Neuropathic pain is frequently comorbidity with cognitive deficits. Neuralized1 (Neurl1)-mediated ubiquitination of CPEB3 in the hippocampus is critical in learning and memory. However, the role of Neurl1 in the cognitive impairment in neuropathic pain remains elusive. Herein, we found that lumbar 5 spinal nerve ligation (SNL) in male rat-induced neuropathic pain was followed by learning and memory deficits and LTP impairment in the hippocampus. The Neurl1 expression in the hippocampal CA1 was decreased after SNL. And this decrease paralleled the reduction of ubiquitinated-CPEB3 level and reduced production of GluA1 and GluA2. Overexpression of Neurl1 in the CA1 rescued cognitive deficits and LTP impairment, and reversed the reduction of ubiquitinated-CPEB3 level and the decrease of GluA1 and GluA2 production following SNL. Specific knockdown of Neurl1 or CPEB3 in bilateral hippocampal CA1 in naïve rats resulted in cognitive deficits and impairment of synaptic plasticity. The rescued cognitive function and synaptic plasticity by the treatment of overexpression of Neurl1 before SNL were counteracted by the knockdown of CPEB3 in the CA1. Collectively, the above results suggest that the downregulation of Neurl1 through reducing CPEB3 ubiquitination and, in turn, repressing GluA1 and GluA2 production and mediating synaptic plasticity impairment in hippocampal CA1 leads to the genesis of cognitive deficits in neuropathic pain.
Animals ; Male ; Neuralgia/metabolism* ; Rats ; Down-Regulation/physiology* ; Ubiquitination/physiology* ; Neuronal Plasticity/physiology* ; Rats, Sprague-Dawley ; CA1 Region, Hippocampal/metabolism* ; Cognitive Dysfunction/metabolism* ; RNA-Binding Proteins/metabolism* ; Receptors, AMPA/metabolism*

ObjectiveTo validate the alleviating effect of Gegen Qinliantang （GGQLT） on insulin resistance in db/db diabetic mice by regulating the silent information regulator 1 （SIRT1）/forkhead transcription factor O1 （FoxO1） autophagy pathway. MethodSeventy-five SPF-grade spontaneous type 2 diabetic db/db mice and 15 control db/m mice were selected and maintained on regular feed for one week before measuring blood glucose. They were randomly divided into six groups， with 15 mice in each group. The groups included a normal group （physiological saline， 0.2 g·kg^-1）， a metformin group （0.2 g·kg^-1）， high-， medium-， and low-dose GGQLT groups （31.9， 19.1， 6.9 g·kg^-1）， and a model group （physiological saline， 0.2 g·kg^-1）. They were orally treated with corresponding drugs for eight weeks， once daily. Fasting blood glucose （FBG） was measured using a Roche glucometer. Serum levels of high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， triglyceride （TG）， and total cholesterol （TC） were measured using an automated biochemical analyzer. Fasting serum insulin （INS） levels were determined using enzyme-linked immunosorbent assay （ELISA）， and the homeostasis model assessment of insulin resistance （HOMA-IR） was calculated. Western blot was used to detect the expression of Beclin-1， microtubule-associated protein 1 light chain 3 （LC3）， and SIRT1/FoxO1 autophagy pathway-related proteins in liver tissues. Immunohistochemistry was performed to assess the expression of SIRT1， FoxO1， Beclin-1， and LC3B proteins in liver tissues. Transmission electron microscopy was used to observe the formation of autophagosomes in the liver. ResultCompared with the normal group， the model group showed significant increases in FBG， FINS， HOMA-IR， TC， TG， LDL-C， and HDL-C levels （P<0.01）， and significant increases in the expression of SIRT1， Beclin-1， LC3， and FoxO1 proteins in liver tissues （P<0.01）. Transmission electron microscopy revealed the highest number of autophagosomes in the model group. Compared with the model group， the metformin group and the low-， medium-， and high-dose GGQLT groups showed significant decreases in serum FBG， FINS， HOMA-IR， TC， TG， LDL-C， and HDL-C levels （P<0.05， P<0.01）， significant decreases in the expression of SIRT1， Beclin-1， LC3 （P<0.05， P<0.01）， and up-regulated FoxO1 protein （P<0.01）. Transmission electron microscopy showed a reduction in the degree of autophagy in the treatment groups. Compared with the metformin group， the medium- and high-dose GGQLT groups showed significant decreases in FBG， FINS， and TG levels （P<0.01）， significant decreases in the expression of SIRT1， Beclin-1， and LC3 in liver tissues （P<0.05， P<0.01）， and reduced FoxO1 protein （P<0.01）. The high-dose GGQLT group showed reduced HOMA-IR， TC， LDL-C， and HDL-C levels （P<0.05， P<0.01）. Transmission electron microscopy revealed a significant reduction in autophagosomes in the medium- and high-dose GGQLT groups. ConclusionGGQLT can significantly improve glucose and lipid metabolism disorders， alleviate insulin resistance in db/db mice， and prevent and treat type 2 diabetes by activating the SIRT1/FoxO1 autophagy pathway.

