A national survey on current state and development needs of clinical and academic emergency medicine in China.

BACKGROUND: To characterize the current state of emergency medicine (EM) and the requirements for advancing EM clinical practice, education and research in China. METHODS: An anonymous electronic survey was conducted by Chinese Society of Emergency Medicine during September to October 2021. The survey contained 30 questions divided into 2 sections: the current state of EM development and the requirements for EM growth. RESULTS: 722 hospitals were included, of 487 were Level III and 235 were Level II hospitals. We found that after 40 years of development, EM had established a mature disciplinary system and refined sub-specialties including critical care, cardiopulmonary resuscitation, toxicology, disaster and emergency rescue. In Level III hospitals, 70.8% of EDs were standardized training centers for EM residents, but master's degree program, Doctor Degree program and post-doctoral degree program was approved in only 37.8%, 8.4% and 2.9% of EDs respectively and postgraduate curriculum was available in 1/4 of EDs. Only 8% have national or provincial key laboratories. In addition to advance clinical practice, there was also a high demand to improve teaching and research capacities, mainly focusing on literature review, research design and delivery, paper writing, residency training. CONCLUSIONS: EM has built a mature discipline system and refined sub-specialties in China. Teaching and research developed parallel with clinical practice. However, there was still a lack of EM master's and doctoral programs and research capacities need to be improved. More outstanding clinical and academic training should be provided to promote the rapid growth of EM in China.

Multicenter, randomized controlled, open label evaluation of the efficacy and safety of arbidol hydrochloride tablets in the treatment of influenza-like cases.

OBJECTIVE: To study the efficacy and safety of arbidol hydrochloride tablets as a treatment for influenza-like diseases. METHODS: In this multicenter, randomized, controlled, open label study, a total of 412 influenza-like cases were collected from 14 hospitals in seven regions of Hebei Province from September 2021 to March 2022. Patients were randomly divided into two groups. The control group (n = 207) were administered oseltamivir phosphate capsules for five days and the experimental group (n = 205) were administered arbidol hydrochloride tablets for five days. The primary endpoint was the time to normal body temperature, and the secondary endpoints included the time to remission of influenza symptoms, incidence of influenza-like complications, and incidence of adverse reactions. RESULTS: Before treatment, there was no significant difference between the two groups in general conditions, blood routine, body temperature, or symptom severity. After treatment, there was no significant difference between the groups in the mean time to fever remission (59.24 h ± 25.21 vs. 61.05 h ± 29.47) or the mean time to remission of influenza symptoms (57.31 h ± 30.19 vs. 62.02 h ± 32.08). Survival analyses using Log-rank and Wilcoxon bilateral tests showed that there was no significant difference in fever relief time or influenza symptom relief time between the two groups. Regarding the incidence of complications and adverse events, there was only one case of tracheitis, one case of nausea, one case of vomiting, and one case of dizziness in the control group. In the experimental group, there was one case of nausea, one case of vomiting, and one case of drowsiness. In addition, one patient in the control group was hospitalized for urinary calculi. CONCLUSION: There was no significant difference between the patients with influenza-like cases treated with arbidol hydrochloride tablets and those treated with oseltamivir phosphate capsules. Further, the patients treated with arbidol hydrochloride tablets had fewer adverse reactions, and thus, the tablets were safe to use.

XueBiJing Injection Versus Placebo for Critically Ill Patients With Severe Community-Acquired Pneumonia: A Randomized Controlled Trial.

OBJECTIVES: To investigate whether XueBiJing injection improves clinical outcomes in critically ill patients with severe community-acquired pneumonia. DESIGN: Prospective, randomized, controlled study. SETTING: Thirty-three hospitals in China. PATIENTS: A total of 710 adults 18-75 years old with severe community-acquired pneumonia. INTERVENTIONS: Participants in the XueBiJing group received XueBiJing, 100 mL, q12 hours, and the control group received a visually indistinguishable placebo. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 8-day improvement in the pneumonia severity index risk rating. Secondary outcomes were 28-day mortality rate, duration of mechanical ventilation and total duration of ICU stay. Improvement in the pneumonia severity index risk rating, from a previously defined endpoint, occurred in 203 (60.78%) participants receiving XueBiJing and in 158 (46.33%) participants receiving placebo (between-group difference [95% CI], 14.4% [6.9-21.8%]; p < 0.001). Fifty-three (15.87%) XueBiJing recipients and 84 (24.63%) placebo recipients (8.8% [2.4-15.2%]; p = 0.006) died within 28 days. XueBiJing administration also decreased the mechanical ventilation time and the total ICU stay duration. The median mechanical ventilation time was 11.0 versus 16.5 days for the XueBiJing and placebo groups, respectively (p = 0.012). The total duration of ICU stay was 12 days for XueBiJing recipients versus 16 days for placebo recipients (p = 0.004). A total of 256 patients experienced adverse events (119 [35.63%] vs 137 [40.18%] in the XueBiJing and placebo groups, respectively [p = 0.235]). CONCLUSIONS: In critically ill patients with severe community-acquired pneumonia, XueBiJing injection led to a statistically significant improvement in the primary endpoint of the pneumonia severity index as well a significant improvement in the secondary clinical outcomes of mortality, duration of mechanical ventilation and duration of ICU stay.

