[Establishment of a risk prediction model for cerebrogenic multiple organ dysfunction syndrome in patients with acute cerebral hemorrhage].

OBJECTIVE: To construct and validate a predictive model for the risk of cerebrogenic multiple organ dysfunction syndrome (CMODS) in patients with acute cerebral hemorrhage. METHODS: Clinical data of 93 patients with acute cerebral hemorrhage admitted to Wannan Rehabilitation Hospital from January 2019 to June 2023 were retrospectively analyzed. Data included baseline information, disease severity score, laboratory examination indicators, cerebral hemorrhage status, treatment status, etc. Patients were divided into CMODS group and non-CMODS group according to whether CMODS occurred during hospitalization. The clinical data of the two groups were compared. Multivariate Logistic regression was used to analyze the risk factors of CMODS in patients with acute cerebral hemorrhage. A nomogram model was constructed to predict the risk of CMODS in patients with acute cerebral hemorrhage, and the model was validated. Receiver operator characteristic curve (ROC curve) was used to evaluate the predictive efficiency of nomogram model for CMODS in patients with acute cerebral hemorrhage. RESULTS: A total of 93 patients with acute cerebral hemorrhage were enrolled, including 26 patients in CMODS group and 67 patients in non-CMODS group. Compared with the non-CMODS group, the ratio of diabetes, acute physiological and chronic health evaluation II (APACHE II)≥35 score, cerebral hemorrhage volume ≥30 mL, endotoxemia, and national institutes of health stroke scale (NIHSS) and intracranial pressure of patients in the CMODS group were significantly higher, while the Glasgow coma score (GCS) was significantly lower and the length of hospital stay was significantly longer, with statistically significant differences (all P < 0.05). Multivariate Logistic regression analysis showed that diabetes mellitus [odds ratio (OR) = 3.615, 95% confidence interval (95%CI) was 1.487-8.785, P = 0.000], APACHE II score (OR = 4.697, 95%CI was 1.933-11.416, P = 0.000), endotoxemia (OR = 4.577, 95%CI was 1.883-11.123, P = 0.000), and cerebral hemorrhage volume (OR = 4.039, 95%CI was 1.662-9.816, P = 0.000) were the risk factors for CMODS in patients with acute cerebral hemorrhage. Taking the above risk factors as predictive variables, a nomogram prediction model was established. The verification results of the nomogram model showed that the C index was 0.804 (95%CI was 0.768-0.841), and the calibration curve was close to the ideal curve with good fit (P > 0.05). ROC curve results showed that the sensitivity and specificity of the nomogram model in predicting CMODS in patients with acute cerebral hemorrhage were 76.92%, 86.57%, respectively, and the area under the ROC curve (AUC) was 0.855 (95%CI was 0.776-0.935). CONCLUSIONS: Diabetes mellitus, APACHE II score, endotoxemia and intracerebral hemorrhage are risk factors for CMODS in patients with acute cerebral hemorrhage. The risk prediction model based on these risk factors is effective in evaluating the risk of CMODS in patients with acute cerebral hemorrhage.

Determination of higenamine in common natural spices by ultrahigh-performance liquid chromatography-tandem mass spectrometry.

Higenamine (HG) is a ß2 receptor agonist and was explicitly added to the Prohibited List of the World Anti-Doping Agency in 2017. This compound is prohibited in both in- and out-of-competition athletes and falls under the category of nonthreshold substances. Because of HG presence in numerous plants, as evidenced by a growing body of research data, an exception was made for HG in the TD2017MRPL document, in which adverse analytical findings (AAFs) were not reported if the urinary HG concentration was less than 10 ng/mL. In this study, a comprehensive and systematic analysis of the HG content in five batches of samples from each of the 48 natural spices selected for this investigation was conducted using UPLC-MS/MS technology. Method validation was carried out in accordance with the ICH Analytical Procedures and Methods Validation for Drugs and Biologics Guidance, and the experimental results demonstrated that the method provided appropriate sensitivity, precision, stability, linearity, and accuracy. HG was detected for the first time in Houttuynia cordata, Zingiber officinale, Cinnamomum cassia, Stevia rebaudiana, Piper nigrum, Siraitia grosuenorii, Platycodon grandiflorus, and Myristica fragrans. Furthermore, the content of HG was found to vary significantly among the different plant parts of Nelumbo nucifera, such as rhizomes, leaves, seeds, and plumules. This paper provides systematic and comprehensive data to support the safe use of spices in athletes' diets, thereby reducing the risk of food-sourced doping violations.

