The innate immune system detects cellular stressors and microbial infections, activating programmed cell death (PCD) pathways to eliminate intracellular pathogens and maintain homeostasis. Among these pathways, pyroptosis, apoptosis, and necroptosis represent the most characteristic forms of PCD. Although initially regarded as mechanistically distinct, emerging research has revealed significant crosstalk among their signaling cascades. Consequently, the concept of PANoptosis has been proposed—an inflammatory cell death pathway driven by caspases and receptor-interacting protein kinases (RIPKs), and regulated by the PANoptosome, which integrates key features of pyroptosis, apoptosis, and necroptosis. The core mechanism of PANoptosis involves the assembly and activation of the PANoptosome, a macromolecular complex composed of three structural components: sensor proteins, adaptor proteins, and effector proteins. Sensors detect upstream stimuli and transmit signals downstream, recruiting critical molecules via adaptors to form a molecular scaffold. This scaffold activates effectors, triggering intracellular signaling cascades that culminate in PANoptosis. The PANoptosome is regulated by upstream molecules such as interferon regulatory factor 1 (IRF1), transforming growth factor beta-activated kinase 1 (TAK1), and adenosine deaminase acting on RNA 1 (ADAR1), which function as molecular switches to control PANoptosis. Targeting these switches represents a promising therapeutic strategy. Furthermore, PANoptosis is influenced by organelle functions, including those of the mitochondria, endoplasmic reticulum, and lysosomes, highlighting organelle-targeted interventions as effective regulatory approaches. Cardiovascular diseases (CVDs), the leading global cause of morbidity and mortality, are profoundly impacted by PCD. Extensive crosstalk among multiple cell death pathways in CVDs suggests a complex regulatory network. As a novel cell death modality bridging pyroptosis, apoptosis, and necroptosis, PANoptosis offers fresh insights into the complexity of cell death and provides innovative strategies for CVD treatment. This review summarizes current evidence linking PANoptosis to various CVDs, including myocardial ischemia/reperfusion injury, myocardial infarction, heart failure, arrhythmogenic cardiomyopathy, sepsis-induced cardiomyopathy, cardiotoxic injury, atherosclerosis, abdominal aortic aneurysm, thoracic aortic aneurysm and dissection, and vascular toxic injury, thereby providing critical clinical insights into CVD pathophysiology. However, the current understanding of PANoptosis in CVDs remains incomplete. First, while PANoptosis in cardiomyocytes and vascular smooth muscle cells has been implicated in CVD pathogenesis, its role in other cell types—such as vascular endothelial cells and immune cells (e.g., macrophages)—warrants further investigation. Second, although pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) are known to activate the PANoptosome in infectious diseases, the stimuli driving PANoptosis in CVDs remain poorly defined. Additionally, methodological challenges persist in identifying PANoptosome assembly in CVDs and in establishing reliable PANoptosis models. Beyond the diseases discussed, PANoptosis may also play a role in viral myocarditis and diabetic cardiomyopathy, necessitating further exploration. In conclusion, elucidating the role of PANoptosis in CVDs opens new avenues for drug development. Targeting this pathway could yield transformative therapies, addressing unmet clinical needs in cardiovascular medicine.

