Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Objective To explore the influencing factors of immune-associated thyroid dysfunction caused by sintilimab treatment in solid tumors and construct a prediction model.Methods Medical records of patients diagnosed with solid tumors and treated with sintilimab at Peking University People's Hospital(Xizhimen Campus,Tongzhou Campus,Shijiazhuang Campus)from January 2023 to September 2024 were collected to explore the influencing factors that caused immune-related thyroid dysfunction using univariate and multifactorial binary logistic regression analyses and to establish a prediction model.The predictive effect of the model was assessed using the receiver operating characteristic(ROC)curve.Results A total of 120 patients were included,and 33 presented with immune-related thyroid dysfunction.Multifactorial logistic regression analysis revealed that thyroid-stimulating hormone(TSH)[OR=2.470,95%CI=(1.279,4.771)]and treatment cycles[OR=1.298,95%CI=(1.117,1.509)]were independent risk factors for the occurrence of immune-associated thyroid dysfunction,and the difference was statistically significant(P＜0.05).The area under the ROC curve was(0.897±0.043)[95%CI=(0.813,0.981)],the Yoden index was 0.703,and the model prediction accuracy was 86.5%.Conclusion The risk of immune-related thyroid dysfunction caused by sintilimab is high,and TSH and treatment cycle are the influencing factors,and the constructed model has certain predictive value and is of reference significance.

Objective To investigate the predictive value of triglyceride glucose-body mass index(TyG-BMI),serum triglyceride-to-high-density lipoprotein cholesterol ratio(TG/HDL-C),and metabolic score for insulin resistance(METS-IR)for fatty pancreatic disease(FPD).Methods A total of 240 patients with FPD treated in The First Affiliated Hospital of Zhengzhou University from January 2020 to November 2023 were included as the case group,while 480 healthy subjects who underwent healthy checks in the same period were randomly selected as the control group.General clinical data and laboratory indicators were collected.The Mann-Whitney U test and chi-square test were used to compare non-normally distributed continuous variables,and categorical variables between groups,respectively.A binary logistic regression model was used to assess the relationship between TyG-BMI,TG/HDL-C,and METS-IR and FPD.The receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to evaluate the predictive diagnostic value of those simplified insulin resistance indicators for FPD in the general population and different sex populations.Results Age,BMI,systolic blood pressure,diastolic blood pressure,fasting plasma glucose,uric acid,alanine aminotransferase,aspartate aminotransferase,gamma-glutamyl transferase,total cholesterol,triglyceride,low-density lipoprotein cholesterol,TyG-BMI,TG/HDL-C,and METS-IR in the case group were significantly higher than those in the control group(all P<0.05).The case group had significantly higher proportions of individuals with hypertension,diabetes,and fatty liver disease than the control group(all P<0.05).The high-density lipoprotein cholesterol level was significantly lower in the case group than in the control group(P<0.05).The multivariable Logistic regression analysis showed that after adjusting for various influencing factors,TyG-BMI,TG/HDL-C,and METS-IR remained as independent risk factors for the development of FPD,with the odds ratios(95%confidence intervals)being 1.027(1.018-1.037),6.964(2.022-23.989),and 1.184(1.123-1.248),respectively.In the ROC curve analysis,the AUCs of METS-IR and TyG-BMI were 0.823 and 0.803,respectively,with their sensitivities being 76.3%and 75.8%,specificities being 74.6%and 71.7%,and optimal cut-off values being 34.86 and 196.70,respectively;the next were BMI(AUC=0.758)and TG/HDL-C(AUC=0.734);in the sex-stratified analysis,the AUC values of METS-IR were highest in both the male and female subgroups,which were 0.834 and 0.810,respectively.Conclusion TyG-BMI,TG/HDL-C,and METS-IR show good predictive value for the development of FPD,in which METS-IR is more excellent.

Objective:To investigate serological characteristics of Rhnull with anti-Rh29 and its rare gene sequence.Methods:Microcolumn gel method was used for ABO and RhCcDEe blood typing,accidental antibody identification and cross matching.RHD/RHCE genotype and sequencing analysis were performed by PCR-SSP method.RHAG gene was sequenced by fluorescence PCR method.Antigen or protein associated with Rh complex was detected by flow cytometry.Results:Blood group of the patient was A,Rh pheno-type was typed as group C-c-D-E-e,presented with symptoms of anemia,proportion of globular and oral erythrocytes in blood smear was 6.0%and 0.8%,respectively,RH genotype was CCDee,and immune anti-Rh29 high-frequency antigen were developed.RHAG gene sequencing revealed exons 8,9 and 10 deletion.Conclusion:Mechanism of"regulator"type Rhnull generation in this study is caused by deletion of exons 8,9 and 10 in RHAG gene.

