Objective To explore the effect and mechanism of microRNA(miR)-155-5p on myocardial pyroptosis in rats with myocardial ischemia-reperfusion injury(IRI).Methods Sixty SD rats were randomly divided into sham group,IRI group,agomir-NC group,miR-155-5p agomir group,antagomir-NC group,and miR-155-5p antagomir group,with 10 rats in each group.Echocardiography was used to measure the left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF),and left ventricular fractional shortening(LVFS)of rats.Enzyme-linked immune absorbent assay(ELISA)was used to detect the levels of creatine kinase isoenzyme(CK-MB),lactate dehydrogenase(LDH),and cardiac troponin T(cTnT)in serum,as well as the levels of interleukin(IL)-1β,IL-6,IL-18,and tumor necrosis factor(TNF)-α in myocardial tissue of rats.Hematoxylin-eosin staining was used to observe pathological changes in rat myocardial tissue.Real-time fluorescent quantitative polymerase chain reaction was used to detect the expression levels of miR-155-5p and silent information regulator 1(SIRT1)messenger RNA(mRNA)in myocardial tissue of rats.Dual-luciferase reporter gene assay was used to verify the targeting relationship between miR-155-5p and SIRT1.Western blot was used to detect the expression levels of SIRT1,NOD-like receptor protein 3(NLRP3),cleaved cysteine aspartate specific proteinase-1(Cleaved Caspase-1),and gasdermin D(GSDMD)proteins in myocardial tissue of rats.Results Compared with the sham group,the LVEDD and LVESD of rats in the IRI group were increased,LVEF and LVFS were decreased,serum levels of CK-MB,LDH,and cTnT were increased,IL-1β,IL-6,IL-18 and TNF-α levels in myocardial tissue were increased,myocardial tissue structure was severely damaged,myocardial fibers were disordered,relative expression of NLRP3,Cleaved Caspase-1,and GSDMD proteins were increased,and the relative expression of SIRT1 protein was decreased(all P<0.05/5).Compared with the IRI group,the rats in the miR-155-5p agomir group had increased LVEDD and LVESD,decreased LVEF and LVFS,increased serum levels of CK-MB,LDH,and cTnT,increased myocardial tissue levels of IL-1β,IL-6,IL-18,TNF-α,aggravated myocardial tissue lesions,increased relative expression of NLRP3,Cleaved Caspase-1,and GSDMD proteins,and decreased relative expression of SIRT1 protein,and the rats in the miR-155-5p antagomir group had decreased LVEDD and LVESD,increased LVEF and LVFS,decreased serum levels of CK-MB,LDH,and cTnT,decreased myocardial tissue levels of IL-1β,IL-6,IL-18,TNF-α,reduced myocardial tissue lesions,decreased relative expression of NLRP3,Cleaved Caspase-1,and GSDMD proteins,and increased relative expression of SIRT1 protein(all P<0.05/5).miR-155-5p was negatively correlated with the expression levels of SIRT1 in rat myocardial tissue,and SIRT1 was a target gene of miR-155-5p.Conclusions miR-155-5p may participate in the regulation of myocardial IRI in rats by targeting the downregulation of SIRT1 and promoting NLRP3-mediated myocardial pyroptosis.

