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1.
Chinese Journal of Anesthesiology ; (12): 1184-1188, 2021.
Article in Chinese | WPRIM | ID: wpr-911338

ABSTRACT

Objective:To evaluate the gastric emptying of orally administered enzyme-hydrolyzed rice flour solution before surgery in the patients undergoing laparoscopic cholecystectomy and effect on insulin resistance.Methods:One hundred patients, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, aged 18-64 yr, with body mass index of 19-30 kg/m 2, scheduled for elective laparoscopic cholecystectomy under general anesthesia, were divided into 2 groups ( n=50 each) using a random number table method: water group (group C) and enzyme-hydrolyzed rice flour group (group M). Routine fasting and water deprivation were executed at 1 day before operation in two groups, and 300 ml water in group C or 300 ml enzyme-hydrolyzed rice flour solution in group M were taken orally at 2-3 h before induction on the day of surgery.Bedside antrum ultrasonography was used to calculate the gastric volume (GV) before oral administration (V 0), immediately after oral administration (V 1), and before induction (V 2), and then the ΔGV (GV 1-GV 0) was calculated.Fasting plasma glucose and insulin CONCENTRATIONS were measured on admission to hospital (T 1) and on an empty stomach on 1st morning after surgery (T 2), and then the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated according to HOMA steady-state model formula.Visual analog scale (VAS) scores for subjective comfort (thirst, hunger, fatigue and anxiety) and grip strength were assessed before anesthesia (T 3) and before leaving PACU (T 4). Reflux and aspiration during induction, nausea and vomiting within 24 h after surgery, and anal exhaust time after surgery were recorded. Results:There was no significant difference in GV at V 0, V 1 and V 2 between the two groups ( P>0.05). Compared with the baseline at V 0, no significant was found in the GV at V 2 in both groups ( P>0.05). The fasting plasma glucose and insulin concentrations and HOMA-IR were significantly increased at T 2 than at T 1 in both groups ( P<0.05 or 0.01). Compared with group C, the fasting plasma glucose and insulin concentrations and HOMA-IR were significantly decreased at T 2, VAS scores for hunger, fatigue and anxiety were decreased at T 3, 4, grip strength was increased at T 3, 4, the postoperative anal exhaust time was shortened, and the incidence of nausea was reduced in group M ( P<0.05). No reflux and aspiration happened during induction in either group. Conclusion:The gastric emptying of 300 ml enzyme-hydrolyzed rice flour solution orally administered at 2 h before surgery is normal in the patients undergoing laparoscopic cholecystectomy, which does not increase the risk of reflux and aspiration during anesthesia induction, reduces postoperative insulin resistance, and increases patient′s subjective comfort, and enhances the postoperative recovery of intestinal function.

2.
Article in Chinese | WPRIM | ID: wpr-911310

ABSTRACT

Objective:To investigate the effect of irisin on pyroptosis in rats with ventilator-induced lung injury.Methods:Thirty-six healthy clean-grade male Sprague-Dawley rats, weighing 200-250 g, aged 6-8 weeks, were divided into 3 groups ( n=12 each) using a random number table method: control group (group C), ventilator-induced lung injury group (group V) and ventilator-induced lung injury plus irisin group (group V+ I). In group V+ I, irisin 1 μg/kg was injected via the tail vein before mechanical ventilation.The animals were mechanically ventilated (tidal volume of 40 ml/kg, respiratory rate 60 breaths/min, inspiratory/expiratory ratio 1∶2, positive end expiratory pressure 0 and inspired oxygen fraction ratio 21%.Blood samples were then taken from the femoral artery for blood gas analysis, and PaO 2 was recorded.Bronchoalveolar lavage fluid (BALF) was collected, the total protein concentrations in BALF were measured, and the concentrations of BALF and serum interleukin-1β (IL-1β) and IL-18 were measure by enzyme-linked immunosorbent assay.The lung tissues were obtained for determination of the pathological changes after HE staining which were scored, wet to dry weight (W/D) ratio, expression of pyroptosis-related proteins N-terminal gasdermin D (GSDMD-N) and caspase-1 protein and mRNA (by Western blot or using real-time polymerase chain reaction). Results:Compared with group C, the lung injury score and W/D ratio were significantly increased, PaO 2 and OI were decreased, the total protein concentrations in BALF, concentrations of IL-1β and IL-18 in BALF and serum were increased, and the expression of caspase-1 and GSDMD-N protein and mRNA was up-regulated in group V ( P<0.01). Compared with group V, the lung injury score and W/D ratio were significantly decreased, PaO 2 and OI were increased, the total protein concentrations in BALF, concentrations of serum IL-1β and IL-18 in BALF and serum were decreased, and the expression of caspase-1 and GSDMD-N protein and mRNA was down-regulated in group V+ I ( P<0.01). Conclusion:The mechanism by which irisin reduces ventilator-induced lung injury is probably related to inhibiting pyroptosis in rats.