Objective To investigate the predictive value of triglyceride glucose-body mass index(TyG-BMI),serum triglyceride-to-high-density lipoprotein cholesterol ratio(TG/HDL-C),and metabolic score for insulin resistance(METS-IR)for fatty pancreatic disease(FPD).Methods A total of 240 patients with FPD treated in The First Affiliated Hospital of Zhengzhou University from January 2020 to November 2023 were included as the case group,while 480 healthy subjects who underwent healthy checks in the same period were randomly selected as the control group.General clinical data and laboratory indicators were collected.The Mann-Whitney U test and chi-square test were used to compare non-normally distributed continuous variables,and categorical variables between groups,respectively.A binary logistic regression model was used to assess the relationship between TyG-BMI,TG/HDL-C,and METS-IR and FPD.The receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to evaluate the predictive diagnostic value of those simplified insulin resistance indicators for FPD in the general population and different sex populations.Results Age,BMI,systolic blood pressure,diastolic blood pressure,fasting plasma glucose,uric acid,alanine aminotransferase,aspartate aminotransferase,gamma-glutamyl transferase,total cholesterol,triglyceride,low-density lipoprotein cholesterol,TyG-BMI,TG/HDL-C,and METS-IR in the case group were significantly higher than those in the control group(all P<0.05).The case group had significantly higher proportions of individuals with hypertension,diabetes,and fatty liver disease than the control group(all P<0.05).The high-density lipoprotein cholesterol level was significantly lower in the case group than in the control group(P<0.05).The multivariable Logistic regression analysis showed that after adjusting for various influencing factors,TyG-BMI,TG/HDL-C,and METS-IR remained as independent risk factors for the development of FPD,with the odds ratios(95%confidence intervals)being 1.027(1.018-1.037),6.964(2.022-23.989),and 1.184(1.123-1.248),respectively.In the ROC curve analysis,the AUCs of METS-IR and TyG-BMI were 0.823 and 0.803,respectively,with their sensitivities being 76.3%and 75.8%,specificities being 74.6%and 71.7%,and optimal cut-off values being 34.86 and 196.70,respectively;the next were BMI(AUC=0.758)and TG/HDL-C(AUC=0.734);in the sex-stratified analysis,the AUC values of METS-IR were highest in both the male and female subgroups,which were 0.834 and 0.810,respectively.Conclusion TyG-BMI,TG/HDL-C,and METS-IR show good predictive value for the development of FPD,in which METS-IR is more excellent.

Objective:To investigate serological characteristics of Rhnull with anti-Rh29 and its rare gene sequence.Methods:Microcolumn gel method was used for ABO and RhCcDEe blood typing,accidental antibody identification and cross matching.RHD/RHCE genotype and sequencing analysis were performed by PCR-SSP method.RHAG gene was sequenced by fluorescence PCR method.Antigen or protein associated with Rh complex was detected by flow cytometry.Results:Blood group of the patient was A,Rh pheno-type was typed as group C-c-D-E-e,presented with symptoms of anemia,proportion of globular and oral erythrocytes in blood smear was 6.0%and 0.8%,respectively,RH genotype was CCDee,and immune anti-Rh29 high-frequency antigen were developed.RHAG gene sequencing revealed exons 8,9 and 10 deletion.Conclusion:Mechanism of"regulator"type Rhnull generation in this study is caused by deletion of exons 8,9 and 10 in RHAG gene.

Purpose To explore the role of translesion synthesis-related gene NmrA like redox sensor 1(NMRAL1)in the development of papillary thyroid carcinoma(PTC).Methods Bioinformatics analysis was em-ployed to investigate the expression of the NMRAL1 gene across various cancer types and its correlation with prognosis.Immunohistochemistry was utilized to analyze the expression pattern of NMRAL1 in PTC and conduct clinicopathological correlation analysis.Additionally,stable cell lines overexpressing NMRAL1 were established in TPC-1 cells.The effects of NMRAL1 overexpression on cell proliferation,migration,and invasion of TPC-1 and Nthy-ori 3-1 cells were assessed using CCK-8 assay,clonogenic assay,Transwell assay,and scratch assay,respectively.Furthermore,RT-qPCR experiments were conducted to investigate the regulatory effect of NMRAL1 on the expression of genes associated with translesion DNA synthesis.Results Bioinformatics analysis revealed that NMRAL1 was highly expressed in all 26 types of tumors compared to normal tissues in the TCGA x GTEx dataset.Patients with high expression of NMRAL1 in thyroid cancer had significantly lower survival rates than those with low expression(P＜0.05).In the immunohisto-chemical validation of 30 PTC samples,NMRAL1 had a positive rate of 73.33％,in PTC tissues,while it was not ex-pressed in adjacent normal thyroid tissues.The staining intensity scores of NMRAL1 in PTC and adjacent tissues exhib-it significant differences(P＜0.000 1).High expression of NMRAL1 was associated with the size of the tumor(P=0.027 4)and lymph node metastasis(P=0.044 1).In vitro functional experiments revealed a significant enhance-ment in both cell proliferation and migration/invasion capacities upon overexpression of NMRAL1(P＜0.05).Moreo-ver,mRNA and protein expression levels of translesion synthesis-related genes were upregulated(P＜0.001).Con-clusion NMRAL1 promotes proliferation and migration of thyroid carcinoma cells,suggesting that this function may be achieved by enhancing DNA damage repair capacity,thereby improving the survival of damaged cells.

