Objective To establish a dynamic prediction model of fatal massive hemorrhage in trauma based on the vital signs time series data and machine learning algorithms.Methods Retrospectively analyze the vital signs time series data of 7522 patients with trauma in the Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ)database from 2008 to 2019.According to the occurrence of posttraumatic fatal massive hemorrhage,the patients were divided into two groups:fatal massive hemorrhage group(n=283)and non-fatal massive hemorrhage group(n=7239).Six machine learning algorithms,including logistic regression(LR),support vector machine(SVM),random forests(RF),adaptive boosting(AdaBoost),gated recurrent unit(GRU),and GRU-D were used to develop a dynamic prediction models of fatal massive hemorrhage in trauma.The probability of fatal massive hemorrhage in the following 1,2,and 3 h was dynamically predicted.The performance of the models was evaluated by accuracy,sensitivity,specificity,positive predictive value,negative predictive value,Youden index,and area under receiver operating characteristic curve(AUC).The models were externally validated based on the trauma database of the Chinese PLA General Hospital.Results In the MIMIC-Ⅳ database,the set of dynamic prediction models based on the GRU-D algorithm was the best.The AUC for predicting fatal major bleeding in the next 1,2,and 3 h were 0.946±0.029,0.940±0.032,and 0.943±0.034,respectively,and there was no significant difference(P=0.905).In the trauma dataset,GRU-D model achieved the best external validation effect.The AUC for predicting fatal major bleeding in the next 1,2,and 3 h were 0.779±0.013,0.780±0.008,and 0.778±0.009,respectively,and there was no significant difference(P=0.181).This set of models was deployed in a public web calculator and hospital emergency department information system,which is convenient for the public and medical staff to use and validate the model.Conclusion A set of dynamic prediction models has been successfully developed and validated,which is greatly significant for the early diagnosis and dynamic prediction of fatal massive hemorrhage in trauma.

In this study,the immunological characteristics of the PhoP protein were explored with a two-component system of Mycobacterium tuberculosis(Mtb).Bioinformatics was used to predict the B and T cell epitopes of the PhoP protein.A re-combinant expression plasmid was constructed by PCR analysis of the phoP sequence and cloning into the prokaryotic expres-sion vector pET-28a(+).Competent Escherichia coli BL21 cells were transformed with the recombinant plasmid and expres-sion was induced with IPTG.The recombinant PhoP protein was purified by affinity chromatography.Serum levels of PhoP-specific antibodies in Mtb-infected mice and tuberculosis(TB)patients were analyzed with an ELISA.BALB/c mice were im-munized with the PhoP recombinant protein by intramuscular injection.Sera of mice were collected and antibody titers were detected with an ELISA and specificity was assessed by West-ern blot analysis.Mouse splenocytes were isolated and the pro-portions of IFN-y-positive cells and cytokine levels were detec-ted with an ELISpot and ELISA,respectively.Bioinformatics i-dentified 24 B cell and 11 T cell epitopes of the PhoP protein.A prokaryotic recombinant vector of PhoP was successfully con-structed and the recombinant PhoP protein was obtained by purification.Specific antibody levels to PhoP in sera of Mtb in-fected mice and TB patients increased significantly,with preci-sion of 99.9％and 82.5％,and specificity of 100％,respectively.PhoP protein immunization successfully induced production of specific antibodies in mice.Stimulated by antigens in vitro,IL-2 and IFN-γ levels were significantly increased in the splenocytes of immunized mice.Immunization with the PhoP protein induce a humoral immune response and Thl-dominated cellular immu-nity,indicating that the PhoP protein was immunogenic with diagnostic efficacy for TB.These results lay a foundation to clari-fy the role of PhoP in Mtb infection and application for diagnosis and prevention of TB.

