BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

Image 1.

Objective The high incidence, disability, and mortality rates of stroke result in a heavy economic and social burden. The aim of this study was to investigate the relationship between triglyceride-glucose (TyG) index and new-onset stroke to assist in the identification of high-risk groups for stroke and to provide ideas for effective prevention. Methods The study was based on data from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018 and included 7630 eligible middle-aged and elderly participants. The association between TyG index and new-onset stroke was assessed by logistic regression modelling and restricted triple spline analysis. Results A total of 431 participants had a new stroke. The TyG index was found to be a risk factor for stroke occurrence when it was >8.523, and there was a positive linear association moderated by gender. Conclusion Elevated TyG index is a risk factor for new stroke. This study provides new ideas for the identification of high-risk groups for stroke and for intervention measures and timing.

Background: Twenty-four-hour urinary free cortisol (UFC) measurement is the initial diagnostic test for Cushing’s syndrome (CS). We compared UFC determination by both direct and extraction immunoassays using Abbott Architect, Siemens Atellica Solution, and Beckman DxI800 with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, we evaluated the value of 24-hr UFC measured by six methods for diagnosing CS. Methods: Residual 24-hr urine samples of 94 CS and 246 non-CS patients were collected.A laboratory-developed LC-MS/MS method was used as reference. UFC was measured by direct assays (D) using Abbott, Siemens, and Beckman platforms and by extraction assays (E) using Siemens and Beckman platforms. Method was compared using Passing–Bablok regression and Bland–Altman plot analyses. Cut-off values for the six assays and corresponding sensitivities and specificities were calculated by ROC analysis. Results: Abbott-D, Beckman-E, Siemens-E, and Siemens-D showed strong correlations with LC-MS/MS (Spearman coefficient r = 0.965, 0.922, 0.922, and 0.897, respectively), while Beckman-D showed weaker correlation (r = 0.755). All immunoassays showed proportionally positive bias. The areas under the curve were 0.975 for Abbott-D, 0.972 for LCMS/MS, 0.966 for Siemens-E, 0.948 for Siemens-D, 0.955 for Beckman-E, and 0.877 for Beckman-D. The cut-off values varied significantly (154.8–1,321.5 nmol/24 hrs). Assay sensitivity and specificity ranged from 76.1% to 93.2% and from 93.0% to 97.1%, respectively. Conclusions Commercially available immunoassays for measuring UFC show different levels of analytical consistency compared to LC-MS/MS. Abbott-D, Siemens-E, and Beckman-E have high diagnostic accuracy for CS.

Aprocitentan is a dual endothelin receptor antagonist.Based on the effective evidence of Ⅲ phases of clinical trials,the drug was approved for marketing by the U.S.Food and Drug Administration on March 19,2024 for the treatment of refractory hypertension.At present,multiple clinical studies have confirmed that Aprocitentan has excellent antihypertensive effects and good tolerability.This article reviews the pharmacological effects,preclinical.

This study was aimed at characterizing the variations in hemagglutinin(HA)and neuraminidase(NA)genes of influenza virus subtype A(H1N1)pdm09 isolated during the 2022-2023 influenza monitoring year in Shandong Province,to provide a scientific basis for influenza prevention and control.A total of 14 A(H1N1)pdm09 subtype influenza strains were se-lected randomly by city by the influenza monitoring network laboratory.The vaccine strains recommended by the WHO served as references for whole gene sequencing analysis.A fluorescence method was used to conduct neuraminidase inhibition experi-ments to evaluate drug sensitivity.The A(H1N1)pdm09 influenza virus in Shandong Province,2022-2023 belonged to the 5a.2a evolutionary cluster in the 6B.1A branch.Nucleotide sequence analysis indicated that the HA and NA genes were closely re-lated to the Northern Hemisphere vaccine strain A/Victoria/2570/2019 in the years 2021-2023,and showed homology of 98.5％to 98.7％and 98.8％to 99.1％,respectively.Amino acid sequence analysis revealed 20 amino acid sequence mutations in the HA protein,but only one virus strain was found to have antigen drift,and three virus strains showed loss of HA protein glycosylation sites.No mutations were found at important sites affecting NA enzymes.The neuraminidase inhibition experiment indicated viral sensitivity to anti-influenza drugs.In conclusion,the monitored virus strains had high overall homology with vac-cine strains but showed some amino acid variation.In the future,continued monitoring of the genetic variation characteristics of influenza viruses will be necessary to understand the risk of influenza epidemics,and the effectiveness of influenza vaccines and therapeutic drugs.

