Immunotherapy following transplantation has long been a central focus in both anti-rejection strategies and the induction of immune tolerance. Regulatory B cells (Bregs) can directly suppress the immune system via the interaction between programmed cell death protein 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1). Additionally, Bregs exert indirect immunosuppressive effects through the secretion of cytokines such as interleukin-10 (IL-10), transforming growth factor-β (TGF-β), and granzyme B (GrB), among which IL-10 plays a particularly critical role. This review summarizes recent progress in the classification, functional characteristics, and activation mechanisms of Bregs, as well as their potential applications in transplantation immunotherapy, aiming to provide a theoretical foundation for Breg-targeted strategies in transplant immune modulation.

To explore the value of general information and rapid laboratory tests obtained from the emergency department in the early diagnosis and prevention of young patients with acute myocardial infarction and acute myocarditis, in order to prevent the disease from progressing to a critical stage. This study employs a retrospective observational study, compiling clinical data from young patients diagnosed with acute myocardial infarction or acute myocarditis who were admitted to the Department of Cardiology or Emergency Department of the Second Affiliated Hospital of Soochow University from January 2015 to September 2024. Demographic information and laboratory test results from both the outpatient and emergency departments were retrieved. The acute myocardial infarction group comprised 267 patients (257 males, 10 females) aged 23-44 ys, while the acute myocarditis group included 134 patients (93 males, 41 females) aged 18-44 ys. A comparative analysis of the clinical data between the two groups was conducted, encompassing variables such as age, gender, comorbidities, high-risk factors, emergency blood routine tests, high-sensitivity C-reactive protein levels, coagulation profiles, renal function tests, NT-proBNP levels, myocardial injury markers, electrocardiogram readings, blood pressure, and heart rate. The results showed that:Compared with the young myocarditis group, the myocardial infarction group was older (ys)[38(35, 42) vs 30(25, 37), U=7 893, P<0.001], more male [257(96.3%) vs 93(69.4%), χ2=57.95, P<0.001], more smoking [211(79.0%) vs 38(28.4%), χ2=97.32, P<0.001], drinking history [125(46.8%) vs 22(16.4%), χ2=35.51, P<0.001], family history of coronary heart disease [45(16.9%) vs 3(2.2%), χ2=18.09, P<0.001], hypertension [100(37.5%) vs 12(9.0%), χ2=36, P<0.001] and diabetes [42(15.7%) vs 4(3.0%), χ2=14.27, P<0.001]. Systolic blood pressure (mmHg)[126(114, 144) vs 119(101, 126), U=11 389.50, P<0.001], diastolic blood pressure (mmHg)[80(70, 93) vs 72(62, 81), U=12 220.50, P<0.001], total white blood cell count (10 9/L)[11.3(9.2, 14.1) vs 8.5(6.6, 11.2), U=10 825.50, P<0.001], hemoglobin (g/L)[157(147, 166) vs 143(129, 154), U=9 404.50, P<0.001], platelet count (10 9/L)[244(206, 297) vs 207(173, 253), U=11 680, P<0.001], uric acid (μmol/L)[380(315, 446) vs 347(265, 412), U=14 805.50, P=0.005], ST segment elevation [204(76.4%) vs 57(42.5%), χ2=73.03, P<0.001] and Q wave formation [76(28.5%) vs 17(12.7%), χ2=12.47, P<0.001] in ECG were higher than those in myocarditis group. The duration of onset (hs) [6(3, 25) vs 48(24, 73), U=27911, P<0.001], heart rate (beats/min)[82(74, 92) vs 92(78, 103), U=22 347, P<0.001], D-dimer (μg/ml)[0.23(0.17, 0.51) vs 0.61(0.30, 1.38), U=25 806, P<0.001], High-sensitivity troponin T/99th percentile upper reference limit [5(1, 36) vs 16(8, 39), U=22 577, P<0.001], NT-proBNP (pg/ml) [204(64, 644) vs 824(189, 4 043), U=25 134, P<0.001], C-reactive protein (mg/L)[6(3, 9) vs 24(6, 55), U=26 349.50, P<0.001] and body temperature (℃) [36.50(36.30, 36.60) vs 37.35(36.50, 38.50), U=26 961, P<0.001] were significantly lower than those in myocarditis group, the symptoms of chest pain in myocardial infarction group was significantly higher than those in myocarditis group [262(98.1%) vs 83(61.9%), χ2=97.24, P<0.001], and the history of prodromal infection [12(4.5%) vs 112(83.6%), χ2=261.26, P<0.001], syncope [11(4.1%) vs 18(13.4%), χ2=11.53, P<0.001] and shock [6(2.2%) vs 22(16.4%), χ2=27.59, P<0.001] in myocardial infarction group were significantly lower than those in myocarditis group. With acute myocardial infarction as the target outcome, 8 influencing factors selected by LASSO regression, and 5 independent influencing factors were found after multiple Logistic regression, those were age ( OR=1.21, 95% CI: 1.12-1.31; P<0.001), pre-infection ( OR=0.02, 95% CI: 0.01-0.06; P<0.001), body temperature ( OR=0.37, 95% CI: 0.18-0.77; P=0.008), chest pain ( OR=26.75, 95% CI: 5.87-121.81; P<0.001) and white blood cell count ( OR=1.27, 95% CI: 1.12-1.44; P<0.001). Younger age, high body temperature and pre-infection are independent predictors for acute myocarditis, while chest pain and elevated white blood cell count are independent predictors for acute myocardial infarction. The five influencing factors selected by multivariate logistic regression and their combined diagnostic model were subjected to ROC analysis. The AUC reached 0.969, sensitivity reached 0.940 and specificity reached 0.925. Calibration curve and decision curve analysis(DCA) demonstrate that the model possesses excellent clinical application value. In conclusion, age, chest pain, pre-infection, body temperature and white blood cell count were independent factors in distinguishing acute myocardial infarction and acute myocarditis in young people. The clinical differential diagnosis model based on 5 independent factors may has high efficiency and good clinical practicability.