Association of Antipsychotic Drugs with Venous Thromboembolism: Data Mining of Food and Drug Administration Adverse Event Reporting System and Mendelian Randomization Analysis.

AIMS: Past observational studies have reported on the association between antipsychotic drugs and venous thromboembolism (VTE); however, the conclusions remain controversial, and its mechanisms are yet to be fully understood. Thus, in this study, we aim to determine the associations of antipsychotic drugs with VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), and their potential mechanisms. METHODS: We first mined the adverse event signals of VTE, DVT, and PE caused by antipsychotic drugs in Food and Drug Administration Adverse Event Reporting System (FAERS). Next, we used two-sample Mendelian randomization (MR) method to investigate the association of antipsychotic drug target gene expression with VTE, DVT, and PE, using single-nucleotide polymorphisms as genetic instruments. We not only used the expression of all antipsychotic drug target genes as exposure to perform MR analyses but also analyzed the effect of single target gene expression on the outcomes. RESULTS: In the FAERS, 1694 cases of VTE events were reported by 16 drugs. However, using the MR approach, no significant association was determined between the expression of all antipsychotic target genes and VTE, DVT, or PE, either in blood or brain tissue. Although the analysis of single gene expression data showed that the expression of nine genes was associated with VTE events, these targets lacked significant pharmacological action. CONCLUSIONS: Adverse event mining results have supported the claim that antipsychotic drugs can increase the risk of VTE. However, we failed to find any genetic evidence for this causal association and potential mechanisms. Thus, vigilance is still needed for antipsychotic drug-related VTE despite the limited supporting evidence.

Conditional survival probability of distant-metastatic hepatocellular carcinoma: A population-based study.

BACKGROUND: The prognosis of many patients with distant metastatic hepatocellular carcinoma (HCC) improved after they survived for several months. Compared with traditional survival analysis, conditional survival (CS) which takes into account changes in survival risk could be used to describe dynamic survival probabilities. AIM: To evaluate CS of distant metastatic HCC patients. METHODS: Patients diagnosed with distant metastatic HCC between 2010 and 2015 were extracted from the Surveillance, Epidemiology and End Results database. Univariate and multivariate Cox regression analysis were used to identify risk factors for overall survival (OS), while competing risk model was used to identify risk factors for cancer-specific survival (CSS). Six-month CS was used to calculate the probability of survival for an additional 6 mo at a specific time after initial diagnosis, and standardized difference (d) was used to evaluate the survival differences between subgroups. Nomograms were constructed to predict CS. RESULTS: Positive α-fetoprotein expression, higher T stage (T3 and T4), N1 stage, non-primary site surgery, non-chemotherapy, non-radiotherapy, and lung metastasis were independent risk factors for actual OS and CSS through univariate and multivariate analysis. Actual survival rates decreased over time, while CS rates gradually increased. As for the 6-month CS, the survival difference caused by chemotherapy and radiotherapy gradually disappeared over time, and the survival difference caused by lung metastasis reversed. Moreover, the influence of age and gender on survival gradually appeared. Nomograms were fitted for patients who have lived for 2, 4 and 6 mo to predict 6-month conditional OS and CSS, respectively. The area under the curve (AUC) of nomograms for conditional OS decreased as time passed, and the AUC for conditional CSS gradually increased. CONCLUSION: CS for distant metastatic HCC patients substantially increased over time. With dynamic risk factors, nomograms constructed at a specific time could predict more accurate survival rates.

