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 To explore the feasibility of applying artificial intelligence (AI) technology in chromosomal aberration (CA) analysis for occupational health surveillance of radiation workers and in biological dose estimation during nuclear emergency responses. Methods Peripheral blood samples from healthy volunteers were irradiated in vitro with X-rays and cobalt-60 (⁶⁰Co) γ rays. Chromosome slides were prepared using an automated harvesting and dropping device. The data training and outcome evaluation of CA analysis was performed on the AI software using chromosome images from occupational medical examination of radiation workers from the current lab or chromosome slides from blood samples irradiated with X-rays. The trained AI software was then used to assist in CA analysis and biological dose estimation among occupational medical examination of radiation workers, with results compared with manual reading and actual exposure doses. Results The trained AI software achieved a CA recognition accuracy of 95.11%. In the occupational health examination of radiation workers, the positive CA detection rate using AI + manual review was 2.25% higher than that in manual reviewing alone. The errors in biological dose estimation for ⁶⁰Co γ rays and X-rays using AI + manual review analysis were 11.86% and 7.33%, respectively, both within the acceptable 20.00% error margin. Conclusion AI + manual review can be effectively applied in CA analysis for occupational health examination and biological dose estimation during nuclear emergencies, significantly improving analysis efficiency.

BACKGROUND: Spatiotemporal disparities exist in the disease burden of non-communicable diseases (NCDs) attributable to kidney dysfunction, which has been poorly assessed. The present study aimed to evaluate the spatiotemporal trends of the global burden of NCDs attributable to kidney dysfunction and to predict future trends. METHODS: Data on NCDs attributable to kidney dysfunction, quantified using deaths and disability-adjusted life-years (DALYs), were extracted from the Global Burden of Diseases Injuries, and Risk Factors (GBD) Study in 2019. Estimated annual percentage change (EAPC) of age-standardized rate (ASR) was calculated with linear regression to assess the changing trend. Pearson's correlation analysis was used to determine the association between ASR and sociodemographic index (SDI) for 21 GBD regions. A Bayesian age-period-cohort (BAPC) model was used to predict future trends up to 2040. RESULTS: Between 1990 and 2019, the absolute number of deaths and DALYs from NCDs attributable to kidney dysfunction increased globally. The death cases increased from 1,571,720 (95% uncertainty interval [UI]: 1,344,420-1,805,598) in 1990 to 3,161,552 (95% UI: 2,723,363-3,623,814) in 2019 for both sexes combined. Both the ASR of death and DALYs increased in Andean Latin America, the Caribbean, Central Latin America, Southeast Asia, Oceania, and Southern Sub-Saharan Africa. In contrast, the age-standardized metrics decreased in the high-income Asia Pacific region. The relationship between SDI and ASR of death and DALYs was negatively correlated. The BAPC model indicated that there would be approximately 5,806,780 death cases and 119,013,659 DALY cases in 2040 that could be attributed to kidney dysfunction. Age-standardized death of cardiovascular diseases (CVDs) and CKD attributable to kidney dysfunction were predicted to decrease and increase from 2020 to 2040, respectively. CONCLUSION NCDs attributable to kidney dysfunction remain a major public health concern worldwide. Efforts are required to attenuate the death and disability burden, particularly in low and low-to-middle SDI regions.
Humans ; Noncommunicable Diseases/epidemiology* ; Global Burden of Disease ; Disability-Adjusted Life Years ; Male ; Female ; Risk Factors ; Middle Aged ; Kidney Diseases/epidemiology* ; Bayes Theorem ; Adult ; Aged ; Global Health ; Quality-Adjusted Life Years