Objective:To evaluate the anesthetic effect of remazolam when combined with sufentanil in elderly patients with liver cirrhosis and esophageal and gastric varices undergoing endoscopic sclerotherapy.Methods:A total of 150 cirrhotic patients with liver cirrhosis and esophageal and gastric varices, regardless of gender, aged 65-80 yr, with body mass index of 18-24 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱor Ⅲ, who underwent endoscopic sclerotherapy under non-intubated general anesthesia from March 2022 to September 2023 in our hospital, were selected and divided into 2 groups ( n=75 each) by a random number table method: sufentanil plus propofol group (PS group) and sufentanil plus remazolam group (RS group). Anesthesia was induced with intravenous propofol 1-2 mg/kg and sufentanil 0.1 μg/kg and maintained by intravenous infusion of propofol 4-10 mg·kg -1·h -1 in PS group. Anesthesia was induced with intravenous remimazolam 0.1-0.2 mg/kg and sufentanil 0.1 μg/kg and was maintained with intravenous infusion of remimazolam 0.5-2.0 mg·kg -1·h -1 in RS group. BIS values were maintained between 40 and 60 during operation in both groups. Endoscopy was placed when the patients lost consciousness (modified observer′s assessment of alertness/sedation score ≤1). Sclerosing agent laurosinol injection was injected into esophageal submucosal varices in both groups. The time to loss of consciousness and recovery of consciousness, intraoperative body movement and cardiovascular events, and postoperative hypoxemia and nausea and vomiting were recorded. The operator-patient satisfaction was assessed by the visual analogue scale. Results:Compared with PS group, no significant changes were found in the incidence of intraoperative bradycardia, time to loss of consciousness and time to recovery of consciousness( P>0.05), the incidence of intraoperative hypotension was significantly decreased, the incidence of postoperative hypoxemia and nausea and vomiting was decreased, and the satisfaction scores for operators and patients were increased in RS group ( P<0.05). No obvious body movement was found in the two groups. Conclusions:Sufentanil combined with remifentanil provides better anesthetic effect than sufentanil combined with propofol in elderly patients with esophageal and gastric varices undergoing endoscopic sclerotherapy.

Objective:To evaluate the effects of different concentrations of ropivacaine on the growth and migration of lung cancer cells.Methods:Human lung adenocarcinoma cell strain A549 cells and human lung squamous cell strain H520 cells were divided into 4 groups ( n=24 each) using a random number table method: control group (group C) and different concentrations of ropivacaine groups (Ⅰ-Ⅲ groups). Cells were commonly cultured in group C. Ropivacaine 3, 5 and 7 mmol/L were added and then the cells were cultured in Ⅰ-Ⅲ groups, respectively. The cell survival rate was determined using the CCK-8 method at 24, 48 and 72 h of treatment (T 1-3). The cell cycle and apoptosis were detected at T 1 using flow cytometry. The expression of Cyclin D1, cyclin-dependent kinase 4 (CDK4), cleaved poly (ADP-ribose) polymerase-1 (PARP-1) and cleaved caspase-3 was detected using Western blot. Wound healing assay was used to measure cell migration distance. The activities of RhoA and Rac1 were detected by microplate spectrophotometry. Results:The cell viability of A549 and H520 cells sequentially decreased at T 1-3, the proportion of G0/G1 phase and apoptosis sequentially increased, the expression of Cyclin D1 and CDK4 was down-regulated sequentially at T 1, the expression of cleaved PARP-1 and cleaved caspase-3 was up-regulated sequentially, and the cell migration distance, RhoA, and Rac1 activity decreased sequentially in C, Ⅰ, Ⅱ and Ⅲ groups ( P<0.05). Conclusions:Ropivacaine can inhibit the growth and migration ability of lung cancer cells in a concentration-dependent manner, which is related to induction of cell cycle arrest and apoptosis.

