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Ischemia reperfusion injury (IRI) of organs is a major challenge for clinicians, but the mechanism is still not elucidated, and the clinical treatment effect is still unsatisfactory. PARP-1-dependent cell death (parthanatos) is a non-apototic programmed cell death pathway involved in the development of the occurrence of IRI of organs. At the same time, parthanatos is also a multi-step pathway. There are many molecules in the parthanatos cascade that can be exploited to create therapeutic interventions for IRI, including PARP1, apoptosis inducing factor (AIF), and macrophage migration inhibitory factor (MIF). These critical molecules are involved in DNA damage, energy depletion and homeostasis imbalance. Therefore, these molecular signals in the parthanatos cascade represent promising therapeutic targets for the treatment of IRI. In the following, we will elaborate on the mechanisms and molecular characteristics of the parthanatos pathway and the relation between parthanatos pathway and IRI of vital organs. It aims to explore the posibility of IRI mechanism research and clinical treatment and to provide new ideas for clinicians and researchers.
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Objective:To observe the effect of esketamine on cardiac index in patients undergoing lumbar surgery in prone position under general anesthesia.Methods:Forty-five patients with prone lumbar surgery after general anesthesia in Hunan Provincial People′s Hospital from March to July 2021 were divided into observation group (24 cases, group A) and control group (21 cases, group B) according to random number table method. Group A received 0.5 mg/kg esketamine intravenously during induction, and 0.15 mg/(kg·h) esketamine intravenously for 2 h after prone position. Group B received the same amount of normal saline. Both groups were given sevoflurane and remifentanil during operation to maintain anesthesia, and sufentanil was given intermittently during operation. The mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic pressure (DBP), cardiac index (CI), and heart rate (HR) before induction (T 0), during endotracheal intubation (T 1), 5 minutes after intubation (T 2), 5 minutes after prone position (T 3), 10 minutes after prone position (T 4), 30 minutes after prone position (T 5), 45 minutes after prone position (T 6), 60 minutes after prone position (T 7), 90 minutes after prone position (T 8), and 120 minutes after prone position (T 9) were recorded; The total dosage of norepinephrine 2 hours after anesthesia to prone position and extubation time after operation were also recorded. The Visual Analogue Scale (VAS) was performed 15 minutes after extubation, 6 and 24 hours after operation. Results:There was no significant difference in CI between T 3-T 9 and T 2 in group A ( P>0.05); the CI of group B at T 3-T 7 was significantly lower than that at T 2 (all P<0.05); there was no significant difference in CI between T 8-T 9 and T 2 in group B (all P>0.05); There was no significant difference in CI between group A and group B at T 0-T 2 (all P>0.05). The CI of group A at T 3-T 9 was significantly higher than that of group B (all P<0.05); The dosage of norepinephrine in group A was significantly lower than that in group B ( P<0.05); There was no significant difference in HR, MAP, SBP and DBP between the two groups at different time points (all P>0.05); there was also no significant difference in extubation time and VAS scores at 15 minutes, 6 hours and 24 hours after extubation between the two groups (all P>0.05). Conclusions:Intraoperative application of esketamine can increase CI after prone position and reduce the amount of norepinephrine during lumbar surgery.
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Objective To evaluate the changes in the expression of c-fos protein in the spinal cord in a rat model of oxycodone dependence or withdrawal response.Methods Thirty SPF adult male Sprague-Dawley rats,aged 6-8 weeks,weighing 180-220 g,were divided into 3 groups (n=10 each) using a random number table method:normal saline group (group NS),oxycodone dependence group (group OD),and oxycodone withdrawal group (group OW).In OD and OW groups,oxycodone was injected subcutaneously in back,5 days in total,with the dose of 2,3,4,5 and 6 mg/kg in turn,3 times a day (8:00/15:00/22:00).The equal volume of normal saline was given instead in group NS.The mechanical paw withdrawal threshold was measured at 3 days before administration and 30 min after the last administration every day.The oxycodone withdrawal was induced by intraperitoneal injection of naloxone 4 mg/kg at 8 h after the last administration of oxycodone on 5th day in group OW.The withdrawal response scores and range of weight changes were recorded within 15 min after giving naloxone or normal saline in NS and OW groups.Spinal cord tissues were collected at 1 h after the last administration on 5th day in group OD and at 1 h after giving normal saline or naloxone on 5th day in NS and OW groups for determination of the expression of c-fos protein by Western blot.Results Compared with group NS,the mechanical paw withdrawal threshold was significantly increased on 1 and 2 days after administration,and the expression of c-fos protein in the spinal cord was up-regulated in OD and OW groups,and withdrawal response scores were significantly increased,and the range of weight change was increased in group OW (P＜0.05).The expression of c-fos protein was significantly down-regulated in group OW as compared with group OD (P＜0.05).Conclusion Oxycodone dependence or withdrawal response may be related to the expression of c-fos protein in the spinal cord of rats,and the expression is up-regulated during oxycodone dependence,while down-regulated during oxycodone withdrawal.
