Cadmium induces apoptosis of pig lymph nodes by regulating the PI3K/AKT/HIF-1α pathway.

OBJECTIVE: This study was aimed to explore the possible mechanism of environmental metal cadmium (Cd) inducing apoptosis of pig lymph nodes. METHOD: 10 healthy 6-week-old weaned piglets were randomly divided into two groups (n = 5 pigs/group). The control group was fed with a basic diet, and the test group was fed with a basic diet of 20 mg/kg CdCl2. RESULTS: The Cd deposition in mesenteric lymph nodes (MLN), inguinal lymph nodes (ILN) and submaxillary lymph nodes (SLN) after Cd exposure was 2.37 folds, 1.4 folds and 1.8 folds of the control group, respectively. And the rate of MLN and ILN apoptotic cells in the Cd group was 4.11 folds and 9.18 folds of the control group, respectively. The mRNA levels of SOD1, SOD2, CAT, GPX1 and GSH in the Cd group were reduced. Similarly, the two-phase detoxification enzymes had a significant downward trend. Cd exposure decreased the activities of GSH, GSH-Px, SOD, CAT, and increased H2O2 and MDA levels. The mRNA and protein levels of Drp1 and Mff in the Cd group were higher than the corresponding control group, and the mRNA and protein levels of Mfn1 and Mfn2 were lower than those in the control group. In addition, the mRNA and protein levels of pro-apoptotic genes in the Cd group were lower than those in the control group. Cd can significantly reduce the expression of PI3K, AKT and HIF-1α in the three lymph nodes. In summary, Cd induces oxidative stress and regulates the PI3K/AKT/HIF-1α signal transduction pathway to cause mitochondrial dynamics disorder, which leads to the apoptosis of pig lymph nodes, suggesting that Cd-induced mitochondrial pathway apoptosis is related to Cd pig lymph nodes play an important role in the toxicity mechanism.

MicroRNA-223 triggers inflammation in porcine aorta by activating NLRP3 inflammasome under selenium deficiency.

Selenium (Se) is an essential trace element in organism. Se deficiency can cause many diseases, including vascular disease. Studies have shown that inflammation is the main inducement of vascular disease, microRNA (miRNA) can influence inflammation in various ways, and Se deficiency can affect miRNAs expression. To study the mechanism of aorta damage caused by Se deficiency, we constructed a Se deficiency porcine aorta model and found that Se deficiency can significantly inhibit miR-223, which downregulates the expression of nucleotide-binding oligomerization domain-like receptor family 3 (NLRP3). Subsequently, we found that in Se deficiency group, NLRP3, and its downstream (caspase-1, apoptosis-related spot-like protein [ASC], IL-18, IL-1ß) expression was significantly increased. In vitro, we cultured pig iliac endothelium cell lines, and constructed miR-223 knockdown and overexpression models. NLRP3 messenger RNA and protein levels were significant increased in the knockdown group, and decreased in the overexpression group. The results of this study show that Se deficiency in porcine arteries can induce inflammation through miR-223/NLRP3.

Influencing factors for early clinical deterioration in patients with mild posterior circulation infarction / 中华行为医学与脑科学杂志