Objective: For patients with atrial fibrillation (AF) complicated with acute coronary syndrome (ACS), both anticoagulant and antiplatelet therapy should be applied, but the use of anticoagulation therapy is still poor in these patients in China. The purpose of this study was to explore the status and adherence of antithrombotic therapy in AF patients with ACS and the impact on 1 year clinical outcomes. Methods: Patients with AF hospitalized for ACS were retrospectively included from 6 tertiary hospitals in China between July 2015 and December 2020. According to the use of anticoagulant drugs at discharge, patients were divided into two groups: anticoagulant treatment group and non-anticoagulant treatment group. Logistic regression model was used to analyze the main factors influencing the use of anticoagulant drugs in patients with atrial fibrillation complicated with ACS. Major adverse cardiac events (MACEs) were defined as all-cause death, non-fatal myocardial infarction or coronary revascularization, and ischemic stroke and Bleeding Academic Research Consortium (BARC) 3 bleeding events were also collected at 1 year after discharge. After propensity score matching, Cox proportional hazards models and Kaplan-Meier analysis were used to evaluate the effect of anticoagulant treatment and non-anticoagulant treatment on 1-year prognosis. The patients were divided into different groups according to whether anticoagulation was performed at discharge and follow-up, and the sensitivity of the results was analyzed. Results: A total of 664 patients were enrolled, and 273 (41.1%) were treated with anticoagulant therapy, of whom 84 (30.8%) received triple antithrombotic therapy, 91 (33.3%) received double antithrombotic therapy (single antiplatelet combined with anticoagulant), and 98 (35.9%) received single anticoagulant therapy. Three hundred and ninety-one (58.9%) patients were treated with antiplatelet therapy, including 253 (64.7%) with dual antiplatelet therapy and 138 (35.3%) with single antiplatelet therapy. After 1∶1 propensity score matching between the anticoagulant group and the non-anticoagulant group, a total of 218 pairs were matched. Multivariate logistic regression analysis showed that history of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention were predictors of the absence of anticoagulant therapy, while history of ischemic stroke and persistent atrial fibrillation were predictors of anticoagulant therapy. At 1-year follow-up, 218 patients (79.9%) in the anticoagulant group continued to receive anticoagulant therapy, and 333 patients (85.2%) in the antiplatelet group continued to receive antiplatelet therapy. At 1-year follow-up, 36 MACEs events (13.2%) occurred in the anticoagulant group, and 81 MACEs events (20.7%) in the non-anticoagulant group. HR values and confidence intervals were calculated by Cox proportional risk model. Patients in the non-anticoagulant group faced a higher risk of MACEs (HR=1.802, 95%CI 1.112-2.921, P=0.017), and the risk of bleeding events was similar between the two group (HR=0.825,95%CI 0.397-1.715, P=0.607). Conclusions: History of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention are independent factors for the absence of anticoagulant therapy in patients with AF complicated with ACS. The incidence of MACEs, death and myocardial infarction is lower in the anticoagulant group, and the incidence of bleeding events is similar between the two groups. The risk of bleeding and ischemia/thrombosis should be dynamically assessed during follow-up and antithrombotic regiments should be adjusted accordingly.
Humans ; Atrial Fibrillation/drug therapy* ; Platelet Aggregation Inhibitors/adverse effects* ; Acute Coronary Syndrome/drug therapy* ; Fibrinolytic Agents/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Anticoagulants ; Myocardial Infarction/complications* ; Hemorrhage ; Percutaneous Coronary Intervention ; Ischemic Stroke/drug therapy* ; Stroke

Dyskeratosis Congenita/genetics* ; Enterocolitis/genetics* ; Fetal Growth Retardation ; Humans ; Intellectual Disability/genetics* ; Microcephaly/genetics*

The incidence of liver disease is increasing year by year. Due to the complex predisposing factors and unclear pathogenesis of liver diseases, the cure rate is still not ideal, so it is urgent to clarify its mechanism to find more effective therapeutic targets and drugs. Long non-coding RNA (lncRNA), as a non-coding RNA with a length of more than 200 nt, is a research hotspot in liver diseases in recent years. Focusing on the main signal transduction pathways in liver diseases, this review mainly summarizes the latest research progress of lncRNA in regulating liver disease-related signaling pathways, and elaborates that lncRNAs participate in various physiological processes such as cell proliferation, apoptosis, invasion, and migration by regulating key signaling pathways in liver diseases, thereby promoting the occurrence and development of liver diseases. This review provides new ideas for studying the mechanism of liver diseases, and new directions for finding new targets and biomarkers for the treatment of liver diseases.

