Objective:To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years.Methods:An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster.Results:The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A′s 44.79 (36.94-54.30) ( P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A′s 15.71 (13.24-18.63) ( P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion:Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).

Objective:To investigate the effects of diquat (DQ) on the expression of intestinal pyroptosis-related proteins and tight junction proteins in rats, and to analyze the role of pyroptosis in the intestinal injury of rats with acute DQ poisoning.Methods:A total of 36 Wistar male rats were randomly divided into control group, and 3 hours, 12 hours, 36 hours and 3 days exposure groups, with 6 rats in each group. Each exposure group was given 1/2 median lethal dose (LD50) of 115.5 mg/kg DQ by one-time gavage. The control group was given the same amount of normal saline by gavage. The control group was anesthetized at 3 hours after DQ gavage to take jejunal tissues; each exposure group was anesthetized at 3 hours, 12 hours, 36 hours, and 3 days after DQ gavage to take jejunal tissues, respectively. The general conditions of the rats were recorded. The pathological changes of jejunum tissue were observed by hematoxylin-eosin (HE) staining. The expression of intestinal pyroptosis-related proteins [NOD-like receptor protein 3 (NLRP3), cysteine aspartate-specific protease 1 (caspase-1), Gasdemin D (GSDMD)] in the intestinal tissues was observed by immunohistochemical staining. Western blotting was used to detect the expression of intestinal pyroptosis-related proteins and intestinal tight junction proteins (Occludin and Claudin-1).Results:Light microscopy showed that pathological changes occurred in jejunum tissue at the early stage of exposure (3 hours), and the injury was the most serious in the 12 hours exposure group, with a large number of inflammatory cells infiltrating in the tissue, and the damage was significantly reduced after 3 days exposure. Immunohistochemical results showed that NLRP3, caspase-1 and GSDMD were expressed in the jejunal mucosa of the control group and the exposure groups, and the positive cells in the control group were less expressed with light staining. The expression of the above proteins in the exposed group was increased significantly and the staining was deep. Western blotting results showed that compared with the control group, the expression of NLRP3 protein in jejunum tissues of all groups was increased, with the most significant increase in the 36 hours group (NLRP3/β-actin: 1.47±0.06 vs. 0.43±0.14, P < 0.01). Compared with the control group, the expression of GSDMD protein in the 3 hours, 12 hours and 36 hours exposure groups increased, and the expression of GSDMD protein in the 3 hours and 12 hours exposure groups increased significantly (GSDMD/β-actin: 1.04±0.40, 1.25±0.15 vs. 0.65±0.25, both P < 0.05). The expression of caspase-1 protein was increased in 36 hours exposure group compared with the control group (caspase-1/β-actin: 1.44±0.34 vs. 0.98±0.19, P > 0.05). Compared with the control group, the expression of Occludin and Claudin-1 proteins in each exposure group decreased, and the expression of Occludin proteins was significantly decreased in the 3 hours, 12 hours, and 36 hours exposure groups decreased significantly (Occludin/β-actin: 0.74±0.17, 0.91±0.20, 0.79±0.23 vs. 1.41±0.08, all P < 0.05). Although the protein expression of Claudin-1 decreased in each exposure group, the difference was not statistically significant. Conclusion:The intestinal injury caused by acute DQ poisoning may be related to the activation of pyroptosis pathway of small intestinal cells and the reduction of the density of intercellular junctions.

Chlorfenapyr,an emerging synthetic pesticide,has been linked to a growing number of poisoning incidents,attributed to heightened human exposure as its application becomes more widespread.However,the toxicokinetics and toxicology of chlorfenapyr remain incompletely understood.Research since the 1990s,including animal experiments,has illuminated the absorption,distribution,excretion,and metabolism of chlorfenapyr.Toxicological investigations have revealed that the primary toxicity of chlorfenapyr is the uncoupling of oxidative phosphorylation.Chlorfenapyr exposure in humans and other animals can lead to various toxic effects,including neurotoxicity,cardiotoxicity,skeletal muscle toxicity,genotoxicity,reproductive and developmental toxicity,renal toxicity,splenic toxicity,and hematotoxicity.This article presents a comprehensive review of the toxicokinetics and toxicology of chlorfenapyr,integrating data from animal experiments,human cell line studies,clinical reports,and human autopsy.Its objective is to raise clinical awareness regarding chlorfenapyr poisoning and offer valuable references for its treatment and management.