Objective:To analyze the efficacy of enzyme replacement therapy and anti-drug antibody production in children with Fabry disease.Methods:The clinical data of 7 children with Fabry disease treated with enzyme replacement therapy for more than 1 year at Children′s Hospital of Zhejiang University School of Medicine from July 2021 to June 2024 were retrospectively analyzed. The basic information and the changes of related clinical indicators before and after treatment were collected. Paired sample t test was used to compare renal function, left heart mass index, pain score and other related indexes before and after treatment. The anti-drug antibodies were detected by enzyme-linked immunosorbent assay. Results:A total of 6 boys and 1 girl were included. The age of diagnosis was (12.2±1.8) years. After 1 year of enzyme replacement therapy, the abnormal substrate globotriaosylsphingosine and brief pain inventory scores of all children were significantly lower than those before treatment ((16±11) vs. (63±42) μg/L, 22±19 vs. 45±29, t=3.88, 3.43, both P<0.05). There were no significant differences in glomerular filtration rate, urinary microalbumin to creatinine and left heart mass index before and after treatment ((124±35) vs. (136±26) ml/(min·1.73 m 2), (9.3±8.3) vs. (3.8±2.5) mg/g, (38±9) vs. (33±6) g/m 2.7, t=1.33, 1.74, 1.19, all P>0.05). Patients 4, 5 and 6 developed anti-drug antibodies at 1 month, 4 months and 1 month after medication, respectively. Patient 4 had persistently high anti-drug antibody titers (absorbance 3.65-3.73) accompanied by urticaria, elevated globotriaosylsphingosine and worsening clinical symptoms. Conclusions:The enzyme replacement therapy can effectively improve the clinical symptoms and reduce the level of globotriaosylsphingosine in children with Fabry disease. The anti-drug antibody is common in patients after long-term enzyme replacement therapy and may diminish the efficacy, which needs dynamic monitoring.

Objective:To investigate the clinical characteristics and survival outcomes of patients with nasopharyngeal carcinoma (NPC) complicated by multiple primary malignancies (MPCs) in a real-world setting.Methods:A retrospective study was performed on 238 NPC patients with MPCs who received radical radiotherapy at Fujian Cancer Hospital between January 1st, 2004 and December 31st, 2023. The primary endpoints were overall survival (OS) and cumulative survival rate. Survival analysis was conducted using the Kaplan-Meier method with log-rank / Breslow tests, and univariate analysis of prognostic factors was performed using the Cox proportional hazards model.Results:A total of 246 primary malignant tumors were identified in 238 patients, involving 12 organ systems and 39 tumor types. The most common coexisting malignancies occurred in the respiratory and intrathoracic organs [25.2% (62/246)], followed by digestive organ malignancies [22.8% (56/246)], malignancies of the lip, oral cavity, and pharynx [22.8% (56/246)], and thyroid and other endocrine gland malignancies [15.4% (38/246)]. The median OS was 186 months, and the 3-, 5-, and 10-year cumulative survival rates were 90.84%, 85.25%, and 69.45%, respectively. Poorer survival was associated with male sex, age>48 years at onset, locally advanced disease (stage IVA), synchronous MPCs and/or digestive system malignancies, fewer total cycles of chemotherapy, and lack of concurrent or adjuvant chemotherapy.Conclusions:In patients with NPC, MPCs most frequently involve the respiratory system, digestive system, and head and neck organs (including the thyroid). Male sex, older age, locally advanced primary NPC, synchronous and/or digestive system MPCs, fewer chemotherapy cycles, and lach of concurrent or adjuvant chemotherapy were significantly associated with poorer prognosis.

Lymphoma is a highly heterogeneous malignancy characterized by complex molecular regulatory mechanisms that result in significant differences in aggressiveness and prognosis across its subtypes.Gene copy number alteration(CNA)analysis,an emerging technology,has become a pivotal tool in the precision re-search and management of lymphoma.By detecting DNA deletions,amplifications,and chromosomal copy number changes,CNA analysis addresses the limitations of traditional cytogenetic techniques,enhances the ac-curacy of subtype classification,and aids in evaluating tumor heterogeneity and disease progression.This re-view provides a comprehensive summary of CNA detection methods and their applications in lymphoma,with a focus on recent advancements in the field.It offers a comparative analysis of CNA detection techniques and discusses their role in precision diagnosis,subtype classification,monitoring disease progression,predicting therapeutic resistance,and assessing prognosis.Additionally,the review explores the potential applications of CNA analysis in uncovering molecular regulatory mechanisms,optimizing therapeutic strategies,and impro-ving patient survival outcomes.