Objective To investigate the relationship between the expression levels of mir-155/Th17 and mir-23b-3p/Tfh in peripheral blood and the prognostic value of secondary atopic dermatitis(AD)in AIDS patients.Methods In this study,80 AIDS patients were treated in our hospital from February 2021 to December 2023.The subjects were divided into AD group and non-AD group according to whether they had secondary AD.The levels of mir-155,Th17,mir-23b-3p and Tfh in peripheral blood of AD group and non-AD group were compared.Spearman method was used to analyze the relationship between levels of mir-155,Th17,mir-23b-3p and Tfh in peripheral blood and secondary AD in AIDS patients.At the same time,according to the prognosis of patients,the subjects were divided into good prognosis group and poor prognosis group,and the risk factors affecting the prognosis of patients were screened by Logistic regression analysis.Receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of peripheral blood mir-155,Th17,mir-23b-3p and Tfh levels on the prognosis of AIDS patients.Results Compared with non-AD group,the levels of miR-155,Th17 and Tfh in peripheral blood of AD group were higher(P＜0.05),and the levels of miR-23b-3p were lower(P＜0.05).The level of miR-155,Th17 and Tfh in peripheral blood were positively correlated with secondary AD of AIDS(r=0.487,0.492,0.495,P＜0.05),and the level of miR-23b-3p in peripheral blood was negatively correlated with secondary AD of AIDS(r=-0.503,P＜0.05).The levels of HIV load(high dose),lymphoma,PLT,NLR,CRP,miR-155,Th17 and Tfh in the poor prognosis group were higher than those in the good prognosis group(P＜0.05),while the levels of albumin and miR-23b-3p in the poor prognosis group were lower than those in the good prognosis group(P＜0.05).Logistic regression analysis showed that lymphoma,PLT,NLR,low albumin,CRP,miR-155,Th17,Tfh and low miR-23b-3p were all risk factors for poor prognosis of AIDS patients(P＜0.05).ROC curve results showed that the AUC(95％CI)and sensitivity of combined detection of peripheral blood miR-155,Th17,Tfh and miR-23b-3p in predicting poor prognosis of AIDS patients were 0.883(0.805～0.992)and 96.70％,respectively.All of them were higher than the above peripheral blood indexes alone(P＜0.05).Conclusion The abnormal expression of miR-155,Th17,Tfh,and miR-23b-3p in peripheral blood is closely related to secondary AD in AIDS patients,and is a risk factor affecting the poor prognosis of AIDS patients.The combined detection of these indicators has a high predictive value for the poor prognosis of AIDS patients.