Objective:To evaluate the role of Nod-like receptor family pyrin domain-containing 2 (NLRP2) in the dorsal root ganglion (DRG) in neuropathic pain (NP) in rats.Methods:Thirty-two male Sprague-Dawley rats in which intrathecal catheters were successfully implanted, aged 2-3 months, weighing 200-250 g, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group (S group), NP group, NP plus NLRP2-siRNA group (NP+ siRNA group) and NP plus NLRP2-scrRNA group (NP+ scrRNA group). The right sciatic nerve was only exposed but not ligated in group S. NP was induced by chronic constriction injury (CCI) to the sciatic nerve in anesthetized rats in group NP, group NP+ siRNA and group NP+ scrRNA.NLRP2-siRNA and NLRP2-scrRNA were intrathecally injected at 3 days before CCI in group NP+ siRNA and group NP+ scrRNA, respectively.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before CCI (T 0) and 1, 3, 7 and 10 days after CCI (T 1-4). The rats were sacrificed after the last measurement of pain threshold, and the L 4, 5 segments of the DRG on the operated side were removed for determination of the expression of NLRP2 and caspase-1 (by Western blot), the expression of NLRP2 mRNA (by real-time polymerase chain reaction) and interleukin-1beta (IL-1β) content (by enzyme-linked immunosorbent assay). Results:The MWT was significantly lower at T 2-4 than at T 0 in group NP, group NP+ siRNA and group NP+ scrRNA ( P<0.05). Compared with group S, the MWT was significantly decreased at T 2-4, the expression of NLRP2 protein and mRNA and caspase-1 was up-regulated, and the content of IL-1β was increased in group NP ( P<0.05). Compared with group NP, the MWT was significantly increased at T 2-4, the expression of NLRP2 protein and mRNA and caspase-1 was down-regulated, and the content IL-1β was decreased in group NP+ siRNA ( P<0.05), and no significant change was found in the parameters mentioned above in group NP+ scrRNA ( P>0.05). Conclusion:NLRP2 in DRG is involved in the development of NP, and the mechanism is related to NLPR2 inflammasomes-induced peripheral neuroinflammation in rats.

OBJECTIVE： To study the effects of cimetidine on low dose rate irradiation-induced liver cell apoptosis in Beagle dogs. METHODS： Healthy male Beagle dogs were randomly divided into normal control group， model control group， positive drug group （lentinan， 21.33 mg/kg） and cimetidine low-dose， medium-dose and high-dose groups （5.33， 10.67， 21.33 mg/kg）， with 4 Beagle dogs each. Except for normal control group， other groups were given 60Co-γ accumulative irradiation （dosage rate： 0.040 8 mGy/min） for 23 d； the medication groups were given relevant medicine orally before irradiation， once a day. Twenty-four hours after stopping irradiation， TUNEL method was used to detect the apoptosis of liver cells in Beagle dogs. The percentage of apoptotic cells was calculated. The expression level of apoptosis-related proteins （Bax， Bcl-2， Caspase-3， p53） in liver tissue was detected by immunohistochemistry. RESULTS： Compared with normal control group， apoptotic cells and Bax， Caspase-3， p53 positive cells were increased significantly in liver tissue of Beagle dogs in model control group； the percentage of apoptotic cells， protein expression levels of Bax， Caspase-3 and p53 were increased significantly； Bcl-2 positive cells were decreased significantly， and its protein expression level was decreased significantly （P＜0.05 or P＜0.01）. Compared with model control group， above positive cells of liver tissue in Beagle dogs were changed to different extents in medication groups； the percentage of apoptotic cells and protein expression levels of p53 in medication groups， protein expression levels of Bax in positive drug group， cimetidine low-dose and high-dose groups as well as protein expression levels of Caspase-3 in cimetidine groups were decreased significantly； protein expression levels of Bcl-2 were increased significantly in cimetidine groups. The percentage of apoptotic cells in cimetidine medium-dose and high-dose groups as well as protein expression levels of Caspase-3 in cimetidine groups were all lower than positive control group. Protein expression level of p53 in cimetidine low-dose group was significantly higher than positive drug group （P＜0.05 or P＜0.01）. CONCLUSIONS： Cimetidine can inhibit the low dose rate irradiation-induced apoptosis of liver cells in Beagle dogs， and certainly protect liver cells against irradiation. The mechanism of it may be associated with up-regulating the protein expression of Bcl-2 and down-regulating the protein expression of Bax， Caspase-3 and p53 in liver cells.