The efficacy of initial ventilation strategy for adult immunocompromised patients with severe acute hypoxemic respiratory failure: study protocol for a multicentre randomized controlled trial (VENIM).

BACKGROUND: Acute respiratory failure (ARF) is still one of the most severe complications in immunocompromised patients. Our previous systematic review showed noninvasive mechanical ventilation (NIV) reduced mortality, length of hospitalization and ICU stay in AIDS/hematological malignancy patients with relatively less severe ARF, compared to invasive mechanical ventilation (IMV). However, this systematic review was based on 13 observational studies and the quality of evidence was low to moderate. The efficacy of NIV in more severe ARF and in patients with other causes of immunodeficiency is still unclear. We aim to determine the efficacy of the initial ventilation strategy in managing ARF in immunocompromised patients stratified by different disease severity and causes of immunodeficiency, and explore predictors for failure of NIV. METHODS AND ANALYSIS: The VENIM is a multicentre randomized controlled trial (RCT) comparing the effects of NIV compared with IMV in adult immunocompromised patients with severe hypoxemic ARF. Patients who meet the indications for both forms of ventilatory support will be included. Primary outcome will be 30-day all-cause mortality. Secondary outcomes will include in-hospital mortality, length of stay in hospital, improvement of oxygenation, nosocomial infections, seven-day organ failure, adverse events of intervention, et al. Subgroups with different disease severity and causes of immunodeficiency will also be analyzed. DISCUSSION: VENIM is the first randomized controlled trial aiming at assessing the efficacy of initial ventilation strategy in treating moderate and severe acute respiratory failure in immunocompromised patients. The result of this RCT may help doctors with their ventilation decisions. TRIAL REGISTRATION: ClinicalTrials.gov NCT02983851 . Registered 2 September 2016.

[The expressions of P38 mitogen-activated protein kinases and JNK mitogen-activated protein kinases in the renal tissue of rats with acute paraquat poisoning and the therapeutical effects of melatonin].

OBJECTIVE: To investigate the expressions of P38 mitogen-activated protein kinases (P38 MAPK), JNK mitogen-activated protein kinases (JNK MAPK) and the therapeutical effects of melatonin in the renal tissue of acute acuteparaquat-induced rats. METHODS: Seventy-eight healthy adult Sprague-Dawley (SD) rats (39 male, 39 female) were randomly divided into three groups: (1) Control group (group A): 6 rats, (2) Poisoned group (group B): 36 rats, (3) Therapeutical group (group C): 36 rats. At 1, 3, 5, 7, 10 and 14 days after poisoning, six rats in Group B and group C were used to assess renal pathological changes and the expression of P38 MAPK, JNK MAPK in kidney were evaluated by immunohistochemistry. RESULTS: Compared with control group, the expression of P38MAPK in renal tissue of poisoned group significantly rose at the first day, reached the peak at the 10th day and afterwards decreased slowly. Expression of JNK MAPK reached the peak at the first day, and kept at relatively high levels up to the 14th day. Melatonin weakened markedly the expressions of P38 MAPK and JNK MAPK in renal tissue of acute acuteparaquat-induced rats. CONCLUSION: P38 MAPK and JNK MAPK play an important role in renal injury of acute paraquat -poisoning rats. Melatonin takes a significant effect on the activation of them.

[Effects of acetamide at different doses on expression of amino acids in cerebral cortex of rats with acute tetramine poisoning].

