BACKGROUND: The protective effect of mesenchymal stem cells (MSCs) on cardiac ischemia-reperfusion (I/R) injury has been widely reported. Dental pulp-derived mesenchymal stem cells (DP-MSCs) have therapeutic effects on various diseases, including diabetes and cirrhosis. This study aimed to determine the therapeutic effects of DP-MSCs on I/R injury and elucidate the underlying mechanism. METHODS: Myocardial I/R injury model mice were treated with DP-MSCs or a miR-19a-3p mimic. The infarct volume, fibrotic area, pyroptosis, inflammation level, and cardiac function were measured. Cardiomyocytes exposed to hypoxia-reoxygenation were transfected with the miR-19a-3p mimic, miR-19a-3p inhibitor, or negative control. Pyroptosis and protein expression in the interferon regulatory factor 8/mitogen-activated protein kinase (IRF-8/MAPK) pathway were measured. RESULTS: DP-MSCs protected cardiac function in cardiac I/R-injured mice and inhibited cardiomyocyte pyroptosis. The upregulation of miR-19a-3p protected cardiac function, inhibited cardiomyocyte pyroptosis, and inhibited IRF-8/MAPK signaling in cardiac I/R-injured mice. DP-MSCs inhibited cardiomyocyte pyroptosis and the IRF-8/MAPK signaling by upregulating the miR-19a-3p levels in cardiomyocytes injured by I/R. CONCLUSION DP-MSCs protected cardiac function by inhibiting cardiomyocyte pyroptosis through miR-19a-3p under I/R conditions.
Animals ; MicroRNAs/metabolism* ; Pyroptosis/genetics* ; Mesenchymal Stem Cells/metabolism* ; Myocytes, Cardiac/cytology* ; Mice ; Male ; Mice, Inbred C57BL ; Dental Pulp/cytology* ; Myocardial Reperfusion Injury/therapy* ; MAP Kinase Signaling System/physiology*

[This corrects the article DOI: 10.1016/j.apsb.2018.08.009.].

When eukaryotic cells are undergoing stimulations like oxidative stress,heat shock,or vi-ral infection,cellular stress response will quickly initiate to stop translation,leading to the produc-tion of a large number of stress granules(SGs).SGs,as dynamic membraneless protein-RNA ag-gregates,play an important role in maintaining cellular homeostasis and regulating host gene ex-pression.Upon viral invasion,the host halts translation to form SGs,thereby arresting the transla-tion of viral proteins within host cells.This process recruits innate immune-related host factors,limiting the virus from exploiting host translation machinery to complete its life cycle.It activates the innate immune pathway.However,some viruses have evolved multiple mechanisms to counter SGs,in order to provide a better intracellular environment for viral replication.Here,we review the generation of SGs,antiviral mechanism of SGs,and the strategies for escaping SGs during virus e-volution,in order to provide a new perspective for the development of antiviral drugs.

Objective:To explore the feasibility of using two-dimensional speckle tracking echocardiography for measuring right ventricular strain and function in healthy adults, and to analyze the impact of age and gender.Methods:This study is a cross-sectional study. Healthy adults who underwent physical examination in the Physical Examination Center of Beijing Hospital from January 1, 2020 to January 1, 2021 were included. Two researchers independently measured various right ventricular longitudinal strain indices using the Echopac software, including (global longitudinal strain (GLS), apical longitudinal strain (ALS), midventricle longitudinal strain (MLS), basal longitudinal strain (BLS), free wall GLS (FWGLS), free wall ALS (FWALS), free wall MLS (FWMLS) and free wall BLS (FWBLS)) as well as tricuspid annular plane systolic excursion (TAPSE) and right ventricle-fraction of area change (RVFAC). The above indicators were taken as the average of two physicians. The consistency of the measurements by two physicians was evaluated by the within-group correlation coefficient ( ICC). Results:A total of 233 subjects were included, including 137 males, aged (58.5±14.2) years. ICC values was all above 0.8 with excellent agreement. The values of FWGLS and GLS in healthy adults were -26.63% and -21.89%, respectively. There was no statistically significant difference in TAPSE ((2.06±0.41)cm vs. (2.10±0.39)cm, P=0.510) and RVFAC ((51.17±9.91)% vs. (50.89±8.65)%, P=0.826) between males and females. The values of various right ventricular long axis strain indicators (GLS, ALS, MLS, BLS, FWGLS, FWMLS, FWMLS, FWBLS) in females aged 18 to 40 and 41 to 65 years were higher than those in males of the same age (all P<0.05), while there was no statistically significant difference in the values of various right ventricular long axis strain indicators between the sexes in subjects aged 65 years and above (all P>0.05). In females, the right ventricular GLS, ALS, MLS, FWGLS, FWALS, FWMLS, and FWBLS values in the groups aged 18 to 40 and 41 to 65 years were significantly higher than those in the group aged 65 years and above (all P<0.05). In contrast, no significant differences were found in these indices among different age groups in males (all P>0.05). Conclusions:Using two-dimensional speckle tracking technology in echocardiography to measure right ventricular strain indicators is feasible and highly reproducible. Gender and age have an impact on right ventricular strain indicators.