Initial studies on the implanting sites of high and low ventricular septa using leadless cardiac pacemakers.

OBJECTIVE: To study the safety and electrical characteristics of various implanting sites of the Micra pacemaker. METHOD: A total of 15 patients from Beijing Anzhen Hospital, Capital Medical University, were included, who were implanted with Micra leadless pacemakers and allocated to either the high ventricular septum group (eight patients) or the low ventricular septum group (seven patients) based on their individual patient factors and clinical conditions. The baseline of the patients, the implanting area, the electrocardiogram change after implantation, the implantation data, the threshold, R wave, impedance, and the date of the 1-month follow-up were then analyzed. With all of the data, the characteristics of different implantation sites of the Micra pacemaker were determined. RESULTS: Overall, the thresholds were low at implantation and remained stable over the 1-, 3-, 6-month, 1-, 2-, 3-, and 4-year follow-ups. On comparing the two groups, there was no difference in QRS duration at pacing (140.00 [40.00] ms vs. 179.00 [50.00] ms), threshold at implantation (0.38 [0.22] mV vs. 0.63 [1.00] mV), R wave at implantation ([10.85 ± 4.71] V vs. [7.26 ± 2.98] V), or impedance at implantation ([906.25 ± 162.39] Ω vs. [750.00 ± 173.40] Ω). While the difference in QRS duration between the two groups was not significant, the QRS duration of the high ventricular septum group exhibited a reduced tendency compared with that of the low ventricular group. The corrected QT interval during pacing exhibited a significant difference (440.00 [80.00] ms vs. 520.00 [100.00] ms; p < .05). For the 1-, 3-, 6-month, 1-, 2-, 3-, and 4-year follow-ups, there was no difference between the threshold of the high ventricular septum group and that of the low ventricular septum group (p > .05). CONCLUSION: High ventricular septum pacing appears to be a safe site for implantation of the Micra pacemaker. It could entail a shorter QRS duration at pacing and could be more physiological than low ventricular septum pacing.

Congenitally corrected transposition of the great arteries and implantation of a leadless pacemaker: a case report.

BACKGROUND: Congenitally corrected transposition of the great arteries (ccTGA) is a rare cardiac anomaly and can lead to abnormal electrical activity of the heart. The implant of a pacemaker in such patients is more complicated than conventional operations. This case report of an adult with ccTGA who had a leadless pacemaker implant will provide a reference for diagnosing and treating such patients. CASE PRESENTATION: A 50-year-old male patient was admitted to hospital having experienced intermittent vision loss for a month. An electrocardiogram and Holter monitoring showed intermittent third-degree atrioventricular block, and echocardiography, cardiac computed tomography and cardiac magnetic resonance imaging confirmed a diagnosis of ccTGA. A leadless pacemaker was successfully implanted into the patient's anatomical left ventricle, and the postoperative parameters were stable. CONCLUSION: Implanting a leadless pacemaker into a patient with a rare anatomical and electrophysiological abnormality, such as ccTGA, is feasible and efficacious, but preoperative imaging evaluation is of considerable importance.

The Global Burden of Appendicitis in 204 Countries and Territories from 1990 to 2019.