This study was aimed at understanding the pollution distribution pattern of avian influenza virus in the environ-ment in poultry related places in Shandong Province,to provide a scientific basis for the prevention,control,prediction,and early warning regarding human infection with avian influenza.From 2020 to 2023,6 523 environmental samples were collected in 16 cities in Shandong Province from four types of poultry-related places.Fluorescence quantitative PCR was used for nucleic acid testing of influenza A virus.Positive samples were further identified for the H5,H7,and H9 subtypes of avian influenza virus.The epidemiological characteristics of avian influenza viruses in the poultry related environment of Shandong Province were described,and inter-rate comparisons were performed with the x2 test.During 2020-2023,6 523 environmental samples were collected,and 1 007 cases positive for avian influenza virus were detected,with a positivity rate of 15.44％.H5,H7,and H9 subtypesand mixed infections were detected.H9 was the main subtype(88.48％)in positive specimens.A significant difference in positivity rates was observed among regions(x2=431.956,P＜0.001),and the highest positivity rate was 28.93％.Significant differences in positivity rates were observed among monitoring sites(x2=304.604,P＜0.001),sample types(x2=109.678,P＜0.001),and quarters(x2=64.963,P＜0.001).The positive detection rate was highest at monitoring sites in urban and rural live poultry markets(20.12％),and the positive detection rate of samples collected by wiping meat cut-ting board surfaces was higher than that of other samples(22.56％).The peak positive detection rate occurred in spring(20.31％).Widespread contamination with avian influenza virus was observed in poultry environments in Shandong Prov-ince.The H9 subtype,the main pathogen,coexisted with H5 and H7 subtypes,thus posing a risk of human infection with avian influenza.Therefore,prevention and control of avian influenza must be strengthened in key seasons,areas,places,and links.

Objective A stable model of acute obstructive suppurative cholangitis was established in rats to detect pathophysiological indexes and provide a reliable standardized animal model for the study of acute cholangitis and cholestasis.Methods SPF-grade male SD rats were selected,and the model was constructed via the injection of toxoid into the lower bile duct,followed by ligation of the common bile duct.Changes in body weight,mortality,major indexes of liver function,and histopathological changes in the liver were evaluated before and after modeling.Results After modeling,the body weight of rats in the model group decreased significantly.There were no deaths and no abnormalities of liver function in the sham-operation group.Three rats died in the model group,and the mortality rate of the model group was 12％.The main indexes of liver function and liver pathology showed obvious cholestasis and injurious changes to hepatic function in the model.Conclusions In this study,an acute obstructive suppurative cholangitis model rat was successfully established.The model has the advantages of ease of operation,minimal injury,low mortality,and a highly successful modeling rate,and it can provide a standardized experimental animal model for studying the mechanisms of and developing drugs for these common diseases.