Objective:To study the effect of Ganoderma triterpenoids combined with exogenous monosialoteterahexosyl ganglioside (GM1) on cognitive dysfunction in rats with epilepsy. Methods:A total of 75 Sprague-Dawley rats were divided randomly into blank control group, epileptic model group, Ganoderma triterpenoids group, GM1 group and GM1 combined with Ganoderma triterpenoids group (combination group), with 15 rats in each group. All the groups, except the blank control group, were intraperitoneally injected with pentylenetetrazol (PTZ) 35 mg/kg once a day for 28 days. Medication groups were given corresponding administration based on daily intraperitoneal injection of PTZ. They were tested with Morris Water Maze; and were observed with transmission electron microscopy and HE staining for hippocampal neurons. Real-time quantitative polymerase chain reaction was used to detect the expression of actin-binding protein (Cofilin), synaptophysin (SYN) and growth-associated protein 43 (GAP-43) mRNA in hippocampus of rats. Results:Compared with the blank control group, the escape lantency prolonged in the epileptic model group in all the time points (P < 0.05). Compared with the epileptic model group, the escape lantency shortened in the treatment groups somewhen (P < 0.05). Compared with the epileptic model group, the number of crossing the platform increased in the treatment groups (P < 0.01), and the time of staying in the target quadrant prolonged (P < 0.01); while the number of pyramidal cells increased, the nuclear lysis and fragmentation reduced, the structure of neurons and the number of synapses improved， as well as the organelle structure. Compared with the blank control group, the expression of Cofilin mRNA increased (P < 0.05), and the expression of SYN mRNA and GAP-43 mRNA decreased (P < 0.05) in the epileptic model group; compared with the epileptic model group, the expression of Cofilin mRNA decreased (P < 0.05), and the expression of SYN mRNA increased (P < 0.05) in all the treatment groups, while the expression of GAP-43 mRNA increased (P < 0.05) only in the combination group. Conclusion:Ganoderma triterpenoids, GM1 and their combination can improve the learning and memory abilities of epileptic rats, which may be associated with increasing the expression of SYN and GAP-43, decreasing the expression of Cofilin, to promote the synaptic remodeling of hippocampal tissue and protect brain neurons from PTZ-induced epilepsy.

Objective: To study and create the algorithm for the diversity (AD) of extensible markup language (XML) tree map, and provide a new tool for the identification of Artemisiae Annuae Herba. Method: According to the literature research, the key information of Artemisiae Annuae Herba was selected from the macroscopic, mesoscopic and microscopic information, etc. Based on the key information, the relevant upper standards of domestic and foreign professional fields were cited to assign the unique identification independent of language for each data element, and the coding rules of relevant data elements were established. The digital coding technology was applied to the flexible structure editor, and the tree map was created, which could be returned as the 5^th version of hypertext markup language (HTML5) or XML format. Based on the diversity related algorithms, the authors innovatively developed the AD of XML tree map of Artemisiae Annuae Herba, which took into account both of topology and semantics, and the expression model of related mathematical functions of Artemisiae Annuae Herba was established. By comparing the calculation results with the reality, the algorithm model was debugged continuously until the convergence of the core-culvert algorithm model. Result: Through the research on AD, the diversity between two XML tree maps could be calculated, and the discrimination or identification model of Artemisiae Annuae Herba also could be finally optimized and established. After calculation and analysis of the tested tree maps, the effective rate of the model was 100%. Conclusion: In this study, the establishment of the AD of XML tree map can effectively assist in the identification of Artemisiae Annuae Herba, which provides certain technical support and theoretical guidance for the research on intelligent application of traditional Chinese medicine.