3.
Article in Chinese | WPRIM | ID: wpr-911282

ABSTRACT

Objective:To evaluate the changes in proteome in hippocampus and bioinformatics analysis in mice with perioperative neurocognitive disorders (PND).Methods:Clean-grade healthy male C57BL/6 mice, aged 15 months, weighing 30-35 g, were divided into 2 groups ( n=9 each) using a random number table method: control group (group C) and group PND.The model of PND was established by performing open tibial fracture with intramedullary fixation under isoflurane anesthesia in anesthetized mice.The Morris water maze test, open field test and fear conditioning test were performed at 1 day before operation and at 1, 3 and 7 days after operation.At 1, 3 and 7 days after operation, 3 mice with worst cognitive performance in each cognitive function assessments were sacrificed in group P, and three mice were randomly sacrificed in group C. The hippocampal tissues were then obtained, the expression of differentially expressed proteins was identified by high-performance liquid chromatography-mass spectrometry, and Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to analyze the differentially expressed proteins. Results:Compared with group C, the escape latency at different time points was significantly prolonged, and the percentage of time spend on target quadrant and the percentage of freezing time in fear conditioning test were decreased in group P ( P<0.05). There were 21 differentially expressed proteins, of which 12 proteins showed up-regulated expression and 9 proteins showed down-regulated expression.The GO functional analysis showed that the differentially expressed proteins were involved in the process such as the metabolism, signal transmission, regulation of biological processes, formed cell components such as synapses and organelles, and were related to molecular function such as binding and transportation.KEGG signaling pathway analysis showed that there were also differences in MAPK signaling pathway, ErbB signaling pathway, AMPK signaling pathway and the transport of SNARE protein in vesicle and etc. Conclusion:There are 21 differentially expressed proteins in the hippocampus of PND mice, and these proteins are involved in the pathophysiological process probably related to PND such as neuroinflammatory responses, abnormal synaptic structure, mitochondrial dysfunction and decreased autophagy.

4.
Article in Chinese | WPRIM | ID: wpr-911225

ABSTRACT

Objective:To evaluate the effect of irisin on ventilator-induced lung injury (VILI) in rats and the relationship with expression of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasomes.Methods:Thirty-six SPF-grade healthy adult male Sprague-Dawley rats, aged 6-8 weeks, weighing 220-300 g, were divided into 3 groups ( n=12 each) using a random number table method: control group (group C), group VILI and irisin group (group I). All the groups underwent tracheotomy and intubation, group C kept spontaneous breathing for 4 h, and the animals were mechanically ventilated for 4 h in VILI and I groups.Irisin 1 μg/kg was injected via the tail vein at 30 min before tracheal intubation in group I, and the equal volume of normal saline mixture (normal saline∶phosphate buffer solution containing 5% trehalose=1∶9) were given in the other 2 groups via the tail vein.The rats were mechanically ventilated with the tidal volume of 20 ml/kg, respiratory rate 80 breaths/min, inspiratory/expiratory ratio 1∶1, inspired oxygen fraction ratio 21% and positive end-expiratory pressure 0.Blood samples from left femoral artery were collected before tracheal intubation and at the end of mechanical ventilation for detection of PaO 2.The animals were sacrificed and the lung tissue samples and bronchoalveolar lavage fluid (BALF) were then collected for examination of the pathological changes (under the light microscope), and for determination of wet to dry weight (W/D) ratio and the concentrations of total protein in BALF and interleukin-1β (IL-1β) and IL-18 in BALF and serum (by enzyme-linked immunosorbent assay), level of reactive oxygen species (ROS) in alveolar macrophages in BALF (by DCFH-DA) and the expression of NLRP3, apoptosis-associated speck-like protein (ASC) and caspase-1 protein and mRNA in lung tissues (by Western blot and by quantitative reverse transcription polymerase chain reaction). The pathological changes of the lung were scored. Results:Compared with group C, PaO 2 was significantly decreased at the end of mechanical ventilation, lung injury score and W/D ratio were increased, concentration of total protein and ROS level in alveolar macrophages in BALF and concentrations of BALF, IL-1β and IL-18 in serum were increased, and the expression of NLRP3, ASC and caspase-1 protein and mRNA in lung tissues was up-regulated in group VILI and group I ( P<0.01). Compared with group VILI, PaO 2 was significantly increased at the end of mechanical ventilation, lung injury score and W/D ratio were decreased, concentration of total protein and ROS level in alveolar macrophages in BALF and concentrations of BALF, IL-1β and IL-18 in serum were decreased, and the expression of NLRP3, ASC and caspase-1 protein and mRNA in lung tissues was down-regulated in group I ( P<0.05). Conclusion:Irisin can reduce VILI, and the mechanism is related to inhibiting activation of NLRP3 inflammasome and reducing inflammatory response in rats.