Objective:To explore the prognostic value of systemic immune-inflammatory index(SII)combined with tumor burden score (TBS) (hereinafter referred to as STS) in patients with intrahepatic cholangiocarcinoma (ICC) after radical resection, and to construct a nomogram model.Methods:The clinical data (including the degree of tumor differentiation, vascular cancer thrombus, and lymph node metastasis, etc.) of 258 ICC patients who received radical resection at People′s Hospital of Zhengzhou University (170 cases, training set) and Cancer Hospital of Zhengzhou University (88 cases, validation set) from January 1, 2016 to January 31, 2020 were retrospectively analyzed and graded by SII, TBS and STS. Multivariate Cox regression analysis were used to identify independent factors affecting the prognosis of patients with ICC. Kaplan-Meier survival curve and receiver operating characteristic curve (ROC) were drawn to evaluate the predictive efficiency of SII, TBS and STS in the overall survival of patients with ICC after radical resection. The nomogram prediction model was constructed and evaluate the performance of nomogram model using consistency index (C-index) and calibration curve.Results:Among 170 ICC patients in the training set, there were 106 cases of SII grade 1 and 64 cases of SII grade 2; 137 cases of TBS grade 1 and 33 cases of TBS grade 2; and 98 cases of STS grade 1, 47 cases of STS grade 2, and 25 cases of STS grade 3. Among 88 ICC patients in the validation set, there were 33 cases of SII grade 1 and 55 cases of SII grade 2; 66 cases of TBS grade 1 and 22 cases of TBS grade 2; and 30 case of STS grade 1, 39 cases of TBS grade 2, and 19 cases of TBS grade 3.The multivariate Cox regression analysis showed that tumor differentiation degree (highly differentiated vs. moderately differentiated HR=0.157, 95% confidence interval(95% CI) 0.045 to 0.546, highly differentiated vs. poorly differentiated HR=0.452, 95% CI 0.273 to 0.750), STS (grade 3 vs. grade 2 HR=1.966, 95% CI 1.148 to 3.469; grade 3 vs. grade 1 HR=1.405, 95% CI 0.890 to 2.216), vascular cancer thrombus ( HR=2.006, 95% CI 1.313 to 3.066), nerve invasion ( HR=1.865, 95% CI 1.221 to 2.850), and lymph node metastasis ( HR=1.802, 95% CI 1.121 to 2.896) were independent influencing factors of overall survival in ICC patients after radical resection (all P<0.05). The Kaplan-Meier survival curve showed that SII, TBS, and STS were independent influencing factors of overall survival in ICC patients (all P<0.05). The results of ROC analysis showed that the areas under the curve of SII, TBS and STS in predicting overall survival of ICC patients after radical resection were 0.566 (95% CI 0.479 to 0.652), 0.585 (95% CI 0.499 to 0.672), and 0.657 (95% CI 0.522 to 0.692), respectively. Tumor differentiation, vascular tumor thrombus, nerve invassion, lymph node metastasis, and STS were included to constract the nomogram model. The C-indexes of the training set and validation set based on the nomogram model were 0.792 (95% CI 0.699 to 0.825) and 0.776 (95% CI 0.716 to 0.833), respectively. The calibration curves of the survival rate of the training set and the validation set were close to the reference lines, and the nomogram model had better predictive ability in both the training set and the validation set. Conclusions:Preoperative STS grading is an effective and practical predictor of overall survival in ICC patients after radical section. Compared with SII and TBS alone, it has better predictive value for the prognosis of patients with ICC.

