1.Effects of the polymorphisms in ABCG1 gene on the transcription activity and the susceptibility with coronary artery disease
Qiujie MA ; Benrong LIU ; Chaowei TIAN ; Xiaohui CHEN
Chinese Journal of Emergency Medicine 2017;26(6):685-692
Objective To investigate the effects of the polymorphisms in the promoter of ATP binding cassette transporter (ABCG1) on the transcription activity,and the relationship of the polymorphisms with the susceptibility to coronary artery disease (CAD).Methods A case-control study was conducted,217 CADpatients and 142 controls were enrolled in this study.Thesingle nucleotide polymorphisms (SNPs) in the promoter of ABCG1 were identified by sequencing.The promoter haplotypes of ABCG1 were determined with allele specific primer sequencing or Gene cloning sequencing.The transcription activity of the promoter haplotypes were evaluated with dual luciferase reporter system.The frequency of SNPs and haplotypes were analyzed between CAD group and the control group,premature CAD and non-premature CAD group,as well as multivessel lesion and single vessel lesion group.The frequency distribution was compared between two groups with x2 test or Fisher exact test.The difference of the luciferase activity was compared between groups by t-test or one-way analysis of variance.Results Only 3 SNPs were found in ABCG1 promoter sequence of about 1 000 bp upstream of the transcription start site,which are-384 (A/G),-204 (A/C) and-134 (T/G),respectively.The 3 SNPs are in strong linkage disequilibrium,Tajima's D =2.655 (P < 0.01),which constituted 3 haplotypes.There was no significant difference in SNPs and haplotype frequency between the CAD group and the normal control group,and the severity of vascular disease and the early onset of coronary heart disease were not associated with the polymorphisms in ABCG1 promoter.There was no significant difference in the transcriptional activity of the three constitutive promoter haplotypes,but the transcriptional activity was notably elevated as the GAT haplotype was mutated into GAG (P < 0.05).Conclusions The 3 SNPs identified in ABCG1 promoter region A did not alter the promoter activity.There was no significant correlation between the frequency distribution of SNPs and promoter haplotypes and the susceptibility to CAD.
2.The role of IDO/TTS mediated tryptophan metabolic pathway in patients with immune thrombocytopenia
Qiujie CHEN ; Yu ZENG ; Yunlong GAO ; Yan MA ; Xinzhong WU
The Journal of Practical Medicine 2014;(21):3441-3444
Objective To discuss the role of indoleamine 2, 3-dioxygenas e (IDO) and tryptophanyl-tRNA synthetase (TTS) mediated tryptophan catabolism in immune thrombocytopenia (ITP) patients treated with high doses of dexamethasone through the expressions of IDO and TTS in T cells , and the concentrations of plasma kynurenine and tryptophan. Methods 20 newly diagnosed or relapse ITP patients were treated with 40 mg/d × 4 d dose of dexamethasone. The heparin anticoagulant blood samples were obtained before treatment and the 5th day after treatment. 20 healthy subjects were selected as the control group. The IDO and TTS expressions in CD4+and CD8+ T cells were analyzed by flow cytometry. The concentrations of plasma kynurenine and tryptophan were detected by liquid-mass spectrometry system. Results Compared with healthy controls group, the plasma tryptophan and kynurenine concentration and the ratio of Kyn/Trp were significantly elevated in ITP patients (P <0.05); the IDO expressions of CD4+ and CD8+ T cells in ITP patients were significantly lower than those in healthy controls (P < 0.05), but the TTS expressions were significantly higher (P < 0.05). The concentration of tryptophan in effective group was significantly lower than before treatment (P < 0.05), in contrast, the kynurenine concentration and the ratio of Kyn/Trp were significantly higher than before (P < 0.05). The expression of IDO in effective group were significantly higher than that before treatment (P < 0.05), conversely, the expression of TTS in effective group were significantly decreased (P < 0.05). No significant difference can be found in ineffective group. Conclusion IDO/TTS-mediated tryptophan catabolism pathway could indicate the onset of ITP. The sensitivity of ITP patients with high dose of dexamethasone treatment can be observed through the level of IDO and TTS.
3.The influence of lack of parental accompaniment, physical abuse and neglect in childhood on the psycholog-ical distress in college entrant students
Xiaojing LI ; Wanjun GUO ; Yukun KANG ; Zeren GESANG ; Na LI ; Yingmei WANG ; Zhengping TAN ; Changbo LIU ; Ying LUO ; Jia FENG ; Qiujie XU ; Ting CHEN ; Xiaohong MA ; Tao LI
Chinese Journal of Nervous and Mental Diseases 2014;(10):590-595
Objective To explore the influence of lack of parental accompaniment, physical abuse and neglect in childhood on the psychological distress of college entrant students. Methods In a comprehensive university in Sichuan Province, 8367 freshmen were surveyed using the 6-item Kessler psychological distress (K6) scale and a questionnaire for lack of parental accompany, physical abuse and neglect in childhood. The students were divided into rural group and urban group for data analysis. Results The months of lack of maternal and/or paternal accompaniment were more in rural group than that in urban group (P<0.05). In rural group, female (standardizedβ’=0.139, P<0.001), neglect (standardizedβ’=0.237, P<0.001) and physical abuse (standardized β’=0.076, P<0.001) were associated with K6 scale. In urban group, female (standardizedβ’=0.091, P<0.001), lack of paternal accompaniment (standardizedβ’=0.050, P<0.001), ne? glect (standardized β’=0.169, P<0.001) and physical abuse (standardized β’=0.095, P<0.001) related with K6 scale. Conclusions Neglect and physical abuse are independent risk factors to freshmen both from rural and urban areas. Lack of paternal accompaniment in childhood is a risk factor only in urban freshmen. Further research should select more rep?resentative samples and also include more factors which may interact with the loss of parental accompaniment such as pa?rental divorce and conditions regarding so calledleft-behindchildren in rural area.
