, ex vivo, and in vivo experiments demonstrated that A-319 and A-2019 are potent antitumor agents and capable of recruiting CD3 positive T cells, enhancing T-cell function, mediating B-cell depletion, and eventually inhibiting tumor growth in Raji xenograft models. The two molecules are complementary in terms of efficacy and specificity profile. The activity of A-319 demonstrated superior to that of A-2019, whereas A-2019 has an additional capability to target CD20 in cells missing CD19, suggesting its potential function against CD19 weak or negative CD20 positive leukemic cells.

Neural mechanism of environmental enrichment improving depression / 中华行为医学与脑科学杂志

Depression is a common psychiatric disorder characterized by low mood with complex pathophysiological mechanisms and poor effect of pharmacological treatment.The animals were placed in greater sensory, physical and/or social stimuli than those of the standard feeding environment, so that they can obtain positive plasticity and adaptability.Environmental enrichment(EE) is a common intervention to improve brain function in laboratory.A large number of studies have shown that EE had significant ameliorative effects on various animal models of depression, but the mechanisms have not been yet fully understood with outcome heterogeneity in ethology.There was no universally accepted and unified paradigm and standard for EE due to its multi-dimensionality and complexity.Therefore, it is necessary to improve the structural components and implementation steps of EE by integrating the existing data.Combined with recent studies on animal models of depression, this paper reviewed the anti-depression mechanism of EE from promoting hippocampal neurogenesis, reducing neuroinflammation, regulating neuroendocrine and affecting epigenetic modifications, in order to provide new ideas for mechanisms research and treatment of depression.As the rise of precision medicine and individualized medicine brings human growing interest in exploring the sources and mechanisms of inter-individual differences and intra-group effects of depression, it will be a challenge to translate EE to the human society in a rational way.

Prediction of cervical lymph node metastasis in papillary thyroid carcinoma using model based on thyroglobulin and clinical features / 中华内分泌外科杂志

Objective:To investigate the relationship between preoperative serum thyroglobulin (Tg) and clinical data with the risk of cervical lymph node metastasis in patients with papillary thyroid carcinoma (PTC) .Methods:Data of 395 PTC patients who underwent surgery from Feb. 2016 to Jun. 2019 at the Second Affiliated Hospital of Soochow University were retrospectively analyzed. Based on whether cervical lymph nodes had metastasis, patients were classified into central lymph node metastasis positive group ( n=195 cases) , central lymph node metastasis negative group ( n=200 cases) , lateral lymph node metastasis positive group ( n=72 cases) , and lateral lymph node metastasis negative group ( n=323 cases) .Then the relationship between age, sex, multifocality, tumor diameter, capsular invasion, preoperative TSH and preoperative Tg with lymph node metastasis were analyzed by SPSS. Comparisons between groups were performed by χ2 test and rank sum test. Prediction efficiency of the preoperative Tg and Logistic regression model was estimated by receiver operating characteristic (ROC) curve. A total of 100 PTC patients confirmed by pathological results in the Second Affiliated Hospital of Soochow University from Jul. 2019 to Apr. 2020 were selected as the validation data. Results:Multi-factor Logistic regression showed that age, tumor diameter, capsular invasion and preoperative Tg were independent risk factors of central cervical lymphatic metastasis ( P<0.05) ; Tumor diameter, capsular invasion, central cervical lymphatic metastasis and preoperative Tg were independent risk factors of lateral cervical lymphatic metastasis ( P<0.05) . The area under the ROC curve (AUC) for diagnosing central lymph node metastasis by preoperative Tg was 0.710, with a sensitivity of 49.2%, and specificity of 88.5%. The AUC for diagnosing lateral lymph node metastasis by preoperative Tg was 0.728, with a sensitivity of 59.7%, and specificity of 89.5%. The AUC for diagnosing central lymph node metastasis by the prediction model was 0.773, with a sensitivity of 78.5%, and specificity of 64.5%.The AUC for diagnosing lateral lymph node metastasis by the prediction model was 0.869, with a sensitivity of 84.7%, and specificity of 70.3%. Conclusions:The preoperative serum Tg level is correlated with cervical lymph node metastasis in PTC patients. But the Logistic regression model based on preoperative Tg and other independent risk factors shows a better predictive value.

Mechanism of estrogen against liver fibrosis in postmenopausal women with chronic liver disease / 临床肝胆病杂志

Metabolic disorders are observed in women after menopause, and the postmenopausal women suffering from chronic liver diseases have an increased risk of progression to liver fibrosis, with a higher risk than male patients of the same age, which may be associated with the decline of ovarian function and the reduction of estrogen level after menopause. This article summarizes the research advances in the molecular mechanism of progression to liver fibrosis from the aspects of estrogen and oxidative stress, activation of hepatic stellate cells, accumulation of extracellular matrix, and immune regulation. It is pointed out supplementation with an appropriate amount of estrogen in the perimenopausal period and the early menopausal period can reduce the risk of liver fibrosis and delay or even reverse the process of liver fibrosis, thereby improving quality of life and prolonging survival time in elderly female patients.

Mechanism of estrogen against liver fibrosis in postmenopausal women with chronic liver disease / 临床肝胆病杂志

Metabolic disorders are observed in women after menopause, and the postmenopausal women suffering from chronic liver diseases have an increased risk of progression to liver fibrosis, with a higher risk than male patients of the same age, which may be associated with the decline of ovarian function and the reduction of estrogen level after menopause. This article summarizes the research advances in the molecular mechanism of progression to liver fibrosis from the aspects of estrogen and oxidative stress, activation of hepatic stellate cells, accumulation of extracellular matrix, and immune regulation. It is pointed out supplementation with an appropriate amount of estrogen in the perimenopausal period and the early menopausal period can reduce the risk of liver fibrosis and delay or even reverse the process of liver fibrosis, thereby improving quality of life and prolonging survival time in elderly female patients.

Expression and correlation of survivin, COX-2 and bcl-2 in non-Hodgkin lymphoma / 白血病·淋巴瘤

ObjectiveTo investigate the expression of survivin,COX-2 and bcl-2 in non-Hodgkin lymphoma(NHL)and the significance and correlation between them.MethodsImmunohistochemistry MaxVision systems for survivin,COX-2 and bcl-2 were conducted on 44 NHL and 20 reactive lymphoid hyperplasia (RH).ResultsThe positive expression rates of survivin,COX-2,bcl-2 in NHL were 70.45 ％(31/44),68.18 ％ (30/44),63.64 ％ (28/44),respectively,and these in RH were 40.00 ％ (8/20),40.00 ％(8/20) and 20.00 ％ (4/20),respectively.There was positive correlation between the expression of COX-2 and survivin (r =0.306,P =0.043),survivin and bcl-2 protein (r =0.339,P =0.040) in NHL.ConclusionCOX-2,survivin,bcl-2 are highly expressed in NHL.To detect the expression of them has clinical value to diagnosis NHL and to estimate the malignant degree of lymphoma.There are a positive correlations between the expression of COX-2 and survivin protein,and between the expression of survivin and bcl-2 protein,which indicates that they may play a synergistic role in the occurrence and development of NHL.