OBJECTIVE: To investigate the effects of acetamide at different doses on the expression of inhibitory amino acids (gamma-aminobutyric acid, GABA) and excitatory amino acid (glutamate, Glu) in the cerebral cortex of rats with acute tetramine (TET) poisoning. METHODS: Eighty Sprague-Dawley rats (SPF) were randomly divided into five groups, with 16 rats in each group: saline control group, dimethyl sulfoxide (DMSO) control group, TET exposure group, high-dose (2.8 g/kg/d) acetamide treatment group, and super-high-dose (5.6 g/kg/d) acetamide treatment group. Rats in the exposure group and treatment groups were exposed to TET by intragastric administration after fasting, and were then intramuscularly injected with saline or different doses of acetamide in the following 5 days. The cortex of the temporal lobe was collected at 3 h, 12 h, 48 h, or 7 d after treatment. The expression levels of GABA and Glu in the cortex of the temporal lobe were determined by average optical density (OD) values in immunohistochemistry. RESULTS: 1) Expression of GABA: The OD value of GABA in TET exposure group started to increase at 12 h after treatment, reached the peak at 48 h, and decreased to the normal level at 7 d. In the high-dose acetamide treatment group, the increase in OD at 12 h was not so significant as that in the TET exposure group, OD value decreased to the normal level at 48 h and was lower than that in the exposure group, and the changes were more like those in the control groups. In the super-high-dose acetamide treatment group, OD value began to increase significantly at 3 h and was significantly higher than that in the TET exposure group (P < 0.01), it reached the peak at 12 h, and was restored to the normal value at 48 h. 2) Expression of Glu: The OD value of Glu in TET exposure group at 3 h after treatment was significantly lower than those in the two control groups, it increased gradually from 12 h to 48 h, and recovered to the normal level at the 7th d. The changes in the high-dose acetamide treatment group were similar to those in the TET exposure group, but became more like those in the control groups after 48 h; the OD value in super-high-dose acetamide treatment group was significantly higher than that in the TET exposure group at 3 h after treatment (P < 0.01), while no significant difference was found at 12 h; it was significantly lower than those of all other groups at 48 h and 7 d (P < 0.01). CONCLUSIONS: Treatment with high dose of acetamide has some curative effect on TET poisoning-induced central nervous lesion, while the effect of super-high-dose acetamide on expression of neurotransmitters is too complex to evaluate.

[Effect of acetamide on histopathology in cerebral cortex of rats with tetramine poisoning].

OBJECTIVE: To observe the effect of different doses of acetamide on the histopathology in the cerebral cortex of rats with tetramine (TET) poisoning and to provide a basis for the treatment of fluoroacetamide poisoning with acetamide. METHODS: Eighty clean Sprague-Dawley rats were randomly divided into five groups: saline control group,dimethylsulfoxide water solution control group,TET poisoning group, acetamide (2.88 g/kg/d) treatment group, and acetamide (5.68 g/kg/d) treatment group, with 16 rats in each group. Rats in the poisoning group and treatment groups were poisoned with TET by intragastric administration after fasting; then, saline was injected intramuscularly into rats of the poisoning group, and different doses of acetamide were injected intramuscularly into rats of treatment groups; the course of treatment was 5 d. At 3 h, 12 h, 48 h, and 7 d after treatment, the cerebral cortex was harvested from rats in each group, and the histopathological changes in the cerebral cortex were evaluated under light and electron microscopes. RESULTS: The light microscopy showed that the TET poisoning group had hypoxia changes in the cerebral cortex, which worsened over time; the treatment groups had reduced hypoxia changes, and the acetamide (2.88 g/kg/d) treatment group had more reduction than the acetamide (5.68 g/kg/d) treatment group. The electron microscopy showed that the apoptosis of neuronal cells were the main pathological changes in the TET poisoning group; the treatment groups had reduced apoptotic changes, and the acetamide (2.88 g/kg/d) treatment group had more reduction than the acetamide (5.68 g/kg/d) treatment group. CONCLUSION: No pathological changes associated with the synergistic toxic effect of acetamide and TET are found in the cerebral cortex. Acetamide (2.88 g/kg/d) could reduce central nervous lesions, but the efficacy is not improved after increasing the dose. For patients who cannot be identified with TET or fluoroacetamide poisoning, acetamide could be considered for treatment.

Analysis of the fatigue status of medical security personnel during the closed-loop period using multiple machine learning methods: a case study of the Beijing 2022 Olympic Winter Games.

