Paraquat is a quaternary ammonium herbicide, which can be distributed in lung, liver, kidney, heart, brain and other organs through blood circulation, leading to multiple organ failure, especially lung injury. Due to the lack of effective treatment methods and specific antidotes, the prognosis of most patients with paraquat poisoning is very poor. The treatment of paraquat poisoning was a big problem for emergency doctors. Previous studies have found that pulmonary fibrosis caused by paraquat poisoning is closely related to a variety of pathological processes, such as oxidative stress, inflammatory reaction, mitochondrial damage, imbalance of extracellular matrixproduction (ECM) and degradation, which involve the activation or inhibition of various signaling pathways. In recent years, many researchers focused on clarifying the mechanism of paraquat induced pulmonary fibrosis, and some signaling pathways related to paraquat poisoning leading to pulmonary fibrosis have been found. A large number of studies have found that adenosine monophosphate activated protein kinase (AMPK) related signaling pathway, transforming growth factor-β/Smad (TGF-β/Smad)signaling pathway, mitogen-activated protein kinase (MAPK) related signaling pathway, Ras homolog gene/Rho associated kinases (Ras/ROCK) and Wnt/β-catenin signal pathways are closely related to paraquat induced pulmonary fibrosis. In this paper, we reviewed signaling pathways related to paraquat induced pulmonary fibrosis, in order to provide more ideas for the clinical treatment of paraquat induced pulmonary fibrosis.

ObjectiveTo observe the therapeutic effects of gastric lavage with fuller earth combined with QingyiⅡ catharsis in treatment of oral paraquat poisoning in rabbits.Methods Thirty healthy adult Japanese white rabbits were randomly divided into five groups: namely control group, model group, gastric lavage group (lavage of 10%fuller earth suspension), catharsis group (QingyiⅡ catharsis), and combination group (10 minutes after gastric lavage of fuller earth suspension liquid, giving QingyiⅡ for catharsis), with 6 rabbits in each group. All groups were challenged with paraquat (100 mg/kg) diluted to 5 mL with normal saline by lavage to reproduce the model of acute poisoning, while the control group was given 5 mL of normal saline instead. Each treatment group was treated accordingly at 1 hour after gavages of paraquat, and treatment continued for 3 days. The animal survival rate was observed. Venous blood samples were collected from ear marginal vein to determine the plasma concentration of paraquat by ultraviolet spectrophotometer at 1, 2, 4, 8 and 24 hours after the poisoning. The animals were sacrificed by intravenous air injection on the 8th day after the poisoning, and the right lower lobe of lung was harvested to observe the lung tissue pathological changes with hematoxylin-eosin (HE) staining.Results① Survival rate: the surviving rate of the combination group (6 rabbits) was higher than that of gastric lavage group (5 rabbits), catharsis group (2 rabbits) and model group (0 rabbit) on the 2nd day with statistically significant difference (P< 0.001). The survival rate on the 7th day in combination group (5 rabbits) was higher than that of gastric lavage group (3 rabbits), and catharsis group (0 rabbit) with statistically significant difference (P = 0.003).② Plasma concentrations of paraquat: plasma paraquat concentration in all groups peaked at 2 hours after intoxication, and its levels in the gastric lavage, catharsis and combination groups were significantly lower than that of the model group (mg/L: 1.830±0.068, 1.890±0.048, 1.800±0.052 vs. 1.960±0.063, allP< 0.01). As the time prolonged, the plasma concentration of paraquat was lowest in combination group than that of gastric lavage group and catharsis group (allP< 0.01). Gastric lavage and catharsis had interaction at 4 hours in combination group [F = 5.194,P = 0.034; the concentrations of paraquat (mg/L) was 0.670±0.057 vs. 1.010±0.018, 1.210±0.052].③ Lung histopathology: obvious expansion and hyperemia of the alveolar capillary, widened alveolar septum, a large number of inflammatory cell infiltrations were observed in model group and catharsis group. Lung histopathology was more improved in combination group and gastric lavage group, and it was improved more obviously in combination group than that in gastric lavage group.Conclusions Early start of gastric lavage with fuller earth combined with QingyiⅡ catharsis, can reduce the animal plasma concentrations of paraquat in oral paraquat poisoning rabbits. At the same time, it can alleviate the degree of lung injury and significantly improve survival rates compared with the single gastric lavage or catharsis alone. Gastric lavage with fuller earth combined with QingyiⅡ catharsis can improve the prognosis of animal synergistically.