Objective:To explore the genotype-phenotype relationship in a child with Opitz G/BBB syndrome (OS) with mild clinical phenotype.Methods:A child with motor developmental delay as the initial symptom admitted to Xi ′an Children′s Hospital on June 10, 2021 was selected for this study. Clinical data were collected, and peripheral blood samples were obtained from the child and his mother. Whole exome sequencing (WES) was performed to identify genetic variant in the child. Candidate variant were verified by Sanger sequencing to assess inheritance patterns and pathogenicity. Real-time fluorescence quantitative PCR (RT-qPCR) and Western blot (WB) analyses were conducted to evaluate the effects of the variant on mRNA and protein expression, respectively, using recombinant expression plasmids generated in vitro. This study was approved by the Medical Ethics Committee of Xi′an Children′s Hospital (Ethics No. 20240045).Results:① The child, a 9-month-and-7-day-old boy, presented with a low nasal bridge, hypertelorism, and difficulty sitting independently. Echocardiography revealed an atrial septal defect. ② WES identified a homozygous variant in the MIDI gene, c. 1483C>T (p.R495X), which was confirmed by Sanger sequencing and found to be inherited from the mother.③ Recombinant expression plasmids were successfully constructed. RT-qPCR analysis showed that the variant significantly reduced MIDI gene mRNA expression, while WB results indicated that the variant led to the production of a truncated protein. Conclusion:The mild clinical phenotype of OS in this child may be attributed to the mRNA degradation escape mechanism induced by the nonsense variant c. 1483C>T(p.R495X) in the MIDI gene. These findings provide valuable diagnostic insights for this pedigree and contribute to the understanding of the genotype-phenotype correlation in OS.

Objective:To explore the impact of the stimulator of interferon genes(STING)-interferon regulatory factor 3(IRF3)pathway on the senescence of rapid pacing HL-1 myocytes.Methods:HL-1 cells were divided into five groups: the control group(HL-1 cells without any treatment), pacing group(HL-1 cells paced for 48 hours), STING siRNA group(HL-1 cells paced for 48 hours and transfected with STING siRNA), NC siRNA group(HL-1 cells paced for 48 hours and transfected with NC siRNA), and H151 inhibitor group(HL-1 cells paced for 48 hours with the addition of 1 μmol/L STING inhibitor H151). Mitochondrial membrane potential was assessed in control and pacing group cells, and mitochondrial MitoTracker and TFAM co-localization staining was performed on these cells.Cellular senescence was evaluated using β-galactosidase staining in each group, and the positive rate of cellular senescence was observed and calculated.Western blotting was employed to detect the expression levels of STING, IRF3, P-IRF3, P16, P21, and P53 proteins in all groups.Immunofluorescence was utilized to examine the expression distribution of STING and P21 across the various groups.ELISA was performed to measure the concentrations of interleukin(IL)-1β, IL-6, and IL-8 in the cell supernatants from each group as part of the senescence-associated secretory phenotype(SASP).Results:Compared with the control group, the ratio of mitochondrial JC-1 multimer to monomer was significantly decreased in the pacing group( t=16.42, P<0.05), the co-localization of mitochondrial MitoTracker and TFAM in the cells was significantly weakened, the proportion of cells with positive cellular senescence-associated β-galactosidase staining significantly increased in the pacing group, the expression levels of STING, P-IRF3/IRF3, P16, P21, and P53 proteins were significantly elevated in the pacing group, and the concentrations of IL-1β, IL-6, and IL-8 in the cell supernatants were markedly increased.Compared with the pacing group, the proportion of cells with positive cellular senescence-associated β-galactosidase staining decreased in the STING siRNA group and H151 inhibitor group ( F= 18.13, P<0.05), the expression levels of STING, P-IRF3/IRF3, P16, P21, and P53 were reduced in the STING siRNA group and H151 inhibitor group ( F=16.84, 26.56, 74.70, 31.80, 31.23, all P<0.05), and the concentrations of IL-1β, IL-6, and IL-8 in the cell supernatants decreased( F=197.80、1 339.00、1 308.00, all P<0.001). Conclusions:Rapid pacing of HL-1 cells can promote mtDNA release into the cytoplasm, activate the STING-IRF3 pathway, accelerate cellular senescence, and enhance the secretion of SASP.Inhibiting the expression of STING can delay the senescence induced by the rapid pacing of HL-1 cells and reduce SASP secretion.