This study investigated the effect of Suanzaoren Decoction on the expression of N-methyl-D-aspartate receptors(NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors(AMPAR) in the hippocampus and synaptic plasticity in rats with conditioned fear-induced anxiety. The effect of Suanzaoren Decoction on rat behaviors were evaluated through open field experiment, elevated plus maze experiment, and light/dark box experiment. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of glutamate(Glu) and γ-aminobutyric acid(GABA) in the rat hippocampus. Real-time fluorescence quantitative PCR(qRT-PCR) and Western blot were employed to assess the gene and protein expression of ionotropic glutamate receptors in the hippocampal region. Transmission electron microscopy was utilized to observe the changes in the ultrastructure of synaptic neurons in the hippocampal region. Long-term potentiation(LTP) detection technique was employed to record the changes in population spike(PS) amplitude in the hippocampal region of mice in each group. The behavioral results showed that compared with the model group, the Suanzaoren Decoction group effectively increased the number of entries into open arms, time spent in open arms, percentage of time spent in open arms out of total movement time, number of entries into open arms out of total entries into both arms(P<0.01), and significantly increased the time spent in the light box and the number of shuttle crossings(P<0.01). There was an increasing trend in the number of grid crossings, entries into the center grid, and time spent in the center grid, indicating a significant anxiolytic effect. ELISA results showed that compared with the model group, the Suanzaoren Decoction group exhibited significantly reduced levels of Glu, Glu/GABA ratio(P<0.01), and significantly increased levels of GABA(P<0.01) in the rat hippocampus. Furthermore, Suanzaoren Decoction significantly decreased the gene and protein expression of NMDAR(GluN2B and GluN2A) and AMPAR(GluA1 and GluA2) compared with the model group. Transmission electron microscopy results demonstrated improvements in synapses, neuronal cells, and organelles in the hippocampal region of the Suanzaoren Decoction group compared with the model group. LTP detection results showed a significant increase in the PS amplitude changes in the hippocampal region of Suanzaoren Decoction group from 5 to 35 min compared with the model group(P<0.05, P<0.01). In conclusion, Suanzaoren Decoction exhibits significant anxiolytic effects, which may be attributed to the reduction in NMDAR and AMPAR expression levels and the improvement of synaptic plasticity.
Rats ; Mice ; Animals ; Receptors, Ionotropic Glutamate/metabolism* ; Hippocampus ; Neuronal Plasticity ; Receptors, N-Methyl-D-Aspartate/genetics* ; Anxiety/genetics* ; gamma-Aminobutyric Acid

Methods The model of heart failure after myocardial infarction was established by left coronary artery liga-tion in rats. Two weeks after modeling, all rats were randomly divided into model group, LGZGD group, and captopril group. Meanwhile sham operation group was set up. The rats were given continuous intragastric administration with drug or distilled water for 28 days, once a day. The behavioral signs of rats in each group were observed. The cardiac function of rats in each group was examined by echocardiography. Serum BNP and NT-ProBNP content were detected by enzyme-linked immunoassay; The changes of myocardial his-topathological and collagen fibers in rats were detected using sirius staining. The contents of oxidative stress index including ROS, SOD in myocardial tissue of rats in each group were observed by DCFH-DA fluorescent probe and Enzyme-linked immunoassay. The ultra-structure of mitochondria was observed by transmission electron microscopy. Expressions of apoptotic proteins ( mitochondrial CytC, cytoplasmic CytC) were detec- ted by Western blot. Expression of proteins related to the Nrf2/BNIP3 pathway were examined by immunoflu-orescence and Western blot. Results LGZGD could significantly improve the cardiac function of rats, reduce the contents of BNP and NT-ProBNP, inhibit the excessive deposition of collagen in myocardial interstiti-um, reduce ROS, increase the content of SOD, improve mitochondrial structure damage, up-regulate the expression of Nrf2 and nuclear translocation, and reduce the expression of BNIP3. Conclusions LGZGD can inhibit the ventricular remodeling and prevent the occurrence of heart failure after myocardial infarction. Its pharmacological effects are mainly related to regulating the Nrf2/BNIP3 pathway, activating Nrf2, promoting its nuclear transfer, and further down-regulating BNIP3 , protecting mitochondrial function, and reducing cardiomyocyte apoptosis.