Objective To compare the cost-effectiveness of non-intubated general anesthesia with conventional general anesthesia for thoracoscopic bulla resection. Methods Sixty patients scheduled for elective thoracoscopic bulla resection, were divided into two groups (30 each) using a random number table: the conventional general anesthesia group (T group) and the non-intubated general anesthesia group (NT group). Patients in group T were induced with conventional general anesthetic, single-lung ventilated after intubation with double-lumen bronchial catheters. Patients in group NT were induced with general anesthesia combined nerve block, and spontaneous breathings were retained. The results of blood gas analysis, anesthesia time, operation time, intraoperative blood loss, time for orientation recovery and modified Aldrete score ≥ 9 minutes were recorded. The intraoperative and postoperative complications, postoperative hospital stay time, VAS and PC A scores 48 h after operation were recorded. Calculate the cost of anesthesia and the total cost of hospitalization. Results Compared with T group, NT group had lower pH value and higher PCO2 at 30 min before and after the thoracic closure, oxygenation index in the NT group increased at 30 min after the thoracic closure (P < 0.05). Compared with T group, anesthesia time, time for orientation recovery and modified Aldrete score ≥ 9 minutes, incidence of postoperative sore throat, postoperative hospital stay time, VAS scores at 6, 12 h and PC A at 48 h after the operation, anesthesia costs, and total hospitalization costs in the NT group were all reduced (P < 0.05). Conclusions Fully considering the safety, compared with the traditional tracheal intubation general anesthesia, non-intubation general anesthesia can not only promote postoperative outcomes but also improve the cost-effectiveness in the patients undergoing thoracoscopic bulla resection.

Objective To evaluate the effect of hydrogen sulfide on myocardial exogenous apoptotic pathway in a rat model of hemorrhagic shock and resuscitation.Methods Sixty clean-grade healthy male Sprague-Dawley rats,aged 8 weeks,weighing 250-300 g,were divided into 4 groups (n =15 each) using a random number table method:sham operation group (group S),sham operation plus sodium sulphid (NaHS) group (group S+NaHS),hemorrhagic shock group (HS group),and hemorrhagic shock plus sodium sulphid group (group HS+NaHS).Rats only underwent arterial and intravenous puncture in group S.Hemorrhagic shock was induced by withdrawing blood from the femoral artery until mean arterial pressure (MAP) was reduced to 35-40 mmHg within 10 min and maintained for 1.5 h.NaHS 28 μmol/kg was intraperitoneally injected at 10 min before resuscitation in group HS+NaHS.The equal volume of NaHS was administered at the same time in group S+NaHS.Immediately before blood letting and at 0,1.5,2,3,4 and 6 h after blood letting (T1-5),MAP was recorded and blood samples were collected from the femoral vein for determination of serum creatine kinase (CK) and lactate dehydrogenase (LDH) concentrations by chemical colorimetry.Rats were then sacrificed and hearts were removed for examination of the pathological changes of myocardial tissues (with a light microscope) and for determination of cell apoptosis (by TUNEL),expression of caspase-3 and caspase-8 (by Western blot) and expression of Fas and FasL (by immunohistochemistry).Apoptosis index was calculated.Results Compared with group S,MAP was significantly decreased at T1-5,the serum CK and LDH concentrations at T1-5 and apoptosis index at T5 were increased,and the expression of Fas,FasL,caspase-3 and caspase-8 was up-regulated in group HS (P＜ 0.05).Compared with group HS,MAP was significantly increased at T1-3,the serum CK and LDH concentrations at T3-5 and apoptosis index at T5 were decreased,and the expression of Fas,FasL,caspase-3 and caspase-8 was down-regulated in group HS+NaHS (P＜0.05).The pathological changes of myocardial tissues were significantly attenuated in group HS+NaHS when compared with group HS.Concclusion The mechanism by which hydrogen sulfide attenuates myocardial injury induced by hemorrhagic shock and resuscitation is associated with inhibiting the exogenous apoptotic pathway in rats.