Objective To investigate the possible mechanism of circ RNA in the pathogenesis of epilepsy.Methods In this study,circRNA expression profiles in peripheral venous blood of epileptic patients and healthy controls were studied by using circRNA gene chip technology,and differentially expressed circrnas were screened.Bioinfor-matics databases such as circPrimer,circMir and TargetScan were used to analyze its possible role in epilepsy and adenovirus vector was constructed.Thirty male adult C57BL/6 mice were randomly divided into control group,empty vector group and circ_0017178 overexpressed group(10 mice/group).Normal saline,empty plasmid ade-novirus vector and circ_0017178 overexpressed adenovirus vector were injected into the hippocampus of the three groups respectively.The change of animal behavior of mice in each group was observed after the establishment of pentetrazole epilepsy model,and the apoptosis of hippocampal tissue cells of mice in each group was analyzed by Tunel staining.Results The results of gene microarray showed that circ_0069272,circ_0033065,circ_0017178,circ_0073442,circ_0033063 and circ_0049415 in epilepsy group were up-regulated significantly compared with the control group.And circ_0083773,circ_0088262,circ_0016396 decreased significantly.Circ_0017178 might be the most associated with epilepsy.Through bioanalysis,circ_0017178 might regulate 39 epilepsy genes by combi-ning 20 miRNA and possess potential m6A,IRES and ORF1 binding sites.In the experiment of pentatetrazole epi-leptic mice,compared with the empty carrier group and the control group,the latency period of epilepsy in the circ_0017178 overexpression group was shortened(P＜0.05),the seizure time was prolonged(P＜0.05),and the seizure frequency increased(P＜0.05).There was no statistical significance between the empty carrier group and the control group(P＞0.05).In animal experiments,compared with the empty vector group and the control group,the apoptosis degree of hippocampal tissue of epileptic mice in the circ_0017178 overexpression group sig-nificantly increased(P＜0.05),but there was no statistical significance between the empty vector group and the control group(P＞0.05).Conclusion Circ_0017178 significantly increases in the expression profile of peripher-al blood mononuclear cells in patients with epilepsy,which may act as a"molecular sponge"of miRNA in epilepsy and has the potential of m6A methylation and protein translation.Circ_0017178 may increase the susceptibility and severity of epilepsy by promoting apoptosis in penetetrazole epileptic mice.

