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 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 investigate the clinical efficacy of percutaneous closure of foramen ovale guided by transthoracic echocardio-graphy with simply delivery sheath.Methods The clinical data of patients with patent foramen ovale underwent interventional closure and percutaneous closure guided by transthoracic echocardiography with simply delivery sheath in our hospital from January 2020 to December 2022 were analyzed retrospectively,the patients were divided into interventional closure group(40 cases)and simply delivery sheath group(39 cases).The operation time,incidence of surgical complications,and surgical success rates of patients in the two groups were compared.The closure effect were evaluated by ultrasound immediately after surgery.All the patients were followed up for 6 months after surgery to evaluate remission of the symptoms.Results The surgical success rate of simply delivery sheath group(100%)was higher than that of interventional closure group(90.0%),with statistically significant difference(P<0.05).The operation time of simply delivery sheath group was longer than that of interventional closure group,with statistically significant difference(P<0.05).One patient in the interventional closure group had small amount of pericardial effusion during the operation.Two patients had decreased blood pressure and slowed heart rate in simply delivery sheath group,and symptoms disappeared after treatment.There was no significant difference in the incidence of complications between the two groups(P>0.05).After 6-month follow-up,all occluders were in good position and no residual leakage was found.The symptoms of headache or dizziness disappeared in 28 patients in interventional closure group,significantly relieved in 8 patients;the symptoms of headache or dizziness disappeared in 30 patients in simply delivery sheath group,and significantly relieved in 9 patients.Conclusion Percutaneous closure for patent foramen ovale under the guidence of transthoracic echocardiography with simply delivery sheath is safe and feasible with satisfactory efficacy and higher successful rate without radiation hazard.It is worthy of clinical promotion.

Objective:To investigate the correlation between food-specific IgG (sIgG) antibodies and phenotypes of chronic spontaneous urticaria (CSU) .Methods:Serum samples were collected from outpatients with active CSU, symptomatic dermographism (SD) , or acute urticaria (AU) , and healthy controls from 5 third-grade class-A hospitals such as the First Hospital of China Medical University between April 2014 and March 2015. Enzyme-linked immunosorbent assay was conducted to detect serum levels of 90 food-sIgG antibodies and total IgE, Western blot analysis to detect levels of 20 allergen-specific IgE antibodies, and chemiluminescent microparticle immunoassay to detect levels of anti-thyroid peroxidase IgG antibodies and anti-thyroglobulin IgG antibodies. Comparisons of normally distributed quantitative data between two groups and among several groups were performed by t test and one-way analysis of variance, respectively; comparisons of non-normally distributed quantitative data between two groups were performed by Mann-Whitney U test; for comparisons of proportions, chi-square test and Fisher′s exact test were used. Results:A total of 248 patients with CSU, 22 with SD, 15 with AU and 13 healthy controls were recruited. The cut-off level for sIgG positivity was 100 U/ml (at least 2+) , and the positive rate of food-sIgG antibodies was slightly higher in the patients with CSU (176/248, 70.97%) , SD (15/22, 68.18%) and AU (11/15) than in the healthy controls (7/13; χ2 = 1.80, P = 0.615) . Among the 248 CSU patients, the proportion of patients with family history of allergic diseases was significantly higher in the sIgG-positive group (71/176, 40.34%) than in the sIgG-negative group (19/72, 26.39%; χ2 = 4.30, P = 0.042) , while no significant difference was observed in the 1-day urticaria activity score (UASday) between the two groups ( Z = 0.18, P = 0.859) . Totally, 177 CSU patients completed 12- to 40-week treatment; their condition could be completely controlled by second-generation H1-antihistamines, and there was no significant difference in the required dosage of second-generation H1-antihistamines between the sIgG-positive group (128 cases) and sIgG-negative group (49 cases; Z = -1.06, P = 0.298) . Conclusions:The prevalence of family history of allergic diseases was relatively high in food-sIgG-positive patients with CSU. However, food-sIgG could not be used as an indicator to reflect the disease activity of CSU and treatment response.