Objective:To study the incidence and influencing factors for clinical deterioration at an early stage in patients with mild posterior circulation infarction (PCI).Methods:Totally 291 patients with mild PCI from January 1, 2016 to January 1, 2020 were retrospectively included. Clinical deterioration within 24 h (CD 24h) and clinical deterioration between 2 d and 14 d (CD 14d) were the endpoint events. IBM SPSS Statistics 19.0 software was used for statistical analysis. Pearson chi-square test or Mann-Whitney U test were used to compare the group differences of corresponding variables. Multivariate logistic regression model was used to analyze the influencing factors of the primary endpoint events. Results:The incidences of CD 24h and CD 14d were 21.6% (63/291) and 30.6% (89/291) respectively, with the reperfusion therapy rate of 13.4% (39/291). The results of multivariate logistic regression analysis with CD 24h as the endpoint event showed that the baseline NIHSS was a positive independent factor increasing the risk of CD 24h ( OR=1.184, 95% CI=1.078-1.300, P<0.01). Cerebellar infarction (compared with brainstem infarction) ( OR=0.250, 95% CI=0.082-0.757, P=0.014)and non-macroatherosclerosis (compared with major atherosclerosis) ( OR=0.026, 95% CI=0.002-0.325, P=0.005) had negative predictive effects on CD 24h. The results of multivariate logistic regression analysis with CD 14d as the endpoint event showed that pulmonary infection complications after stroke ( OR=28.085, 95% CI=6.863-114.927, P<0.01) and baseline NIHSS ( OR=1.114, 95% CI=1.001-1.240, P=0.048) were independent factors of CD 14d. Reperfusion therapy ( OR=0.089, 95% CI=0.013-0.613, P=0.014) could reduce the risk of CD 14d.Top of basilar syndrome(compared with single brainstem infarction) ( OR=7.526, 95% CI=1.565-36.188, P=0.012) increased the risk of CD 14d, while the non-macroatherosclerotic (compared with the macroatherosclerotic subtype) ( OR=0.076, 95% CI=0.009-0.683, P=0.021) negatively predicted the risk of CD 14d. Baseline NIHSS ( OR=0.834, 95% CI=0.758-0.918, P<0.01), CD 14d ( OR=0.048, 95% CI=0.018-0.130, P<0.01) and pulmonary infection complications ( OR=0.045, 95% CI=0.012-0.167, P<0.01) were negatively predicted the good clinical prognosis (modified Rankin score 14 days after onset ≤2). Conclusion:Early clinical deterioration has a negative predictive effect on clinical prognosis improvement of patients with mild PCI. Large artery atherosclerotic stenosis subtype and basilar apex syndrome are the risk factors of CD 24h and CD 14d of patients with mild PCI, and pulmonary infection is the risk factor of CD 14d. Reperfusion therapy in acute phase is helpful to reduce the risk of early clinical deterioration and improve clinical prognosis in patients with mild PCI.

Predictors of clinically important stress-related gastrointestinal bleeding after acute stroke and their impact on short-term outcome / 国际脑血管病杂志

Objective:To investigate the predictors of clinically important stress-related gastrointestinal bleeding (CIS-GIB) after acute stroke and their impact on short-term outcome.Methods:Consecutive acute stroke patients diagnosed as stress ulcer (SU) and admitted to Beijing Friendship Hospital from January 1, 2016 to January 1, 2020 were enrolled retrospectively. The primary outcome event was CIS-GIB and was defined as dominant gastrointestinal bleeding and corresponding clinical manifestations occurred within 24 h after bleeding. The second outcome event was the short-term clinical outcome assessed by the modified Rankin Scale score at 14 d after onset, and ≤2 was defined as a good outcome. Multivariate logistic regression model was used to analyze the independent influencing factors of CIS-GIB and short-term outcome. Results:A total of 96 patients with post-stroke SU were included, accounting for 2.5% (96/3 819) of all patients with acute stroke; among them, 16 patients (16.7%) developed CIS-GIB, accounting for 0.4% (16/3 819) of all patients with acute stroke. Among the included patients, there were 27 women (29.2%), with a median age of 70 years (interquartile range, 62-79 years). The median National Institutes of Health Stroke Scale (NIHSS) score was 8 (interquartile range, 3-17), and a median time interval between SU and the index stroke event was 2 d (interquartile range, 1-5 days). Compared with the non-CIS-GIB group, the baseline NIHSS score and the proportion of patients with supratentorial stroke were higher, the time interval between SU and the index stroke event was longer, the proportion of patients with coagulation dysfunction, using nasogastric tube and ventilator, receiving gastrointestinal invasive hemostasis and erythrocyte component transfusion were higher, and the risks of poor outcome and death were higher in the CIS-GIB group (all P<0.05). Multivariate logistic regression analysis showed that the baseline NIHSS score (odds ratio [ OR] 1.146, 95% confidence interval [ CI] 1.029-1.275; P=0.013), glycosylated hemoglobin ( OR 1.567, 95% CI 1.025-2.395; P=0.038), history of chronic gastric diseases ( OR 24.900, 95% CI 1.446-428.728; P=0.027), supratentorial stroke ( OR 5.701, 95% CI 1.002-32.443; P=0.050) and activated partial thromboplastin time ≥34.0 s ( OR 11.036, 95% CI 1.154-105.560; P=0.037) were the independent risk factors for CIS-GIB; the baseline NIHSS score was an independent influencing factor for poor outcome ( OR 1.366, 95% CI 1.029-1.812; P=0.031). Conclusion:The incidence of CIS-GIB in patients with acute stroke is about 0.4%, which significantly increases the risk of short-term adverse outcome. High glycosylated hemoglobin level, prolonged activated partial thromboplastin time, high baseline NIHSS score, supratentorial stroke and history of chronic gastric diseases are the independent risk factors for CIS-GIB.