OBJECTIVE: To investigate the clinical manifestations pathologic features, treatment options and prognosis of patients with bone lymphoma. METHODS: The clinical characteristics, pathologic features, treatment and prognosis of 34 BL patients diagnosed by histopathologic method or/and PET-CT and treated in first hospital of peking university from January 2004 to April 2018 were analyzed retrospectively. RESULTS: The median age of 34 BL patients was 56 years old, the male and female ratio was 1.43∶1 (24 /10). Among 34 patients, the patients with primary bone lymphoma(PBL) were 8 cases, the patients with secondary bone lymphoma(SBL) was 26 cases, the PBL and SBL ratio was 0.31∶1. Bone lymphoma lacks typical systemic symptoms, and its onset began mostly from bone pain and pathologic bone fracture. The most frequent pathological type of bone lymphoma in our study was diffuse large B-cell lymphoma (DLBCL), accounting for 55.88%. At present, the conventional treatment for bone lymphoma includes chemotherapy, or chemotherapy combined with radiotherapy and surgery, as well as hematopoietic stem cell transplantation. The average and median OS time of BL patients were 349 years and 3 years respectively, meanwhile the OS rate for three years and two years were 56.25% and 78.16%, respectively. Factors that affect survival of BL patients were PBL and SBL classification, pathological type, blood LDH level, and treatment methods. CONCLUSION Bone lymphoma is usually concealed onset，an adequate and adequate combination therapy can improve the survival rate and transplantation therapy plays an important role. Primary bone lymphoma is rare, the prognosis of patients with primary bone lymphoma is good, whereas the prognosis of patients with secondary bone lymphoma is poor.
Bone Neoplasms ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma, Large B-Cell, Diffuse ; Male ; Middle Aged ; Positron Emission Tomography Computed Tomography ; Prognosis ; Retrospective Studies

BackgroundPlacebo was defined as any therapy that is used for its nonspecific psychological and physiologic effect but has no specific pharmacologic impact on the condition being treated. Besides medication therapies, studies have found that the optimal dietary approach as well as physical activity and education are useful to control hyperglycemia in patients with type 2 diabetes (T2DM). The aim of this study was to evaluate the placebo effects of antidiabetic therapies in Asian and Caucasian T2DM patients and make a comparison between the two ethnicities.

MethodsA search using the MEDLINE database, EMBASE, and Cochrane Database was performed, from when recording began until December 2016. The main concepts searched in English were sulfonylurea (SU); alpha glucosidase inhibitors (AGI); metformin (MET); thiazolidinediones (TZD); dipeptidyl peptidase-4 inhibitors (DPP-4i); sodium-glucose cotransporter 2 inhibitors (SGLT2i); glucagon-like peptide-1 receptor agonist (GLP-1RA); type 2 diabetes (T2DM); placebo controlled; and randomized controlled trials. Using the Cochrane instrument, we evaluated the adequacy of randomization, allocation concealment procedures, and blinding.

ResultsThis study included 63 studies with a total of 7096 Asian patients involved and 262 studies with a total of 27,477 Caucasian patients involved. In Caucasian population, the use of placebo led to significant reductions of glycosylated hemoglobin (HbA1c), -0.683% (P = 0.008) in SU monotherapy treatment, -0.193% (P = 0.001) in DPP-4i treatment, and -0.230% (P < 0.001) in SGLT2i treatment, respectively. In Asian population, the use of placebo resulted in significant decreases of HbA1c, -0.162% (P = 0.012) in DPP-4i treatment and -0.269% (P = 0.028) in GLP-1RA add-on therapy, respectively. The placebo also significantly reduced body weight. In Caucasian population, placebo use resulted in 0.833 kg (P = 0.006) weight loss by SU treatment and 0.953 kg (P = 0.006) weight loss by GLP-1RA treatment. In Asian population, the placebo led to a weight change of 0.612 kg (P < 0.001) by GLP-1RA analog treatment. The changes of HbA1c and weight due to the placebo effect in other treatments were not significant in both Asian and Caucasian population. Comparisons of the placebo effect on HbA1c change and weight change in each treatment group indicated that no significant difference was found between Asian and Caucasian population.

