Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

OBJECTIVE: To assess the relationship between blood pressure reactivity index (BPRI) and in-hospital mortality risk in patients with sepsis-associated acute kidney injury (SA-AKI). METHODS: A retrospective cohort study was conducted to collect data from patients admitted to the intensive care unit (ICU) and clinically diagnosed with SA-AKI between 2008 and 2019 in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database in the United States. The collected data included demographic characteristics, comorbidities, vital signs, laboratory parameters, sequential organ failure assessment (SOFA) and simplified acute physiology scoreII(SAPSII) within 48 hours of SA-AKI diagnosis, stages of AKI, treatment regimens, mean BPRI during the first and second 24 hours (BPRI_0_24, BPRI_24_48), and outcome measures including primary outcome (in-hospital mortality) and secondary outcomes (ICU length of stay and total hospital length of stay). Variables with statistical significance in univariate analysis were included in LASSO regression analysis for variable selection, and the selected variables were subsequently incorporated into multivariate Logistic regression analysis to identify independent predictors associated with in-hospital mortality in SA-AKI patients. Restricted cubic spline (RCS) analysis was employed to examine whether there was a linear relationship between BPRI within 48 hours and in-hospital mortality in SA-AKI patients. Basic prediction models were constructed based on the independent predictors identified through multivariate Logistic regression analysis, and receiver operator characteristic curve (ROC curve) was plotted to evaluate the predictive performance of each basic prediction model before and after incorporating BPRI. RESULTS: A total of 3 517 SA-AKI patients admitted to the ICU were included, of whom 826 died during hospitalization and 2 691 survived. The BPRI values within 48 hours of SA-AKI diagnosis were significantly lower in the death group compared with the survival group [BPRI_0_24: 4.53 (1.81, 8.11) vs. 17.39 (5.16, 52.43); BPRI_24_48: 4.76 (2.42, 12.44) vs. 32.23 (8.85, 85.52), all P < 0.05]. LASSO regression analysis identified 20 variables with non-zero coefficients that were included in the multivariate Logistic regression analysis. The results showed that respiratory rate, temperature, pulse oxygen saturation (SpO₂), white blood cell count (WBC), hematocrit (HCT), activated partial thromboplastin time (APTT), lactate, oxygenation index, SOFA score, fluid balance (FB), BPRI_0_24, and BPRI_24_48 were all independent predictors for in-hospital mortality in SA-AKI patients (all P < 0.05). RCS analysis revealed that both BPRI showed "L"-shaped non-linear relationships with the risk of in-hospital mortality in SA-AKI patients. When BPRI_0_24 ≤ 14.47 or BPRI_24_48 ≤ 24.21, the risk of in-hospital mortality in SA-AKI increased as BPRI values decreased. Three basic prediction models were constructed based on the identified independent predictors: Model 1 (physiological indicator model) included respiratory rate, temperature, SpO₂, and oxygenation index; Model 2 (laboratory indicator model) included WBC, HCT, APTT, and lactate; Model 3 (scoring indicator model) included SOFA score and FB. ROC curve analysis showed that the predictive performance of the basic models ranked from high to low as follows: Model 3, Model 2, and Model 1, with area under the curve (AUC) values of 0.755, 0.661, and 0.655, respectively. The incorporation of BPRI indicators resulted in significant improvement in the discriminative ability of each model (all P < 0.05), with AUC values increasing to 0.832 for Model 3+BPRI, 0.805 for Model 2+BPRI, and 0.808 for Model 1+BPRI. CONCLUSIONS BPRI is an independent predictor factor for in-hospital mortality in SA-AKI patients. Incorporating BPRI into the prediction model for in-hospital mortality risk in SA-AKI can significantly improve its predictive capability.
Humans ; Acute Kidney Injury/mortality* ; Sepsis/complications* ; Retrospective Studies ; Hospital Mortality ; Prognosis ; Blood Pressure ; Intensive Care Units ; Male ; Female ; Length of Stay ; Middle Aged ; Aged ; Adult ; Logistic Models

Stress and illness connection is complex and involves multiple physiological systems. Panax ginsengs, reputed for their broad-spectrum "cure-all" effect, are widely prescribed to treat stress and related illnesses. However, the identity of ginseng's "cure-all" medicinal compounds that relieve stress remains unresolved. Here, we identify ginsentides as the principal bioactives that coordinate multiple systems to restore homeostasis in response to stress. Ginsentides are disulfide-rich, cell-penetrating and proteolytic-stable microproteins. Using affinity-enrichment mass spectrometry target identification together with in vitro, ex vivo and in vivo validations, we show that highly purified or synthetic ginsentides promote vasorelaxation by producing nitric oxide through endothelial cells via intracellular PI3K/Akt signaling pathway, alleviate α1-adrenergic receptor overactivity by reversing phenylephrine-induced constriction of aorta, decrease monocyte adhesion to endothelial cells via CD166/ESAM/CD40 and inhibit P2Y12 receptors to reduce platelet aggregation. Orally administered ginsentides were effective in animal models to reduce ADP-induced platelet aggregation, to prevent collagen and adrenaline-induced pulmonary thrombosis as well as anti-stress behavior of tail suspension and forced swimming tests in mice. Together, these results strongly suggest that ginsentides are the principal panacea compounds of ginsengs because of their ability to target multiple extra- and intra-cellular proteins to reverse stress-induced damages.

Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious impact on global public health and the economy. SARS-CoV-2 infiltrates host cells via its surface spike protein, which binds to angiotensin-converting enzyme 2 on the host cell membrane. As a result, small molecules targeting spike protein have emerged as a hotspot in anti-SARS-CoV-2 drug research. Activity screening is an important step in seeking small molecule drugs. Therefore, this article aims to review the biological activity evaluation methods of small molecule inhibitors targeting SARS-CoV-2 spike protein, with the goal of laying the foundation for the discovery of new anti-SARS-CoV-2 drugs.

Small-molecule phenolic substances widely exist in animals and plants, and have some shared biological activities. The metabolism of phenylalanine and tyrosine in the human body, and especially the metabolism of catecholamine neurotransmitters, produces endogenous small-molecule phenols. Endogenous small-molecule phenolic substances are functionally related to the important physiological processes and the occurrence of mental diseases in humans and some animals, which are systematically sorts and summarized in this review. Integrating the previous experimental research and literature analysis on natural small-molecule phenols by our research group, the understanding of the hypothesis that "small-molecule phenol are pharmacological signal carriers" was deepened. Based on above, the concept of "phenolomics" was further proposed, analyzed the research direction and research content which can bring into the knowledge framework of phenolomics. The induction of phenolomics will provide wider perspectives on explaining the pharmacological mechanism of drugs, discovering new drug targets, and finding biomarkers of mental diseases.

The analysis of ammonia nitrogen in real water samples is challenging due to matrix interferences and difficulties for rapid on-site analysis.On the basis of the standard method,i.e.water quality-determination of ammonia nitrogen-salicylic acid spectrophotometry(HJ 536-2009),a simple device for online detecting ammonia nitrogen was developed using a sequential injection analysis(SIA)system in this work.The ammonia nitrogen transformation system,color reaction system,and detection system were built in compatible with the SIA system,respectively.In particular,the detection system was assembled by employing light-emitting diode as the light source,photodiode as the detector,and polyvinylchloride tube as the cuvette,thus significantly reducing the volume,energy consumption and fabricating cost of the detection system.As a result,the accurate analysis of ammonia nitrogen in complex water samples was achieved.A quantitative detection of ammonia nitrogen in water sample was obtained in 12 min,along with linear range extending to 1000 μmol/L,precisions(Relative standard deviation,RSD)of 4.3%(C=10 μmol/L,n=7)and 4.2%(C=500 μmol/L,n=7),and limit of detection(LOD)of 0.65 μmol/L(S/N=3,n=7).The results of interfering experiments showed that the detection of ammonia nitrogen by the developed device was not interfered by the common coexisting ions and components,therefore the environmental water could be directly analyzed,such as reservoir water,domestic sewage,sea water and leachate of waste landfill.The analytical results were consistent with those obtained by the environmental protection standard method(Water quality determination of ammonia nitrogen-salicylic acid spectrophotometry,HJ 536-2009).In addition,the spiking recoveries were in the range of 92.3%-98.1%,further confirming the accuracy and practicality of the developed device.

The core of theory of visceral manifestation of spleen is about'spleen in charge of transportation and transformation,spleen qi dispersing the essence'.Middle-jiao spleen-earth has the functions of digesting food and transporting food essence,and maintaining the homeostasis of glucose and lipid metabolism in the body.'Spleen in charge of transportation and transformation,spleen qi dispersing the essence'functions like the glucose and lipid metabolism at physiological state.The deficiency of spleen results in the dysfunction of food in-take and digestion and the susceptibility to external pathogens;qi deficiency and blood stasis lead to the interior damp-heat,and the long-term accumulation of damp-heat develops into stasis and then turns into toxins,which eventually induces inflammation-to-tumor transition.The pathogenesis of'spleen deficiency being the root cause and stasis blended with toxins'is correlated with the pathological changes of inflammation-to-tumor transition.The therapy of strengthening the spleen,dispersing essence and removing turbidity is effective on improving the disorder of glucose and lipid metabolism,and the therapy of strengthening the spleen,resolving stasis and removing toxin is effective on restraining the process of inflammation-to-tumor transition in the stomach.It has become a new direction in the field of spleen-stomach research to expound the scientific connotation of the essence of spleen function of'spleen in charge of transportation and transformation,spleen qi dispersing the essence'from the perspective of glucose and lipid metabolism,to focus on the inflammation-to-tumor transition process of major diseases of digestive system,to explore the evolution of the traditional Chinese medicine syndromes of inflammatory diseases and precancerous lesions of the digestive tract,and to reveal the pharmacological mechanism of treatment from the perspective of spleen,which will enrich the scientific connotation of theory of visceral manifestation of spleen and promote the modernization and internationalization of traditional Chinese medicine.