Objective: Appendicitis is a common surgical emergency. This study aimed to estimate the worldwide burden and trends of appendicitis from 1990 to 2019. Methods: Data on appendicitis were derived from the Global Burden of Disease 2019. Incidence and disability-adjusted life-years (DALYs) data were analyzed at global, regional, and national levels and stratified by sex, age, and socio-demographic index. The estimated annual percentage change and relative change were used to assess changing trends. Pearson's correlation test was used to assess the correlation between different measures. Results: Global incidence grew by 63.55% between 1990 and 2019, age-standardized incidence rate climbed by an estimated percentage change of 0.58 per year, whereas the number of DALY declined by 31.93% during the same period, with an estimated annual percentage change of -2.77. In 2019, the areas of Andean Latin America and the Caribbean had the highest age-standardized rates of incidence and DALYs. While South Asia saw the largest increase in age-standardized incidence rates, Andean Latin America saw the biggest decline in age-standardized rates of incidence and DALYs. At the national level, Bangladesh, Bhutan, and Peru were the top three countries in terms of age-standardized incidence rates in 2019, and Honduras, Haiti, and the Central African Republic held the highest age-standardized DALY rates. Ethiopia experienced the most age-standardized incidence rate increase, and Peru saw the largest decline in age-standardized rate of incidence and DALYs. Significant negative correlations between age-standardized DALY rates and socio-demographic index, between estimated annual percentage change and age-standardized incidence rates, were observed at the national level. Conclusion: Appendicitis remains a major global health concern. Although the trends in DALYs decreased, the burden of incidence increased from 1990 to 2019. Policymakers should create health policies adapted to local conditions to manage the burden of appendicitis globally.

CHA2DS2-VASc score as a prognostic indicator in patients with atrial fibrillation undergoing coronary stenting.

BACKGROUND: Patients with atrial fibrillation (AF) and coronary stenting had a poor prognosis. This study aimed to assess the accuracy of CHA2DS2-VASc score for predicting and grading adverse clinical outcomes in this population. METHODS: We reviewed the clinical data of all patients with previously documented nonvalvular AF who underwent coronary stenting between January 2010 and June 2015 in 12 hospitals of Beijing, China. The study population was divided into three groups: 1) Low CHA2DS2-VASc score, ≦ 2 points, 2) Intermediate score, 3-4 points, and 3) High score, ≧ 5 points. Major adverse cardiac/cerebrovascular events (MACCE) were defined as a composite of all-cause death, nonfatal myocardial infarction, repeat revascularization and ischemic stroke/systemic thromboembolism (IS/SE). RESULTS: A total of 2394 patients (men: 72.3% vs. women: 27.7%, median age: 67 years) were included, with the CHA2 DS2-VASc score of 3.6 ± 1.6. The median follow-up duration was 36.2 months. All-cause mortality increased 3 folds from the low score (4.8%) to the high score group (15.8%). The high score group had more IS/SE (7.4%) and MACCE (26.3%). The CHA2 DS2-VASc score ≧ 5 points was independently associated with all-cause death (hazard ratio [HR]: 2.303, 95% confidence interval [CI]: 1.492- 3.555), IS/SE (HR: 4.169, 95% CI: 2.216-7.845) and MACCE (HR: 1.468, 95% CI: 1.113-1.936) on multivariate Cox proportional hazards regression. The area under the receiver operating characteristic curve of the CHA2DS2-VASc score was 0.644 (95% CI: 0.624-0.663) for all-cause death, 0.647 (95% CI: 0.627-0.666) for IS/SE, and 0.592 (95% CI: 0.572-0.611) for MACCE. DISCUSSION: CHA2DS2-VASc score was a reliable prognostic indicator in patients with AF and coronary stenting.

Drug-induced kidney injury in Chinese critically ill pediatric patients.

Background: Drug-induced acute kidney injury (DIKI) is a common adverse drug reaction event but is less known in pediatric patients. The study explored the DIKI in Chinese pediatric patients using the Pediatric Intensive Care database (PIC). Method: We screened pediatric patients with acute kidney injury (AKI) using the KDIGO criteria from the PIC and then assessed the relationship between their drugs and DIKI using the Naranjo scale. For the fifteen frequently used DIKI-suspected drugs, we divided patients into drug-exposed and non-exposed groups, using the outcome of whether DIKI was presented or not. Propensity score matching (PSM) was used to control for the effects of four confounders, age, gender, length of hospital stay, and major diagnosis. Unconditional logistic regression was used to identify statistically significant differences between the two groups. Results: A total of 238 drugs were used 1,863 times by the 81 patients with DIKI during their hospital stay. After screening the Naranjo scale to identify the top 15 suspected DIKI drugs with a high frequency of use, we found that furosemide injection (p = 0.001), midazolam injection (p = 0.001), 20% albumin prepared from human plasma injection (p = 0.004), fentanyl citrate injection (p = 0.001), compound glycyrrhizin injection (p = 0.026), vancomycin hydrochloride for intravenous (p = 0.010), and milrinone lactate injection (p = 0.009) were associated with DIKI. Conclusion: In critically ill pediatric patients, DIKI is more likely to occur after using furosemide injection, midazolam injection, 20% albumin prepared from human plasma injection, fentanyl citrate injection, compound glycyrrhizin injection, vancomycin hydrochloride for intravenous, milrinone lactate injection.

