Objective To investigate the effect of tritiated water on the immune system of zebrafish and its potential molecular mechanism. Methods Zebrafish embryos (2.5 to 3 hours post-fertilization [hpf]) were exposed to 3.7 × 10⁴ Bq/mL tritiated water (tritiated water group), and those exposed to E3 culture medium were used as the control group. The mortality rate, hatching rate, deformity rate, heart rate, body length, yolk sac area, neutrophil count in the tail, immune-related gene expression, and immune-related protein expression of zebrafish in the two groups were determined. Then transcriptome technology was used to further analyze the possible mechanism of tritiated water affecting the immune system of zebrafish. Results Compared with the control group, zebrafish at 72 hpf in the tritiated water group had no significant changes in the mortality rate, hatching rate, deformity rate, body length, and yolk sac area((t = 0.9045, 0.5000, 1.0000, 0.7238, 0.0337, P = 0.4169, 0.6433, 0.3739, 0.4785, 0.9735), but had significantly increased heart rate(t = 4.575，P = 0.002). At 4 days post-fertilization (dpf), the neutrophil count in the tail of zebrafish in the tritiated water group was significantly increased(t = 2.563，P = 0.0196), the mRNA expression of TNF-α was significantly decreased(t = 2.891, P = 0.045), the protein expression of nuclear factor-kappa B (NF-κB) was significantly increased(t = 3.848, P = 0.018), and the protein expression of NLRP3 was significantly decreased(t = 14.98, P = 0.001). At 7 dpf, the neutrophil count in the tail and the protein expression levels of NF-κB, NLRP3, and interleukin-1β were significantly decreased(t = 3.772, 7.048, 15.620, 4.423, P = 0.014, 0.002, 0.0001, 0.012). Transcriptome sequencing revealed that differentially expressed genes were mainly enriched in the “neutrophil activation” and “platelet activation pathways” at 4 dpf and in the “neutrophil apoptosis”, “ferroptosis”, and “necroptosis” pathways at 7 dpf. Conclusion Tritiated water exposure induces a temporally dynamic immune response in zebrafish, potentially affecting immune homeostasis by regulating neutrophil activation and apoptosis, as well as the expression of NF-κB and NLRP3.

OBJECTIVE: To explore the application effectiveness of multidisciplinary team (MDT) in the diagnosis and treatment of chronic refractory wounds, and to provide new ideas for optimizing the clinical diagnosis and treatment of such diseases. METHODS: A retrospective analysis was performed on the clinical data of patients with chronic refractory wounds who underwent surgery at Peking University Third Hospital from January 2015 to October 2023, and a total of 456 patients, including 290 males and 166 females, with an average age of (49.4±16.9) years. According to whether preoperative MDT discussion was conducted, the patients were divided into MDT discussion group and non-MDT discussion group. The overall implementation process of MDT included: Starting and recording with the medical office, collecting data and discussing the initial MDT, informing the patient of the treatment plan and strictly implementing it, and the change of the condition needs to be discussed again by MDT. The general clinical data, anesthesia risk grade, complications (hypertension, diabetes, coronary heart disease), and the etiology and location of chronic refractory wounds between the two groups were compared. The main observational measurements and outcome indicators of treatment effectiveness included the number of surgeries required to achieve wound healing after admission, the recurrence rate after wound healing, the incidence of perioperative complications (pulmonary infection, severe cardiovascular event, vein thrombus embo-lism, cerebral stroke and delirium, etc.), and patient satisfaction score. RESULTS: There were 189 patients in the MDT discussion group and 267 patients in the non-MDT discussion group. There was no significant statistical difference in the clinical data, such as age, gender, body mass index, American Society of Anesthesiologists, comorbidities, etiology, and location of chronic refractory wounds between the two groups (P>0.05). The average number of surgeries required for wound healing in MDT discussion group and non-MDT discussion group was 2.1±1.1 and 2.8±1.6, respectively, with a statistically significant difference (P < 0.001). This difference was also significant in chronic refractory wounds caused by three etiologies: Diabetic ulcer, infection after trauma or surgery, and non-union after radiotherapy (P < 0.05). The recurrence rate of the patients in the non-MDT discussion group after wound healing was 18.0%, slightly higher than that in the MDT discussion group of 14.3% (P>0.05). In terms of perioperative complications, the non-MDT discussion group also had a higher incidence (3.7% vs. 2.6%), but the difference was not statistically significant (P>0.05). In terms of patient satisfaction, the MDT discussion group scored significantly higher (96.5 vs. 91.1, P=0.028). CONCLUSION The MDT mode can significantly reduce the number of surgeries for patients with chronic refractory wounds, improve the effectiveness of therapy and increase patient satisfaction. It is a recommended model for optimizing the clinical diagnosis and treatment effectiveness of chronic refractory wounds.
Humans ; Patient Care Team ; Retrospective Studies ; Chronic Disease ; Male ; Female ; Middle Aged ; Wound Healing ; Aged ; Adult ; Wounds and Injuries/surgery*