5.
Article in Chinese | WPRIM | ID: wpr-910184

ABSTRACT

Objective:To study the difference between BRCA gene mutations in hereditary breast and ovarian cancer syndrome (HBOC) and in sporadic ovarian cancer (SOC).Methods:This study was for exploratory research, the inclusion criteria were 284 patients with ovarian cancer admitted at Shanxi Provincial Cancer Hospital from November 2018 to December 2019, with high-throughput DNA sequencing including the full coding regions and exon-intron link regions of BRCA1 and BRCA2 gene. Pathogenic mutations in the BRCA gene of patients with ovarian cancer were collected and mutation site analysis was performed to compare phenotypic differences in pathogenic mutations between HBOC syndrome and SOC patients.Results:(1) Of the 284 ovarian cancer patients, seventy-seven had BRCA pathogenic mutations with a mutation rate of 27.1% (77/284), with BRCA1 mutation rate of 19.7% (56/284), BRCA2 gene 6.7% (19/284) and BRCA1/2 common mutation rate of 0.7% (2/284). Of the 284 patients with ovarian cancer, the pathogenic mutation rate in the BRCA gene in HBOC syndrome patients was 43.8% (32/73), which were significantly higher than that in SOC patients [21.3% (45/211); χ2=13.905, P<0.01]. Among BRCA1 gene mutation, the mutation rate in HBOC syndrome was higher than that of SOC [87.5% (28/32) vs 62.2% (28/45)], the BRCA2 gene mutation rate in patients with HBOC syndrome was lower than that in SOC patients [6.2% (2/32) vs 37.8% (17/45)], and there were statistically significant differences (all P<0.05). Two of the 77 patients with pathogenic mutations in the BRCA gene were multisite mutations, including one simultaneous two site mutation, one simultaneous three site mutation. There were 80 mutation sites with frameshift deletion mutations (55.0%, 44/80) and nonsense mutations (31.2%, 25/80). (2) Of the 73 patients with HBOC syndrome, 32 cases had pathogenic mutations in BRCA gene, including 28 cases in BRCA1, mainly in exon 11 and 24 (9 and 7 cases, respectively), and only two cases in BRCA2, both in exon 11; another two had multiple locus mutations. Of the 211 patients with SOC, 45 cases had pathogenic mutants in BRCA gene, including 28 cases in BRCA1, mainly in exon 11 and 24 (15 and 2 cases, respectively), and 17 cases in BRCA2, mainly in exon 11 (11 cases). (3) Thirty-four pathogenic mutation sites in BRCA gene were found newly, twenty of them were located in the BRCA1 gene, including a locus located on the intron 6, 301+1G>A, and the remaining 19 sites were located on the exons, including 283_286delCTTG, 68_69delAG, 132C>T, 514_547+3del37, 742delA, 1126_1129delAATA, 1196delA, 1352_1364del, 1465G>T, 2171delC, 2341G>T, 3359_3363delTTAAT, 4085_4086ins11, 4161_4162delTC, 4165_4166delAG, 4258G>T, 4338_4339del8insAGAA, 4468G>T, and 4783delA; fourteen sites were located in the BRCA2 gene, including a locus located on the intron 7, 631+1G>A, and the remaining 13 sites were located on the exons, including 2648delT, 2914A>T, 2950_2951insG, 4357+1G>A, 5054C>T, 5257A>T, 5291_5292insTC, 5913delT, 3593delA, 6091_6092insA, 6135_6136delTT, 7452delT, 9097_9098insA. A tal of 28 repeat mutations were located in the BRCA1 gene; among them, the site 5470_5477del8 was repeated 6 times, while 3 times in 981_982delAT. Conclusions:Patients with HBOC syndrome have a significantly higher rate of pathogenic mutation in the BRCA gene than that in patients with SOC. BRCA gene pathogenic mutation sites in HBOC syndrome patients occur commonly in exon 11 and 24 of BRCA 1 gene, while SOC patients occur mainly in exon 11 and 24 of BRCA1 gene and exon 11 of BRCA2 gene. The two loci of BRCA1∶5470_5477del8, BRCA1∶981_982delAT may be ancestor mutations in Chinese ovarian cancer patients, and 34 newly discovered pathogenic mutations in the BRCA gene, enriching the BRCA gene mutation spectrum in the Chinese population.

6.
Article in Chinese | WPRIM | ID: wpr-885068

ABSTRACT

Objective:To evaluate the role of miR-188-5p in oxygen-glucose deprivation and restoration (OGD/R) injury to mouse neuroblastoma (N2a) cells and its relationship with small ubiquitin-like modifier-specific proteases 3 (SENP3).Methods:N2a cells were cultured and divided into 5 groups ( n=23 each) using a random number table method: control group (group C), OGD/R group, group NC, transfection of mir-188-5p agonist group (group M) and transfection of mir-188-5p inhibitor group group (group I). Cells in group C were cultured routinely.Cells in group NC, group M and group I were transfected with mir-188-5p negative control miRNA, agonist and inhibitor, respectively.N2a cells were subjected to OGD for 3 h followed by restoration of oxygen-glucose supply to establish the model of OGD/R injury.At 24 h of oxygen-glucose restoration, the cell viability was recorded by the cell counting kit-8 assay, the amount of lactic dehydrogenase (LDH) released was detected, the expression of miR-188-5p and SENP3 mRNA was detected by quantitative real-time polymerase chain reaction, and SENP3 expression was determined by Western blot.The targeting relationship between miR-188-5p and SENP3 mRNA was detected using dual luciferase reporter assay. Results:Compared with group C, the cell viability was significantly decreased, amount of LDH released was increased, and expression of SENP3 and its mRNA was up-regulated in the other 4 groups, miR-188-5p expression was down-regulated in OGD/R and I groups, and miR-188-5p expression was up-regulated in group M ( P<0.05 or 0.01). Compared with group OGD/R, the cell viability was significantly decreased, amount of LDH released was increased, and expression of SENP3 and its mRNA was up-regulated, and miR-188-5p expression was down-regulated in group I, and the cell viability was increased, amount of LDH released was decreased, expression of SENP3 and its mRNA was down-regulated, and miR-188-5p expression was up-regulated in group M ( P<0.05 or 0.01). The dual luciferase reporter assay showed that miR-188-5p could act directly on SENP3. Conclusion:miR-188-5p is involved in OGD/R injury, which is associated with targeted down-regulation of SENP3 expression in N2a cells.

7.
Article in Chinese | WPRIM | ID: wpr-885043

ABSTRACT

Objective:To compare the efficacy of different concentrations of ropivacaine for interscalene brachial plexus block in patients undergoing arthroscopic shoulder surgery under general anesthesia.Methods:Ninety American Society of Anesthesiologists physical statusⅠor Ⅱ patients (NYHA classⅠorⅡ) of both sexes, aged 18-64 yr, with body mass index of 18.0-26.9 kg/m 2, undergoing elective arthroscopic shoulder surgery were selected, and were divided into 3 groups ( n=30 each) using a random number table method: 0.25% ropivacaine group (group A), 0.375% ropivacaine group (group B) and 0.5% ropivacaine group (group C). Interscalene brachial plexus block was performed with 0.25%, 0.375% and 0.5% ropivacaine 20 ml in A, B and C groups, respectively.Before operation (T 0) and at 30 min (T 1), 4 h (T 2), 6 h (T 3), 8 h (T 4), 10 h (T 5) and 12 h (T 6) after administration, the diaphragmatic mobility was measured and recorded using M-mode ultrasound and forced expiratory volume in the first second (FEV 1) and forced vital capacity (FVC) were measured using portable spirometer.The occurrence of phrenic paralysis was recorded at T 1-6.The duration of sensory and motor block was recorded.When visual analogue scale score>3 within 24 h after operation, flurbiprofen axetil 50 mg was injected intravenously for analgesia and the consumption was recorded.The adverse reactions such as cardiovascular events, local anesthetic intoxication, Horner syndrome, pneumothorax, and nausea and vomiting within 24 h after administration were recorded. Results:Compared with group A, the diaphragmatic mobility was significantly decreased during quiet breathing at T 1-3 and was decreased during deep breathing at T 2-5, and the diaphragmatic paralysis rate was increased during quiet and deep breathing at T 2-3 in group B, diaphragmatic mobility was decreased during quiet and deep breathing at T 1-6, diaphragmatic paralysis rate was increased during quiet and deep breathing at T 1-4, FEV 1% and FVC% were decreased at T 1 and FVC% was decreased at T 2 in group C, and the duration of sensory and motor block was prolonged in B and C groups ( P<0.05 or 0.01). Compared with group B, the diaphragmatic mobility was significantly decreased during quiet breathing at T 4-6 and was decreased during deep breathing at T 1-6, the diaphragmatic paralysis rate during quiet breathing was increased at T 2-4 ( P<0.05) was increased during deep breathing at T 3-4, and FEV 1 % and FVC % at T 1 were decreased in group C ( P<0.05). There was no significant difference in the postoperative requirement for flurbiprofen axetil and the incidence of adverse reactions within 24 h after administration among the 3 groups ( P>0.05). Conclusion:0.25% ropivacaine 20ml provides better efficacy when used for interscalene brachial plexus block in the patients undergoing arthroscopic shoulder surgery.