Effect of intraperitoneally injected dexmedetomidine on abdominal adhesions in rats and the role of cholinergic anti-inflammatory pathway / 中华麻醉学杂志

Objective To evaluate the effect of intraperitoneally injected dexmedetomidine on abdominal adhesions in rats and the role of cholinergic anti-inflammatory pathway.Methods Forty cleangrade healthy adult male Sprague-Dawley rats,weighing 220-250 g,were divided into 4 groups (n =10 each) using a random number table method:sham operation group (Sham group),abdominal adhesion group (AA group),dexmedetomidine group (DEX group) and dexmedetomidine plus methyllycaconitine group (DEX-M group).The rat model of abdominal adhesions was established by cecal friction method.In Sham group,abdominal cavity was only opened and then sutured.Normal saline 2 ml was injected into the abdominal cavity and tail vein in group AA.In DEX and DEX-M groups,normal saline 2 ml and α7 nicotinic acetylcholine receptor antagonist methyllycaconitine 2.4 μg/g (dissolved in 2 ml normal saline) were injected,respectively,and dexmedetomidine 10μg/kg (dissolved in 2 ml normal saline) was intraperitoneally injected at the same time.The abdominal incision was opened under anesthesia at 7 days after establishing the model to observe the formation of abdominal adhesion,Phillips method was used for scoring,and enzyme-linked immunosorbent assay was used to determine the transforming growth factor-beta1 (TGF-β1) concentrations in ascites and tumor necrosis factor-alpha (TNF-α) concentrations in serum.The rats were then sacrificed,and the caecum tissue and its contralateral peritoneum and adhesion fibrous strips were obtained for examination of the pathological changes with a light microscope.Results Compared with group Sham,the abdominal adhesion score and serum TNF-α concentrations were significantly increased in AA and DEX-M groups,and the TGF-β1 concentration in ascites was significantly increased in AA,DEX and DEX-M groups (P＜0.05).Compared with group AA,the serum TNF-α concentrations and TGF-β1 concentration in ascites were significantly decreased in group DEX-M,and the abdominal adhesion score was significantly decreased (P＜0.05),and the pathological changes of caecum tissue,contralateral peritoneum and adhesion fibrous strips were significantly attenuated in group DEX.Compared with group DEX-M,the serum TNF-o concentrations were significantly increased (P＜0.05),no significant change was found in TGF-1 concentration in ascites (P＞0.05),and the pathological changes of caecum tissue,contralateral peritoneum and adhesion fibrous strips were accentuated in group DEX.Conclusion Intraperitoneally injected dexmedetomidine can mitigate abdominal adhesions,and the mechanism is related to activating cholinergic anti-inflammatory pathway and reducing systemic inflammatory response in rats.

Effect of intraperitoneally injected dexmedetomidine on abdominal adhesions in rats and the role of cholinergic anti-inflammatory pathway / 中华麻醉学杂志

