Purpose To explore the molecular features of diffuse large B-cell lymphoma(DLBCL)with high expression of MYC.Methods The clinical data of 45 cases of DLBCL were collected.Immunohistochemical EnVision method was used to classify the patients into the group with high expression of MYC and the group with low expression of MYC.All samples were subjected to DNA targeted sequencing and molecular typing was performed using the LymphGen online tool.Cellular origin was determined by using the Lymph2Cx method.The correlation be-tween MYC overexpression and clinicopathological parameters was analyzed by the x2 test and Fisher precise test.Survival curves were drawn and survival-related factors were analyzed u-sing Cox univariate and multivariate regression.ResultsCases were classified into DLBCL with high expression of MYC(n=17)and DLBCL with low expression of MYC(n=28).Com-pared to the group with low expression of MYC,the group with high expression of MYC had more PIM1,MYD88,CD79B,CD58 and PRDM1 mutations(76.5％vs 28.6％,70.6％vs 32.1％,58.8％vs28.6％,29.4％vs3.6％,29.4％vs 3.6％,P＜0.05),MCD were more frequently found(58.8％vs 10.7％,P=0.001),GCB were rarely found(17.6％vs 50.0％,P=0.030).Overall survival was significantly shorter in DLBCL with high expression of MYC(P＜0.05).Cox multi-factorial analysis showed that age was an independent prognostic factor for DLBCL(P＜0.05).Conclusion Patients with high expression of MYC were frequently characterized as MCD and ABC,and PIM1,MYD88,CD79B,CD58 and PRDM1 muta-tions were common.Patients with high expression of MYC had a poorer prognosis.

Objective:To analyze the clinicopathological features and differential diagnosis of large B-cell lymphoma with IRF4 rearrangement, aiming enhance its recognition and prevent misdiagnosis.Methods:The clinicopathological features, immunophenotype, and fluorescence in situ hybridization (FISH) results of six cases diagnosed with IRF4 rearrangement-positive B-cell lymphoma at the Affiliated Hospital of Xuzhou Medical University from 2015 to 2023 were retrospectively analyzed. Additionally, a comprehensive review of the literature was conducted.Results:Six patients with IRF4 rearrangement-positive large B-cell lymphoma were included. Patients 1 to 5 included three males and two females with a median age of 19 years ranging from 11 to 34 years. Four patients presented with head and neck lesions, while the other one had a breast nodule; all were in clinical Ann Arbor stages I to Ⅱ. Morphologically, entirely diffuse pattern was present in two cases, purely follicular pattern in one case, and diffuse and follicular patterns in other two cases. The tumor cells, predominantly centroblasts mixed with some irregular centrocytes, were of medium to large size, with a starry sky appearance observed in two cases. Immunophenotyping revealed all cases were positive for bcl-6 and MUM1, with a Ki-67 index ranging from 70% to 90%, and CD10 was positive in two cases. IRF4 rearrangement was confirmed in all cases by FISH analysis, with dual IRF4/bcl-6 rearrangements identified in two cases, leading to a diagnosis of LBCL-IRF4. Case 6, a 39-year-old female with a tonsillar mass and classified as clinical Ann Arbor stage Ⅳ, displayed predominantly diffuse large B-cell lymphoma (DLBCL) morphology with 20% high-grade follicular lymphoma characteristics. Immunohistochemistry showed negative CD10 and positive bcl-6/MUM1, with a Ki-67 index of approximately 80%. Triple rearrangements of IRF4/bcl-2/bcl-6 were identified by FISH, leading to a diagnosis of DLBCL with 20% follicular lymphoma (FL). All six patients achieved complete remission after treatment, with no progression or relapse during a follow-up period of 31-100 months.Conclusions:Large B-cell lymphoma with IRF4 rearrangement is a rare entity with pathological features that overlap with those of FL and DLBCL. While IRF4 rearrangement is necessary for diagnosing LBCL-IRF4, it is not specific and requires differentiation from other aggressive B-cell lymphomas with IRF4 rearrangement.

The aim of this study is to establish a simple and accurate method for vaccine immune e-valuation of porcine pseudorabies virus.In this research,PRV-gD recombinant protein was ex-pressed from mammalian cell HEK-293F as coating antigen,and then the reaction conditions of gD-iELISA were optimized according to checkerboard titration method.The gD-iELISA was used to detect the antibody levels of 211 clinical pig serum samples and the consistency with the neu-tralizing antibody levels wasanalyzed.The results showed that the antigen coating concentration was 0.90 mg/L;the serum to be detected was diluted 1∶100 and incubated at 37 ℃ for 30 min;goat anti-pig IgG-HRP antibody was diluted 1∶55 000 and incubated at 37 ℃ for 30 min;TMB sub-strate was developed at 37 ℃ for 20 min.The method could detect 1∶6 400 diluted PRV positive serum.The results of CSFV,PRRSV,PCV-2,PEDV and FMDV positive sera were all negative by gD-iELISA,and there was no cross-reaction between the method and the above positive sera.The coincidence rate of gD-iELISA and commercial kits was 95.26％,and the intra-and inter-batch co-efficients of variation were both less than 10％.Correlation analysis showed that the correlation coefficient(r)between gD antibody level and neutralizing antibody level was significantly greater than that of gB antibody level,and the gD antibody level had a good linear relationship with the neutralizing antibody level.The results indicated that gD-iELISA was more suitable for vaccine im-mune evaluation of PRV than gB-iELISA.Therefore,the method will have a good prospect of ap-plication in the immunization control of the PRV.