8.
Cancer Research and Clinic ; (6): 473-476, 2021.
Article in Chinese | WPRIM | ID: wpr-912908

ABSTRACT

Epithelial ovarian cancer (EOC) is the most common ovarian malignancy. Because the early lesions are not easy to be found and the advanced cases lack effective treatments, the fatality rate ranks the first among all kinds of gynecological malignant tumors. Pelvic tuberculosis is a specific inflammation of female genitalia. The long incubation period makes the primary tuberculosis foci heal completely, and then presents the clinical "triad" similar to ovarian cancer, namely: abdominal distension, ascites and pelvic mass, accompanied by an abnormal increase in serum carbohydrate antigen 125. For the differential diagnosis of the two diseases, imaging examination combined with laboratory examination is widely used in clinical practice, but the evaluation effect of the two diseases is different to some extent. This paper reviews the progress of the significance of imaging examination and laboratory examination in differential diagnosis and prognosis evaluation of EOC and pelvic tuberculosis.

9.
Cancer Research and Clinic ; (6): 318-322, 2020.
Article in Chinese | WPRIM | ID: wpr-872503

ABSTRACT

Objective:To investigate the differential expressions of AT-rich interacting domain-containing protein 1A (ARID1A) gene and its encoding protein BAF250a and serum carbohydrate antigen 125 (CA125) in different ovarian serous tumor tissues.Methods:The tumor tissues of 97 patients with serous ovarian tumors who were treated by surgery and confirmed by surgical pathological results in Shanxi Provincial Cancer Hospital from August 2015 to September 2018 were collected. Among them, 11 cases were benign lesions (serous cystadenoma, serous fibroadenoma, serous surface papilloma, control group), 21 cases were borderline lesions (atypical proliferative serous tumor, AP group). There were 35 cases in low-grade serous carcinoma (LC) group and 30 cases in high-grade serous carcinoma (HC) group (including 5, 7, 9 and 9 cases in stage Ⅰ-Ⅳ). Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression of ARID1A mRNA in tumor tissues of each group, Western blot and immunohistochemistry were used to detect the expression and morphology of BAF250a protein in tumor tissues, and enzyme-linked immunosorbent assay was used to detect the concentration of serum CA125 in each group. The differences of ARID1A gene, BAF250a protein and serum CA125 expressions in each group were compared, and the correlation of their expressions in HC group with the clinical stage of patients was analyzed.Results:The relative expressions of ARID1A mRNA and BAF250a protein in the tumor tissues of the control group, AP group, LC group, and HC group decreased in sequence, and the serum CA125 concentration increased in sequence, the differences were statistically significant [1.37±0.02, 0.68±0.03, 0.42±0.04, and 0.29±0.14, F = 3.753, P = 0.008; 1.33±0.11, 0.81±0.11, 0.51±0.11, and 0.39±0.11, F = 10.753, P = 0.001; (23.72±2.26), (36.83±13.11), (412.55±41.71), and (529.96±61.44) U/ml, F = 10.440, P = 0.003]. Immunohistochemistry showed that the high expression rates of BAF250a protein in the control group, AP group, LC group, and HC group were 90.0% (10/11), 85.7% (18/21), 70.0% (21/35), and 33.3% (10/30). In HC group, the serum CA125 concentration increased with the increase of clinical stage [stage Ⅰ-Ⅳ: (461.33±23.18), (483.51±41.21), (507.78±33.41), and (543.19±47.82) U/ml, r = 0.510, P = 0.015], and the relative expressions of ARID1A mRNA and BAF250a protein decreased with the increase of clinical stage (stage Ⅰ-Ⅳ: 0.33±0.10, 0.28±0.11, 0.21±0.08, and 0.17±0.07, r = -0.329, P = 0.030; 3.83±0.13, 3.08±0.16, 2.61±0.18, and 2.07±0.13, r = -0.651, P = 0.002). Conclusion:The decrease of expressions of ARID1A gene and its encoding protein BAF250a, and the increase of CA125 expression in ovarian serous tumor tissues may indicate the malignant change and invasion of tumors.

10.
Article in Chinese | WPRIM | ID: wpr-871274

ABSTRACT

Inflammasomes are a group of multiprotein complexes in cells that could be activated when they perceive external microbial invasions and intrinsic aseptic stress signals. However, the activation of inflammasomes and the association between their structures and functions have not been elucidated. New progress has been made in the study of the structure and activation mechanism of NLRC4 inflammasome, which helps to fill the gaps. NLRC4 inflammasome plays an important role in systemic inflammation and programmed cell death, which provides important clues for the study of NLRC4-related inflammatory diseases including metabolic diseases, tumors and autoimmune diseases.