Objective To investigate the effects of spontaneous agonal respiration on coronary perfusion pressure (CPP) during untreated cardiac arrest (ventricular fibrillation) in swine model.Methods Ten male healthy domestic swines (25.0 ± 1.5) kg were anaesthetised,intubated and mechanically ventilated.The catheterizations were separately inserted into the right atrium and thoracic aorta to monitor aortic pressure (AOP) and right atrial pressure (RAP).A pacing electrode was inserted into the right ventricle to induce ventricular fibrillation (VF).VF was induced by intra-ventricular stimulation withalternating electric current and untreated for 8 minutes.AOP and RAP were recorded until respiratory activity ceased.The CPP before and after agonal respiration was calculated and analyzed by paired-sample T test.Results All animals presented with agonal respiration from 1 to 6 minutes after VF during the first attempt.The CPP was (7.18 ±4.22) mmHg at 1 sec before agonal respiration,(11.78 ±5.16) mmHg at 0 sec after agonal respiration,(8.75 t:4.38) mmHg at 5 sec after agonal respiration and (8.23 ± 4.55)mmHg at 6 sec after agonal respiration.The CPP at 0 sec after agonal respiration was higher than that before agonal respiration (t =-3.140,P =0.012).The CPP at 5 sec after agonal respiration was higher than that at 1 sec before agonal respiration (t =-2.828,P =0.020).There was no difference in CPP between at 6 sec after agonal respiration and at 1 sec before agonal respiration (t =-1.778,P =0.109).Conclusions Agonal respiration accompanies ventricular fibrillation.After agonal respiration,the coronary perfusion pressure is increased for 5 seconds being in favor of cardiaopulmonary resuscitation.

Objective To observe the effect of different doses of sufentanil on intubation guided by fiber bronchoscope in diffi‐cult airways .Methods One hundred and eighteen patients with difficult airways who underwent tracheal intubation were randomly divided into 3 groups [groupⅠ(n=40) ,groupⅡ (n=42) ,and groupⅢ (n=36)] .First all group received 1 μg/kg dexmedetomi‐dine ,then groupⅠ ,groupⅡ and group Ⅲ received sufentanil 0 .1μg/kg ,0 .2 μg/kg ,0 .3μg/kg infusion in bolus respectively .Heart rate(HR) ,mean arterial pressure(MAP)and saturation of pulse oximetry(SpO2 )were recorded at 5 min after patients arriving at operation room (T0 ) ,after drug infusion(T1 ) ,the time of intubation and seeing the epiglottis (T2 ) ,1 min(T3 )and 5 min(T4 )after intubation .side effect was recorded throughout the process .Results HR at T2 and T3 in groupⅡ and group Ⅲ were significantly lower than those in group Ⅰ(P<0 .05) .MAP at T2 and T3 in groupⅡ and group Ⅲ were significantly lower than those in groupⅠ(P<0 .05) .SpO2 at T2 in group Ⅲ was significantly lower than those of groupⅠ and groupⅡ(P<0 .05) .Cough reflex in groupⅠwas much frequent than others .Only group Ⅲ had respiratory inhibition .Conclusion Intravenous sufentanil (0 .2 μg/kg)could in‐hibit effectively stress reaction from endotracheal intubation ,in which less side effects such as haemodynamic changes and respirato‐ry depression occur .

Objective To investigate the effects of sustained abdominal aorta compression (SAAC) method combined with sim-plex chest compression (SCC) on partial pressure of end-tidal CO2 (PETCO2 ) ,return of spontaneous circulation(ROSC) ,resuscita-tion success rate and 24 h survival rate of the cardiac arrest model in domestic swines .Methods 20 healthy domestic swines were randomly divided into two groups ;the standard cadiopulmonary resuscitation group (S-CPR) by adopting SCC and the SAAC-CPR group by adopting SCC combined with SAAC during the resuscitation process .The cardiac arrest model was established by the ven-tricular fibrillation induced through the right atrium electrode alternating current stimulation .After 9 min of untreated interval ,CPR was performed .The two groups were firstly given SCC ,after 30 s ,the SAAC-CPR group was added with SAAC .PETCO2 ,coronary perfusion pressure(CPP) ,ROSC rate ,resuscitation success rates ,and 24 h survival rate were compared between the two groups .Re-sults PETCO2 in the SAAC-CPR group was higher than that during the SCC period in the SAAC-CPR group and in the S-CPR group during CPR[(22 .50 ± 3 .17 )mm Hg vs .(11 .80 ± 2 .57) mm Hg ,(13 .40 ± 3 .53) mm Hg ,P<0 .01)] .CPP in the SAAC-CPR group was also higher than that during SCC in the SAAC-CPR group and the S-CPR group[(50 .30 ± 6 .49) mm Hg vs .(14 . 12 ± 3 .01)mm Hg ,(14 .62 ± 2 .59)mm Hg ,P<0 .01)] .3 cases in the S-CPR group and 9 cases in the SAAC-CPR group restored ROSC within 3 times defibrillation ,succeeded in resuscitation after 20 min ROSC and underwent 24 h survival .The ROSC rate ,the resuscitation success rate and the 24 h survival rate in the SAAC-CPR group were significantly higher than those in the S-CPR group(P<0 .05) .No abdominal viscera damage was found in post mortem examinations of all the swines subjects .Conclusion SAAC combined with SCC can elevate PETCO2 ,CPP ,ROSC ,resuscitation success rate and 24 h survival rate ,which is conducive to CPR ,safe and easy to operate .