Objective To investigate the effect of Changyuning prescription on PTEN,TLR2,Caspase-3,Caspase-9 in phosphatidylinositol-3 kinase/protein kinase B(PI3K/AKT)signaling pathway in colon tissue of 2,4,6-trinitrobenzenesulfonic acid(TNBS)-induced ulcerative colitis(UC)rats.Methods After adaptive feeding for 7 days,70 SPF rats were divided into blank group of 10 and modeling group of 60.The rats in the modeling group were given TNBS/ethanol solution enema to induce UC model.The rats that successfully bulit the model were randomly divided into model group,mesalazine group,Changyuning high-dose,medium-dose and low-dose groups,and Changyuning high-dose,medium-dose and low-dose groups,respectively,and the equivalent amount of crude drug was 4 g·mL-1,2 g·mL-1,1 g·mL-1 of Changyuning prescription solution 10 mL·kg-1,the mesalamine group was given 10 mL·kg-1 of mesalamine suspension equivalent to 0.2 g·kg-1 crude drug,the blank control group and model group were given an equal volume of 10 mL·kg-1 of normal saline was given by gavage.The rats in each group were given intragastric administration once a day for 14 consecutive days.Rats were sacrificed after the last administration.Disease activity index was evaluated;colon changes were observed by HE staining;colon tissue damage index was evaluated;The expression of PI3K,AKT,PTEN,TLR2,Caspase-3,and Caspase-9 proteins was detected by Western Blotting in colon tissue.Results Compared with the blank group,the protein expression levels of PI3K,AKT,Caspase-3,Caspase-9 and TLR2 in the model group were increased(P<0.05),and the protein expression level of PTEN was decreased(P<0.05).Compared with the model group,the expression levels of PI3K,AKT,Caspase-3,Caspase-9 and TLR2 proteins in the Changyuning high-dose group were significantly decreased(P<0.05),and the protein expression levels of PTEN were significantly increased(P<0.05);The levels of PI3K,AKT and Caspase-3 in the salazine group and Changyuning medium dose were decreased(P<0.05),the expression level of PTEN protein was increased(P<0.05),and there was no statistical significance in the expression of Caspase-9;There was no statistical significance in the expression of each protein between the Changyuning low-dose group and the model group.Conclusion Changyuning recipe has a significant effect on the treatment of UC,and its mechanism may be related to the regulation of PI3K/AKT signaling pathway and its related proteins PTEN,TLR2,Caspase-3,and Caspase-9,which can effectively relieve the symptoms of UC rats and reduce colon pathological damage.

Objective:To observe the effects of sparrow-pecking moxibustion at Shenque(CV8)and Guanyuan(CV4)on the writhing reaction and score,the temperature and blood flow perfusion of moxibustion point area and uterus,the serum levels of arginine vasopressin(AVP),prostaglandin(PG)F2α,and thromboxane(TX)B2 in rats with primary dysmenorrhea(PD)due to cold-dampness stagnation,and to explore the possible mechanism of sparrow-pecking moxibustion in treating PD.Methods:Thirty-two healthy non-pregnant female Wistar rats were randomly divided into a normal group,a model group,an ibuprofen group,and a sparrow-pecking moxibustion group,with 8 rats in each group.Except for the normal group,the other three groups were subjected to modeling with cold water bath combined with estradiol benzoate and oxytocin injection.Rats in the sparrow-pecking moxibustion group were treated with sparrow-pecking moxibustion at Shenque(CV8)and Guanyuan(CV4)on the 8th day of modeling,30 min/time,once a day for 3 d;those in the ibuprofen group were treated with 0.8 mL ibuprofen solution(a specification of 125 mg in 10 mL)on the 8th day of modeling,once a day for 3 d;those in the normal group and the model group were given 0.8 mL normal saline,once a day for 3 d.On the 11th day,rats in each group were intraperitoneally injected with oxytocin(2 U/rat),and the writhing incubation period and writhing score in 20 min were observed;the temperature and the blood perfusion of Shenque(CV8),Guanyuan(CV4),and uterus in vivo were detected;the serum levels of AVP,PGF2α,and TXB2 were determined.Results:The writhing incubation period was significantly longer(P<0.01)and the writhing score was significantly lower(P<0.01)in the sparrow-pecking moxibustion group and the ibuprofen group than in the model group;compared with the ibuprofen group,the writhing incubation period was prolonged(P<0.01)and the writhing score was decreased(P<0.01)in the sparrow-pecking moxibustion group;compared with the normal group,the temperature and the blood perfusion of Shenque(CV8),Guanyuan(CV4),and uterus were significantly decreased,while the serum PGF2α,AVP,and TXB2 levels were significantly increased(P<0.01)in the model group;compared with the model group,the temperature and the blood perfusion of Shenque(CV8),Guanyuan(CV4),and uterus were significantly increased,and the serum levels of PGF2α,AVP,and TXB2 were significantly decreased in the ibuprofen group and the sparrow-pecking moxibustion group(P<0.05 or P<0.01);compared with the ibuprofen group,the temperature and the blood perfusion of Shenque(CV8),Guanyuan(CV4),and uterus were significantly increased(P<0.05),the serum AVP and TXB2 levels were significantly decreased(P<0.05),while the serum PGF2α level had no statistical difference in the sparrow-pecking moxibustion group(P>0.05).Conclusion:Sparrow-pecking moxibustion had a remarkable analgesic effect on the rats with PD due to cold-dampness stagnation,and the mechanism may be related to the increased temperature and blood perfusion of the moxibustion point area and uterus,as well as the decreased serum PGF2α,AVP,and TXB2 levels.