Clinically Significant Cytochrome P450-Mediated Drug-Drug Interactions in Children Admitted to Intensive Care Units.

Objectives: Children admitted to intensive care units (ICUs) often require multiple medications due to the complexity and severity of their disease, which put them at an increased risk for drug interactions. This study examined cytochrome P450-mediated drug-drug interactions (DDIs) based on the Pediatric Intensive Care (PIC) database, with the aim of analyzing the incidence of clinically significant potential drug-drug interactions (pDDIs) and exploring the occurrence of actual adverse reactions. Methods: The Lexicomp database was used to screen cytochrome P450-mediated DDI pairings with good levels of reliability and clear clinical phenotypes. Patients exposed to the above drug pairs during the same period were screened in the PIC database. The incidence of clinically significant pDDIs was calculated, and the occurrence of adverse reactions was explored based on laboratory measurements. Results: In total, 84 (1.21%) of 6920 children who used two or more drugs were exposed to at least one clinically significant pDDI. All pDDIs were based on CYP3A4, with nifedipine + voriconazole (39.60%) being the most common drug pair, and the most frequent being the J02 class of drugs. Based on laboratory measurements, 15 adverse reactions were identified in 12 patients. Conclusions: Clinically significant cytochrome P450-mediated pDDIs existed in the children admitted to ICUs, and some of the pDDIs led to adverse clinical outcomes. The use of clinical decision support systems can guide clinical medication use, and clinical monitoring of patients' needs has to be enhanced.

Occurrence of ventricular septal perforation in patients with permanent left bundle branch pacing followed up using echocardiographic and computed tomography images.

OBJECTIVE: To explore short-term changes after left bundle branch pacing (LBBP) using echocardiography and computed tomography (CT), especially for postoperative ventricular septal perforation. METHODS: Between January and September 2019, 33 patients with atrioventricular block underwent LBBP at Beijing Anzhen Hospital. All the patients were evaluated using electrocardiography, pacing, parameters and echocardiographic measurements, including for major complications, during the 1, 3, 6, 12 and 24-month follow-up. Interval perforations were examined during a 1-month follow-up echocardiogram and CT. RESULTS: Left bundle branch pacing was successfully performed in 100% (33/33) of patients. The mean seizure threshold was stable and unchanged postoperatively at the 1, 3, 6, 12 and 24-month follow-up. The paced QRS duration of the LBBP was 119.72 ± 2.53 ms and <130 ms in all patients. Unipolar impedance during the procedure was higher than 500 Ω (662.00 ± 181.50 Ω). No ventricular septal perforation occurred at the end of the procedure. At the 1-month follow-up, two patients reported transthoracic echocardiography, with CT revealing septal lead perforation. Through CT, two other patients were found to have septal lead perforation, and echocardiography indicated that the pacing lead had penetrated the interventricular septum and entered the left subendocardium. At the 1, 3, 6, 12 and 24-month follow-up, these four patients exhibited no significant increase in pacing threshold or impedance (p > .05). No ventricular thrombus or stroke was detected. CONCLUSION: Permanent LBBP is safe and feasible in patients with bradycardia. Echocardiography and/or CT can more accurately evaluate changes in cardiac structure and function after LBBP.

Use of liquid chromatography-tandem mass spectrometry for determination of higenamine in urine following oral administration of traditional Chinese medicine.