Aim To analyze the genotype-phenotype characteristics of voltage-gated potassium channels (Kv) associated genetic epilepsy and evaluate the efficacy of anti-seizure medications(ASMs). Methods PubMed database was searched and patients meeting the inclusion criteria were included for analysis. We divided the patients into “benign”, “encephalopathic” and other phenotypes according to the clinical characteristics. We performed descriptive statistical analysis of patients' mutated genes, clinical phenotype and drug efficacy, and used logistic regression to explore the influencing factors of treatment outcome. Results Data of 474 children were included for analysis. There were significant differences among different phenotypes in mutated genes, source of mutations and so on. In terms of clinical characteristics, there were also significant differences between patients with different phenotypes in age of onset, combined developmental delay and so on. In terms of monotherapy, phenobarbital was the most common treatment choice for children with “benign” phenotype, and sodium channel blockers (SCBs) were the most common treatment choice for children with “encephalopathy” phenotype, and the efficacy of SCBs monotherapy was superior to that of other ASMs. Multivariate Logistic analysis of the children receiving monotherapy showed that whether the children were combined with developmental delay and whether SCBs were used were significant factors influencing the efficacy of drug therapy. Conclusions Patients with the “benign” and “encephalopathic” phenotypes differ in several aspects of genetic variation, clinical characteristics, and drug selection. These results suggest that SCBs may be one of the recommended options for monotherapy.

Objective: To explore the value of catheter-based adrenal ablation in treating Cushing's syndrome (CS)-associated hypertension. Methods: A clinical study was conducted in patients with CS, who received catheter-based adrenal ablation between March 2018 and July 2023 in Daping Hospital. Parameters monitored were blood pressure (outpatient and 24-hour ambulatory), body weight, clinical characteristics, serum cortisol and adrenocorticotropic hormone (ACTH) at 8 am, 24-hour urinary free cortisol (24 h UFC), fasting blood glucose and postoperative complications. Procedure effectiveness was defined as blood pressure returning to normal levels (systolic blood pressure<140 mmHg (1 mmHg=0.133 kPa) and diastolic blood pressure<90 mmHg), cortisol and 24 h UFC returning to normal and improvement of clinical characteristics. The parameters were monitored during follow up in the outpatient department at 1, 3, 6, and 12 months after catheter-based adrenal ablation. Results: A total of 12 patients (aged (40.0±13.2) years) were reviewed. There were 5 males, with 5 cases of adenoma and 7 with hyperplasia from imaging studies. Catheter-based adrenal ablation was successful in all without interruption or surgical conversion. No postoperative complication including bleeding, puncture site infection, adrenal artery rupture or adrenal bleeding was observed. The mean follow up was 28 months. Compared to baseline values, body weight declined to (59.48±11.65) kg from (64.81±10.75) kg (P=0.008), fasting blood glucose declined to (4.54±0.83) mmol from (5.53±0.99) mmol (P=0.044), outpatient systolic blood pressure declined to (128±21) mmHg from (140±19) mmHg (P=0.005), diastolic blood pressure declined to (78±10) mmHg from (86±11) mmHg (P=0.041), and the mean ambulatory daytime diastolic blood pressure declined to (79±12) mmHg from (89±8) mmHg (P=0.034). Catheter-based adrenal ablation in 8 patients was defined as effective with their 24 h UFC significantly reduced after the procedure (1 338.41±448.06) mmol/L from (633.66±315.94) mmol/L, P=0.011). The change of 24 h UFC between the effective treatment group and ineffective group was statistically significant (P=0.020). The postoperative systolic blood pressure in the treated adenoma group was significantly lower than those of hyperplasia group (112±13) mmHg vs. (139±20) mmHg, P=0.026). Conclusions: For patients with CS-associated hypertension who are unwilling or unable to undergo surgical treatment, catheter-based adrenal ablation could improve the blood pressure and cortisol level. Catheter-based adrenal ablation could be a safe, effective, and minimally invasive therapy. However, our results still need to be validated in further large-scale studies.
Male ; Humans ; Cushing Syndrome/complications* ; Hydrocortisone ; Adrenal Gland Neoplasms/surgery* ; Feasibility Studies ; Blood Glucose ; Hyperplasia/complications* ; Hypertension/complications* ; Adenoma/complications* ; Body Weight ; Catheters/adverse effects*