Objective:To explore the prognostic effect and safety of neurally adjusted ventilatory assist (NAVA) mode on the patients with severe neurological cerebrovascular disease undergoing mechanical ventilation.Methods:A prospective study was conducted. Fifty-four patients with cerebrovascular disease undergoing mechanical ventilation admitted to the neurosurgery intensive care unit (NSICU) of the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital) from December 2020 to May 2022 were enrolled. They were divided into NAVA group and pressure support ventilation (PSV) group by computer random number generator with 27 patients in each group. The ventilation time of the two groups was ≥72 hours. The general basic data of the two groups were recorded. The time without mechanical ventilation 28 days after enrollment, total length of mechanical ventilation, survival rate of 90 days after enrollment, length of NSICU stay, total length of hospital stay, NSICU mortality, in-hospital mortality, Glasgow outcome score (GOS), complications related to mechanical ventilation, and changes of respiratory mechanics indexes, arterial blood gases, vital signs, and diaphragm function indexes were observed.Results:The time without mechanical ventilation 28 days after enrollment in the NAVA group was significantly longer than that in the PSV group [days: 22 (15, 26) vs. 6 (0, 23), P < 0.05]. However, there were no significant differences in the total length of mechanical ventilation, 90-day survival rate, length of NSICU stay, total length of hospital stay, NSICU mortality, in-hospital mortality, GOS score, and incidence of mechanical ventilator-related complications between the two groups. In terms of respiratory mechanics parameters, the expiratory tidal volume (VTe) on 3 days after mechanical ventilation of patients in the NAVA group was significantly lower than that on 1 day and 2 days, and significantly lower than that in the PSV group [mL: 411.0 (385.2, 492.6) vs. 489.0 (451.8, 529.4), P < 0.01]. Minute ventilation (MV) at 2 days and 3 days in the NAVA group was significantly higher than that at 1 day, and significantly higher than that in the PSV group at 2 days [L/min: 9.8 (8.4, 10.9) vs. 7.8 (6.5, 9.8), P < 0.01], while there was no significant change of MV in the PSV group. At 1 day, peak airway pressure (Ppeak) and mean airway pressure (Pmean) in the NAVA group were significantly lower than those in the PSV group [Ppeak (cmH 2O, 1 cmH 2O≈0.098 kPa): 14.0 (12.2, 17.0) vs. 16.6 (15.0, 17.4), Pmean (cmH 2O): 7.0 (6.2, 7.9) vs. 8.0 (7.0, 8.2), both P < 0.05]. However, there was no significant difference in the Ppeak or Pmean at 2 days and 3 days between the two groups. In terms of arterial blood gas, there was no significant difference in pH value between the two groups, but with the extension of mechanical ventilation time, the pH value at 3 days of the two groups was significantly higher than that at 1 day. Arterial partial pressure of oxygen (PaO 2) at 1 day in the NAVA group was significantly lower than that in the PSV group [mmHg (1 mmHg≈0.133 kPa): 122.01±37.77 vs. 144.10±40.39, P < 0.05], but there was no significant difference in PaO 2 at 2 days and 3 days between the two groups. There was no significant difference in arterial partial pressure of carbon dioxide (PaCO 2) or oxygenation index (PaO 2/FiO 2) between the two groups. In terms of vital signs, the respiratory rate (RR) at 1, 2, and 3 days of the NAVA group was significantly higher than that of the PSV group [times/min: 19.2 (16.0, 25.2) vs. 15.0 (14.4, 17.0) at 1 day, 21.4 (16.4, 26.0) vs. 15.8 (14.0, 18.6) at 2 days, 20.6 (17.0, 23.0) vs. 16.7 (15.0, 19.0) at 3 days, all P < 0.01]. In terms of diaphragm function, end-inspiratory diaphragm thickness (DTei) at 3 days in the NAVA group was significantly higher than that in the PSV group [cm: 0.26 (0.22, 0.29) vs. 0.22 (0.19, 0.26), P < 0.05]. There was no significant difference in end-expiratory diaphragm thickness (DTee) between the two groups. The diaphragm thickening fraction (DTF) at 2 days and 3 days in the NAVA group was significantly higher than that in the PSV group [(35.18±12.09)% vs. (26.88±8.33)% at 2 days, (35.54±13.40)% vs. (24.39±9.16)% at 3 days, both P < 0.05]. Conclusions:NAVA mode can be applied in patients with neuro-severe cerebrovascular disease, which can prolong the time without mechanical ventilation support and make patients obtain better lung protective ventilation. At the same time, it has certain advantages in avoiding ventilator-associated diaphragm dysfunction and improving diaphragm function.