11.
Article in Chinese | WPRIM | ID: wpr-869974

ABSTRACT

Objective:To evaluate the effect of rapamycin on the activity of NOD-like receptor C4 (NLRC4) inflammasomes in the rats with ventilator-induced lung injury (VILI).Methods:Thirty-six healthy clean-grade male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-250 g, were divided into 3 groups ( n=12 each) using a random number table method: control group (group C), VILI group and rapamycin group (group RAPA). In group RAPA, rapamycin 4 mg·kg -1·d -1 was intraperitoneally injected once a day for 3 consecutive days before establishing the model, while the equal volume of normal saline was given instead in group C and group VILI.The patients were mechanically ventilated for 4 h (tidal volume 20 ml/kg, respiratory rate 80 breaths/min, inspiratory/expiratory ratio 1∶1, fraction of inspired oxygen 21%) in VILI and RAPA groups.Blood samples were collected from the femoral artery after the end of ventilation for blood gas analysis and for determination of serum interleukin-1β (IL-1β) and interleukin-18 (IL-18) concentrations (by enzyme-linked immunosorbent assay), and PaO 2 was recorded.The bronchoalveolar lavage fluid (BALF) was collected for determination of the neutrophil count and IL-1β and IL-18 concentrations by enzyme-linked immunosorbent assay.The lung tissues were obtained for examination of the pathological changes (under the light microscope) after HE staining which were scored and for determination of wet to dry weight (W/D) ratio, and expression of mammalian target of rapamycin (mTOR), NLRC4 and caspase-1 (by Western blot) and expression of NLRC4 mRNA (by real-time polymerase chain reaction). Results:Compared with group C, the W/D ratio, lung injury score, neutrophil counts in BALF, and concentrations of IL-1β and IL-18 in serum and BALF were significantly increased, PaO 2 was decreased, and the expression of mTOR, NLRC4, caspase-1 and NLRC4 mRNA was up-regulated in group VILI and group RAPA ( P<0.01). Compared with group VILI, the W/D ratio, lung injury score, neutrophil counts in BALF, and concentrations of IL-1β and IL-18 in serum and BALF were significantly decreased, PaO 2 was increased, and the expression of mTOR, NLRC4, caspase-1 and NLRC4 mRNA was down-regulated in group RAPA ( P<0.05). Conclusion:The mechanism by which rapamycin alleviates VILI may be related to inhibiting activation of mTOR signaling pathway and inhibiting the activity of NLRC4 inflammasomes in rats.

12.
Article in Chinese | WPRIM | ID: wpr-869972

ABSTRACT

Objective:To evaluate the obesity factor on ventilator-induced lung injury (VILI) in rats.Methods:Forty-five clean-grade male Sprague-Dawley rats, aged 6-8 weeks, were divided into 3 groups ( n = 15 each)according to the body weight: normal weight control group (group C), normal weight VILI group (group CV) and obese VILI group (group FV). The body weight was 233-267 g in C and CV groups and 288-332 g in FV group.In group C, the tidal volume (V T) was 10 ml/kg.In CV and FV groups, the rats were ventilated for 4 h with the V T set at 40 ml/kg, respiratory rate 40 breaths/min, inspiratory/expiratory ratio 1∶2, PEEP 0 mmHg, and fraction of inspired oxygen 21% to establish the VILI model.The arterial blood samples were collected immediately before tracheal intubation and at 4 h of mechanical ventilation for blood gas analysis and PaO 2 recording.The remaining blood samples were used for plasma collection.The rats were sacrificed after blood collection at 4 h of ventilation, and the bilateral lung tissues were isolated to collect the bronchoalveolar lavage fluid (BALF). The concentrations of leptin in plasma and tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and interleukin-6 (IL-6) in plasma and BALF were detected by enzyme-linked immunosorbent assay.The wet/dry weight (W/D) ratio of lung tissues was measured.The pathological changes of lung tissues were observed after HE staining, and the lung injury score was evaluated.The expression of NF-κB p65 in lung tissues was detected by Western blot. Results:Compared with group C and group CV, the plasma leptin concentration was significantly increased in group FV( P<0.01). Compared with group C, the concentrations of TNF-α, IL-6 and IL-1β in plasma and BALF were significantly increased, PaO 2 was decreased, the lung injury score and W/D ratio of lung tissues were increased, and NF-κB p65 expression was up-regulated at 4 h of ventilation in CV and FV groups ( P<0.01). Compared with group CV, the concentrations of TNF-α, IL-6 and IL-1β in plasma and BALF were significantly decreased, PaO 2 was increased, the lung injury score and W/D ratio of lung tissues were decreased, and NF-κB p65 expression was down-regulated at 4 h of ventilation in group FV ( P<0.05). Conclusion:Obesity factor can reduce VILI in rats, and the mechanism may be related to the increase in plasma leptin levels.

