木耳菌丝体及其醇提物的药理作用

木耳菌丝体小鼠ip给药能明显提高外周血T淋巴细胞百分率,使环磷酰胺引起的半数溶血值HC₅₀减少恢复正常;其醇提物体内外均能明显抑制ADP诱导大鼠血小板聚集作用,缩短小鼠红细胞电泳时间。     

Didymin attenuates doxorubicin-induced cardiotoxicity by inhibiting oxidative stress

Objective: This study was designed to investigate the protective effects of didymin (Did) on doxorubicin (DOX)-induced cardiotoxicity. Methods: After pretreatment with Did (2, 4, 8 mg/kg intraperitoneal i.p.) for 7 d, the male C57 mice were injected with single dose of DOX (20 mg/kg i.p.). The cardioprotective effect of Did was observed on the 7th day after DOX treatment. Results: DOX delayed body growth and caused cardiac tissue injury, oxidative stress, and mitochondrial dysfunction. Similar experiments in H9C2 cardiomyocytes showed that DOX reduced cell viability, increased generation of reactive oxygen species (ROS) and fragmentation of DNA, decreased mitochondrial membrane potential, and induced cardiomyocyte apoptosis. However, all of these adverse effects were suppressed by Did pretreatment. Did increased protein expression of glutamate-L-cysteine ligase catalytic subunit (GCL), heme oxygenase 1 (HO-1), and nuclear factor erythroid 2-related factor 2 (Nrf2). Besides, Did also induced activation of PI3K/AKT. Conclusion: These findings indicated Did prevented DOX-induced cardiac injury and apoptosis via activating PI3K/AKT/Nrf2 signaling pathway.     

大鼠视神经钳伤后外侧膝状体细胞损伤的研究

目的　探讨大鼠视神经钳伤后 ,外侧膝状体 (lateralgeniculatebody,LGB)细胞的损伤情况。方法　用 4 0g视神经损伤钳 ,压迫Sprague Dawley(SD)大鼠双侧视神经 30s,制成视神经部分定量损伤的动物模型。对LGB连续梯度切片 ,7d后用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法 (teriminaldeoxynucleotidyltransferase mediateddUTPnickend labeling ,TUNEL)对LGB细胞进行凋亡检测。 1个月后通过免疫组化染色技术 ,用兔抗鼠神经丝 (neurofilament,NF)单克隆抗体对LGB的神经元进行检测。同时经视觉中枢注入荧光染料颗粒蓝 ,对LGB细胞进行逆行荧光标记 ,在 70 0nm波长荧光显微镜下对连续切片的LGB标记细胞进行平均密度计数 ,并与对照组比较。结果　TUNEL法染色证实LGB细胞发生凋亡。对照组神经丝免疫组化染色呈清晰的条索状 ,而实验组明显减少。对照组LGB细胞密度均值为 (5 172± 2 4 8)个 /mm2 ,而损伤组LGB细胞密度均值为 (414 4± 6 1)个 /mm2 ,两组比较差异有非常显著意义 (t=8 995 ,P <0 0 1)。结论　在大鼠视神经钳伤后 ,LGB细胞受损 ,其损伤机制与凋亡有关     

Association of admission blood glucose level and clinical outcomes in elderly community‐acquired pneumonia patients with or without diabetes

IntroductionCommunity‐acquired pneumonia (CAP) is the major cause of infection‐related mortality worldwide. Patients with CAP frequently present with admission hyperglycemia.ObjectivesThe aim of this study was to evaluate the association between admission blood glucose (ABG) level and clinical outcomes in elderly CAP patients (≥80 years of age) with or without diabetes.MethodsIn this single center retrospective study, 290 elderly patients diagnosed with CAP were included. Demographic and clinical information were collected and compared. The associations between admission blood glucose level and the 30‐day mortality as well as intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) in elderly CAP patients with or without diabetes were assessed.ResultsOf the 290 eligible patients with CAP, 159 (66.5%) patients were male, and 64 (22.1%) had a known history of diabetes at hospital admission. After adjusting for age and sex, the logistic regression analysis had identified several risk factors that might be associated with clinical outcomes in elderly patients with CAP. Multivariable logistic regression analysis revealed that admission glucose level > 11.1 mmol/L was significant associated with ICU admission, IMV, and 30‐day mortality both in non‐diabetic and diabetic patients. Furthermore, Kaplan–Meier analysis indicated that patients with higher admission glucose level were correlated statistically significantly with 30‐day mortality in patients with CAP (P < 0.001).ConclusionAdmission blood glucose is correlated with 30‐day hospital mortality, ICU admission, and IMV of CAP in elderly patients with and without diabetes. Specially, admission glucose > 11.1 mmol/L was a significant risk factor for 30‐day hospital mortality.     