Research indicates that microbe activity within the human body significantly influences health by being closely linked to various diseases. Accurately predicting microbe-disease interactions (MDIs) offers critical insights for disease intervention and pharmaceutical research. Current advanced AI-based technologies automatically generate robust representations of microbes and diseases, enabling effective MDI predictions. However, these models continue to face significant challenges. A major issue is their reliance on complex feature extractors and classifiers, which substantially diminishes the models' generalizability. To address this, we introduce a novel graph autoencoder framework that utilizes decoupled representation learning and multi-scale information fusion strategies to efficiently infer potential MDIs. Initially, we randomly mask portions of the input microbe-disease graph based on Bernoulli distribution to boost self-supervised training and minimize noise-related performance degradation. Secondly, we employ decoupled representation learning technology, compelling the graph neural network (GNN) to independently learn the weights for each feature subspace, thus enhancing its expressive power. Finally, we implement multi-scale information fusion technology to amalgamate the multi-layer outputs of GNN, reducing information loss due to occlusion. Extensive experiments on public datasets demonstrate that our model significantly surpasses existing top MDI prediction models. This indicates that our model can accurately predict unknown MDIs and is likely to aid in disease discovery and precision pharmaceutical research. Code and data are accessible at: https://github.com/shmildsj/MDI-IFDRL.

Recent studies have shown that stress can substantially facilitate breast cancer metastasis,which can be reduced by nonselective β1/β2-adrenergic receptor(β1/β2-AR)blocker.However,several side effects were identified.Thus,it is extremely warranted to explore more effective and better-tolerated β2-AR blocker.Currently,we demonstrated that baicalin(BA),a major bioactive component of Scutellaria bai-calensis Georgi,could significantly attenuate stress hormones especially epinephrine(Epi)-induced breast cancer cell migration and invasion in vitro.Mechanistically,we identified that β2-AR was a direct target of BA via the drug affinity responsive target stability(DARTS)combined with mass spectrum assay,and BA photoaffinity probe with pull-down assay,which was further confirmed by a couple of bio-physical and biochemical assays.Furthermore,we demonstrated that BA could directly bind to the Phe-193 and Phe-289 of β2-AR,subsequently inhibit cyclic adenosine monophosphate-protein kinase A-focal adhesion kinase(cAMP-PKA-FAK)pathway,and thus impede epithelial-mesenchymal transition(EMT),thereby hindering the metastatic progression of the chronic stress coupled with syngeneic and xenograft in vivo orthotopic and tail vein mouse model.These findings firstly identify BA as a potential β2-AR inhibitor in the treatment of stress-induced breast cancer metastasis.