OBJECTIVES: To establish a method for the simultaneous quantitative analysis of etomidate and its metabolite etomidate acid in blood, and to discuss its application value in actual cases. METHODS: Acetonitrile precipitate protein method was used, and C₁₈ column was selected. Gradient elution was performed with acetonitrile and 5 mmol/L ammonium acetate within 6 min. Electrospray ionization source in positive ion mode was used. The internal standard etomidate acid-d₅ was obtained by etomidate-d₅ alkaline hydrolysis reaction. Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used for quantitative analysis. The methodological verification was conducted. RESULTS: Etomidate and etomidate acid in blood showed good linear relationship in the quantitative linear range (r>0.999), with the lower limit of quantification was 2.5 ng/mL and 7.5 ng/mL, respectively. The accuracy, precision, recovery rate, and matrix effect of the method met the professional verification standards. The practical application results showed that etomidate and etomidate acid could be detected in the blood of the abusers, and their mass concentrations ranged from 17.24 to 379.93 ng/mL. CONCLUSIONS The method established in this study can simultaneously quantify etomidate and etomidate acid in blood, which is simple and convenient to operate with accuracy. It can meet the detection needs of actual cases and provide technical support for law enforcement to crack down on etomidate abuse.
Chromatography, High Pressure Liquid/methods* ; Chromatography, Liquid ; Etomidate ; Tandem Mass Spectrometry/methods* ; Liquid Chromatography-Mass Spectrometry ; Acetonitriles

Objective: To explore the value of catheter-based adrenal ablation in treating Cushing's syndrome (CS)-associated hypertension. Methods: A clinical study was conducted in patients with CS, who received catheter-based adrenal ablation between March 2018 and July 2023 in Daping Hospital. Parameters monitored were blood pressure (outpatient and 24-hour ambulatory), body weight, clinical characteristics, serum cortisol and adrenocorticotropic hormone (ACTH) at 8 am, 24-hour urinary free cortisol (24 h UFC), fasting blood glucose and postoperative complications. Procedure effectiveness was defined as blood pressure returning to normal levels (systolic blood pressure<140 mmHg (1 mmHg=0.133 kPa) and diastolic blood pressure<90 mmHg), cortisol and 24 h UFC returning to normal and improvement of clinical characteristics. The parameters were monitored during follow up in the outpatient department at 1, 3, 6, and 12 months after catheter-based adrenal ablation. Results: A total of 12 patients (aged (40.0±13.2) years) were reviewed. There were 5 males, with 5 cases of adenoma and 7 with hyperplasia from imaging studies. Catheter-based adrenal ablation was successful in all without interruption or surgical conversion. No postoperative complication including bleeding, puncture site infection, adrenal artery rupture or adrenal bleeding was observed. The mean follow up was 28 months. Compared to baseline values, body weight declined to (59.48±11.65) kg from (64.81±10.75) kg (P=0.008), fasting blood glucose declined to (4.54±0.83) mmol from (5.53±0.99) mmol (P=0.044), outpatient systolic blood pressure declined to (128±21) mmHg from (140±19) mmHg (P=0.005), diastolic blood pressure declined to (78±10) mmHg from (86±11) mmHg (P=0.041), and the mean ambulatory daytime diastolic blood pressure declined to (79±12) mmHg from (89±8) mmHg (P=0.034). Catheter-based adrenal ablation in 8 patients was defined as effective with their 24 h UFC significantly reduced after the procedure (1 338.41±448.06) mmol/L from (633.66±315.94) mmol/L, P=0.011). The change of 24 h UFC between the effective treatment group and ineffective group was statistically significant (P=0.020). The postoperative systolic blood pressure in the treated adenoma group was significantly lower than those of hyperplasia group (112±13) mmHg vs. (139±20) mmHg, P=0.026). Conclusions: For patients with CS-associated hypertension who are unwilling or unable to undergo surgical treatment, catheter-based adrenal ablation could improve the blood pressure and cortisol level. Catheter-based adrenal ablation could be a safe, effective, and minimally invasive therapy. However, our results still need to be validated in further large-scale studies.
Male ; Humans ; Cushing Syndrome/complications* ; Hydrocortisone ; Adrenal Gland Neoplasms/surgery* ; Feasibility Studies ; Blood Glucose ; Hyperplasia/complications* ; Hypertension/complications* ; Adenoma/complications* ; Body Weight ; Catheters/adverse effects*