Objective:To investigate the knowledge, attitudes, and practices (KAP) of pulse oximetry among pediatric healthcare providers in China and analyze the factor influencing the KAP.Methods:A self-developed questionnaire was used for an online research on the KAP of 11 849 pediatric healthcare providers from 31 provinces, autonomous regions, and municipalities of China from March 11 to 14, 2022.The factors influencing the KAP of pulse oximetry among pediatric healthcare providers were examined by Logistic regression. Results:The scores of KAP, of pulse oximetry were 5.57±0.96, 11.24±1.25 and 11.19±4.54, respectively.The corresponding scoring rates were 69.61%, 74.95%, and 55.99%, respectively. Logistic regression results showed that the gender and working years of pediatric healthcare providers, the region they were located, and whether their medical institution was equipped with pulse oximeters were the main factors affecting the knowledge score (all P<0.05). Main factors influencing the attitude score of pediatric healthcare providers included their knowledge score, gender, educational background, working years, region, medical institution level, and whether the medical institution was equipped with pulse oximeters (all P<0.05). For the practice score, the main influencing factors were the knowledge score, gender, age, and whether the medi-cal institution was equipped with pulse oximeters (all P<0.05). Conclusions:Chinese pediatric healthcare providers need to further improve their knowledge about and attitudes towards pulse oximetry.Pulse oximeters are evidently under-used.It is urgent to formulate policies or guidelines, strengthen education and training, improve knowledge and attitudes, equip more institutions with pulse oximeters, and popularize their application in medical institutions.

Objective:To explore the effect of natural decay of exogenously added fibrous roots on the growth and development of Paris polyphylla var. yunnanensis and its medicinal quality. Method:The effects of natural decay of fibrous roots at different amounts on mycorrhizal infection rate， physiological and biochemical indexes， and saponin contents of P. polyphylla var. yunnanensis were studied in pot culture experiments at room temperature. Result:The results showed that the infection rate of arbuscular mycorrhizal （AM） fungi in the root of P. polyphylla var. yunnanensis was not significantly affected by different fibrous root treatments， but there were significant differences in infection intensity. The photosynthetic pigment content in the leaves declined significantly with the increase in fibrous root amount， and the total chlorophyll was decreased by 78.7% at most. The contents of soluble protein， soluble sugar and malondialdehyde in the leaves of P. polyphylla var. yunnanensis showed an overall upward trend. The activities of the three protective enzymes varied. The peroxidase and malondialdehyde were reduced by 181.6% and 200.0% at most. In the root system of P. polyphylla var. yunnanensis， the contents of the above-mentioned six components decreased to varying degrees， with the largest reductions of peroxidase and malondialdehyde reaching 44.6% and 69.7%. Different fibrous root treatments resulted in a decrease in active component content of P. polyphylla var. yunnanensis. The total content of the four saponins was decreased by 58.9% at most， and the total saponin content by 46.9%. Conclusion:The natural decay of fibrous roots affects the soil microbial environment of root system， reduces the photosynthetic pigment content in leaves， and destroys the stability of cells， thus interfering with the growth and development of P. polyphylla var. yunnanensis， reducing its medicinal components， and causing continuous cropping obstacles.

OBJECTIVE: To analyze the effect of clinical features, routine laboratory examination and related gene mutation on the OS of patients with myelodysplastic syndrome (MDS) after hematopoietic stem cell transplantation (HSCT). METHODS: 121 patients diagnosed as MDS and underwent hematopoietic stem cell transplantation in the First Affiliated Hospital of Soochow University from October 2013 to August 2018 were selected. Basic information of the patients was collected, and blood cells, bone marrow blasts at initial diagnosis, chromosomal karyotypes and gene mutations of the patients were detected.The effect of different factors on overall survival (OS) was analyzed by statistical method. RESULTS: Kaplan-Meier univariate analysis shows that OS was significanly different among different age groups. The 3-year OS rate of patients aged 0-29 years was (83.3±7.7) %, the 3-year OS rate in patients aged 30-49 years was (58.1±7.7 %), and the 3-year OS rate of patients aged 50-69 years was (31.0±22.6) %, which was statistically different (P＜0.05) between different groups. There were also significant differences in OS among patients with different transplantation types. 3-year OS rate: HLA-matched sibling HSCT＞unrelated HLA-matched HSCT＞haploidentical HSCT＞micro HSCT. The OS rate of patients with bone marrow blasts≥10% seems lower than blasts＜10%, but there was no statistical difference.The 3-year OS rate of patients with chromosomal karyotype complex abnormality was (47.7±11.5) %, and that of patients without complex abnormality was (80±4.2) % which was statistical difference (P＜0.05). Patients with DNMT3A, NRAS, TP53 and GATA2 mutations had shorter OS time compared with patients without mutation of these genes, which shows statistically significant (P＜0.05). COX multivariate analysis showed that age, chromosome karyotype, DNMT3A, TET2, GATA2 and NRAS were the independent factors influencing OS of patients after HSCT, with statistically significant difference. CONCLUSION age of patients, donor selection of HSCT, chromosome karyotype, DNMT3A, NRAS, TP53, GATA2 and TET2 gene mutations are all independent factors affecting the OS of patients after HSCT. Therefore, the assessment of the OS of MDS patients with transplantation requires comprehensive consideration.
Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Infant ; Infant, Newborn ; Middle Aged ; Myelodysplastic Syndromes ; Prognosis ; Retrospective Studies ; Siblings ; Survival Analysis ; Young Adult