Objective To explore the regularity of incidence of agonal respiration (AR) and agonal respiration frequency rate (ARFR) during untreated cardiac arrest (CA) after ventricular fibrillation (VF) in a swine model.Methods Ten healthy male domestic pigs weighing (25.0± 3.0) kg were employed in this experiment.VF was induced by intraventricular shock with alternating current without treatment for 8 minutes.The incidence of AR and ARFR per minute were recorded for 8 minutes.Statistical analysis was performed using SPSS 19.0 system software.Results AR occurred in all animals after VF induced CA within 8 minutes.There was 1 animal showed AR at the first minute with ARFR (0.2±0.1) times/min,4 animals showed AR at the second minute with ARFR (1.2 ± 1.0) times/min,7 animals showed AR at the third minute with ARFR (2.7 ± 1.4) times/min,all animals showed AR at the fourth to fifth minute with ARFR (3.7 ± 1.6) times/min and (3.2 ± 1.9) times/min,7 animals showed AR at the sixth minute with ARFR (1.3 ± 1.0) times/min,no animal showed AR at the seventh minute,and 1 animal showed AR at the eighth minute with ARFR (0.2±0.1) times/min.The first and the last AR were observed at (2.02±0.84) minutes and (5.21 ± 1.12) minutes respectively.Occurrence of AR reached its peak at the fourth to fifth minute,and it was absent at the seventh minute.ARFR after CA showed a crescendo-decrescendo pattern,which increased from (0.2±0.1) times/min to (3.7±1.6) times/min followed by a fall to (0.2±0.1) times/min.Conclusions AR is one of the symbolic signs after CA.AR occurred in all animals during untreated VF,and it reaches its peak at the fomrth to fifth minute,with a crescendo-decrescendo pattern of ARFR.Effective identification and treatment in victim with AR timely can help to improve the success rate of cardiopulmonary resuscitation and survival rate.