Prevalence and risk factors for postinfectious cough in discharged patients with coronavirus disease 2019 (COVID-19)

BackgroundCough is one of the most common symptoms of coronavirus disease 2019 (COVID-19). However, the prevalence of persistent cough in recovered patients with COVID-19 during a longer follow-up remained unknown. This study aims to investigate the prevalence, and risk factors for postinfectious cough in COVID-19 patients after discharge.MethodsWe conducted a follow-up study for 129 discharged patients with laboratory-confirmed COVID-19 in two large hospitals located in Hubei Province, China from January 2020 to December 2020. Baseline demographics, comorbidities and smoking history were extracted from the medical record. Current symptoms and severity were recorded by a uniform questionnaire. Spirometry, diffuse function and chest computed tomography (CT) were performed on part of patients who were able to return to the outpatient department at follow-up.ResultsThe median (interquartile range) follow-up time was 8.1 (7.9–8.5) months after discharge. The mean (standard deviation) age was 51.5 (14.9) years and 57 (44.2%) were male. A total of 27 (20.9%) patients had postinfectious cough (>3 weeks), 6 patients (4.7%) had persistent cough by the end of follow-up, including 3 patients with previous chronic respiratory diseases or current smoking. Other symptoms included dyspnea (6, 4.7%), sputum (4, 3.1%), fatigue (4, 3.1%), and anorexia (4, 3.1%) by the end of follow-up. Thirty-six of 41 (87.8%) patients showed impaired lung function or diffuse function, and 39 of 50 (78.0%) patients showed abnormal CT imaging. Patients with postinfectious cough demonstrated more severe and more frequent cough during hospitalization (P<0.001), and more chronic respiratory diseases (P=0.01). In multivariate logistic regression analysis, digestive symptoms during hospitalization [odds ratio (OR) 2.95, 95% confidence interval (CI): 1.10–7.92] and current smoking (OR 6.95, 95% CI: 1.46–33.14) were significantly associated with postinfectious cough of COVID-19.ConclusionsA small part of patients developed postinfectious cough after recovery from COVID-19, few patients developed chronic cough in spite of a higher proportion of impaired lung function and abnormal lung CT image. Current smoking and digestive symptoms during hospitalization were risk factors for postinfectious cough in COVID-19.     

Drug D,a Diosgenin Derive,Inhibits L-Arginine-Induced Acute Pancreatitis through Meditating GSDMD in the Endoplasmic Reticulum via the TXNIP/HIF-1α Pathway

Acute pancreatitis (AP) is one of the most common causes of hospitalization for gastrointestinal diseases, with high morbidity and mortality. Endoplasmic reticulum stress (ERS) and Gasdermin D (GSDMD) mediate AP, but little is known about their mutual influence on AP. Diosgenin has excellent anti-inflammatory and antioxidant effects. This study investigated whether Diosgenin derivative D (Drug D) inhibits L-arginine-induced acute pancreatitis through meditating GSDMD in the endoplasmic reticulum (ER). Our studies were conducted in a mouse model of L-arginine-induced AP as well as in an in vitro model on mouse pancreatic acinar cells. The GSDMD accumulation in ER was found in this study, which caused ERS of acinar cells. GSDMD inhibitor Disulfiram (DSF) notably decreased the expression of GSDMD in ER and TXNIP/HIF-1α signaling. The molecular docking study indicated that there was a potential interaction between Drug D and GSDMD. Our results showed that Drug D significantly inhibited necrosis of acinar cells dose-dependently, and we also found that Drug D alleviated pancreatic necrosis and systemic inflammation by inhibiting the GSDMD accumulation in the ER of acinar cells via the TXNIP/HIF-1α pathway. Furthermore, the level of p-IRE1α (a marker of ERS) was also down-regulated by Drug D in a dose-dependent manner in AP. We also found that Drug D alleviated TXNIP up-regulation and oxidative stress in AP. Moreover, our results revealed that GSDMD^-/- mitigated AP by inhibiting TXNIP/HIF-1α. Therefore, Drug D, which is extracted from Dioscorea zingiberensis, may inhibit L-arginine-induced AP by meditating GSDMD in the ER by the TXNIP /HIF-1α pathway.     