Since higenamine (HG) was first included in the World Anti-doping Agency (WADA) 2017 Prohibited List, an increasing number of plants have been found to contain this ingredient. As a result, doctors are hesitant to prescribe traditional Chinese medicine (TCM) to athletes. Thus, it is very important to assess the risks of doping violations due to HG following the oral administration of TCM. We determined the drug concentration-time curves for HG in urine by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after single or multiple administrations of lotus seed powder on volunteers, the single dose was equivalent to 750 µg of HG, and the multiple doses were equivalent to 90 µg of HG each, 3 times daily for 5 consecutive days. For the single-dose group, the HG could be detected in urine 0.5 h after administration and reached a maximum concentration of 16.5 ng/mL 1 h after administration. For the multiple-dose group, the HG concentrations in urine showed two peaks at 29 and 77 h post-administration with 22.6 and 23.1 ng/mL, respectively. At the dosage used in this study, the maximum concentration of HG in some urine samples exceeded the WADA limit of 10.0 ng/mL; the risk was still very high, so athletes must avoid this amount of HG when using TCM. In addition, our study provided further data supporting the presence of sulfonated metabolites of HG in urine samples.

Exact distributions for stochastic gene expression models with arbitrary promoter architecture and translational bursting.

Gene expression in individual cells is inherently variable and sporadic, leading to cell-to-cell variability in mRNA and protein levels. Recent single-cell and single-molecule experiments indicate that promoter architecture and translational bursting play significant roles in controlling gene expression noise and generating the phenotypic diversity that life exhibits. To quantitatively understand the impact of these factors, it is essential to construct an accurate mathematical description of stochastic gene expression and find the exact analytical results, which is a formidable task. Here, we develop a stochastic model of bursty gene expression, which considers the complex promoter architecture governing the variability in mRNA expression and a general distribution characterizing translational burst. We derive the analytical expression for the corresponding protein steady-state distribution and all moment statistics of protein counts. We show that the total protein noise can be decomposed into three parts: the low-copy noise of protein due to probabilistic individual birth and death events, the noise due to stochastic switching between promoter states, and the noise resulting from translational busting. The theoretical results derived provide quantitative insights into the biochemical mechanisms of stochastic gene expression.

Predictive models for adverse clinical outcomes in Chinese patients with atrial fibrillation undergoing percutaneous coronary intervention with stenting.

OBJECTIVE: This study aimed to evaluate predictors for adverse cardiovascular outcomes in patients with atrial fibrillation (AF) undergoing coronary stenting. METHODS: We retrospectively recruited consecutive patients with previously documented non-valvular AF who underwent coronary stenting between January 2010 and June 2015 in 12 hospitals of Beijing, China. Major adverse cardiac/cerebrovascular events (MACCE) were a composite of all-cause death, non-fatal myocardial infarction, repeat revascularization, and ischaemic stroke/systemic thromboembolism (IS/STE). Major bleeding referred to grade 2 or higher of Bleeding Academic Research Consortium criteria. RESULTS: A total of 2394 patients (men: 72.3% vs. women: 27.7%, median age: 67 years) were included. The CHA2DS2-VASc and HAS-BLED were 3.6 ± 1.6 and 1.9 ± 0.7, respectively. The median follow-up duration was 36.2 months. There were 230 (9.6%) deaths, 96 (4.0%) IS/STE, 426 (17.8%) MACCE, and 72 (3.0%) major bleeding. Multivariate Cox regression yielded predictive models for (1) all-cause death: diabetes, prior myocardial infarction, chronic kidney disease (CKD), ST-segment elevation myocardial infarction (STEMI) at presentation, heart failure, no use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and statins; (2) IS/STE: advanced age, prior history of ischaemic stroke and intracranial haemorrhage; (3) MACCE: prior history of myocardial infarction and ischaemic stroke, CKD, STEMI, heart failure, and no statin use; (4) major bleeding: prior major bleeding, prior myocardial infarction, CKD and use of oral anticoagulants. CONCLUSION: Chinese patients with AF and coronary stenting had high mortality and incidence of MACCE. We compiled separate predictive models for all-cause death, IS/STE, MACCE, and major bleeding.