OBJECTIVE: To observe whether metformin (MET) inhibits transforming growth factor-β₁ (TGF-β₁)/Smad3 signaling pathway by activating adenosine activated protein kinase (AMPK), so as to alleviate the pulmonary fibrosis caused by paraquat (PQ) poisoning in mice. METHODS: Male C57BL/6J mice were randomly divided into the Control group, PQ poisoning model group (PQ group), MET intervention group (PQ+MET group), AMPK agonist group (PQ+AICAR group), and AMPK inhibitor group (PQ+MET+CC group), according to a random number table method. A mouse model of PQ poisoning was established by one-time peritoneal injection of 1 mL PQ solution (20 mg/kg). The Control group was injected with the same volume of normal saline. After 2 hours of modeling, the PQ+MET group was given 2 mL of 200 mg/kg MET solution by gavage, the PQ+AICAR group was given 2 mL of 200 mg/kg AICAR solution by intraperitoneal injection, the PQ+MET+CC group was given 2 mL of 200 mg/kg MET solution by gavage and then 1 mL complex C (CC) solution (20 mg/kg) was intraperitoneally injected, the Control group and PQ group were given 2 mL of normal saline by gavage. The intervention was given once a day for 21 consecutive days. The 21-day survival rate of ten mice in each group was calculated, and the lung tissues of remaining mice were collected at 21 days after modeling. The pathological changes of lung tissues were observed under light microscope after hematoxylin-eosin (HE) staining and Masson staining, and the degree of pulmonary fibrosis was evaluated by Ashcroft score. The content of hydroxyproline in lung tissue and oxidative stress indicators such as malondialdehyde (MDA) and superoxide dismutase (SOD) were detected. The protein expressions of E-cadherin, α-smooth muscle actin (α-SMA), phosphorylated AMPK (p-AMPK), TGF-β₁ and phosphorylated Smad3 (p-Smad3) in lung tissue were detected by Western blotting. RESULTS: Compared with the Control group, the 21 days survival rate was significantly reduced, lung fibrosis and Ashcroft score were significantly increased in PQ group. In addition, the content of hydroxyproline, MDA and the protein expressions of α-SMA, TGF-β₁ and p-Smad3 in lung tissue were significantly increased, while the activity of SOD and the protein expressions of E-cadherin and p-AMPK were significantly decreased in PQ group. Compared with the PQ group, the 21 days survival rates of mice were significantly improved in the PQ+MET group and PQ+AICAR group (70%, 60% vs. 20%, both P < 0.05). The degree of pulmonary fibrosis and the Ashcroft score were significantly reduced (1.50±0.55, 2.00±0.63 vs. 6.67±0.52, both P < 0.05). The content of hydroxyproline and MDA in lung tissue, as well as α-SMA, TGF-β₁ and p-Smad3 protein expressions were significantly reduced [hydroxyproline (mg/L): 2.03±0.11, 3.00±0.85 vs. 4.92±0.65, MDA (kU/g): 2.06±1.48, 2.10±1.80 vs. 4.06±1.33, α-SMA/GAPDH: 0.23±0.06, 0.16±0.06 vs. 1.00±0.09, TGF-β₁/GAPDH: 0.28±0.03, 0.53±0.05 vs. 0.92±0.06 p-Smad3/GAPDH: 0.52±0.04, 0.69±0.06 vs. 1.11±0.10, all P < 0.05], SOD activity and the protein expressions of E-cadherin and p-AMPK were significantly increased [SOD (μmol/g): 39.76±1.35, 33.03±1.28 vs. 20.08±1.79, E-cadherin/GAPDH: 0.91±0.08, 0.72±0.08 vs. 0.26±0.04, p-AMPK/GAPDH: 0.62±0.04, 0.60±0.01 vs. 0.20±0.04, all P < 0.05]. However, these protective effects of MET were inhibited by the addition of AMPK inhibitor CC solution. CONCLUSIONS MET can effectively alleviate the degree of pulmonary fibrosis in mice poisoned with PQ, and its mechanism may be related to the activation of AMPK and inhibition of TGF-β₁/Smad3 signaling pathway, which can be inhibited by AMPK inhibitor CC.
Mice ; Male ; Animals ; Pulmonary Fibrosis/drug therapy* ; Paraquat ; AMP-Activated Protein Kinases/pharmacology* ; Metformin/pharmacology* ; Hydroxyproline/pharmacology* ; Saline Solution ; Mice, Inbred C57BL ; Lung/metabolism* ; Transforming Growth Factor beta1/pharmacology* ; Cadherins ; Superoxide Dismutase

Objective Cardiac arrest is a major problem that cannot be ignored both at home and abroad. So far, cardiac arrest survival rates are very low. Epinephrine has been used as a major cardiopulmonary resuscitation (CPR) drug for more than half a century, but there are still many controversies about it, such as increasing the risk of malignant arrhythmia, reducing the long-term survival rate and good prognosis rate of neurological function. The history, mechanism and research progress of epinephrine in CPR is reviewed to provide a more comprehensive understanding of epinephrine and new ideas about epinephrine reasonable usage.

Objective:To investigate the ocular clinical manifestations in pediatric patients with incontinentia pigmenti (IP).Methods:A case series study was carried out and a retrospective analysis was performed.Clinical data of 13 pediatric patients with IP treated from January 2013 to December 2019 in Xijing Hospital were collected.All the patients underwent regular ophthalmologic examination.Three patients accepted fundus fluorescein angiography and six eyes of five patients were treated with retinal photocoagulation or anti-vascular endothelial growth factor (VEGF) intravitreal injection according to severity of the condition.The follow-up period ranged from 6 months to 6 years.The medical history, family history, systemic manifestations, ocular characteristics, diagnosis, treatment as well as ocular and systemic changes during follow-up were recorded and analyzed.This study followed the Declaration of Helsinki and the study protocol was approved by the Ethics Committee of Xijing Hospital, Fourth Military Medical University (No.KY20203287-1).Results:All the 13 patients were female aged from 5 days to 42 months at first visit, with the average age of 2.0 (1.0, 8.5) months.As for the main skin lesions at first visit, there were 4 cases in erythematous vesicle stage, 3 cases in verrucous exanthema stage, and 6 cases in hyperpigmented stage.There were 7 cases in shrinkage stage during follow-up.Among the 26 eyes of 13 patients, 18 eyes of 10 patients showed ocular anomalies, accounting for 76.9% of total patients (69.2% of total eyes). Among the 13 patients, 8 patients presented bilateral ocular involvement, 2 patients showed unilateral anomalies, and 3 patients had no ocular lesions.The retina was involved in all patients with ocular manifestations.The typical retinal lesions included avascular zone of peripheral retina in 13 eyes, tortuous and dilated retinal vessels in 10 eyes, increased vascular branch in 7 eyes, white linear retinal arteries and partial vascular occlusion in 4 eyes, retinal neovascularization in 3 eyes, total retinal detachment in 2 eyes, and retinal fold with macular lamellar hole in 1 eye.In addition, there was retinal hemorrhage in 11 eyes, retinal pigment changes in 4 eyes, grey ridge lesions in 3 eyes, macular dysplasia in 2 eyes, choroidal atrophy in 1 eye, optic gliosis in 1 eye and yellowish-white retinal exudate in 1 eye.There were also 4 patients with other ocular manifestations, such as strabismus and eyeball atrophy.Retinal photocoagulation was performed in 4 eyes of 3 patients and anti-VEGF intravitreal injection in 2 eyes of 2 patients.The retinal lesions regressed and the condition of patients kept stable during follow-up.Conclusions:The ocular clinical manifestations in patients with IP are usually typical and diverse, and the retinal vascular lesion is the main type.Early diagnosis and timely treatment are of great significance.