Experiment and Theoretical Investigation on Fatigue Life Prediction of Fracturing Pumpheads Based on a Novel Stress-Field Intensity Approach

Fracturing pumpheads are typical pressure vessels that experience frequent fatigue failure under the effect of notches in their cross-bore. To enhance the fatigue life of fracturing pumpheads, the study of the notch effect is indispensable and important to establish a reliable mathematical model to predict their fatigue life. In the present paper, two novel fatigue life prediction models are proposed for notched specimens. In these models, two new geometric fatigue failure regions are defined to improve the weight function. Finally, the elaborated novel stress-field intensity approach was applied to three different types of notched specimens. Experiment results indicate that the new SFI approach achieves 47.82%, 39.48%, and 31.85% higher prediction accuracy than the traditional SFI approach, respectively. It was found that the modified SFI approach provided better predictions than the traditional SFI approach and the TCD method. The II-th novel SFI approach had the highest accuracy, and the I-th novel SFI approach was more suitable for sharply notched specimens.     

Assessing the Association between Important Dietary Habits and Osteoporosis: A Genetic Correlation and Two-Sample Mendelian Randomization Study

Objective: Osteoporosis (OP) is the most common bone disease. The genetic and metabolic factors play important roles in OP development. However, the genetic basis of OP is still elusive. The study aimed to explore the relationships between OP and dietary habits. Methods: This study used large-scale genome-wide association study (GWAS) summary statistics from the UK Biobank to explore potential associations between OP and 143 dietary habits. The GWAS summary data of OP included 9434 self-reported OP cases and 444,941 controls, and the GWAS summary data of the dietary habits included 455,146 participants of European ancestry. Linkage disequilibrium score regression (LDSC) was used to detect the genetic correlations between OP and each of the 143 dietary habits, followed by Mendelian randomization (MR) analysis to further assess the causal relationship between OP and candidate dietary habits identified by LDSC. Results: The LDSC analysis identified seven candidate dietary habits that showed genetic associations with OP including cereal type such as biscuit cereal (coefficient = −0.1693, p value = 0.0183), servings of raw vegetables per day (coefficient = 0.0837, p value = 0.0379), and spirits measured per month (coefficient = 0.115, p value = 0.0353). MR analysis found that OP and PC17 (butter) (odds ratio [OR] = 0.974, 95% confidence interval [CI] = (0.973, 0.976), p value = 0.000970), PC35 (decaffeinated coffee) (OR = 0.985, 95% CI = (0.983, 0.987), p value = 0.00126), PC36 (overall processed meat intake) (OR = 1.035, 95% CI = (1.033, 1.037), p value = 0.000976), PC39 (spirits measured per month) (OR = 1.014, 95% CI = (1.011, 1.015), p value = 0.00153), and servings of raw vegetables per day (OR = 0.978, 95% CI = (0.977, 0.979), p value = 0.000563) were clearly causal. Conclusions: Our findings provide new clues for understanding the genetic mechanisms of OP, which focus on the possible role of dietary habits in OP pathogenesis.     

胎儿端脑突触素表达和突触发育的研究

为了探讨突触素(SYN)在不同周龄阶段胎儿端脑额叶中的表达与胎儿额叶皮质突触发育的关系,本研究采用免疫组织化学方法观察突触素在不同周龄阶段胎儿额叶的表达水平,利用计算机图像分析技术测量不同周龄阶段胎儿额叶突触素表达的平均光密度;同时取材、常规电镜技术处理、透射电镜观察额叶突触发育的超微结构变化。结果显示:(1)光镜下各组均可见SYN免疫阳性产物主要表达于胎儿的额叶皮层,其表达量随周龄的增加而增强,各组间呈现显著性差异(P<0.05),其中16～24周胎儿额叶的阳性产物位于神经元的胞浆内,呈均匀的浅黄色,神经元突起内未见阳性产物;25～29周额叶的阳性产物呈黄色,在胞浆和突起内均可见,但阳性产物的量却下降;而30～39周额叶的SYN阳性产物呈棕黄色的点状或颗粒状,主要位于神经元的突起内,神经元胞浆内未见阳性产物,阳性产物的量显著增加;(2)透射电镜下19～36周胎儿大脑额叶均可见到突触样结构,随着周龄的增加,突触的数量逐渐增多,结构逐渐清晰和完整。上述结果提示SYN的表达可以反映胎儿神经系统发育的程度,SYN的表达与突触的发育是一致的;SYN在胎儿大脑额叶的表达部位经历由神经元胞浆内表达为主到神经元终末表达为主的这一过程,可能是由于SYN先是在神经元胞浆内合成,再随着神经元的发育而逐步转移到神经元突起的末梢部位。