OBJECTIVE: To investigate the therapeutic effect of Yixin Ningshen Tablet (YXNS) on comorbidity of myocardial infarction (MI) and depression in rats and explore the underlying mechanism. METHODS: The Sprague-Dawley rats were randomly divided into 5 groups with 7 rats in each group according to their weights, including control, model, fluoxetine (FLXT, 10 mg/kg), low-dose YXNS (LYXNS, 100 mg/kg), and high-dose YXNS (HYXNS, 300 mg/kg) groups. All rats were pretreated with corresponding drugs for 12 weeks. The rat model of MI and depression was constructed by ligation of left anterior descending coronary artery and chronic mild stress stimulation. The echocardiography, sucrose preference test, open field test, and forced swim test were performed. Myocardial infarction (MI) area and myocardial apoptosis was also detected. Serum levels of interleukin (IL)-6, IL-1β, tumor necrosis factor-α (TNF-α), 5-hydroxytryptamine (5-HT), adrenocorticotrophic hormone (ACTH), corticosterone (CORT), and norepinephrine (NE) were determined by enzyme linked immunosorbent assay. The proteins of adenosine 5'-monophosphate -activated protein kinase (AMPK), p-AMPK, peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and nuclear respiratory factor 1 (NRF1) in heart were detected by Western blot analysis. The expression levels of TNF-α, IL-6, indoleamine 2,3-dioxygenase (IDO1), kynurenine 3-monooxygenase (KMO), and kynureninase (KYNU) in hippocampus were detected by real-time quantitative polymerase chain reaction. RESULTS: Compared with the model group, the cardiac function of rats treated with YXNS improved significantly (P<0.01). Meanwhile, YXNS effectively reduced MI size and cardiomyocytes apoptosis of rats (P<0.01 or P<0.05), promoted AMPK phosphorylation, and increased PGC-1α protein expression (P<0.01 or P<0.05). HYXNS significantly increased locomotor activity of rats, decreased the levels of TNF-α, IL-6 and IL-1β, and increased the serum levels of 5-HT, NE, ACTH, and CORT (all P<0.05). Moreover, HYXNS decreased the mRNA expressions of IDO1, KMO and KYNU (P<0.05). CONCLUSIONS YXNS can relieve MI by enhancing myocardial energy metabolism. Meanwhile, YXNS can alleviate depression by resisting inflammation and increasing availability of monoamine neurotransmitters. It may be used as a potential drug to treat comorbidity of MI and depression.
AMP-Activated Protein Kinases/metabolism* ; Adrenocorticotropic Hormone ; Animals ; Comorbidity ; Depression/drug therapy* ; Energy Metabolism ; Interleukin-6/metabolism* ; Myocardial Infarction/pathology* ; Neurotransmitter Agents ; Rats ; Rats, Sprague-Dawley ; Serotonin/metabolism* ; Tablets ; Tumor Necrosis Factor-alpha/metabolism*

Alzheimer Disease/genetics* ; Animals ; Apolipoprotein E4/metabolism* ; Gene-Environment Interaction ; Hippocampus/metabolism* ; Male ; Noise/adverse effects* ; Rats