OBJECTIVE: To observe the effect of Tongdu Tiaoshen (promoting the circulation of the governor vessel and regulating the spirit) electroacupuncture (EA) pretreatment on pyroptosis mediated by peroxisome proliferators-activated receptor γ (PPARγ) of the cerebral cortex in rats with cerebral ischemia reperfusion injury (CIRI) and explore the potential mechanism of EA for the prevention and treatment of CIRI. METHODS: A total of 110 clean-grade male SD rats were randomly divided into a sham-operation group, a model group, an EA group, an EA + inhibitor group and an agonist group, 22 rats in each group. In the EA group, before modeling, EA was applied to "Baihui" (GV 20), "Fengfu" (GV 16) and "Dazhui" (GV 14), with disperse-dense wave, 2 Hz/5 Hz in frequency, 1 to 2 mA in intensity, lasting 20 min; once a day, consecutively for 7 days. On the base of the intervention as the EA group, on the day 7, the intraperitoneal injection with the PPARγ inhibitor, GW9662 (10 mg/kg) was delivered in the EA + inhibitor group. In the agonist group, on the day 7, the PPARγ agonist, pioglitazone hydrochloride (10 mg/kg) was injected intraperitoneally. At the end of intervention, except the sham-operation group, the modified thread embolization method was adopted to establish the right CIRI model in the rats of the other groups. Using the score of the modified neurological severity score (mNSS), the neurological defect condition of rats was evaluated. TTC staining was adopted to detect the relative cerebral infarction volume of rat, TUNEL staining was used to detect apoptosis of cerebral cortical nerve cells and the transmission electron microscope was used to observe pyroptosis of cerebral cortical neural cells. The positive expression of PPARγ and nucleotide-binding to oligomerization domain-like receptor protein 3 (NLRP3) in the cerebral cortex was detected with the immunofluorescence staining. The protein expression of PPARγ, NLRP3, cysteinyl aspartate specific protease-1 (caspase-1), gasdermin D (GSDMD) and GSDMD-N terminal (GSDMD-N) in the cerebral cortex was detected with Western blot. Using the quantitative real-time fluorescence-PCR, the mRNA expression of PPARγ, NLRP3, caspase-1 and GSDMD of the cerebral cortex was detected. The contents of interleukin (IL)-1β and IL-18 in the cerebral cortex of rats were determined by ELISA. RESULTS: Compared with the sham-operation group, the mNSS, the relative cerebral infarction volume and the TUNEL positive cells rate were increased (P<0.01), pyroptosis was severe, the protein and mRNA expression levels of PPARγ, NLRP3, caspase-1 and GSDMD were elevated (P<0.01); and the protein expression of GSDMD-N and contents of IL-1β and IL-18 were increased (P<0.01) in the model group. When compared with the model group, the mNSS, the relative cerebral infarction volume and the TUNEL positive cells rate were decreased (P<0.01), pyroptosis was alleviated, the protein and mRNA expression levels of PPARγ were increased (P<0.01), the protein and mRNA expression levels of NLRP3, caspase-1 and GSDMD were decreased (P<0.01), the protein expression of GSDMD-N was reduced (P<0.01); and the contents of IL-1β and IL-18 were lower (P<0.01) in the EA group and the agonist group; while, in the EA + inhibitor group, the protein expression of PPARγ was increased (P<0.01), the protein and mRNA expression levels of NLRP3 and GSDMD were decreased (P<0.01, P<0.05), the mRNA expression of caspase-1 was reduced (P<0.01); and the contents of IL-1β and IL-18 were lower (P<0.01). When compared with the EA + inhibitor group, the mNSS, the relative cerebral infarction volume and the TUNEL positive cells rate were decreased (P<0.05, P<0.01), pyroptosis was alleviated, the protein and mRNA expression levels of PPARγ were increased (P<0.01), the protein and mRNA expression levels of NLRP3, caspase-1 and GSDMD were decreased (P<0.01), the protein expression of GSDMD-N was reduced (P<0.01); and the contents of IL-1β and IL-18 were declined (P<0.01) in the EA group. Compared with the agonist group, in the EA group, the relative cerebral infarction volume and the TUNEL positive cells rate were increased (P<0.05, P<0.01), the mRNA expression of PPARγ was decreased (P<0.01) and the protein expression of GSDMD-N was elevated (P<0.05); and the contents of IL-1β and IL-18 were higher (P<0.01). CONCLUSION Tongdu Tiaoshen EA pretreatment can attenuate the neurological impairment in the rats with CIRI, and the underlying mechanism is related to the up-regulation of PPARγ inducing the inhibition of NLRP3 in the cerebral cortex of rats so that pyroptosis is affected.
Male ; Animals ; Rats ; Rats, Sprague-Dawley ; PPAR gamma/genetics* ; Pyroptosis ; Interleukin-18 ; Electroacupuncture ; NLR Family, Pyrin Domain-Containing 3 Protein ; Cerebral Cortex ; Cerebral Infarction/therapy* ; Caspases ; RNA, Messenger