Objective:To analyze the distribution of clopidogrel metabolism-related gene variability in Kawasaki disease (KD) children with coronary artery lesions (CAL) across different age groups and the impact of genetic variability on the efficacy of clopidogrel antiplatelet therapy.Methods:A retrospective cohort study was conducted. Clinical data were collected from 46 KD children with CAL who were hospitalized in the Cardiovascular Center of Children′s Hospital of Fudan University between January 2021 and August 2022 and were treated with clopidogrel, including gender, age, body mass index, course of KD, CAL severity grade, and baseline platelet count. According to their age, the children were divided into ≥2-year-old group and <2-year-old group. Their platelet responsiveness was assessed by adenosine diphosphate-induced platelet inhibition rate (ADPi) calculated via thromboelastography, and children were categorized into high on-treatment platelet reactivity (HTPR) and normal on-treatment platelet reactivity (NTPR) groups. Genotypes of CYP2C19, PON1 and ABCB1 were detected. The t test, one-way analysis of variance and Chi-square test were used for intergroup comparison. Results:Among the 46 KD children with CAL, 34 were male and 12 were female; 37 were ≥2-year-old and 9 were <2-year-old; 25 cases were in the HTPR group and 21 cases were in the NTPR group, with 19 HTPR and 18 NTPR in the ≥2-year-old group, and 6 HTPR and 3 NTPR in the <2-year-old group. Genetic analysis showed that 92 alleles among the 46 children, with frequencies of CYP2C19*1, CYP2C19*2, CYP2C19*3, CYP2C19*17, PON1 192Q, PON1 192R, ABCB1 3435C, ABCB1 3435T at 59% (54/92), 32% (29/92), 9% (8/92), 1% (1/92), 36% (36/92), 64% (59/92), 63% (58/92) and 37% (34/92), respectively. Analysis of the impact of genotype on ADPi revealed that in children aged ≥2 years, those with CYP2C19*1/*3 genotype had significantly lower ADPi than those with CYP2C19*1/*1 genotype ((34±15)% vs. (61±29)%, t=2.18, P=0.036). There were also no significant difference in ADPi among children with PON1 192Q homozygous, PON1 192R heterozygote and PON1 192R homozygous genotypes ((40±22)% vs. (52±33)% vs. (65±27)%, F=2.17, P=0.130), or among those with ABCB1 3435C homozygous, ABCB1 3435T heterozygote and ABCB1 3435T homozygous genotypes ((55±34)% vs. (60±27)% vs. (49±24)%, F=0.33, P=0.719). In <2-year-old group, there were no significant differences in ADPi across CYP2C19*1/*1, CYP2C19*1/*2 and CYP2C19*2*2 genotypes ((40±20)% vs. (53±37)% vs. (34±16)%, F=0.37, P>0.05). There were no significant differences in ADPi across CYP2C19*1/*1 and CYP2C19*1/*3 genotypes ((44±27)% vs. (42±20)%, t=0.08, P>0.05). There were no significant differences in ADPi across PON1 192Q homozygous, PON1 192R heterozygote and PON1 192R homozygous genotypes (45% vs. (55±27)% vs. (24±5)%, F=1.83, P>0.05). There were no significant differences in ADPi across ABCB1 3435C homozygous, ABCB1 3435T heterozygote and ABCB1 3435T homozygous genotypes ((36±16)% vs. (50±35)% vs. 45%, F=0.29, P>0.05). The risk analysis of HTPR in different genotypes revealed that in children aged ≥2 years, carrying at least 1 or 2 loss-of-function alleles of CYP2C19 was a risk factor for HTPR ( OR=4.69, 10.00, 95% CI 1.11-19.83, 0.84-119.32, P=0.033, 0.046, respectively), and PON1 192R homozygosity and carrying at least one PON1 192R allele were protective factors against HTPR ( OR=0.08, 0.13, 95% CI 0.01-0.86, 0.01-1.19, P=0.019, 0.043, respectively). Conclusion:KD children aged ≥2 years carrying CYP2C19 loss-of-function alleles and PON1 192Q are more likely to develop HTPR.

Patients with severe tumors do not refer to the patients with end-stage tumors,but rather to the patients with a performance status(PS)score between 2 and 4 in certain stages due to various reasons,such as acute or chronic comorbidities,tumor itself,or treatment-related adverse events.To these patients,there is a high probability of achieving survival benefit and/or improvement in PS scores after synergistic management of available life-support technologies and anti-tumor therapies based on dynamic and precise testing.Elderly patients with tumors frequently present with one or more chronic illnesses and have poor toler-ance and compliance to treatment.Moreover,their treatment regimens often lack high-quality clinical evidence,making them more susceptible to developing severe tumors.The management of severe tumors in the elderly is based on three basic diagnosis and treatment technologies:dynamic and precise detection,powerful life support technologies,and skillful application of current anti-tumor treatments.In specific clinical practice,the following 7 flexible and individualized treatment strategies should be adopted for different tumor types:1.concurrent management of cancer and comorbidities,2.upgrading and downgrading of anti-tumor drugs based on PS score,3.dynamic accurate detection,4.skillful combinations for increasing efficacy and reducing toxicity,5.complete overview,paying equal attention to systemic therapy and local therapy,6.safety first in medication for the elderly,7.multi-discipli-nary participation,individualized and comprehensive treatment.This article introduced the concept of severe tumors in the elderly and the associated management strategies,to increase awareness and provide feasible guidance for clinical practice.

Objective:To test the validity and reliability of the Chinese Social Anxiety Questionnaire for A-dults(CSAQ-A).Methods:Totally 555 participants[aged 18 to 60 years,average age(29±8)years old]were recruited to complete the CSAQ-A.The Liebowitz Social Anxiety Scale(LSAS),Brief Fear of Negative Evaluation Scale(BFNE),Penn State Worry Questionnaire(PSWQ),State-Trait Anxiety Inventory-Trait(STAI-T),and Beck Depression Scale-Second Edition(BDI-Ⅱ)were conducted to test the criterion validity.After 4 weeks,143 subjects were retested.Results:Confirmatory factor analysis demonstrated that the five-dimensional structure of the CSAQ-A exhibited excellent fit indices(x2/df=3.06,CFI=0.92,TLI=0.91,RMSEA=0.06,SRMR=0.05).The CSAQ-A scores were positively correlated with the scores of LSAS,BFNE,PSWQ,STAI-T and BDI-Ⅱ(ICC=0.40-0.67,Ps＜0.001).The Cronbach α coefficient of the CSAQ-A scale was 0.96,and the test-retest reliability was 0.80.Conclusion:The Chinese Social Anxiety Questionnaire for Adults has good validity and reliability and could effectively evaluate social anxiety in the Chinese adult population.