Objective:A predictive nomogram model for the prognosis of intrahepatic cholangiocarcinoma (ICC) patients after curative resection was constructed based on the albumin-bilirubin score and tumor burden score (ATS) grade, and the predictive performance of the nomogram model was evaluated.Methods:Retrospective analysis of clinical data was made, from ICC patients who underwent curative resection at Zhengzhou University People's Hospital and Zhengzhou University Cancer Hospital from January 2016 to January 2020. A total of 258 patients were included in the study, with 140 males and 118 females, with an average age of (56.5±9.5) years. The 258 ICC patients were randomly divided into a training set ( n=174) and a testing set ( n=84) in a 7∶3 ratio. Single-factor and multi-factor Cox regression analyses were performed to identify prognostic factors for ICC patients of the training set, and then a nomogram model was constructed. The performance of the nomogram model was evaluated by using the concordance index (C-index), calibration curve, and risky decision curve analysis. Results:In the training set, univariate Cox regression analysis indicated that albumin-bilirubin (ALBI), tumor burden score (TBS), carcinoembryonic antigen (CEA), tumor differentitation, lymphvascular invasion and ATS significantly influenced overall survival after radical resection for ICC (all P<0.05). Multifactorial Cox regression analysis revealed that ATS grade, CEA, tumor differentiation, lymphovascular invasion, and AJCC N stage are independent risk factors for the prognosis of ICC patients after curative resection (all P<0.05). Assessment of the postoperative survival prediction model based on multifactorial Cox regression yielded a C-index of 0.775(95% CI: 0.747-0.841) for the training set and 0.731(95% CI: 0.668-0.828) for the testing set. The calibration curves for both the training and testing sets indicated strong predictive capability of the model. Additionally, the risk decision curve also suggested high net benefit of the model. Conclusions:The preoperative ATS grade is an independent factor affecting the survival after ICC radical resection. The nomogram model constructed based on ATS grade demonstrates excellent predictive value for postoperative prognosis in ICC patients.

Objective:To evaluate the value of autologous platelet-rich plasma (aPRP) separation-retransfusion for blood conservation in the patients undergoing thoracolumbar laminectomy.Methods:Sixty American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients, aged 18-60 yr, with body mass index of 19-30 kg/m 2, scheduled for elective thoracolumbar laminectomy, were divided into 2 groups ( n=30 each) using a random number table method: conventional blood conservation group (group C) and aPRP blood conservation group (group aPRP). Group C received tranexamic acid and autologous blood salvage-retransfusion. Group aPRP received aPRP separation-retransfusion, tranexamic acid and autologous blood salvage-retransfusion. The volume of allogeneic blood transfused, percentage of patients who did not need the allogeneic blood transfusion and adverse reactions were recorded. Venous blood samples were collected for blood routine examination and for determination of the plasma concentrations of interleukin-6 (IL-6) and IL-10 at 1 day before operation (T 0), when the volume of blood loss reached 500 ml (T 1), immediately after surgery (T 2), and at 24 and 48 h after surgery (T 3, 4). The incidence of hypoxemia and amount of 24-h wound drainage were recorded. Results:Compared with group C, the amount of allogeneic red blood cells, plasma transfused and 24-h wound drainage were significantly decreased ( P<0.05), the percentage of patients who did not need the allogeneic red blood cell and plasma transfusion was increased (30% vs 47%, 10% vs 60%, P<0.05), the plasma concentrations of IL-6 and IL-10 at T 2-4 were significantly decreased ( P<0.05), and the incidence of hypoxemia in PACU was decreased in group aPRP (27% vs 10%, P<0.05). Conclusions:aPRP separation-retransfusion can provide marked improvement in conventional blood conservation in the patients undergoing thoracolumbar laminectomy.