Using machine learning methods to analyze the fatigue status of medical security personnel and the factors influencing fatigue (such as BMI, gender, and wearing protective clothing working hours), with the goal of identifying the key factors contributing to fatigue. By validating the predicted outcomes, actionable and practical recommendations can be offered to enhance fatigue status, such as reducing wearing protective clothing working hours. A questionnaire was designed to assess the fatigue status of medical security personnel during the closed-loop period, aiming to capture information on fatigue experienced during work and disease recovery. The collected data was then preprocessed and used to determine the structural parameters for each machine learning algorithm. To evaluate the prediction performance of different models, the mean relative error (MRE) and goodness of fit (R2) between the true and predicted values were calculated. Furthermore, the importance rankings of various parameters in relation to fatigue status were determined using the RF feature importance analysis method. The fatigue status of medical security personnel during the closed-loop period was analyzed using multiple machine learning methods. The prediction performance of these methods was ranked from highest to lowest as follows: Gradient Boosting Regression (GBM) > Random Forest (RF) > Adaptive Boosting (AdaBoost) > K-Nearest Neighbors (KNN) > Support Vector Regression (SVR). Among these algorithms, four out of the five achieved good prediction results, with the GBM method performing the best. The five most critical parameters influencing fatigue status were identified as working hours in protective clothing, a customized symptom and disease score (CSDS), physical exercise, body mass index (BMI), and age, all of which had importance scores exceeding 0.06. Notably, working hours in protective clothing obtained the highest importance score of 0.54, making it the most critical factor impacting fatigue status. Fatigue is a prevalent and pressing issue among medical security personnel operating in closed-loop environments. In our investigation, we observed that the GBM method exhibited superior predictive performance in determining the fatigue status of medical security personnel during the closed-loop period, surpassing other machine learning techniques. Notably, our analysis identified several critical factors influencing the fatigue status of medical security personnel, including the duration of working hours in protective clothing, CSDS, and engagement in physical exercise. These findings shed light on the multifaceted nature of fatigue among healthcare workers and emphasize the importance of considering various contributing factors. To effectively alleviate fatigue, prudent management of working hours for security personnel, along with minimizing the duration of wearing protective clothing, proves to be promising strategies. Furthermore, promoting regular physical exercise among medical security personnel can significantly impact fatigue reduction. Additionally, the exploration of medication interventions and the adoption of innovative protective clothing options present potential avenues for mitigating fatigue. The insights derived from this study offer valuable guidance to management personnel involved in organizing large-scale events, enabling them to make informed decisions and implement targeted interventions to address fatigue among medical security personnel. In our upcoming research, we will further expand the fatigue dataset while considering higher precisionprediction algorithms, such as XGBoost model, ensemble model, etc., and explore their potential contributions to our research.

[Mechanism of intestinal injury induced by acute diquat poisoning in rats].

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/ß-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/ß-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/ß-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/ß-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. CONCLUSIONS: 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.

Ferritinophagy: A novel insight into the double-edged sword in ferritinophagy-ferroptosis axis and human diseases.

Nuclear receptor coactive 4 (NCOA4), which functions as a selective cargo receptor, is a critical regulator of the particularly autophagic degradation of ferritin, a process known as ferritinophagy. Mechanistically, NCOA4-mediated ferritinophagy performs an increasingly vital role in the maintenance of intracellular iron homeostasis by promoting ferritin transport and iron release as needed. Ferritinophagy is not only involved in iron-dependent responses but also in the pathogenesis and progression of various human diseases, including metabolism-related, neurodegenerative, cardiovascular and infectious diseases. Therefore, ferritinophagy is of great importance in maintaining cell viability and function and represents a potential therapeutic target. Recent studies indicated that ferritinophagy regulates the signalling pathway associated with ferroptosis, a newly discovered type of cell death characterised by iron-dependent lipid peroxidation. Although accumulating evidence clearly demonstrates the importance of the interplay between dysfunction in iron metabolism and ferroptosis, a deeper understanding of the double-edged sword effect of ferritinophagy in ferroptosis has remained elusive. Details of the mechanisms underlying the ferritinophagy-ferroptosis axis in regulating relevant human diseases remain to be elucidated. In this review, we discuss the latest research findings regarding the mechanisms that regulate the biological function of NCOA4-mediated ferritinophagy and its contribution to the pathophysiology of ferroptosis. The important role of the ferritinophagy-ferroptosis axis in human diseases will be discussed in detail, highlighting the great potential of targeting ferritinophagy in the treatment of diseases.