OBJECTIVE: To explore the application of targeted mRNA sequencing in fusion gene diagnosis of hematologic diseases. METHODS: Bone marrow or peripheral blood samples of 105 patients with abnormally elevated eosinophil proportions and 291 acute leukemia patients from January 2015 to June 2023 in the First Affiliated Hospital of Soochow University were analyzed and gene structural variants were detected by targeted mRNA sequencing. RESULTS: Among 105 patients with abnormally elevated eosinophil proportions, 6 cases were detected with gene structural variants, among which fusion gene testing results in 5 cases could serve as diagnostic indicators for myeloid neoplasms with eosinophilia. In addition, a IL3∷ETV6 fusion gene was detected in one patient with chronic eosinophilic leukemia, not otherwise specified. Among 119 patients with acute myeloid leukemia (AML), 38 cases were detected structural variants by targeted mRNA sequencing, accounting for 31.9%, which was significantly higher than 20.2% (24/119) detected by multiple quantitative PCR (P < 0.05). We also found one patient with AML had both NUP98∷PRRX2 and KCTD5∷JAK2 fusion genes. A total of 104 patients were detected structural variants by targeted mRNA sequencing in 172 cases with acute B-lymphoblastic leukemia who were tested negative by multiple quantitative PCR, with a detection rate of 60.5% (102/172). CONCLUSION Targeted mRNA sequencing can effectively detect fusion gene and has potential clinical application value in diagnosis and classificatation in hematologic diseases.
Humans ; Hematologic Diseases/diagnosis* ; RNA, Messenger/genetics* ; Oncogene Proteins, Fusion/genetics* ; Sequence Analysis, RNA ; Leukemia, Myeloid, Acute/diagnosis*

Objective:To improve the understanding of recurrent adult Langerhans cell histiocytosis complicated with diabetes insipidus.Methods:The clinical data of 1 patient with recurrent adult Langerhans cell histiocytosis complicated with diabetes insipidus admitted to the First Affiliated Hospital of Shihezi University in January 2024 was collected. Its disease characteristics, effectiveness and safety of treatment scheme were analyzed, and literatures were reviewed.Results:The 42-year-old female patient was diagnosed as Langerhans cell histiocytosis in June 2021. After treated with cytarabine, the symptoms improved and the patient achieved sustained remission. In January 2024, the patient was admitted to the hospital due to pain in the middle part of the front chest. The PET-CT results indicated disease progression, which was manifested by new bone destruction, enlarged lymph nodes, and increased nocturnal urination, with urine volume of 3-5 L within 24 h. Based on the clinical manifestations such as cranial bone lesions, periorbital soft tissue lesions, and enlarged lymph nodes at onset, multiple systems and multiple foci involvement was considered. The diagnosis of combined diabetes insipidus was confirmed through the water deprivation and pressure test. After MACOP-B regimen (doxorubicin liposome, cyclophosphamide, vincristine, bleomycin, prednisone), the patient's bone pain was completely relieved, and no serious complications occurred.Conclusions:Recurrent adult Langerhans cell histiocytosis complicated with diabetes insipidus is rare; MACOP-B regimen is safe and effective in treatment of the disease.

Objective To explore the application effect of five kinds of sarcopenia assessment scales in the sarcopenia screening in the patients with bone tumors.Methods The convenience sampling method was a-dopted to select 198 patients with bone tumor in this hospital from August 2023 to February 2024 were select-ed as the study subjects.The Simplified Five-Item Scoring Questionnaire(SARC-F),the Modified Simplified Five-Item Scoring Questionnaire(SARC-Calf),the Simplified Five-Item Scoring Questionnaire Combined with Age and BMI(SARC-F+EBM),the Mini Sarcopenia Risk Assessment 7-Item Questionnaire(MSRA-7)and the Mini Sarcopenia Risk Assessment 5-Item Questionnaire(MSRA-5)were used for conducting the screen-ing.The Asian Sarcopenia Working Group-2019(AWGS-2019)screening criteria for sarcopenia were used as diagnostic criteria.The receiver operating characteristic(ROC)curve and area under the curve(AUC)were used to analyze the predictive efficiency.The sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV)and Kappa value were compared among various screening tools.Results According to the AWGS-2019 screening criteria for sarcopenia,there were 144 cases in the non-sarcopenia group and 54 ca-ses in the sarcopenia group,and the incidence rate of sarcopenia was 27.27％.SARC-Calf and MSRA-5 had the highest sensitivity(81.48％).SARC-F+EBM had the highest specificity(91.67％).SARC-F+EBM had the highest PPV(70.00％).SARC-Calf had the highest NPV(91.49％);SARC-F+EBM had the highest AUC(0.890),the corresponding cut-off value was 8.5 points,the sensitivity was 83.30％and specificity was 80.60％.The Kappa values of SARC-F,MSRA-5 and MSRA-7 were 0.206,0.336 and 0.324 respectively,pos-sessing the ordinary consistency,while the Kappa values of SARC-Calf and SARC-F+EBM were 0.544 and 0.474 respectively,possessing the medium consistency.Conclusion SARC-F+EBM could be used as the best screening tool of clinical medical staff for sarcopenia in the patients with bone tumor.