13.
Article in Chinese | WPRIM | ID: wpr-869903

ABSTRACT

Objective:To evaluate the relationship between protein kinase C-delta (PKCδ) and pyroptosis during ventilator-induced lung injury (VILI) in rats.Methods:Thirty-six clean-grade healthy adult male Sprague-Dawley rats, weighing 200-250 g, were divided into 3 groups ( n=12 each) using a random number table method: control group (group C), group VILI, and VILI plus specific PKCδ inhibitor KAI 9803 group (group K). Phosphate buffer solution 200 μl was injected through the tracheal tube after intubation in group VILI, and KAI 9803 200 μg/kg was given instead in group K. The patients were mechanically ventilated (tidal volume 40 ml/kg, respiratory rate 60 breaths/min, inspiratory/expiratory ratio 1∶2, fraction of inspired oxygen 21%, positive end-expiratory pressure 0) for 4 h. Blood samples were taken from the femoral artery at the end of mechanical ventilation for blood gas analysis, and PaO 2 was recorded.Animals were sacrificed at the end of ventilation, lung tissues were removed, and bronchoalveolar lavage fluid (BALF) was prepared.The total protein concentrations in BALF were measured by coomassie blue staining, and concentrations of interleukin-18 (IL-18) and IL-1β in BALF by enzyme-linked immunosorbent assay.Lung tissues were obtained for microscopic examination of the pathological changes which were scored and for determination of wet/dry weight ratio (W/D ratio) and expression of PKCδ and gasdermin D N terminal fragment (GSDMD-N) protein and mRNA (by Western blot or by quantitative real-time polymerase chain reaction). Results:Compared with group C, the lung injury score, W/D ratio, and concentrations of total protein, IL-18 and IL-1β in BALF were significantly increased, PaO 2 was decreased, and the expression of PKCδ and GSDMD-N protein and mRNA was up-regulated in VILI and K groups ( P<0.01). Compared with group VILI, the lung injury score, W/D ratio, and concentrations of total protein, IL-18 and IL-1β in BALF were significantly decreased, PaO 2 was increased, and the expression of PKCδ and GSDMD-N protein and mRNA was down-regulated in group K ( P<0.05 or 0.01). Conclusion:PKCδ can mediates the pathophysiological process of VILI in which pyrolysis is involved in rats.

14.
Article in Chinese | WPRIM | ID: wpr-869858

ABSTRACT

Objective:To evaluate the role of protein kinase C-delta (PKC-δ) in ventilator-induced lung injury (VILI) and the relationship with NLR family CARD domain-containing protein 4 (NLRC4) in rats.Methods:Thirty-six clean-grade healthy adult male Sprague-Dawley rats, weighing 200-250 g, were divided into 3 groups ( n=12 each) using a random number table method: control group (group C), VILI group (group V) and VILI plus KAI 9803 group (group VK). In V and VK groups, tracheal tubes were placed for mechanical ventilation after tracheotomy, ventilator settings were adjusted with a tidal volume of 40 ml/kg, respiratory rate of 60 breaths/min, and inspiratory/expiratory ratio of 1∶2, and air was inhaled.Group C received no mechanical ventilation after tracheal intubation.Immediately after completion of intubation, PKC-δ specific inhibitor KAI 9803 200 μg/kg was intratracheally injected in group VK, and the equal volume of phosphate buffer saline was given instead in the other two groups.Blood samples were taken from the femoral artery at 4 h of mechanical ventilation to record PaO 2.The chest was opened at the end of mechanical ventilation, lung tissues were removed, and the left lung tissues were lavaged to collect bronchoalveolar lavage fluid (BALF). The pathological changes of lung tissues were examined with a light microscope and scored.Enzyme-linked immunosorbent assay was used to detect the concentrations of interleukin-1beta (IL-1β) and IL-18 in BALF, Western blot was used to detect the expression of NLRC4, caspase-1 and PKC-δ in the right lower lobe of the lung, and the expression of NLRC4 mRNA in the right lower lobe of the lung was determined by real-time polymerase chain reaction, and the wet/dry weight ratio (W/D ratio) of the right middle lobe of the lung was calculated. Results:Compared with group C, the pathological score and W/D ratio were significantly increased, PaO 2 was decreased, the concentrations of IL-1β and IL-18 in BALF were increased, and the expression of NLRC4, caspase-1 and NLRC4 mRNA was up-regulated in V and VK groups, and the expression of PKC-δ was significantly up-regulated ( P<0.01), and a large amount of edema fluid was seen in the alveolar space, with inflammatory cell infiltration in group V ( P<0.01). Compared with group V, the pathological score and W/D ratio were significantly decreased, PaO 2 was increased, the concentrations of IL-1β and IL-18 in BALF were decreased, the expression of NLRC4, caspase-1, PKC-δ and NLRC4 mRNA was down-regulated ( P<0.05), and fluid exudation in the alveolar space and the degree of inflammatory cell infiltration were significantly attenuated in group VK. Conclusion:PKC-δ is involved in VILI, which is related to inhibiting NLRC4 expression in rats.

15.
Article in Chinese | WPRIM | ID: wpr-869789

ABSTRACT

Objective:To evaluate the effect of electroacupuncture (EA) preconditioning on expression of cortical Ubc9 during cerebral ischemia-reperfusion (I/R) in rats.Methods:A total of 80 healthy clean-grade male Sprague-Dawley rats, aged 8-12 weeks, weighing 200-250 g, were divided into 4 groups ( n=20 each) using a random number table method: sham operation group (group S), group I/R, EA preconditioning group (group E) and sham EA group (group SE). Blood vessels were only exposed, without occlusion in group S. In the other three groups, the cerebral I/R model was established by middle cerebral artery occlusion using suture-occluded method, and the suture was removed after 2-h occlusion to restore the perfusion in anesthetized rats.EA was performed at 5 days before establishing the model in group E and group SE.Baihui acupoints were stimulated with an electric stimulator (2/12 Hz disperse-dense waves, intensity 1 mA) for 30 min once a day for 5 consecutive days, and the model was established at 24 h after the last stimulation.EA was performed at the points 1 cm lateral to the acupoints of Baihui, and the other operating parameters were the same as those previously described in group E. Neurological deficit scores (NDSs) were evaluated at 24 and 48 h of reperfusion.Then the rats were sacrificed, and tissues in the ischemic penumbra of cerebral cortex were obtained for determination of cell apoptosis (by TUNEL) and expression of Ubc9 and conjugated small ubiquitin-like modifier (SUMO) 2/3 (by Western blot). The apoptosis rate was calculated. Results:Compared with group S, NDSs at 24 and 48 h of reperfusion and apoptosis rate were significantly increased, and the expression of Ubc9 and conjugated SUMO2/3 was up-regulated in the other three groups ( P<0.05). Compared with group I/R and group SE, NDSs at 24 and 48 h of reperfusion and apoptosis rate were significantly decreased, and the expression of Ubc9 and conjugated SUMO2/3 was up-regulated in group E( P<0.05). Conclusion:The mechanism by which EA preconditioning reduces cerebral I/R injury is related to up-regulating Ubc9 expression and thus enhancing SUMO2/3ylation in rats.