ConclusionsThe overall differences of the placebo effect on HbA1c changes as well as on body weight changes were not significant between Asian and Caucasian T2DM patients. The placebo effect on HbA1c changes and weight changes was not associated with baseline age, gender, baseline body mass index, baseline HbA1c, duration of diabetes, or study duration.

Objective: To investigate the cause of massive hemoptysis in critical patients, and to evaluate the effect of bronchial artery embolization (BAE) on critical patients with massive hemoptysis. Methods: A retrospective controlled analysis was conducted. The clinical data of 35 patients with life-threatening massive hemoptysis admitted to intensive care unit (ICU) of the First Hospital Affiliated to Guangzhou Medical University from January 2009 to December 2017 were analyzed. The patients were divided into BAE and non-BAE group according to whether receiving BAE or not. BAE patients were subdivided into subgroups: hemoptysis after ventilation and hemoptysis before ventilation subgroups, as well as survival and non-survival subgroups. The etiology of all massive hemoptysis was analyzed. The gender, age, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, amount of hemoptysis, whether presence of pleural thickening in chest CT, the length of ICU stay, total length of hospital stay, the duration of mechanical ventilation (MV), clinical effective and prognostic indicators of patients were recorded. The correlation between variables was analyzed by Spearman correlation analysis. Results: All 35 patients were enrolled in the finally analysis. The main cause of critical patients with massive hemoptysis was fungal infection [37.1% (13/35)], followed by pneumonia and abnormal coagulation [17.1% (6/35)], bronchiectasis [11.4% (4/35)], tumor [8.6% (3/35)], etc. In all 35 patients, 27 were treated with BAE and 8 were treated without BAE. There was no difference in gender, age, the length of ICU stay, total length of hospital stay, the duration of MV, amount of hemoptysis, APACHEⅡ score, whether use antiplatelet agents or anticoagulants, or whether presence of pleural thickening in chest CT between the two groups. The rate of hemoptysis remission in BAE group was significantly higher than that of non-BAE group [92.6% (25/27) vs. 25.0% (2/8), P < 0.01], but there was no statistically significant difference in hospital survival as compared with that of non-BAE group [48.1% (13/27) vs. 25.0% (2/8), P > 0.05]. Subgroup analysis showed that 64.3% (9/14) of patients with hemoptysis after ventilation was caused by pulmonary fungal infection, which was significantly higher than those with hemoptysis before ventilation [15.4% (2/13), P = 0.018]. Compared with hemoptysis after ventilation group, the length of ICU stay and the duration of MV in hemoptysis before ventilation group were significantly shortened [the length of ICU stay (days): 12.0 (14.0) vs. 30.0 (81.8), the duration of MV (days): 10.0 (16.0) vs. 25.0 (68.3)], the patients using antiplatelet drugs or anticoagulant drugs was decreased significantly (case: 1 vs. 9, all P < 0.05). However, there was no statistically significant difference in gender, age, total length of hospital stay, amount of hemoptysis, APACHEⅡ score, whether presence of pleural thickening in chest CT, the rate of hemoptysis remission, the incidence of secondary BAE or hospital survival rate between the two groups. Compared with the survival subgroup (n = 13), more patients in the non-survival subgroup (n = 14) were treated with antiplatelet or anticoagulants (P < 0.05); and Spearman correlation analysis showed that the survival of the patients with BAE was negatively correlated with the use of antiplatelet or anticoagulants (r = -0.432, P = 0.024). There was no significant difference in the gender, age, the length of ICU day, total length of hospitalization, duration of MV, estimated hemoptysis, APACHE Ⅱ score, or the proportion of pleural thickening between the two groups. Conclusions The study indicated that the etiology of massive hemoptysis in critical patients was complicated. Fungal infection was the main cause in patients with hemoptysis after ventilation. BAE was effective in the control of massive hemoptysis in ICU, but it was not ideal for patients with abnormal coagulation function or abnormal platelet count or platelet dysfunction from antiplatelet or anticoagulant drugs, the overall survival rate was still low.