Objective To evaluate the feasibility of emergency percutaneous coronary intervention(PCI)with extracorporeal membrane oxygenation(ECMO)support in critically ill patients with acute myocardial infarction(AMI)and cardiogenic shock(CS).Methods Retrospective analysis of clinical data of AMI combined with CS patients admitted to the department of emergency of the Second Hospital of Hebei Medical University from December 2018 to December 2021,including gender,age,body mass index(BMI),past history(smoking,coronary heart disease,arrhythmia,diabetes,hypertension,hyperlipidemia,cerebrovascular disease);acute physiology and chronic health evaluation Ⅱ(APACHEⅡ)score,highest vasoactive-inotropic score(VIS)within 24 hours of admission,the worst auxiliary examination values within 24 hours after admission:blood lactic acid(Lac),arterial partial pressure of oxygen(PaO2),cardiac troponin I(cTnI),alanine aminotransferase(ALT),total bilirubin(TBil),creatinine(Cr),serum potassium,left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF)],presence of malignant arrhythmia or cardiac arrest during emergency PCI,completion of PCI,and the 30-day prognosis,etc.Patients were divided into an ECMO group and a non-ECMO group based on whether ECMO was applied,to analyze differences in the above indicators between the two groups.Results There were no statistically significant differences between the ECMO group and the non-ECMO group in terms of gender,age,BMI,past history,APACHEⅡ,VIS and the worst auxiliary examination value within 24 hours after admission.The incidence of malignant arrhythmia or cardiac arrest events and 30-day mortality rate during emergency PCI in the ECMO group were significantly lower than those in the non-ECMO group[the incidence of malignant arrhythmia or cardiac arrest during emergency PCI was 17.9％(7/39)vs.45.0％(9/20),and the 30-day mortality was 46.2％(18/39)vs.75.0％(15/20),both P<0.05].The completion rate of PCI in the ECMO group was significantly higher than that in the non-ECMO group[100.0％(39/39)vs.80.0％(16/20),P<0.05].Conclusions For critically ill patients with AMI combined with CS,ECMO support can reduce the risk of malignant arrhythmia or cardiac arrest during emergency PCI,increase the completion rate of PCI,and reduce the 30-day mortality.With the support of the ECMO team,ECMO support emergency PCI is feasible.