Identification and validation of lipid metabolism-related key genes as novel biomarkers in acute myocardial infarction and pan-cancer analysis.

BACKGROUND: Acute myocardial infarction (AMI) is associated with high morbidity and mortality, and is associated with abnormal lipid metabolism. We identified lipid metabolism related genes as biomarkers of AMI, and explored their mechanisms of action. METHODS: Microarray datasets were downloaded from the GEO database and lipid metabolism related genes were obtained from Molecular Signatures Database. WGCNA was performed to identify key genes. We evaluated differential expression and performed ROC and ELISA analyses. We also explored the mechanism of AMI mediated by key genes using gene enrichment analysis. Finally, immune infiltration and pan-cancer analyses were performed for the identified key genes. RESULTS: TRL2, S100A9, and HCK were identified as key genes related to lipid metabolism in AMI. Internal and external validation (including ELISA) showed that these were good biomarkers of AMI. In addition, the results of gene enrichment analysis showed that the key genes were enriched in inflammatory response, immune system process, and tumor-related pathways. Finally, the results of immune infiltration showed that key genes were concentrated in neutrophils and macrophages, and pan-cancer analysis showed that the key genes were highly expressed in most tumors and were associated with poor prognosis. CONCLUSIONS: TLR2, S100A9, and HCK were identified as lipid metabolism related novel diagnostic biomarkers of AMI. In addition, AMI and tumors may be related through the inflammatory immune response.

Prognostic value of plasma diquat concentration in patients with acute oral diquat poisoning: a retrospective study.

Objectives: Diquat poisoning is an important public health and social security agency. This study aimed to develop a prognostic model and evaluate the prognostic value of plasma diquat concentration in patients with acute oral diquat poisoning, focusing on how its impact changes over time after poisoning. Methods: This was a retrospective cohort study using electronic healthcare reports from the Second Hospital of Hebei Medical University. The study sample included 80 patients with acute oral Diquat poisoning who were admitted to the hospital between January 2019 and May 2022. Time-to-event analyses were performed to assess the risk of all-cause mortality (30 days and 90 days), controlling for demographics, comorbidities, vital signs, and other laboratory measurements. The prognostic value of plasma DQ concentration on admission was assessed by computing the area under a time-dependent receiver operating characteristic curve (ROC). Results: Among the 80 patients, 29 (36.25%) patients died, and 51 (63.75%) patients survived in the hospital. Non-survivors had a median survival time (IQR) of 1.3(1.0) days and the longest survival time of 4.5 days after DQ poisoning. Compared with non-survivors, survivors had significantly lower amounts of ingestion, plasma DQ concentration on admission, lungs injury within 24 h after admission, liver injury within 24 h after admission, kidney injury within 24 h after admission, and CNS injury within 36 h after admission, higher APACHE II score and PSS within 24 h after admission (all p < 0.05). Plasma Diquat concentration at admission (HR = Exp (0.032-0.059 × ln (t))) and PSS within 24 h after admission (HR: 4.470, 95%CI: 1.604 ~ 12.452, p = 0.004) were independent prognostic factors in the time-dependent Cox regression model. Conclusion: Plasma DQ concentration at admission and PSS within 24 h after admission are independent prognostic factors for the in-hospital case fatality rate in patients with acute oral DQ poisoning. The prognostic value of plasma DQ concentration decreased with time.

The crosstalk between mitochondrial quality control and metal-dependent cell death.

Mitochondria are the centers of energy and material metabolism, and they also serve as the storage and dispatch hubs of metal ions. Damage to mitochondrial structure and function can cause abnormal levels and distribution of metal ions, leading to cell dysfunction and even death. For a long time, mitochondrial quality control pathways such as mitochondrial dynamics and mitophagy have been considered to inhibit metal-induced cell death. However, with the discovery of new metal-dependent cell death including ferroptosis and cuproptosis, increasing evidence shows that there is a complex relationship between mitochondrial quality control and metal-dependent cell death. This article reviews the latest research results and mechanisms of crosstalk between mitochondrial quality control and metal-dependent cell death in recent years, as well as their involvement in neurodegenerative diseases, tumors and other diseases, in order to provide new ideas for the research and treatment of related diseases.