Objective To investigate the protective effect of 5-aminosalicylic acid (5-ASA) on renal injury poisoned by paraquat (PQ) in rats and its mechanism. Methods Twenty-four healthy clean male Sprague-Dawley (SD) rats were randomly divided into four groups: normal saline (NS) control group, 5-ASA control group, PQ model group and 5-ASA treatment group, with 6 rats in each group. The rat model of PQ poisoning was reproduced by intraperitoneal injection of 2% PQ solution 20 mg/kg, and the same volume of NS was given in NS control group and 5-ASA control group. Two hours later, the rats in 5-ASA control group and 5-ASA treatment group were intragastrically administered with 1 mL 5-ASA (75 mg/kg) for one time after NS or PQ administration, and those in NS control group and PQ model group were administered with 1 mL double distilled water. Behavioral changes were observed in rats. Then the rats were sacrificed at 24 hours after starting of the experiment for cardiac blood harvest which could be used to detect the biomarkers of renal injury and oxidative stress parameters. The kidney tissue was collected, and the hematein-eosin (HE) staining was conducted for observation of pathological changes in renal tissue, and protein expressions of Nrf 2 and heme oxygenase-1 (HO-1) were determined by Western Blot. Results At 30 minutes after PQ poisoning, rats appeared obvious poisoning symptoms and signs. Twenty-four hours after PQ poisoned, hemocoel of glomerular capillary, swelling of renal tubular epithelial cell and serious micronecrosis appeared under the light microscope. Compared with NS control group, blood urea nitrogen (BUN), serum creatinine (SCr), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT) and glutathione (GSH) levels were significantly abnormal in PQ model group, and Nrf 2 and HO-1 protein expressions in renal tissue were increased. After administration of 5-ASA, the morphological changes and pathological damage were mitigated as compared with those of PQ model group, the levels of BUN, SCr and MDA were decreased significantly [BUN (mmol/L): 11.98±1.81 vs. 18.56±2.32, SCr (μmol/L): 30.67±2.31 vs. 43.67±9.02, MDA (μmol/L):5.28±0.43 vs. 6.81±1.00], and the SOD activity, CAT and GSH contents were significantly increased [SOD (kU/L):125.49±7.63 vs. 106.76±7.94, CAT (ng/L): 30.68±3.51 vs. 23.05±1.55, GSH (μmol/L): 3.81±0.44 vs. 3.14±0.17], while the protein expressions of Nrf 2 and HO-1 were further increased [Nrf 2 protein (gray value): 0.76±0.04 vs. 0.52±0.03, HO-1 protein (gray value): 0.56±0.02 vs. 0.31±0.02, all P < 0.05]. Only 5-ASA intervention had no significant effect on behavior, pathology, renal injury markers and oxidative stress parameters, but it could induce the expressions of Nrf 2 and HO-1 protein in renal tissue, which were significantly higher than those of NS control group [Nrf 2 protein (gray value): 0.78±0.02 vs. 0.41±0.04, HO-1 protein (gray value): 0.51±0.03 vs. 0.23±0.01, both P < 0.01]. Conclusion 5-ASA attenuates the damage of acute renal injury (AKI) caused by PQ, which mechanism may be related with the activation of Nrf 2-antioxidant response element (ARE) signaling pathway.