OBJECTIVE: To observe the toxicokinetic parameters, absorption characteristics and pathomorphological damage in different parts of the gastrointestinal tract of rats poisoned with different doses of diquat (DQ). METHODS: Ninety-six healthy male Wistar rats were randomly divided into a control group (six rats) and low (115.5 mg/kg), medium (231.0 mg/kg) and high (346.5 mg/kg) dose DQ poisoning groups (thirty rats in each dose group), and then the poisoning groups were randomly divided into 5 subgroups according to the time after exposure (15 minutes and 1, 3, 12, 36 hours; six rats in each subgroup). All rats in the exposure groups were given a single dose of DQ by gavage. Rats in the control group was given the same amount of saline by gavage. The general condition of the rats was recorded. Blood was collected from the inner canthus of the eye at 3 time points in each subgroup, and rats were sacrificed after the third blood collection to obtain gastrointestinal specimens. DQ concentrations in plasma and tissues were determined by ultra-high performance liquid chromatography and mass spectrometry (UPHLC-MS), and the toxic concentration-time curves were plotted to calculate the toxicokinetic parameters; the morphological structure of the intestine was observed under light microscopy, and the villi height and crypt depth were determined and the ratio (V/C) was calculated. RESULTS: DQ was detected in the plasma of the rats in the low, medium and high dose groups 5 minutes after exposure. The time to maximum plasma concentration (Tmax) was (0.85±0.22), (0.75±0.25) and (0.25±0.00) hours, respectively. The trend of plasma DQ concentration over time was similar in the three dose groups, but the plasma DQ concentration increased again at 36 hours in the high dose group. In terms of DQ concentration in gastrointestinal tissues, the highest concentrations of DQ were found in the stomach and small intestine from 15 minutes to 1 hour and in the colon at 3 hours. By 36 hours after poisoning, the concentrations of DQ in all parts of the stomach and intestine in the low and medium dose groups had decreased to lower levels. Gastrointestinal tissue (except jejunum) DQ concentrations in the high dose group tended to increase from 12 hours. Higher doses of DQ were still detectable [gastric, duodenal, ileal and colonic DQ concentrations of 6 400.0 (1 232.5), 4 889.0 (6 070.5), 10 300.0 (3 565.0) and 1 835.0 (202.5) mg/kg respectively]. Light microscopic observation of morphological and histopathological changes in the intestine shows that acute damage to the stomach, duodenum and jejunum of rats was observed 15 minutes after each dose of DQ, pathological lesions were observed in the ileum and colon 1 hour after exposure, the most severe gastrointestinal injury occurred at 12 hours, significant reduction in villi height, significant increase in crypt depth and lowest V/C ratio in all segments of the small intestine, damage begins to diminish by 36-hour post-intoxication. At the same time, morphological and histopathological damage to the intestine of rats at all time points increased significantly with increasing doses of the toxin. CONCLUSIONS The absorption of DQ in the digestive tract is rapid, and all segments of the gastrointestinal tract may absorb DQ. The toxicokinetics of DQ-tainted rats at different times and doses have different characteristics. In terms of timing, gastrointestinal damage was seen at 15 minutes after DQ, and began to diminish at 36 hours. In terms of dose, Tmax was advanced with the increase of dose and the peak time was shorter. The damage to the digestive system of DQ is closely related to the dose and retention time of the poison exposure.
Animals ; Male ; Rats ; Diquat/toxicity* ; Gastrointestinal Diseases ; Intestines ; Poisons ; Rats, Wistar ; Toxicokinetics

Objective To analyze the prognosis and influencing factors of patients with acute myocardial infarction(AMI)complicated with cardiogenic shock(CS)under extracorporeal membrane oxygenation(ECMO)support.Methods Retrospective analysis of the clinical data of ECMO supported coronary angiography and percutaneous coronary intervention(PCI)treatment for AMI complicated with CS patients who visited the department of emergency medicine of the Second Hospital of Hebei Medical University from December 2018 to December 2021,including gender,age,body mass index(BMI),past history(smoking history,coronary heart disease,diabetes,hypertension,hyperlipidemia,cerebrovascular disease),acute physiological and chronic health evaluationⅡ(APACHEⅡ),vasoactive-inotropic score(VIS),the worst auxiliary examination indicators within 24 hours before ECMO[arterial lactate acid,white blood cell count(WBC),cardiac troponin I(cTnI),alanine transferase(ALT),total bilirubin(TBil),creatinine(Cr),serum potassium(K+),left ventricular ejection fraction(LVEF)],time from onset to PCI,coronary angiography results(involved anterior descending branch,circumflex branch,right coronary artery,three-vessel lesions,left main artery lesions),whether to use intra aortic-balloon counterpulsation(IABP)and continuous renal replacement therapy(CRRT).Patients were divided into survival and death groups based on the prognosis after 30 days of onset.Univariate analysis was used to compare the differences in the above indicators between the two groups with different prognoses,Logistic regression analysis was used to analyze the independent risk factors affecting the prognosis of AMI patients with CS under ECMO support coronary angiography and PCI treatment,and the receiver operator characteristic curve(ROC curve)was drawn to evaluate the predictive value of risk factors on patient prognosis.Results Out of 39 patients,21 cases(53.8%)survived and 18 cases(46.2%)died.Compared with the survival group,the VIS score,lactate acid,time from onset to PCI,involvement of the circumflex artery,three-vessel disease,and left main artery lesions significantly increased in the death group(all P＜0.05).Logistic regression analysis showed that lactate acid and three-vessel lesions were independent risk factors affecting the 30-day prognosis of AMI patients with CS[odds ratio(OR)and 95%confidence interval(95%CI)were 1.845(1.018-3.342)and 107.171(1.307-8 785.901),all P＜0.05].ROC curve analysis showed that lactate acid and three-vessel lesions has predictive value for the prognosis of AMI combined with CS patients undergoing ECMO supported coronary angiography and PCI treatment,the area under the ROC curve(AUC)were 0.756 and 0.752,95%CI were 0.601-0.911 and 0.588-0.916,P value were 0.007 and 0.008.When the cut-off value of lactic acid was 5 mmol/L,the sensitivity and specificity of predicting the prognosis of AMI combined with CS patients undergoing coronary angiography and PCI treatment were 94.1%and 57.1%,respectively.Conclusions The indications for using ECMO in critically ill patients with AMI combined with CS need to be further refined.VIS score,lactate acid,time from onset to PCI,three-vessel lesions,and left main artery lesions are risk factors for patient death.When using ECMO support for high lactate,high VIS score,and three-vessel lesions,caution should be exercised.Early ECMO support can improve the prognosis of appropriate patients by reducing lactate,reducing the use of vasoactive drugs,and shortening the time from onset to PCI.