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Objective To investigate the expression of survivin/Human leukocyte antigen class I ( HLA-Ⅰ) proteins and its physiological significance in clear cell renal cell carcinoma ( CCRCC ) . Methods Immunohistochemistry was used to analyze survivin/HLA-Ⅰ protein expression in 90 cases of CCRCC and 10 normal tissues to study relationships with clinical symptoms and disease prognosis . Resutl s The level of survivin protein expression was found to be significantly higher in CCRCC tissues 82.2%( 74/90) than in normal tissues( 0/10).However, the relative amount of HLA-Ⅰprotein in colorectal cancer tis-sue was also found to be significantly lower 67.8%(61/90) than in normal tissues 90%(9/10).Survivin expression was associated with tumor grade , stage,and lymph node metastasis ( P=0.000, P=0.016, and P=0.001, respectively ) .Conversely , lost HLA-Ⅰexpression did not have any associations with clinicopath-ological data (P>0.05).Survivin negative patients (25.0%, 4/16) had a higher tumor-free survival rate than patients (52.7%, 39/74)with survivin expression (P=0.037).Patients (27.6%, 8/29) with normal HLA-Ⅰlevels had a higher tumor-free survival rate than those ( 60.7%, 37/61) with reduced HLA-Ⅰlev-els (P=0.020).The univariate and multivariate analyses indicated that expression of survivin and HLA indi -vidually and in combination were independent predictors for CCRCC patient survival . Conclusions Over-expression of survivin but reduced HLA-Ⅰ expression is associated with CCRCC development and progres-sion.
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Objective To investigate the significance of aldehyde dehydrogenase 1 (ALDH1)expression in appraising the prognosis of nasopharyngeal squamous carcinoma (NPC).Methods The expression of ALDH1 protein was detected by immunohistochemistry in human specimens obtained from 120 NPC patients without the history of radiotherapy or chemothetapy.Results A relatively high expression of ALDH1 were observed in 40.0 ％ (48/120) patients of NPC,the expression of ALDH1 in the edge of the cancer nests and stroma,particularly spindle cancer cells were strongly positive.The positive expression of ALDH1 was closely associated with patients' nasopharyngeal tumor size (P =0.011),lymphatic metastasis (P =0.005) and clinic stage (P =0.001),but not associated with their gender and age (both P ＞ 0.05).The Kaplan-Merier and Cox regression analysis indicated that ALDH 1 closely correlated with clinical progrosis of the patients.It showed that ALDH1 was an independent risk factor which may affect the prognosis of NPC patients.Conclusion The expression of ALDH1 protein closely correlate with clinic outcome of NPC,suggesting that ALDH1 is a risk factor for clinic progrosis of NPC patients.
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Objective To evaluate musical therapy combined with sufentanil postoperative intravenous analgesia on hemodynamic changes in patient accepted lung cancer operation.Methods Sixty lung cancer surgery patients (ASA Ⅰ-Ⅱ grade) were selected and divided randomly into musical therapy (group M; n =30) and control (group C; n =30).In group M,patients accepted music relaxation training for fifteen minutes before surgery,and music intervention for one hour at 3,7,15,19 hour after surgery.Whereas,in Group C,patients did not listen to any music during the same period.In the intensive care unit,patients were connected to a patient controlled analgesia (PCA) device.The PCA device (sufentanil 2 μg/kg,100 ml saline) was set to deliver a bolus of 2 ml,with a lockout interval of 10 min and background infusion volume of 0.5 ml/h.Hemodynamic changes,the visual analog scale (VAS) and consumption of sufentanil were recorded at the 4th,8th,12th,16th,20th and 24th hour after operation.Results SBP,DBP,HR and VAS of group M were significantly decreased compared to the group C,respectively (P ＜0.05),and significant difference was found in the PCA delivery frequency [group C (30.96 ± 4.00),group M (19.06 ± 3.49),t =12.39,P ＜ 0.01] and postoperative sufentanil consumption[group C (82.65±6.19)μg,group M (52.68 ±7.07)μg,t =20.00,P ＜0.01].Conclusions Musical therapy combined with sufentanil postoperative intravenous analgesia was able to produce better analgesic effect in the treatment of patient accepted lung cancer operation,which decreased postoperative sufentanil consumption and effectively reduced SBP,DBP and HR,and relieved the patient's anxiety.