Objective: To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison. Methods: Peking University People's Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated. Results: ①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample's highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories' results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample's highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH. Conclusion: The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.
China ; Core Binding Factor Alpha 2 Subunit ; Humans ; Leukemia, Myeloid, Acute ; RUNX1 Translocation Partner 1 Protein ; Real-Time Polymerase Chain Reaction ; Transcription, Genetic ; WT1 Proteins

Objective:To compare the biomechanical effects between oblique Ban-pulling manipulation and lumbar erection-rotation manipulation in sitting position in treating lumbar intervertebral disc herniation (LIDH). Methods:A three-dimensional finite element model of L3-S1 was developed to carry out a comparative study between oblique Ban-pulling manipulation and lumbar erection and rotation manipulation in sitting position. The disc protrusion was assumed to be on the rear left of L4 disc, and the manipulations were performed on the right side. The loading process was simulated by two steps. In the first step, only the compression loading was imposed, and in the second step, both the compression loading and axial rotation moment were imposed. The displacement and stress distribution in L4 disc were investigated. Results:The values of stress and displacement in the second step were lower than those in the first step in each manipulation. The stress and displacement differences between the two steps were respectively 1.79 times and 3.03 times larger in oblique Ban-pulling manipulation than those in lumbar erection-rotation manipulation in sitting position. Conclusion: Oblique Ban-pulling manipulation may result in a better biomechanical effect than lumbar erection-rotation manipulation in sitting position for LIDH.

Objective To study the relationship between bronchial asthma and smoking status in Chinese people.Methods Asthma epidemiological survey and stratified-cluster-random method survey were performed in residents over 14 years in 8 provinces (cities) of China from February 2010 to August 2012.Asthma was diagnosed based upon case history,clinical signs and lung function test.Smoking status was investigated by questionnaire.Results Sampling population was 180 099 and 164 215 were valid.A total of 2 034 subjects were diagnosed as asthma including 79 692 men and 84 523 women.The overall prevalence rate of asthma was 1.24％ (2 034/164 215).Smokers were 23.8％ (39 137/164 215) in the whole population.Smokers were 34.5％ (702/2 034) in asthmatic patients,compared with 23.7％ (38 435/ 162 181) in no-asthmatic population.The incidence of asthma was 1.79％ and 1.06％ in smokers and nonsmokers respectively (P ＜0.001),suggesting that OR of smoking was 1.70 (95％ CI 1.55-1.86,P ＜ 0.001).According to asthma control test (ACT) score,the level of asthma control in non smoking group was higher than that in smoking group(43.2％ vs 35.3％).The times of hospitalization due to acute exacerbations (0.51 vs 0.41 events/person/year),total hospitalization rate (27.35 ％ vs 20.12％),annual emergency room visits (0.80 vs 0.60 events/person/year) and emergency room visit rate (31.77％ vs 24.47％) were all much higher in smoking asthmatic patients than those in non smoking asthmatic patients,indicating that the level of asthma control in smoking patients was significantly worse than in non smoking patients.Conclusions The smoking rate in Chinese people over 14 years is still high.The prevalence rate of asthma in smokers is significantly higher than that of non-smokers.The level of asthma control in smokers is significantly worse than that in non smokers.