Food-Borne Poisoning Accident from Amanitin Toxin in Wild Mushrooms - Xingtai City, Hebei Province, China, 2023.

What is already known about this topic?: Fatal poisonings caused by wild mushrooms containing amanita toxins pose a significant threat in the southern regions of China. These toxins primarily induce gastrointestinal symptoms initially, which are then followed by potentially life-threatening acute liver damage. What is added by this report?: This report contributes to the existing knowledge on these cases of poisoning by documenting the second occurrences in Hebei Province and the first occurrences in Xingtai City. Five individuals reported consuming wild mushrooms from the same origin, and laboratory tests confirmed the presence of α-amanitin in their blood samples. What are the implications for public health practice?: This underscores the risk associated with the collection and consumption of amanita toxin-containing mushrooms in Hebei. It is important to note that the identification of toxic and non-toxic mushrooms should not solely rely on personal experience or appearance.

[Experimental study on the toxicokinetics and gastrointestinal damage in rats poisoned with acute diquat poisoning at different exposure doses].

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.

A simple and sensitive LC-MS/MS method for therapeutic drug monitoring of digoxin in children.

This short communication introduced a simple and sensitive LC-MS/MS method for therapeutic drug monitoring of digoxin in children with the lower limit of quantitation of 0.2 ng/mL based on 30 µL of plasma. The plasma sample was pretreated by one-step protein precipitation. Then the chromatographic separation was performed on a short C-18 column with a total run time of 2.4 min. The detection was achieved through multiple reaction monitoring using positive ionization mode on a triple quadrupole mass spectrometer. The linear range of digoxin in human plasma was among 0.2-6.4 ng/mL. The intra-day and inter-day accuracies of digoxin ranged from -6.0 % to 10.1 % and imprecisions were less than 8.8 %. The extraction recovery rate of digoxin in plasma samples was above 90 %. Matrix factor normalized by internal standard was within acceptance criteria. This method was fully verified and applied to determine the plasma digoxin concentrations of 43 pediatric patients. It is approved appropriate and practical for the therapeutic drug monitoring of digoxin in routine clinical laboratory practice, especially for children.

Anisodamine hydrobromide in the treatment of critically ill patients with septic shock: a multicenter randomized controlled trial.

BACKGROUND: Septic shock is the development of sepsis to refractory circulatory collapse and metabolic derangements, characterized by persistent hypotension and increased lactate levels. Anisodamine hydrobromide (Ani HBr) is a Chinese medicine used to improve blood flow in circulatory disorders. The purpose of this study was to determine the therapeutic efficacy of Ani HBr in the treatment of patients with septic shock. METHODS: This was a prospective, multicenter, randomized controlled trial focusing on patients with septic shock in 16 hospitals in China. Patients were randomly assigned in a 1:1 ratio to either the treatment group or the control group. The primary endpoint was 28-day mortality. The secondary outcomes included 7-day mortality, hospital mortality, hospital length of stay, vasopressor-free days within 7 days, etc. These indicators were measured and collected at 0, 6h, 24h, 48h, 72h and 7d after the diagnosis. RESULTS: Between September 2017 and March 2021, 404 subjects were enrolled. 203 subjects received Ani HBr and 201 subjects were assigned to the control group. The treated group showed lower 28-day mortality than the control group. Stratified analysis further showed significant differences in 28-day mortality between the two groups for patients with a high level of illness severity. We also observed significant differences in 7-day mortality, hospital mortality and some other clinical indicators between the two groups. CONCLUSION: Ani HBr might be an important adjuvant to conventional treatment to reduce 28-day mortality in patients with septic shock. A large-scale prospective randomized multicenter trial is warranted to confirm our results.

Additional predictive value of serum potassium to Thrombolysis In Myocardial Infarction risk score for early malignant ventricular arrhythmias in patients with acute myocardial infarction.