OBJECTIVE: To investigate the cause of massive hemoptysis in critical patients, and to evaluate the effect of bronchial artery embolization (BAE) on critical patients with massive hemoptysis. METHODS: A retrospective controlled analysis was conducted. The clinical data of 35 patients with life-threatening massive hemoptysis admitted to intensive care unit (ICU) of the First Hospital Affiliated to Guangzhou Medical University from January 2009 to December 2017 were analyzed. The patients were divided into BAE and non-BAE group according to whether receiving BAE or not. BAE patients were subdivided into subgroups: hemoptysis after ventilation and hemoptysis before ventilation subgroups, as well as survival and non-survival subgroups. The etiology of all massive hemoptysis was analyzed. The gender, age, acute physiology and chronic health evaluation II (APACHE II) score, amount of hemoptysis, whether presence of pleural thickening in chest CT, the length of ICU stay, total length of hospital stay, the duration of mechanical ventilation (MV), clinical effective and prognostic indicators of patients were recorded. The correlation between variables was analyzed by Spearman correlation analysis. RESULTS: All 35 patients were enrolled in the finally analysis. The main cause of critical patients with massive hemoptysis was fungal infection [37.1% (13/35)], followed by pneumonia and abnormal coagulation [17.1% (6/35)], bronchiectasis [11.4% (4/35)], tumor [8.6% (3/35)], etc. In all 35 patients, 27 were treated with BAE and 8 were treated without BAE. There was no difference in gender, age, the length of ICU stay, total length of hospital stay, the duration of MV, amount of hemoptysis, APACHE II score, whether use antiplatelet agents or anticoagulants, or whether presence of pleural thickening in chest CT between the two groups. The rate of hemoptysis remission in BAE group was significantly higher than that of non-BAE group [92.6% (25/27) vs. 25.0% (2/8), P < 0.01], but there was no statistically significant difference in hospital survival as compared with that of non-BAE group [48.1% (13/27) vs. 25.0% (2/8), P > 0.05]. Subgroup analysis showed that 64.3% (9/14) of patients with hemoptysis after ventilation was caused by pulmonary fungal infection, which was significantly higher than those with hemoptysis before ventilation [15.4% (2/13), P = 0.018]. Compared with hemoptysis after ventilation group, the length of ICU stay and the duration of MV in hemoptysis before ventilation group were significantly shortened [the length of ICU stay (days): 12.0 (14.0) vs. 30.0 (81.8), the duration of MV (days): 10.0 (16.0) vs. 25.0 (68.3)], the patients using antiplatelet drugs or anticoagulant drugs was decreased significantly (case: 1 vs. 9, all P < 0.05). However, there was no statistically significant difference in gender, age, total length of hospital stay, amount of hemoptysis, APACHE II score, whether presence of pleural thickening in chest CT, the rate of hemoptysis remission, the incidence of secondary BAE or hospital survival rate between the two groups. Compared with the survival subgroup (n = 13), more patients in the non-survival subgroup (n = 14) were treated with antiplatelet or anticoagulants (P < 0.05); and Spearman correlation analysis showed that the survival of the patients with BAE was negatively correlated with the use of antiplatelet or anticoagulants (r = -0.432, P = 0.024). There was no significant difference in the gender, age, the length of ICU day, total length of hospitalization, duration of MV, estimated hemoptysis, APACHE II score, or the proportion of pleural thickening between the two groups. CONCLUSIONS The study indicated that the etiology of massive hemoptysis in critical patients was complicated. Fungal infection was the main cause in patients with hemoptysis after ventilation. BAE was effective in the control of massive hemoptysis in ICU, but it was not ideal for patients with abnormal coagulation function or abnormal platelet count or platelet dysfunction from antiplatelet or anticoagulant drugs, the overall survival rate was still low.
APACHE ; Bronchial Arteries ; Hemoptysis ; Humans ; Intensive Care Units ; Prospective Studies ; Retrospective Studies