OBJECTIVE: To investigate the incidence and potential risk factors associated with postoperative spinal epidural hematoma (SEH) following anterior cervical spine surgery (ACSS). METHODS: A retrospective analysis was conducted on the clinical data of patients who underwent ACSS for cervical spondylosis at Peking University Third Hospital between March 2013 and February 2022. Patients who developed postoperative SEH were categorized as the SEH group, while those in the cohort without SEH were randomly selected as the non-SEH group by individually matching with the same operator, same gender, same surgery year, and similar age (±5 years) at a ratio of 4 ∶ 1. The general condition, preoperative comorbidities, anticoagulant or antiplatelet therapy, preoperative coagulation and platelet counts, American society of Anesthesiologists physical status classification, cervical spondylosis classification, preoperative modified Japanese Orthopaedic Society score and cervical disability index score, surgical modality, surgical segment levels, ossification of the posterior longitudinal ligament among the surgical level, surgery duration, estimated blood loss, postoperative drainage volume, preoperative mean arterial pressure, mean arterial pressure during postoperative awakening periods, hospital stay and hospitalization cost were compared between the two groups. A bivariate Logistic regression model was applied to screen out the independent risk factors and calculate the odds ratios of indicators associated with SEH. Receiver operating characteristic curve and area under the curve (AUC) were used to describe the discrimination ability of the indicators. RESULTS: A total of 85 patients were enrolled in the study, including 17 patients in the SEH group and 68 patients in the non-SEH group. Seventeen patients with SEH underwent hematoma evacuation, and all of them were successfully treated and discharged from the hospital. Corpectomy (OR=7.247; 95%CI: 1.962-26.766; P=0.003) and the highest mean arterial pressure during awakening (OR=1.056; 95%CI: 1.002-1.113; P=0.043) were independent risk factors for SEH. The AUC values were 0.713 (95%CI: 0.578-0.848) and 0.665 (95%CI: 0.51-0.82) respectively. The patients with SEH had longer hospital stays (P < 0.001) and greater hospitalization costs (P=0.035). CONCLUSION Corpectomy and elevated maximum mean arterial pressure during awakening are independent risk factors for the development of postoperative SEH following ACSS. High-risk patients should be closely monitored during the perioperative period.
Humans ; Risk Factors ; Cervical Vertebrae/surgery* ; Retrospective Studies ; Hematoma, Epidural, Spinal/epidemiology* ; Incidence ; Male ; Female ; Postoperative Complications/etiology* ; Spondylosis/surgery* ; Logistic Models ; Length of Stay ; Middle Aged

Objective To investigate effect of remote ischemic preconditioning(RIPC)com-bined with transcutaneous vagus nerve stimulation(tVNS)on reperfusion injury in ST-segment eleva-tion myocardial infarction(STEMI).Methods A total of 132 STEMI patients were selected,and were randomly divided into control group,tVNS group and combined group(RIPC combined with tVNS)before percutaneous coronary intervention(PCI).A total of 9 of the 132 patients were exclu-ded,including 42 in the control group,40 in the tVNS group,and 41 in the combination group.The area under the curve(AUC)of creatine kinase isoenzyme(CK-MB)within 72 h and the ventricular arrhythmia(VAs)within 24 h after reperfusion were compared among the three groups.The levels of interleukin-6(IL-6),high mobility group protein B1(HMGB1),tumor necrosis factor-α(TNF-α)and left ventricular ejection fraction(LVEF)of the three groups were compared at admission and 24 h after reperfusion.Results The AUC of CK-MB in the combination group was significantly lower than that in the control group within 72 h(P＜0.05).The total number of premature ventricular beats and the number of ventricular tachycardia in the tVNS group and combined group were significantly lower than those in the control group within 24 h after reperfusion(P＜0.05).The levels of IL-6,HMGB1 and TNF-α in the combination group were significantly lower than those in the control group 24 h after reperfusion(P＜0.05).LVEF in the combination group was significantly higher than that in the light group at 7 days after reperfusion(P＜0.05).Conclusion The tVNS significantly reducs the incidence of VAs after PCI in STEMI patients,but has little effect on the level of reperfusion inflam-matory markers,myocardial infarction size,and acute left ventricular systolic function.The tVNS com-bined with RICP can produce significant benefits in the above indexes.