OBJECTIVE: The aim of this study was to evaluate the additional predictive value of serum potassium (SK) to Thrombolysis In Myocardial Infarction (TIMI) risk score for malignant ventricular arrhythmias (MVA) in patients within 24 hours of acute myocardial infarction (AMI). METHODS: This was a 6-year retrospective study. The receiver operating characteristic curve was used to evaluate the predictive value of SK and TIMI risk score for MVA attack. In addition, SK-modified TIMI risk score was created by incorporating SK information into the usual score; the accuracy of new score was compared with that of the usual TIMI risk score by comparing the area under the receiver operating characteristic curves (AUC). RESULTS: Among the 468 patients enrolled, the incidence of MVA 24 hours after AMI was 9.4%, and it was higher in the hypokalemia group compared with that of the normokalemic group (27.3% vs 7.5%, P < .001; odds ratio, 4.594; 95% confidence interval [CI], 2.159-9.774). A significant predictive value of SK was indicated by AUC of 0.787 (95% CI, 0.747-0.823, P < .01). Serum potassium remained a predictor of MVA after being adjusted by the variables in TIMI risk score. The AUC of TIMI risk score in relation to MVA was 0.586 (95% CI, 0.54-0.631; P = .0676). The incorporation of SK into TIMI risk score improved its predictive value for MVA attack (AUC = 0.66; 95% CI, 0.568-0.753; P < .001), with significant difference between AUC of the new score and that of the original risk score (Z = 2.474, P = .013). CONCLUSIONS: Serum potassium on admission to the emergency department may be used as a valuable predictor and could add predictive information to some extent to TIMI risk score for MVA attack during 24-hour post-AMI.

[Study the effects of Salvia miltiorrhiza monomer IH764-3 on the expression of matrix metalloproteinase in lungs of rats exposed to Paraquat (PQ)].

OBJECTIVE: To observe the expression of the matrix metalloproteinase 2 (MMP-2) and membrane-type 1 metalloproteinase (MT1-MMP) in lung of rats exposed to paraquat (PQ) and the effects of Salvia miltiorrhiza monomer IH764-3 on above expression. METHODS: Ninety adult healthy Sprague-Dawley (SD) rats were randomly divided into the control group (group A, 6 rats), the exposure group (group B, 42 rats) and the group treated by Salvia miltiorrhiza monomer IH764-3 (group C, 42 rats). The group B and C were treated intragastrically with 1ml of PQ (50 mg/kg), and the group A was treated intragastrically with normal saline. The group C was treated intraperitoneally with 1 ml Salvia miltiorrhiza monomer IH764-3 at the dose of 40 mg/kg a day. The group A and B were treated intraperitoneally with 1 ml normal saline day. The expression of MMP-2 and MT1-MMP was detected on the 1st, 3rd, 7th, 14th, 21st, 28th and 35th days after exposure for all groups. RESULTS: As compared with the expression level (0.305 ± 0.045) of MMP-2 mRNA in group A, the expression levels of MMP-2 mRNA in Group B significantly increased, which were 0.654 ± 0.077, 0.623 ± 0.051, 0.637 ± 0.024, 0.533 ± 0.043 and 0.552 ± 0.050 on the 1st, 3rd, 7th, 14th, 21st days after exposure, respectively (P < 0.01). As compared with group A, the the expression levels of MMP-2 mRNA on the 1st, 3rd, 7th days in Group C slightly increased, but the expression levels of MMP-2 mRNA on the 1st, 3rd, 7th, 14th, 21st days in Group C were 0.523 ± 0.074, 0.567 ± 0.097, 0.514 ± 0.058, 0.359 ± 0.018 and 0.374 ± 0.020, respectively, which were significantly lower than those in group B (P < 0.01). As compared with the expression level (0.391 ± 0.058) of MT1-MMP mRNA in group A, the expression levels of MT1-MMP mRNA in Group B significantly increased, which were 0.796 ± 0.021, 0.762 ± 0.043, 0.590 ± 0.010, 0.803 ± 0.076 and 0.680 ± 0.034 on the 1st, 3rd, 7th, 14th and 21st days after exposure, respectively (P < 0.01). As compared with group A, the expression levels of MT1-MMP mRNA in Group C significantly increased, which were 0.594 ± 0.010, 0.653 ± 0.044 and 0.564 ± 0.009 on the 1st, 3rd and 21st days after exposure, respectively (P < 0.01). The expression levels of MT1-MMP mRNA in Group C were significantly lower than those in group B (P < 0.05 or P < 0.01). CONCLUSION: The expression changes of MMP-2 and MT1-MMP genes of lungs in rats intragastrically exposed to PQ could result in the unbalance the synthesis and degradation of ECM, which may be a cause of lung fibrosis. The Salvia miltiorrhiza monomer IH764-3 could affect the expression of MMP-2 and MT1-MMP genes to a certain extent, resulting in the reduction of lung fibrosis.