A Survey of Pharmacogenomics Testing Among Physicians, Pharmacists, and Researchers From China.

To elucidate current domestic factors influencing pharmacogenomics (PGx) implementation and its future in China, we conducted a questionnaire survey on PGx applications and testing. A questionnaire-based survey was created on the popular online professional survey platform "Wenjuanxing" (www.wjx.cn) and performed via the social media platform WeChat. Among 422 participants, there were physicians (27.7%), pharmacists (31.3%), and researchers (41.0%). We found that less than 50% of physicians were aware of the importance of PGx in drug therapy, while over 50% of pharmacists and researchers recognized the importance. Only 38.5% of physicians, 40.9% of pharmacists, and 55.5% of researchers concurred that PGx analysis could lower the economic burdens for patients. However, most of the responders affirmed that PGx should be effectively implemented in clinical practices. A lack of sector standards, a lack of clinical research, and a lack of guidelines were found to be the major factors for hindering PGx clinical application. Among drugs associated with PGx assays, the most common were warfarin and clopidogrel. Although PGx research has advanced rapidly in recent years in mainland China, the clinical implementation of PGx has a long way to go.

Discovery of isoliquiritigenin analogues that reverse acute hepatitis by inhibiting macrophage polarization.

Screening a natural product library of 850 compounds yield isoliquiritigenin as an effective anti-inflammatory agent by inhibiting the production of pro-inflammatory NO induced by Pam3CSK4, while its activity accompanied by toxicity. Further studies obtained the optimized isoliquiritigenin derivative SMU-B14, which can inhibit Pam3CSK4 triggered toll-like receptor 2 (TLR2) signaling with low toxicity and high potency. Preliminary mechanism studies indicated that SMU-B14 worked through TLR2/MyD88, phosphorylation of IKKα/ß, leading to the reduce degradation of NF-κB related IKBα and p65 complex, then inhibited the production of inflammatory cytokines, such as TNF-α, IL-6, IL-1ß both in human and murine cell lines. Subsequent polarization experiments showed SMU-B14 significant reversed the polarization of M1 phenotype primary macrophage activated by Pam3CSK4in vitro, and reduced the infiltration of neutrophil and polarization of M1-type macrophage, decreased serum alanine transaminase (ALT), as a result protected liver from being injured in vivo. In summary, we obtained an optimized lead compound SMU-B14 and found it functionally blocked TLR2/MyD88/NF-κB signaling pathway to down-regulate the production of inflammatory cytokines resulted significant liver protection property.

Causality Evaluation of Drug-Induced Liver Injury in Newborns and Children in the Intensive Care Unit Using the Updated Roussel Uclaf Causality Assessment Method.

Purpose: Drug-induced liver injury (DILI) is a common adverse reaction in the clinic; however, there are relatively few reports of DILI in critically ill newborns and children. Making use of the Pediatric Intensive Care database (PIC), this study identifies which drugs are related to DILI in neonates and children in China. Methods: Using the PIC, we screened for patients whose liver was suspected of being injured by drugs during hospitalization. The medicine they used was then assessed by the Roussel Uclaf Causality Assessment Method (RUCAM). At the same time, we also collated drug combinations that may affect CYP (Cytochrome P) enzyme metabolism, which may cause DILI. Results: A total of 13,449 patients were assessed, of whom 77 newborns and 261 children were finally included. The main type of liver injury in neonates was mixed (83.1%), while the hepatic injury types of children were mostly distributed between hepatocellular (59.4%) and cholestatic (28.4%). In terms of the RUCAM assessment, the drugs that were most considered to cause or be associated with hepatic injury in newborns were medium and long chain fat emulsions (17%), sodium glycerophosphate (12%), and meropenem (9%); while omeprazole (11%), methylprednisolone sodium succinate (10%), and meropenem (8%) were the primary culprits of DILI in children. Drug combinations frequently seen in neonates that may affect CYP enzyme metabolism are omeprazole + budesonide (16.9%), dexamethasone + midazolam (10.4%), and midazolam + sildenafil (10.4%). In children, the commonly used drug combinations are fentanyl + midazolam (20.7%), ibuprofen + furosemide (18.4%), and diazepam + omeprazole (15.3%). Conclusions: In this study, medium and long chain fat emulsions and sodium glycerophosphate have been strongly associated with DILI in newborns, while omeprazole and methylprednisolone sodium succinate play an important role in the DILI of children. Also, attention should be paid to the effect on CYP enzymes when using multiple drugs at the same time. In future DILI cases, it is advisable to use the latest RUCAM for prospective study design so that complete case data and high RUCAM scores can be collected.