16.
Article in Chinese | WPRIM | ID: wpr-868153

ABSTRACT

Objective:To compare the long-term oncological outcomes between laparoscopic and abdominal surgery in stage Ⅰa1 (lymph-vascular space invasion-positive, LVSI +)- Ⅰb1 cervical cancer patients with different tumor sizes. Methods:Based on the Big Database of Clinical Diagnosis and Treatment of Cervical Cancer in China (1538 project database), patients with stage Ⅰa1 (LVSI +)-Ⅰb1 cervical cancer who treated by laparoscopic or abdominal surgery were included. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) between the two surgical approaches were compared under 1∶1 propensity score matching (PSM) in different tumor diameter stratification. Results:(1) A total of 4 891 patients with stage Ⅰa1 (LVSI +)-Ⅰb1 cervical cancer who underwent laparoscopy or laparotomy from January 1, 2009 to December 31, 2016 were included in the 1538 project database. Among them, 1 926 cases in the laparoscopic group and 2 965 cases in the abdominal group. There were no difference in 5-year OS and 5-year DFS between the two groups before matching. Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS ( HR=1.367, 95% CI: 1.105-1.690, P=0.004). After 1∶1 PSM matching, 1 864 patients were included in each group, and there was no difference in 5-year OS between the two groups (94.1% vs 95.4%, P=0.151). While, the inferior 5-year DFS was observed in the laparoscopic group (89.0% vs 92.3%, P=0.004). And the laparoscopic surgery was associated with lower 5-year DFS ( HR=1.420, 95% CI: 1.109-1.818, P=0.006). (2) In stratification analysis of different tumor sizes, and there were no difference in 5-year OS and 5-year DFS between the laparoscopic group and abdominal group in tumor size ≤1 cm, >1-2 cm and >2-3 cm stratification (all P>0.05). Cox multivariate analysis showed that laparoscopic surgery were not related to 5-year OS and 5-year DFS ( P>0.05). In the stratification of tumor size >3-4 cm, there was no difference in 5-year OS between the two groups ( P>0.05). The 5-year DFS in the laparoscopic group was worse than that in the abdominal group (75.7% vs 85.8%, P=0.025). Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS ( HR=1.705, 95% CI: 1.088-2.674, P=0.020). Conclusions:For patients with stage Ⅰa1 (LVSI +)-Ⅰb1 cervical cancer, laparoscopic surgery is associated with lower 5-year DFS, and the adverse effect of laparoscopic surgery on oncology prognosis is mainly reflected in patients with tumor size >3-4 cm. For patients with tumor sizes ≤1 cm, >1-2 cm and >2-3 cm, there are no difference in oncological prognosis between the two surgical approaches.

17.
Acta Pharmaceutica Sinica B ; (6): 861-877, 2020.
Article in English | WPRIM | ID: wpr-828838

ABSTRACT

Previously, we proposed a new perspective of triptolide (TP)-associated hepatotoxicity: liver hypersensitivity upon lipopolysaccharide (LPS) stimulation. However, the mechanisms for TP/LPS-induced hepatotoxicity remained elusive. The present study aimed to clarify the role of LPS in TP/LPS-induced hepatotoxicity and the mechanism by which TP induces liver hypersensitivity upon LPS stimulation. TNF- inhibitor, etanercept, was injected intraperitoneally into mice to investigate whether induction of TNF- by LPS participated in the liver injury induced by TP/LPS co-treatment. Mice and hepatocytes pretreated with TP were stimulated with recombinant TNF- to assess the function of TNF- in TP/LPS co-treatment. Additionally, time-dependent NF-B activation and NF-B-mediated pro-survival signals were measured and . Finally, overexpression of cellular FLICE-inhibitory protein (FLIP), the most potent NF-B-mediated pro-survival protein, was measured and to assess its function in TP/LPS-induced hepatotoxicity. Etanercept counteracted the toxic reactions induced by TP/LPS. TP-treatment sensitized mice and hepatocytes to TNF-, revealing the role of TNF- in TP/LPS-induced hepatotoxicity. Mechanistic studies revealed that TP inhibited NF-B dependent pro-survival signals, especially FLIP, induced by LPS/TNF-. Moreover, overexpression of FLIP alleviated TP/LPS-induced hepatotoxicity and TP/TNF--induced apoptosis . Mice and hepatocytes treated with TP were sensitive to TNF-, which was released from LPS-stimulated immune cells. These and other results show that the TP-induced inhibition of NF-B-dependent transcriptional activity and FLIP production are responsible for liver hypersensitivity.