Objective To screen out the predictive factors for prognosis of migraine patients with patent foramen ovale(PFO)after occlusion,and to observe the value of predictive model based on these factors.Methods A total of 102 migraine patients with PFO who underwent occlusion of PFO were retrospectively included.Based on right to left shunt(RLS)grade in contrast-enhanced transcranial Doppler(TCD)and changes of migraine disability assessment(MIDAS)grade after occlusion,the patients were divided into effective group(n=56)and ineffective group(n=46).Patients'basic data and imaging data including contrast-enhanced TCD and transesophageal echocardiography(TEE)before occlusion were compared between groups.Independent predictive factors were screened using multivariate logistic regression,then a predictive model was established,and its performance was evaluated.Results Compared with ineffective group,effective group had a lower proportion of female patients,a higher proportion of patients with aura symptoms,also higher MIDAS scores before occlusion,lower left to right shunt(LRS)velocities through the defect,and higher RLS grades in contrast-enhanced TCD and TEE right heart contrast echocardiography before occlusion(all P＜0.05).Patients'gender,LRS velocity through the defect and RLS grade in TEE right heart contrast echocardiography before occlusion were all predictive factors for prognosis of migraine patients with PFO after occlusion of PFO(all P＜0.05).The established model demonstrated good discrimination,calibration and clinical net benefit.Conclusion Patients'gender,LRS velocity through the defect and RLS grade in TEE right heart contrast echocardiography before occlusion were all significant predictors of prognosis of migraine patients with PFO after occlusion,and the predictive model established based on these factors demonstrated certain clinical value.

Objective To explore the value of artificial intelligence-assisted compressed sensing(ACS)-MR cine imaging(Cine)for assessing biventricular function and left ventricular myocardial strain compared with conventional cardiac Cine and united compressed sensing(uCS)-Cine.Methods A total of 30 subjects who underwent conventional Cine,uCS-Cine and ACS-Cine were prospectively enrolled.Based on a 5-point scale,subjective scoring of image quality was performed and compared among 3 sequences.Biventricular function parameters and myocardial strain parameters of the left ventricle,including left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),left ventricular ejection fraction(LVEF),left ventricular end-diastolic mass(LVEDM),right ventricular end-diastolic volume(RVEDV),right ventricular end-systolic volume(RVESV),right ventricular ejection fraction(RVEF),left ventricular global radial strain(LVGRS),left ventricular global circumferential strain(LVGCS)and left ventricular global longitudinal strain(LVGLS)were measured and compared among sequences.Results The subjective image quality scores of all 3 sequences were≥3,of ACS-Cine and conventional Cine were not significantly different(adjusted P=0.306)but both slightly higher than that of uCS-Cine(both adjusted P＜0.05).LVEDV,LVEF and LVEDM based on ACS-Cine and uCS-Cine were not significantly different(all adjusted P＞0.05),but all lower than those of conventional Cine(all adjusted P＜0.05).No significant difference of LVESV was found between each two sequences(all adjusted P＞0.05).RVEDV based on ACS-Cine was lower than that based on conventional Cine,RVESV based on ACS-Cine was higher than that based on uCS-Cine,and RVEF based on ACS-Cine was lower than that based on uCS-Cine and conventional Cine(all adjusted P＜0.05),while no significant difference of right ventricular functional parameters was observed between uCS-Cine and conventional Cine(all adjusted P＞0.05).Both ACS-Cine and uCS-Cine had lower LVGRS and LVGCS than conventional Cine(all adjusted P＜0.05),with no significant difference was found between uCS-Cine and ACS-Cine(both adjusted P＞0.05).No significant difference of LVGLS was observed among 3 sequences(P＞0.05).Conclusion ACS-Cine could be used as appropriate supplement to conventional Cine for clinical assessment of biventricular function and left ventricular myocardial strain.