Objective:To study the risk factors of axillary lymph node metastasis by analyzing the acoustic image characteristics of the automated breast volume scanner (ABVS) of breast cancer masses.Methods:The imaging features of ABVS of 212 patients with breast cancer, unilaterally and singly, confirmed by pathological examination admitted in Hangzhou First People’s Hospital from Jan. 2016 to Dec. 2018 were retrospectively analyzed. There were 83 cases with axillary lymph node metastasis (metastatic group) and 129 cases without (non-metastatic group) . The correlation of clinical and the imaging features of ABVS with axillary lymph node metastasis was analyzed using univariate analysis and multivariate logistic regression. ROC curve was used to analyze the cut-off value of the maximum diameter of the mass in predicting the breast cancer axillary lymph node metastasis. The sensitivity, specificity, positive predictive value, and negative predictive value of each risk factor were analyzed for predicting breast cancer axillary lymph node metastasis.Results:The retraction phenomenon and micro-calcification of breast cancer in the metastatic group (60.2%, 65.1%) were higher than those in the non-metastatic group (43.4%,37.2%) ( P=0.017 vs P<0.001) . The maximum diameter of the breast cancer in the metastatic group was bigger than in the non-metastatic group ( Z=2.18, P=0.029) . Multivariate logistic regression analysis showed that the micro-calcification of breast cancer ( OR=2.522, P=0.003) was an independent predictor of lymph node metastasis in breast cancer. The area under the curves and the cut-off value of the maximum diameter of the mass in predicting the breast cancer axillary lymph node metastasis were 0.589 and 2.85 cm. The sensitivity was 34.9%, the specificity was 82.9%, the positive predictive value was 56.9%, and the negative predictive value was 66.5%. The sensitivities of micro-calcification and retraction phenomenon to predict the occurrence of axillary lymph node metastasis in breast cancer patients were 65.1% and 60.2%, specificities were 62.8% and 56.6%, positive predictive values were 52.9% and 47.2%, and negative predictive values were 73.6% and 68.9%. Conclusion:The study suggests that the maximum diameter, micro-calcification, and retraction phenomenon of masses are associated with the occurrence of the axillary lymph node metastasis in breast cancer.

Objective:To analysis the impact of public health emergencies on mood fluctuations of depression and the related factors in the elderly in Shanghai, in order to provide a new evidence for early psychological intervention.Methods:A cross-sectional survey was conducted among 983 elderly in the Department of Geriatrics of Xinhua Hospital Affiliated to Shanghai Jiaotong University and two communities in Changning and Hongkou Districts of Shanghai by using a self-compiled social life questionnaire and Geriatric Depression Scale(GDS-30)during corona virus disease(COVID)-19 outbreak from 1 February to 15 February 2020.The mood fluctuations of depression and the related influencing factors were analyzed by comparing the current GDS-30 scores with the scores within previous six months.Results:Of 983 questionnaires, 867 were valid.The incidence of mild fluctuations of depression was increased from 20.9%(181/867)to 27.2%(235/867)during the public health emergencies( P<0.05), with 3 cases of newly emerged severe depression.The GDS-30 scores were higher during the public health emergencies than before the emergencies(9.88±3.85 vs.7.67±3.54, P<0.05). The four risk factors inducing fluctuations of depression in the elderly were the number of coexisted chronic diseases ≥2( P=0.036), the lack of visits or communication from families( P=0.015), the family members exposing a risk to COVID-19( P<0.01), and the daily viewing of epidemic news more than 4 h( P=0.023). Linear regression analysis showed that cough, sore throat, dizziness, sleep disturbance and dyspnea were significantly related to the aggravation of depression(based on the increase of GDS-30 score)( P<0.05). Conclusions:Public health emergencies may exacerbate depression in the elderly.They are more likely to experience the aggravation of depression when they suffer from multiple chronic diseases, lack the child visits or communications, have the family members exposing a risk to COVID-19 and pay excessive attention to the epidemic.

In the original publication the grant number is incorrectly published. The correct grant number should be read as "17140901600". The corrected contents are provided in this correction article. This work was partially supported by grants from the National Natural Science Foundation of China (Nos. 81670470 and 81600149), a grant from the Shanghai Municipal Commission for Science and Technology (17140901600, 18411953500 and 15JC1400201) and a grant from National Key Research and Development Program (2016YFC0905100).