4.Role of PKC-δ in ventilator-induced lung injury in rats: relationship with NLRC4
Xiao ZHANG ; Lingnan CHEN ; Qiujie LI ; Lixin SUN ; Fuguo MA ; Mingshan WANG
Chinese Journal of Anesthesiology 2020;40(4):486-489
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.
5.Effect of obesity factor on ventilator-induced lung injury in rats
Guiru LI ; Yanyan SUI ; Qiujie LI ; Fuguo MA ; Lixin SUN ; Fei SHI ; Mingshan WANG
Chinese Journal of Anesthesiology 2020;40(8):941-944
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.
6.Effect of rapamycin on activity of NLRC4 inflammasomes in rats with ventilator-induced lung injury
Lingnan CHEN ; Zuoyan SONG ; Fuguo MA ; Qiujie LI ; Lixin SUN ; Mingshan WANG ; Wei HAN
Chinese Journal of Anesthesiology 2020;40(8):950-954
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.
7.Efficacy of oxycodone combined with thoracic paravertebral block for postoperative analgesia in pa-tients undergoing minimally invasive direct coronary artery bypass grafting
Qiujie LI ; Bin WANG ; Lixin SUN ; Fuguo MA ; Yanping ZHANG ; Mingshan WANG
Chinese Journal of Anesthesiology 2018;38(8):942-945
Objective To evaluate the efficacy of oxycodone combined with thoracic paravertebral block ( TPVB) for postoperative analgesia in patients undergoing minimally invasive direct coronary artery bypass grafting ( MIDCABG) . Methods Thirty-two American Society of Anesthesiologists physical statusⅡorⅢpatients of both sexes, aged 60-75 yr, weighing 50-85 kg, scheduled for elective MIDCABG un-der general anesthesia, were divided into 2 groups ( n=16 each) using a random number table method:morphine plus TPVB group ( group MT) and oxycodone plus TPVB group ( group OT) . Paravertebral cathe-ter was placed at T4,5 before induction of anesthesia to perform left thoracic paravertebral puncture, patients were tracheally intubated, and 0. 375% ropivacaine 15 ml was injected followed by continuous infusion of 0. 375% ropivacaine 5 ml∕h until 0. 5 h before the end of surgery. Both groups received patient-controlled analgesia ( PCA) after surgery. The PCA solution contained 1 mg∕ml morphine 60 ml in group MT or 1 mg∕ml oxycodone 60 ml in group OT, and the PCA pump was set up to deliver a 1 mg bolus dose with a 10-min lockout interval and background infusion at 1 ml∕h after a loading dose of 2 mg, with the maximum dose of 20 mg every 4 h. Pethidine 50 mg was intravenously injected as a rescue analgesic to maintain visual ana-log scale≤4. The intraoperative consumption of fentanyl, consumption of analgesics for PCA within 48 h after surgery, ratio of total to effective pressing times of PCA, consumption of analgesics for rescue analge-sia, requirement for rescue analgesia, score of satisfactory analgesia, extubation time, duration of inten-sive care unit stay and length of hospital stay were recorded. The development of nausea and vomiting, pru-ritus, respiratory depression, atelectasis and somnolence was recorded within 72 h after surgery. Results Compared with group MT, the intraoperative consumption of fentanyl, consumption of analgesics for PCA, consumption of analgesics for rescue analgesia, requirement for rescue analgesia and ratio of total to effec-tive pressing times of PCA were significantly decreased, the score of satisfactory analgesia was increased, the extubation time and duration of intensive care unit stay were shortened, and the incidence of nausea and vomiting, pruritus, respiratory depression and somnolence was decreased in group OT (P<0. 05). Con-clusion Oxycodone combined with TPVB provides safe and effective efficacy for postoperative analgesia in patients undergoing MIDCABG.
8.Effect of irisin on ventilator-induced lung injury in rats: relationship with expression of NLRP3 inflammasomes
Luyang ZHANG ; Bing LIU ; Fuguo MA ; Qiujie LI ; Lixin SUN ; Mingshan WANG ; Wei HAN
Chinese Journal of Anesthesiology 2021;41(4):496-501
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.
9.Effect of irisin on pyroptosis in rats with ventilator-induced lung injury
Qiujie LI ; Luyang ZHANG ; Fuguo MA ; Xiaopeng SUN ; Gaofeng ZHANG ; Lixin SUN ; Mingshan WANG
Chinese Journal of Anesthesiology 2021;41(8):970-974
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.
10.Clinical analysis of surgical therapy in differentiated thyroid cancer
China Modern Doctor 2014;(24):22-24
Objective To investigate the treatment of differentiated thyroid cancer surgery. Methods Retrospective ana-lyzed the clinical data in our hospital from January 2011 to December 2013, 82 cases of patients with differentiated thyroid cancer from the thyroid and neck lymph node resection removals, and investigated the treatment of differentiat-ed thyroid cancer. Results Among 82 patients with differentiated thyroid cancer, 25 patients with unilateral thyroid cancer, 35 patients with bilateral, and lymph node metastasis in 22 patients (16 cases of unilateral, bilateral 6 cases). Bilateral thyroid cancer patients were treated with total thyroidectomy or near total resection; Unilateral thyroid cancer patients with unilateral thyroid lobe + isthmus resection; The patients after surgery with fewer postoperative complica-tions, the incidence rate was 3.66%. After 1 to 10 years of follow-up, only one patient died in the forth year after surgery. Conclusion For patients with differentiated thyroid cancer treatment, need to take a different surgical tech-niques based on patient specific prevalence, and give patients after oral thyroid hormone therapy.