Sex difference in clinical outcomes of Chinese patients with atrial fibrillation and coronary stenting according to age.

OBJECTIVE: Sex differences in the clinical outcomes of patients with atrial fibrillation (AF) and coronary stenting should be assessed according to age. METHODS: We analyzed the clinical data of all patients with nonvalvular AF who underwent coronary stenting between January 2010 and June 2015 in 12 hospitals of Beijing, China. RESULTS: A total of 2,146 patients (71.8% men and 28.2% women) were included in the study. The mean age of the patients was 66.6±9.4 years. Women in this study were older and had higher prevalence of hypertension, diabetes, chronic kidney disease (CKD), and anemia. Smoking history was found to be higher in men, and women were less likely to be current smokers. The mean follow-up duration was 39.7 months. Women younger than 65 years had a remarkably higher mortality (11.2% vs. 5.3%, p=0.012) and a significantly lower rate of repeat revascularization (1.6% vs. 6.3%, p=0.034) than men. Female gender remained an independent predictor for all-cause mortality [hazard ratio (HR)=2.03, 95% confidence interval (CI): 1.09-3.79, p=0.025], along with heart failure (HR=3.64, 95% CI: 2.02-6.57, p<0.001) and CKD (HR=2.46, 95% CI: 1.09-5.57, p=0.031) after multivariate regression analysis. No significant difference was noted between men and women with regard to mortality, ischemic events, and major bleeding in elderly patients. CONCLUSION: In Chinese patients younger than 65 years with AF and coronary stenting, female gender was independently associated with increased mortality; men were more likely to receive repeat revascularization possibly due to the current smoking. Whether it was a biological difference or a recognition disparity of the disease between men and women warrants further investigation.

Inversion of PM2.5 atmospheric refractivity profile based on AlexNet model from the perspective of electromagnetic wave propagation.

Human civilization has reached an unprecedented height, but the industrialization of economic development also brings global warming, ozone depletion, acid rain, fresh water resources crisis, energy shortage, and environmental problems. In autumn and winter, haze becomes the usual state in the modern society, and PM2.5 has been becoming an important form of air pollution. The research found that PM2.5 brings great influence to the human body or daily life. To some extent, the PM2.5 also affects the propagation of electromagnetic waves near the ground, reducing the transmission performance of electromagnetic wave. Based on Mie scattering theory, this paper qualitatively analyzed the scattering effects of PM2.5 particles on every frequency band of electromagnetic wave in daily use. Then the paper takes the satellite navigation signals as a research example, selecting university of Wyoming Davis stations in Antarctica sounding data by measuring the tropospheric atmospheric meteorological parameters (including the atmosphere pressure, geopotential height of different layers, dew point temperature, relative humidity and specific humidity, wind direction, wind speed, and temperature). The paper inversed the refractive index distribution of the troposphere based on AlexNet model and described the error quantitatively. The simulation results show that the estimated error is less than 5.1455%, proving the high accuracy of the AlexNet model. To test the influence of PM2.5, the paper takes Jiuquan, a city with serious pollution, as an example. Comparison between the inversion results and IGS products shows that high concentration of PM2.5 pollution has little influence on the inversion of refractive index profile.