Objective To investigate the effect of body position angle on gastric insufflation during the induction of general anesthesia in pediatric patients undergoing day surgery.Methods A total of 111 children scheduled for elective tracheal intubation under general anesthesia at the First Affiliated Hospital of Guangxi Medical University from December 2022 to March 2023 were selected as study subjects.Six children were ex-cluded due to unclear sonographic visualization of the gastric antrum,resulting in 105 children ultimately in-cluded in the study.The children were divided into three groups using a random number table method:Group D0(supine position),Group D5(5° head-up position),and Group D10(10° head-up position),with 35 children in each group.The presence of a"comet-tail artifact"on ultrasound was used as the criterion for determining gastric insufflation during anesthesia induction.The gastric antrum cross-sectional area(CSA)of the gastric antrum was measured before mask ventilation after loss of consciousness(T1)and immediately after tracheal intubation following mask ventilation(T2).The incidence of gastric insufflation,changes in CSA and their differences,and vital sign changes at T1 and T2,were compared among the three groups.Results Compared with Group D0,the incidence of gastric insufflation was significantly lower in Groups D5 and D10[25.7％(9/35)vs.20.0％(7/35)vs.54.0％(19/35)],and the difference was statistically significant(P＜0.05).Howev-er,there was no significant difference between Group D5 and Group D10(P＞0.05).No significant difference was observed in CSA at T1 among the three groups(P＞0.05).At T2,a statistically significant difference in CSA was found among the three groups(P＜0.05),with Group D10 showing a smaller CSA than Group D0(P＜0.05).The difference in CSA changes was statistically significant among the three groups(P＜0.05),with Groups D5 and D10 exhibiting smaller changes than Group D0,and Group D10 showing a smaller change than Group D5(P＜0.05).No significant differences were observed in mean artery pressure(MAP),heart rate,pulse oxygen saturation(SpO2)and pressure of end-tidal carbon dioxide(PETCO2)at T1 and T2 among the three groups(P＞0.05).A total of 6 children(5.7％)required brief adjustments in jaw support due to irregular PETCO2 waveforms or abnormal peak airway pressure.Conclusion In pediatric patients undergoing day sur-gery under general anesthesia,a 5° head-up position during induction significantly reduces the incidence of gas-tric insufflation and minimizes changes in gastric antral CSA,while a 10° head-up position does not provide ad-ditional benefits.

OBJECTIVE To analyze the chemical components that were the absorbed in blood and liver tissue of rats after intragastric administration of aqueous extract from Abrus cantoniensis， and to speculate its possible metabolic pathways， providing reference for basic analysis of pharmacological substance in A. cantoniensis. METHODS Male SD rats were randomly divided into A. cantoniensis group （0.63 g/kg， calculated by crude drug） and blank group； they were given relevant drug solution/ultrapure water intragastrically. After a single dose， plasma and liver samples of rats in each group were collected. UPLC-Q-TOF/MS technology was used to identify chemical components that were absorbed in the blood and liver tissue of rats. RESULTS Totally， 30 chemical constituents were identified from the water extracts of A. cantoniensis， including alkaloids， flavonoids， organic acids， iridoids （such as L-abrine， schaftoside， isoshaftoside）. Ten prototype components and nine metabolites （such as decarboxylation and sulfation metabolites of protocatechuic acid， reduced sulfated metabolites of p-hydroxybenzoic acid） were identified from plasma samples； six prototype components and five metabolites （such as sulfated metabolites of p-hydroxybenzoic acid， decarboxylation and sulfation metabolites of p-hydroxybenzoic acid） were identified from liver samples. The main metabolic pathways included hydroxylation， demethylation， methylation， sulfation， glucuronidation， etc. CONCLUSIONS Alkaloids， flavonoids and organic acids are the main components of the aqueous extract from A. cantoniensis that are absorbed into the blood and liver， their metabolism mainly involves hydroxylation，demethylation， and sulfation.

Neuropathic pain(NPP)is a recurrent and intractable pain syndrome,and microglial polarization is closely related to it.Recent studies have shown that after cell polarization,M1 pro-inflammatory and M2 anti-inflammatory types could be formed,and M1 and M2 microglial cells are involved in NPP through the modulation of inflammatory responses.The two types of microglial cells have different roles in NPP,just like a double-edged sword.M1 pro-inflammatory type plays an injurious role in NPP through the release of pro-inflammatory factors and noxious substances,whereas M2 anti-inflammatory type plays a protective role by secreting anti-inflammatory factors.In this article,the role of microglia polarization on NPP are reviewed.