18.
China Pharmacy ; (12): 1940-1945, 2019.
Article in Chinese | WPRIM | ID: wpr-817210

ABSTRACT

OBJECTIVE: To establish HPLC fingerprints of Nauclea officinalis extract syrup, and to determine the contents of 9 components. METHODS: HPLC method was adopted. The determination was performed on Diamonsil C18(2)column with mobile phase consisted of acetonitrile-0.1% phosphoric acid solution (gradient elution) at the flow rate of 1.0 mL/min. The detection wavelength was set at 240 nm, and column temperature was 30 ℃. The sample size was 10 μL. Using strictosamide as reference, HPLC chromatograms of 20 batches of N. officinalis extract syrup were drawn. The similarity of HPLC chromatograms were evaluated by using TCM Fingerprint Similarity Evaluation System (2004A edition) to confirm common peaks. The contents of 9 components were determined by standard curves. RESULTS: There were 26 common peaks in 20 batches of HPLC chromatograms, and the similarity was higher than 0.98. Compared with mixed control, 9 chemical components were identified, such as 3,4-dihydroxybenzoic acid, neochlorogenic acid, loganic acid, chlorogenic acid, cryptochlorogenic acid, swertioside, pumiloside, strictosamide and vincosamide. The linear range of 9 components were 17.24-275.84, 7.56-120.96, 15.40-246.40, 7.84-125.44, 8.64-138.24, 7.96-127.36, 8.40-134.40, 48.56-776.96, 4.16-66.56 μg/mL(all r≥0. 999), respectively. The limits of detection were 0.043 1, 0.126 0, 0.038 5, 0.130 7, 0.144 0, 0.066 3, 0.070 0, 0.012 1, 0.052 0 μg/mL, respectively. The limits of quantitation were 0.215 5, 0.189 0, 0.077 0, 0.196 0, 0.288 0, 0.132 7, 0.105 0, 0.097 6, 0.138 7 μg/mL, respectively. RSDs of precision, stability and reproducibility tests were all lower than 2.0% (n=6). Average recoveries were 99.6%、106.3%、100.1%、102.0%、98.4%、100.0%、99.3%、100.6% and 101.2%, and RSDs were 1.20%、0.24%、0.59%、1.00%、0.73%、1.30%、1.10%、1.80%、1.90%(n=6). CONCLUSIONS: Established HPLC fingerprints and quantitative determination method of N. officinalis extract syrup are accurate, specific and sensitive. It can provides reference for quality control of N. officinalis extract syrup.

19.
Cancer Research and Clinic ; (6): 577-580, 2019.
Article in Chinese | WPRIM | ID: wpr-798251

ABSTRACT

Objective@#To investigate the expression of programmed death ligand 1 (PD-L1) in liver cancer tissues and its clinical significance.@*Methods@#The expression levels of PD-L1 in 110 liver cancer tissues, including 95 cases of hepatocellular carcinoma and 15 cases of cholangiocarcinoma were detected by using immunohistochemical staining method, and the relationship between PD-L1 expression and the clinicopathological characteristics of patients with hepatocellular carcinoma was analyzed.@*Results@#Immunohistochemistry results showed that the positive rate of PD-L1 in liver cancer tissues was 69.1% (76/110), and the positive rate of membrane and cytoplasm was 46.4% (51/110) and 22.7% (25/110), respectively. The positive rate of PD-L1 expression in hepatocellular carcinoma was higher than that in cholangiocarcinoma [78.9% (75/95) vs. 6.7% (1/15)], and the difference was statistically significant (χ 2 = 31.693, P < 0.01). The positive expression of PD-L1 was closely associated with the depth of invasion and TNM stage of hepatocellular carcinoma (both χ2 = 4.629, both P = 0.031), but there was no relationship with the patients'age, gender and pathological grade (all P > 0.05). Further analysis showed that protein expression localization of PD-L1 was closely related to the pathological grade in hepatocellular carcinoma (P = 0.013).@*Conclusion@#The positive expression of PD-L1 in hepatocellular carcinoma is closely associated with depth of invasion and TNM stage, which provides a theoretical basis for the immunotherapy of liver cancer targeting PD-L1.

20.
Cancer Research and Clinic ; (6): 653-657, 2019.
Article in Chinese | WPRIM | ID: wpr-797222

ABSTRACT

Objective@#To explore the diagnostic value of combined detection of serum human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125) for ovarian epithelial cancer.@*Methods@#Patients who underwent surgery for the adnexal tumor at Shanxi Provincial Cancer Hospital from January 2012 to December 2017 were enrolled. According to the postoperative pathological results, these patients were divided into the ovarian epithelial cancer group (494 cases) and benign ovarian disease group (462 cases). The serum expressions of HE4 and CA125 in the two groups were detected by enzyme-linked immunosorbent assay (ELISA) and chemiluminescence immunoassay. The diagnostic value of detection of HE4 and CA125 alone or in combination for ovarian epithelial cancer was analyzed.@*Results@#The median levels (P 25 - P 75) of serum CA125 and HE4 in ovarian epithelial cancer group were 273.34 U/ml (39.34 U/ml, 709.74 U/ml) and 199.08 pmol/L (75.81 pmol/L, 449.20 pmol/L), which were higher than those in ovarian benign disease group [16.30 U/ml (6.30 U/ml, 53.60 U/ml) and 39.54 pmol/L (29.57 pmol/L, 53.80 pmol/L)] (both P < 0.05). There was a positive correlation between serum CA125 and HE4 levels in ovarian epithelial cancer group (r = 0.481, P < 0.01). Serum CA125 and HE4 levels in patients with stage Ⅲ and Ⅳ were higher than those in patients with stage Ⅰ and Ⅱ (both P < 0.05), and serum CA125 and HE4 levels in patients with poor differentiation were higher than those in patients with moderate differentiation (P < 0.05). Compared with CA125, the specificity and positive predictive value of serum HE4 for the diagnosis of ovarian epithelial cancer were higher (both P < 0.01). Compared with HE4 alone, the sensitivity of CA125 combined with HE4 increased (P = 0.004) and the specificity decreased (P = 0.044). When both CA125 and HE4 were positive for positive results, compared with HE4 alone, the specificity and positive predictive value increased (both P < 0.01), but the sensitivity decreased (both P < 0.01). In patients with CA125+ HE4-, the sensitivity and specificity decreased, while in CA125- HE4+ patients, the specificity was elevated, but the difference was not statistically significant (P = 0.892). When one of CA125 and HE4 was positive for positive results, the sensitivity and negative predictive value increased (both P < 0.01), but the specificity and positive predictive value decreased (both P < 0.01). The area under the curve of serum CA125 and HE4 combined detection was 0.911, indicating its clinical diagnostic value was better than that of the two alone.@*Conclusions@#In the diagnosis of epithelial ovarian cancer, the specificity of serum HE4 is higher than that of CA125, but the sensitivity is lower than that of CA125. The combined detection of HE4 and CA125 is more conducive to improve the diagnostic accuracy of ovarian epithelial cancer.

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