Objective:To explore the clinical features of acute diquat (DQ) poisoning, and further improve the awareness of acute DQ poisoning.Methods:A retrospective analysis was performed on the clinical data of patients with acute DQ poisoning diagnosed in the emergency department of the Second Hospital of Hebei Medical University from January 1, 2019 to December 31, 2021. The clinical data included age, gender, exposure routes, presence of pesticides (drugs) mixture poisoning, dosage of poison, the time from taking poisoning to admitting in the emergency department, clinical manifestations, laboratory data, treatment, hospital days, prognosis and survival days.Results:The number of cases who firstly complained of acute DQ poisoning in the past three years were 19 cases in 2019, 28 cases in 2020, and 51 cases in 2021. A total of 12 patients were excluded due to being diagnosed paraquat (PQ) poisoning by toxicology detection. Finally, 86 cases of acute DQ poisoning were included, including 80 cases of oral DQ poisoning, 1 case of intramuscular injection, 1 case of binocular contact and 4 cases of dermal exposure. In 80 cases of oral DQ poisoning, there were 70 cases of diquat poisoning alone (42 cases survived, 28 cases died) and 10 cases of pesticide mixture poisoning (6 cases survived, 4 cases died). The time from oral poisoning to admitting in the emergency department was 0.5-96.0 hours, with an average of (8.6±5.8) hours. The time of intramuscular injection poisoning to admitting in the emergency department was 3 hours. The time of dermal exposure to admitting in the emergency department was relatively long, with an average of 66.1 hours. The time from oral simple DQ poisoning to death was 12.0-108.0 hours, and the time from oral mixed DQ poisoning to death was 24.0-576.0 hours. A total of 70 patients with oral diquat poisoning alone presented various degrees of multiple organ injuries. All patients presented gastrointestinal symptoms such as nausea and vomiting. Renal injury and central nervous system injury were the most significant and closely related to the prognosis.Conclusions:Acute oral DQ poisoning can cause to multiple organ injuries, and the clinical manifestations are related to the dose of the poison. In severe cases, acute renal failure and refractory circulatory failure occur within 24 hours after poisoning, and severe central nervous system injury with disturbance of consciousness as the primary manifestation occurs within 36 hours, followed by multiple organ failure until death.