Objects To study the protective effects of cimetidine against oxidative stress in rats induced by cumulative low-dose irradiation.Methods Sixty SD rats were randomly divided into 6 groups (10 each):normal control group,model control group,lentinan group [89mg/(kg.d)] and 3 dose groups of cimetidine.After oral administration,all the rats were exposed to γ-ray irradiation 8 hours/day for 12 days,and sacrificed on the 13th day.The activities of superoxide dismutase (SOD),glutathione peroxidase (GPx),catalase (CAT) and the content of malondialdehyde (MDA) in serum,liver,thymus and spleen were determined.By using the superoxide anion radical system,hydroxyl radical system,H2O2 radical system,oxidation system of linoleic acid induced by alkane radical system and diphenyl picryl hydrazinyl radical (DPPH) radical system,the antioxidation activities of cimetidine were detected.Results The activities of SOD in liver and thymus decreased significantly,the GPx activity in serum,liver and spleen decreased significantly and MDA level in serum,liver and spleen increased significantly after 0.3Gy cumulative ionizing radiation.Cimetidine enhanced the activities of antioxidant enzymes in serum and organs,and reduced the MDA level.In a certain concentration range,cimetidine had different scavenging effects onto these radical systems,and showed good performance in hydroxyl radical.Conclusion Cimetidine can effectively ameliorate the oxidative stress from low-dose cumulative irradiation by scavenging free radicals,increase the activity of antioxidant enzymes and reduce the content of lipid peroxidation products,thus presents a potential radio protective effect.

Objective To investigate the radioprotective effect of cimetidine on survival rate and hematopoietic system in acutely irradiated mice.Methods The total body irradiation doses were 6.0Gy and 8.0Gy respectively at 1.01Gy/min rate. Sixty healthy male C57BL/6 mice were randomly divided into control group, model group, positive-drug (523) group and cimetidine groups (33.3mg/kg, 100mg/kg and 300mg/kg). Each group had ten mice. The mice were given intragastric administration of cimetidine for 6d before the irradiation in cimetidine groups, and 523 was administered before irradiation once a day for one day in 523 group, and at 5h after irradiation, was given again. The 30d survival rate after 8.0Gy irradiation was recorded. The peripheral blood cells, bone marrow DNA content and frequency of micronucleated polychromatic erythrocytes (fMNPCE) were determined 30d after 6.0Gy irradiation.Results After 8.0Gy irradiation, all the mice died on 21th day in model control group. The survival rates in cimetidine groups were 50%, 20% and 30%, respectively. After 6.0Gy irradiation on 30th day, compared with control group, the peripheral white blood cells (WBC) and bone marrow DNA content were decreased significantly (P<0.01,P<0.05) in model group, and fMNPCE was increased significantly (P<0.05). Compared with model group, WBC was significantly increased in 300mg/kg cimetidine group (P<0.01). In cimetidine groups, the bone marrow DNA content was increased significantly after irradiation (P<0.01 orP<0.05), and the fMNPCE was decreased significantly (P<0.01 orP<0.05) and tended towards normal.Conclusion Cimetidine could improve 30d survival rate of acutely irradiated mice and has good protective effect on hematopoietic system.

OBJECTIVE: To establish the cell model using human leukemia cell line HL-60 for exposure of coke oven emissions( COE) in vitro and to explore the mechanism of COE-induced acute toxicity in HL-60 cells. METHODS: HL-60 cells were collected in their logarithmic growth phase and cultured in medium that had final concentrations of COE in 2. 5,5. 0,10. 0 and 20. 0 mg / L for 24 hours. Cell survival rate was examined by CCK-8 assay. The cytotoxicity was evaluated using lactate dehydrogenase release assay. Reactive oxygen species( ROS) production was determined by the 2',7'-dichlorofluorescein diacetate and nitroblue tetrazolium method. The activation of nuclear factor-κB( NF-κB) pathway was evaluated by western blot. RESULTS: With the increasing exposure concentrations of COE,the cytotoxicity of HL-60 cells increased( P < 0. 01),the cell survival rate decreased( P < 0. 01),intracellular ROS decreased( P < 0. 01),whereas extracellular ROS increased( P < 0. 01). These changes had a dose-effect relationship. The levels of phospho-nuclear factor-kappa B p65 and phospho-inhibitor of kappa Bα were higher in all the COE-treated cells compared with untreated cells( P < 0. 05),with no dose-effect relationship. CONCLUSION: COE could cause acute toxicity in HL-60 cells in a doseeffect relationship. The mechanism may be related to the COE-induced in-balanced ROS release and removal,leading to the activation of NF-κB pathway. HL-60 cells can be used as a common cell line for COE hematotoxicity analysis.