ObjectiveTo investigate the anti-inflammatory, antioxidant, and goblet cell-stimulating effects of a suspension of Ophiopogon japonicus (L. f.) Ker Gawl. (O. japonicus, Mai Dong) extract combined with hyaluronic acid (HA) in the mouse model with dry eye disease (DED).MethodsA DED mouse model was induced using benzalkonium chloride (BAK), followed by treatment with O. japonicus extract-containing eye drops at varying concentrations. Experimental groups included a normal control, a DED model control, a positive control, and an O. japonicus extract-treated group. Corneal fluorescein staining and tear break-up time (TBUT) were used to assess tear film stability and ocular surface integrity. Enzyme-linked immunosorbent assay (ELISA) measured inflammatory factor levels in corneal and conjunctival tissues, whereas Western blot (WB) analyzed key antioxidant and inflammatory markers, including nuclear factor erythroid 2-related factor (2Nrf2) and heme oxygenase 1 (HO-1). Periodic acid-schiff (PAS) staining and immunofluorescence were used to evaluate goblet cell density and mucin secretion.ResultsO. japonicus extract significantly improved corneal damage, reduced fluorescein staining scores, prolonged TBUT, and increased tear secretion. It downregulated inflammatory markers, including interleukin-8 (IL-8), interleukin-1β (IL-1β), and interferon-γ (IFN-γ) while upregulating Nrf2, HO-1, and the interleukin-13 (IL-13)/IFN-γ ratio, alleviating oxidative stress and inflammation. PAS staining showed increased conjunctival goblet cell density and restored mucin secretion, enhancing tear film stability.ConclusionO. japonicus extract demonstrated significant anti-inflammatory, antioxidant, and goblet cell-stimulating effects in a DED model, with good biocompatibility and promising therapeutic potential. Future research should optimize extraction processes and validate their efficacy and safety in clinical settings.

OBJECTIVE: To explore the genotype-phenotype relationship in a child with Opitz G/BBB syndrome (OS) with mild clinical phenotype. METHODS: A child with motor developmental delay as the initial symptom admitted to Xi'an Children's Hospital on June 10, 2021 was selected for this study. Clinical data were collected, and peripheral blood samples were obtained from the child and his mother. Whole exome sequencing (WES) was performed to identify genetic variant in the child. Candidate variant were verified by Sanger sequencing to assess inheritance patterns and pathogenicity. Real-time fluorescence quantitative PCR (RT-qPCR) and Western blot (WB) analyses were conducted to evaluate the effects of the variant on mRNA and protein expression, respectively, using recombinant expression plasmids generated in vitro. This study was approved by the Medical Ethics Committee of Xi'an Children's Hospital (Ethics No. 20240045). RESULTS: The child, a 9-month-and-7-day-old boy, presented with a low nasal bridge, hypertelorism, and difficulty sitting independently. Echocardiography revealed an atrial septal defect. WES identified a homozygous variant in the MIDI gene, c.1483C>T (p.R495X), which was confirmed by Sanger sequencing and found to be inherited from the mother.Recombinant expression plasmids were successfully constructed. RT-qPCR analysis showed that the variant significantly reduced MIDI gene mRNA expression, while WB results indicated that the variant led to the production of a truncated protein. CONCLUSION The mild clinical phenotype of OS in this child may be attributed to the mRNA degradation escape mechanism induced by the nonsense variant c.1483C>T (p.R495X) in the MIDI gene. These findings provide valuable diagnostic insights for this pedigree and contribute to the understanding of the genotype-phenotype correlation in OS.
Humans ; Male ; Infant ; Transcription Factors/metabolism* ; Microtubule Proteins/genetics* ; Craniosynostoses/genetics* ; Hypospadias/genetics* ; Codon, Nonsense/genetics* ; RNA, Messenger/metabolism* ; Female ; RNA Stability/genetics* ; Phenotype ; Nuclear Proteins/genetics* ; Ubiquitin-Protein Ligases ; Esophagus/abnormalities* ; Hypertelorism

Autologous blood donation is an important strategy of blood conservation. The Administrative Measures for the Clinical Use of Blood in Medical Institutions (Order No. 85 of the National Health Commission) requires medical institutions to promote the implementation of autologous blood donation actively. The clinical practice guidelines for patient blood management also recommend the proactive use of autologous blood donation to reduce the reliance on allogeneic blood. Preoperative autologous blood donation (PABD) is one of the autologous blood donation with wide range of indications, easy to operate, and can effectively reduce the transfusion of allogeneic blood. However, the performance of PABD in China is unsatisfactory due to various factors such as the patient composition of medical institutions, the implementation of outpatient department of blood transfusion, the level of attention paid to this issue, and the fact that traditional PABD do not meet clinical requirements. Therefore, improving the PABD model and exploring new PABD technology, as well as promoting their clinical application, are critical measures to meet the development requirements of patient blood management and to alleviate the shortage of blood supply. This article summarizes the improvements in the PABD model, and a novel PABD technology of PABD—preoperative deep apheresis of autologous red blood cells and/or platelets (deep apheresis autologous blood storage technology), and the current situation of clinical application of PABD to provide paradigm for clinical transfusion.