One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

Objective To observe the value of ovarian-adnexal reporting and data system ultrasound 2022 version(O-RADS US v2022)and it combined with risk of malignancy index 4(RMI4)for differential diagnosis of benign and malignant adnexal tumors.Methods Data of 126 patients with adnexal tumors confirmed by surgical pathology were retrospectively analyzed.O-RADS US v2022 was used to classify:1-3 as benign lesion and 4-5 as malignant lesion.RMI4 classification took 450 as the critical value.And classification was performed based on the two combination.Taking pathological results as gold standard,receiver operating characteristic(ROC)curve was drawn to evaluate the efficacy of O-RADS US v2022 and RMI4 alone or combination for the differential diagnosis of benign and malignant adnexal tumors.Results Among 126 cases,94 were benign and 32 were malignant tumors.The sensitivity,specificity,accuracy and area under the curve(AUC)of O-RADS US v2022 were 78.13％,80.85％,80.16％and 0.795,respectively.The diagnostic results of RMI4 were 71.88％,84.04％,80.95％and 0.780,respectively.The specificity and accuracy of the combination of the two(93.62％,92.06％)were higher than those of O-RADS US v2022(x2=7.322,5.967,P=0.007,0.015)or RMI4(x2=4.625,5.331,P=0.032,0.021),while no significant difference in sensitivity and AUC(87.50％,0.906)was found with O-RADS US v2022 or RMI4(all P＞0.05).Conclusion O-RADS US v2022 could effectively differentiate benign and malignant adnexal tumors,and combined with RMI4 could improve the diagnostic specificity and accuracy.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular mortality in patients with diabetes mellitus but the protective mechanism remains elusive. Here we demonstrated that the SGLT2 inhibitor, Empagliflozin (EMPA), suppresses cardiomyocytes autosis (autophagic cell death) to confer cardioprotective effects. Using myocardial infarction (MI) mouse models with and without diabetes mellitus, EMPA treatment significantly reduced infarct size, and myocardial fibrosis, thereby leading to improved cardiac function and survival. In the context of ischemia and nutritional glucose deprivation where autosis is already highly stimulated, EMPA directly inhibits the activity of the Na⁺/H⁺ exchanger 1 (NHE1) in the cardiomyocytes to regulate excessive autophagy. Knockdown of NHE1 significantly rescued glucose deprivation-induced autosis. In contrast, overexpression of NHE1 aggravated the cardiomyocytes death in response to starvation, which was effectively rescued by EMPA treatment. Furthermore, in vitro and in vivo analysis of NHE1 and Beclin 1 knockout mice validated that EMPA's cardioprotective effects are at least in part through downregulation of autophagic flux. These findings provide new insights for drug development, specifically targeting NHE1 and autosis for ventricular remodeling and heart failure after MI in both diabetic and non-diabetic patients.
Animals ; Diabetes Mellitus ; Diabetes Mellitus, Type 2/drug therapy* ; Glucose ; Humans ; Mice ; Myocardial Infarction/metabolism* ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use* ; Ventricular Remodeling

Objective To evaluate the value of color flow angio(CFA)in judging the status of thyroid function by analyzing the ultrasonographic features and quantitatively measuring the blood flow signals in patients with thyroid diffuse lesions.Methods Totally 100 patients with thyroid diffuse lesions diagnosed by ultrasonography between Oct.2016 and Jun.2017 were divided into three groups:hyperthyroidism group(n=30),hypothyroidism group(n=34)and euthyroid group(n=36).Moreover,30 cases of healthy volunteers were chosen as control group.The blood flow index including vascularity index(VI)value and Vascularity value of region of interest from all cases was measured through CFA imaging technique.The differences of VI and Vascularity from above 4 groups were compared using one-way analysis of variance.Comparison among groups was carried out by SNK-q test.The subjects' work curves(ROC curves)were plotted and analyzed using clinical diagnosis as gold standard.At the same time,the correlation between VI and thyroid function in hyperthyroid group and hypothyroidism group was analyzed through Pearson correlation coefficient.Results The levels of VI and Vascularity in hyperthyroid group,hypothyroid group,euthyroid group and control group were decreased gradually with significant differences between every two groups.VI : control vs hyperthyroid,hypothyroid and euthyroid group: q=13.67,7.00 and 3.93,all P＜0.01.Euthyroid vs hyperthyroidism and hypothyroid group: q=10.35,P＜0.01 and q=3.27,P＜0.05.Hyperthyroidism vs hypothyroid group: q=7.09,P＜0.01.Vascularity: control vs hyperthyroid,hypothyroid and euthyroid group: q=15.23,10.16 and 6.58,all P＜0.01.Euthyroid vs hyperthyroidism and hypothyroid group: q=9.33 and 3.83,both P＜0.01.Hyperthyroidism vs hypothyroid group: q=5.55,P＜0.01.The area under the curve of hyperthyroidism group and hypothyroidism group was 0.733,with 9.526%as the diagnostic cutoff point.The sensitivity and specificity were 70.0%and 76.5%respectively.The area under the curve of the abnormal group and normal group was 0.768,with 7.404%as the diagnostic cutoff point.The sensitivity and specificity were 62.5%and 88.9%,respectively.The VI value of hyperthyroidism group was positively correlated with FT3 and FT4(r=0.584,0.499,both P＜0.05),and negatively correlated with TSH(r=-0.447,P＜0.05).The VI value of hypothyroidism group was negatively correlated with FT4(r=-0.342,P＜0.05),and had no significant correlation with FT3 and TSH(r=0.121,-0.007,P＞0.05).Conclusion CFA imaging technology can quantitatively measure the blood flow signals of thyroid parenchyma and evaluate the thyroid function in patients with thyroid diffuse lesions.

Objective To investigate the effects of a novel scientific research practice model on medical undergraduates'!cognition and behavior. Method Totally, 60 medical undergraduates took part in the research. All of them accepted scientific research training by using improved tutorial system + team-based learning (TBL) combat training models. Before and after training, students completed the same ques-tionnaires respectively. The content included the purpose of participating in scientific research activities, the interest of scientific research, and the confidence and satisfaction of publishing scientific research papers, etc.. SPSS 16.0 was used to conduct non parametric Mann-Whitney test or Wilcoxon non parametric test to the pre and post survey data. Results Fifty-seven students (95.0%) were satisfied with the novel teaching model. Before and after training, the liking scores for scientific research practice rose from 1.12 (95%CI=0.65 to 1.59) to 5.87 (95%CI=5.34 to 6.39), P=0.001. Fifty-three students (88.3%) proactively participated in research work after training compared with 21 students (35.0%) before training, P=0.000. More students had confidence in publishing academic papers on Chinese core journals or Science Citation Index journals after training (P=0.000, P=0.003 respectively). 57 students (95%) said they were very satisfied or satisfied with the training of scientific research and practice. Conclusion Improved tutorial system+TBL research combat training model can stimulate students'!interest in scientific research and make them have more pos-itive cognition and behavior on scientific research work.