Adenosine ; genetics ; Adenosine Deaminase ; genetics ; metabolism ; Animals ; CRISPR-Associated Protein 9 ; genetics ; metabolism ; CRISPR-Cas Systems ; genetics ; Embryo, Mammalian ; metabolism ; Gene Editing ; Genetic Variation ; genetics ; Mice ; Mice, Inbred C57BL ; Rats ; Rats, Sprague-Dawley

This study aimed to elucidate the effect of tryptophan (Trp) on gut hormone secretion as well as the roles of the calcium-sensing receptor (CaSR) and its downstream signaling pathway in gut hormone secretion by assessing swine duodenal perfusion in vitro. Swine duodenum was perfused with Krebs-Henseleit buffer as a basal solution. Various concentrations (0, 10, and 20 mM) of Trp were applied to investigate its effect on gut hormone secretion. A CaSR antagonist was used to detect the involvement of CaSR and its signal molecules. The 20 mM Trp concentration promoted the secretion of cholecystokinin (CCK) and glucose-dependent insulinotropic peptide (GIP), elevated the mRNA level of CaSR, and upregulated the protein levels of CaSR, protein kinase C (PKC), and inositol trisphosphate receptor (IP3R). However, NPS 2143, an inhibitor of CaSR, attenuated the CCK and GIP release, reduced the mRNA level of CaSR, and decreased the protein levels of CaSR, PKC, and IP3R with 20 mM Trp perfusion. The results indicate that CCK and GIP secretion can be induced by Trp in swine duodenum in vitro, and the effect is mediated by CaSR and its downstream signal molecules PKC and IP3R.
Cholecystokinin ; Duodenum ; Gastric Inhibitory Polypeptide ; In Vitro Techniques ; Inositol ; Perfusion ; Protein Kinase C ; Receptors, Calcium-Sensing ; RNA, Messenger ; Swine ; Tryptophan

The Internet Public Opinion Monitoring and Early Warning System for medical and health industry was designed and implemented due to the frequent occurrence of Internet public opinion, which has all-directional data collecting and analyzing functions, including big data collection, near duplicate detection, spam filtration, key public opinion early warning, region identification and tendency analysis, and can thus provide evidence for relevant departments to take effective measures for the control of Internet public opinion.

Objective: To investigate the effect of the gene interfering technology on fatty acid synthase (FAS) gene silencing for lipid contents in human hepatic cell line HepG2 and to study the lipid metabolism related gene expression in HepG2 cells. Methods: A total of 3 pairs of small interfering RNA (siRNA) targeting different sequences of FAS mRNA were synthesized as FAS-siRNA-1, FAS-siRNA-2 and FAS-siRNA-3, meanwhile, 2 controls were established as Blank control group, in which HepG2 cells were not treated, and Negative control group, in which HepG2 cells were transfected by non-effective siRNA. The mRNA, and protein expression levels of FAS in HepG2 cells were examined by real-time lfuorescence quantitative RCR and Western blot analysis to screen the most effective pair of siRNA for FAS gene silencing; and that speciifc siRNA was transtected to HepG2 cells for 48 hours to detect the intra-/extra-cellular TG, TC levels and the mRNA expression related to lipid metabolism in HepG2 cells. Results: The screening experiment indicated that FAS-siRNA-3 was most effective for FAS gene silencing. Compared with Blank control group, the mRNA and protein expressions in FAS-siRNA-3 transfected HepG2 cells (Transfected group)decreased to (52.33 ± 3.07) % and (51.57 ± 3.14) % respectively. Compared with Blank control group, Transfected group had the reduced intra-/extra-cellular TG levels and reduced extracellular TC level; while increased mRNA expression of hepatic lipase,P<0.0001 and decreased mRNA expression of TG transfer protein in HepG2 microsome,P<0.05. Conclusion: FAS gene silencing could signiifcantly decrease the intra-/extra- cellular TG level and extracellular TC level in HepG2 cells, those ifndings need to be conifrmed by furtherin vivo andin vitro studies.

Objective To investigate the correlation of serum ferritin (SF) and hypersensitive C-reactive protein (hs-CRP) with carotid intima-medium thickness (CIMT) in aged type 2 diabetes mellitus ( T2DM) patients.Methods sixty patients with T2DM, 60 with impaired glucose regulation (IGR) and 60 normal control subjects were recruited .SF, hs-CRP, fasting blood glucose (FBG), 2h postprandial blood glucose(2h PBG) along with glycosylated hemoglobin (HbA1c), fasting insulin (FINS), triglyceride (TG) and total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were assayed, while CIMT of the participants were measured using B mode colorful Doppler ultrasonography .Results FBG, 2hPBG, HbA1c, FINS, homeostasis model assessment insulin resistance (HOMA-IR), TG, TC and LDL-C showed significant difference be -tween patients with T2DM and normal controls ( P <0.05).FBG, 2hPBG, HbA1c, FINS, HOMA-IR showed significant difference between patients with IGR and normal controls ( P <0.05).FBG, 2hPBG, HbA1c, FINS, HOMA-IR, TG and LDL-C showed sig-nificant difference between patients with T 2DM and IGR (P <0.05).Compared with patients with IGR and controls , SF、hs -CRP and bilateral CIMT were found significantly increased in the T 2DM group (P <0.05), the similar differences which was also found comparing IGR group and normal control group .Besides, SF had positive correlation with hs -CRP and bilateral CIMT in both T2DM group ( r =0.89, P <0.05; r =0.82, P <0.05) and IGR group ( r =0.79, P <0.05; r =0.75, P <0.05).Conclusions SF and hs -CRP might contribute to the pathogenesis of diabetic macroangiopathy ,which means they could be useful clinically as vascular risk factors.