Objective@#To evaluate the effect of intraperitoneally injected dexmedetomidine on abdominal adhesions in rats and the role of cholinergic anti-inflammatory pathway.@*Methods@#Forty clean-grade healthy adult male Sprague-Dawley rats, weighing 220-250 g, were divided into 4 groups (n = 10 each) using a random number table method: sham operation group (Sham group), abdominal adhesion group (AA group), dexmedetomidine group (DEX group) and dexmedetomidine plus methyllycaconitine group (DEX-M group). The rat model of abdominal adhesions was established by cecal friction method.In Sham group, abdominal cavity was only opened and then sutured.Normal saline 2 ml was injected into the abdominal cavity and tail vein in group AA.In DEX and DEX-M groups, normal saline 2 ml and α7 nicotinic acetylcholine receptor antagonist methyllycaconitine 2.4 μg/g (dissolved in 2 ml normal saline) were injected, respectively, and dexmedetomidine 10 μg/kg (dissolved in 2 ml normal saline) was intraperitoneally injected at the same time.The abdominal incision was opened under anesthesia at 7 days after establishing the model to observe the formation of abdominal adhesion, Phillips method was used for scoring, and enzyme-linked immunosorbent assay was used to determine the transforming growth factor-beta1 (TGF-β1) concentrations in ascites and tumor necrosis factor-alpha (TNF-α) concentrations in serum.The rats were then sacrificed, and the caecum tissue and its contralateral peritoneum and adhesion fibrous strips were obtained for examination of the pathological changes with a light microscope.@*Results@#Compared with group Sham, the abdominal adhesion score and serum TNF-α concentrations were significantly increased in AA and DEX-M groups, and the TGF-β1 concentration in ascites was significantly increased in AA, DEX and DEX-M groups (P<0.05). Compared with group AA, the serum TNF-α concentrations and TGF-β1 concentration in ascites were significantly decreased in group DEX-M, and the abdominal adhesion score was significantly decreased (P<0.05), and the pathological changes of caecum tissue, contralateral peritoneum and adhesion fibrous strips were significantly attenuated in group DEX.Compared with group DEX-M, the serum TNF-α concentrations were significantly increased (P<0.05), no significant change was found in TGF-β1 concentration in ascites (P>0.05), and the pathological changes of caecum tissue, contralateral peritoneum and adhesion fibrous strips were accentuated in group DEX.@*Conclusion@#Intraperitoneally injected dexmedetomidine can mitigate abdominal adhesions, and the mechanism is related to activating cholinergic anti-inflammatory pathway and reducing systemic inflammatory response in rats.

Clinical Efficacy Observation of Bromfenac Sodium Eye Drops in the Treatment of Xerophthalmia / 中国药房

OBJECTIVE:To observe the clinical efficacy and safety of Bromfenac sodium eyed drops in the treatment of xe-rophthalmia. METHODS:80 patients with xerophthalmia were randomly divided into observation group and control group,with 40 cases in each group. Control group was given 0.1% Sodium hyaluronate,one drop,qd;observation group was given 0.1% Sodi-um hyaluronate eye drops,one drop,bid. Both groups received 14 d of treatment. The subjective symptom and sign,the time of lacrimal film break-up,fluorescent staining score and schemer test were observed in 2 groups before treatment,3,7,14 d after treatment. Clinical efficacy and the occurrence of ADR were observed in 2 groups. RESULTS:There was no statistical significance in subjective symptom and sign,the time of lacrimal film break-up,fluorescent staining score and tear between 2 groups before treatment,3,7 d after treatment(P>0.05). 14 d after treatment,subjective symptom and sign and fluorescent staining score of 2 groups were decreased significantly,and the time of lacrimal film break-up was prolonged and secretion was increased significant-ly;the observation group was significantly better than the control group,with statistical significance (P0.05). CONCLUSIONS:Sodium hyaluronate eye drops is effective for xerophthalmia,and can relieve the symptoms with good safety.

Preliminary study on the mechanism of spontaneous rhythmic contraction in rabbit portal vein / 生物医学工程学杂志

This study sought to probe into the mechanism of spontaneous contraction of portal vein. The morphological and electrophysiological characteristics of the freshly isolated interstitial cells (ICs) of rabbit portal vein were investigated by using immunohistochemical and conventional whole-cell patch clamp techniques. The isolated interstitial cells exhibited stellate-shaped or spindle-shaped bodies with a variable number of thin processes projecting from cell bodies, and these cells were noted to be c-Kit immunopositive. Under conventional whole-cell patch clamp configuration, the membrane potential was held at -60 mV, the spontaneous rhythmic inward currents were recorded in ICs, and the frequencies of which were similar to those of spontaneous contraction of portal vein. The inward currents were insensitive to nicardipine (an L-type calcium channel blocker) but could be abolished by gadolinium (a non-selective cation channel blocker). The results suggested that the spontaneous rhythmic inward currents recorded in freshly isolated ICs may be pacemaker currents which elicit the spontaneous contraction of portal vein.