Objective:To investigate the current situation of emergency medical service (EMS) system and its effect on treatment of the acute stage and short- and long-term prognosis in patients with acute myocardial infarction in Hebei province.Methods:Totally 2 961 patients with acute myocardial infarction who were admitted to major tertiary and some representative secondary hospitals in Hebei province from January 2016 to December 2016 were collected. According to the pattern of arriving hospital, all the patients were divided into the EMS group and self-transport group. The general conditions, time from onset to treatment, treatment methods, in-hospital mortality rate and 3-year mortality rate were compared between the two groups.Results:Of the included 2 961 patients, 33.13% of them were transported through EMS and 66.87% of them by private transport. Patients with a history of hypertension and ST-segment elevation myocardial infarction were more likely to choose EMS, and the difference was statistically significant ( P<0.05). Moreover, patients in the EMS group were more likely to go to tertiary hospitals for treatment (88.58% vs 85.76%, P=0.033). The time from onset to treatment of the EMS group was significantly shorter than that of the self-transport group (160 min vs 185 min, P<0.01), and the proportion of patients in the EMS group from onset-to-door time in <3 h and 3-6 h was higher than that of the self-transport group (55.76% vs 49.14%, 21.41% vs 19.09%, P<0.01). Compared with the self-transport group, the EMS group has a higher rate of reperfusion therapy (67.48% vs 61.67%, P=0.002). Patients in the EMS group had a higher in-hospital mortality rate in the acute stage (7.03% vs 4.44%, P=0.003), but its 3-year mortality rate was lower than that of the self-transport group (17.31% vs 20.77%, P<0.05). Conclusions:EMS can shorten symptom-onset-to-arrival time, increase the rate of reperfusion therapy and improve long-term prognosis of patients with acute myocardial infarction.

In order to improve the clinical attention to the poisoning of chlorfenapyr, the diagnosis and treatment strategy of chlorfenapyr poisoning were discussed. This paper collected 4 cases of chlorfenapyr in the emergency department of the Second Hospital of Hebei Medical University and 4 cases of literature review, summarized the clinical characteristics of pesticide poisoning cases containing chlorfenapyr in China, and summarized and analyzed the clinical data of the cases. Seven of the 8 patients died from poisoning by chlorfenapyr. Exposure to chlorfenapyr through respiratory tract and digestive tract showed high mortality. Fever, hyperhidrosis, elevated muscle enzymes and progressive central nerve damage were its prominent clinical characteristics. Most of the initial symptoms of exposure were not serious. Some patients, especially those with low exposure dose, had a relatively stable stage with or without clinical diagnosis and treatment. In case of sweating, obvious fever and disturbance of consciousness, the condition would deteriorate rapidly, respiratory and circulatory failure and eventually die. With the increase of production capacity and market launch, people have more opportunities to be exposed to chlorfenapyr. It is urgent to strengthen the basic and clinical research of chlorfenapyr poisoning; Attention should be paid to the observation and treatment in the initial stable stage of poisoning, which can be used as a reference for the treatment of oxidative phosphoric acid dissolving coupling agent (sodium pentachlorophenol) poisoning.

Objective:To explore the effect of risk assessment and follow-up management combined with early ultrasound intervention on reducing perioperative pressure ulcer in infants.Methods:A total of 469 perioperative infants and young children admitted to Children's Hospital Affiliated to Zhengzhou University from June 2019 to June 2020 were selected as the research subjects. They were divided into observation group ( n=243) and control group ( n=226) by random number table. Children in the control group were treated with routine care for preventing pressure ulcers. Children in the observation group were treated with risk assessment and follow-up management combined with ultrasound on the basis of the control group. The incidence of pressure ulcers was compared between the two groups at 3 and 7 days after surgery. Results:The incidence of pressure ulcers in the observation group was significantly lower than that of the control group at 3 days and 7 days after operation, and the difference was statistically significant ( P<0.05) . It could be seen that the severity of pressure injury in the observation group was lower than that in the control group. Conclusions:Risk assessment and follow-up management combined with ultrasound in early intervention can significantly reduce the risk of pressure ulcers in infants and young children during the perioperative period, which is worthy of promotion and application.