Asari Radix et Rhizoma （AR） is a traditional Chinese medicine with a history of more than 2 000 years of medication and has been included in ancient herbal works in the past dynasties. It is effective in releasing the exterior， dispersing cold， dispelling wind， relieving pain， opening orifices， warming the lung， and resolving fluids， and is still widely used in the clinical treatment of influenza， coronavirus disease-2019 （COVID-19） pneumonia， asthma， allergic rhinitis， eye pain， headache， toothache， oral ulcer， eczema， etc. Modern pharmacological studies have shown that AR has antipyretic， anti-inflammatory， analgesic， antibacterial， antiviral， relieving cough and asthma， anti-allergy， and other effects. AR contains a variety of chemical components， in which essential oil is not only associated with functions such as dispelling cold， relieving heat， relieving pain， and resisting inflammation and allergy， but is also toxic. AR also contains lignans， flavonoids， amides， phenanthrenes， alkaloids， and other non-volatile oil components， which play an important role in immunity regulation， anti-inflammation， pain relief， heart strengthening， and blood vessel expansion. The phenanthrene compounds are mainly aristolochic acid analogues， such as aristolochic acid Ⅳ_a and aristolochic lactam Ⅰ. Aristolochic acid Ⅳ_a has been proven to have a significant anti-inflammatory effect. The toxicity of AR is related to safrole， aristolochic acids and their analogues， and is also affected by many factors， such as preparation method， dosage， origin， collection time， medicinal part， and decocting time， which should be comprehensively considered in clinical application. Based on the relevant literature in China and abroad， the present study reviewed the correlation of chemical composition and pharmacological and toxicological effects of AR， and the safety of AR， aristolochic acid， safrole， and other components to provide a new perspective for an objective understanding of AR safety， as well as references for rational clinical application， production risk prevention and control， and drug scientific supervision of AR.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS^E） technique， we identified qualitatively the metabolites of aristolochic acid（AAs） in rat in order to analyze the metabolic differences between water extract of Aristolochiae fructus（AFE） and Aristolochic acid Ⅰ（AAⅠ）. MethodSD rats were selected and administered AFE（110 g·kg^-1·d^-1） or AAⅠ（5 mg·kg^-1·d^-1） by oral for 5 days， respectively. Serum， urine and feces were collected after administration. Through sample pretreatment， ACQUITY UPLC BEH C₁₈ column（2.1 mm×100 mm， 1.7 μm） was used with the mobile phase of 0.01% formic acid methanol（A）-0.01% formic acid water（B， containing 5 mmol·L^-1 ammonium acetate） for gradient elution（0-1 min， 10%B； 1-7 min， 10%-75%B； 7-7.2 min， 75%-95%B； 7.2-10.2 min， 95%B； 10.2-10.3 min， 95%-10%B； 10.3-12 min， 10%B） at a flow rate of 0.3 mL·min^-1. Positive ion mode of electrospray ionization（ESI⁺） was performed in the scanning range of m/z 100-1 200. In combination with UNIFI 1.9.4.053 system， the Pathway-MS^E was used to qualitatively analyze and identify the AAs prototype and related metabolites in biological samples（serum， urine and feces）， and to compare the similarities and differences of metabolites in rats in the subacute toxicity test between AFE group and AAⅠ group. ResultCompared with AAⅠ group， 6， 10， 13 common metabolites and 14， 20， 30 unique metabolites were identified in biological samples（serum， urine and feces） of AFE group， respectively. Moreover， the main AAs components always followed the metabolic processes of demethylation， nitrate reduction and conjugation. Compared with common metabolites in AAⅠ group， prototype components of AAⅠ in serum and most metabolic derivatives of AAⅠ［AAⅠa， aristolochic lactam Ⅰ（ALⅠ）a， 7-OHALⅠ and its conjugated derivatives］ in biological samples were significantly increased in AFE group（P<0.05， P<0.01）， except that the metabolic amount of ALⅠ in feces of AFE group was remarkably lowed than that of AAⅠ group（P<0.01）. In addition， a variety of special ALⅠ efflux derivatives were also identified in the urine and feces of the AFE group. ConclusionAlthough major AAs components in AFE all show similar metabolic rules as AAⅠ components in vivo， the coexistence of multiple AAs components in Aristolochiae Fructus may affect the metabolism of AAⅠ， and achieve the attenuating effect by increasing the metabolic effection of AAⅠ and ALⅠ.

The tea beverages will be endowed with distinct aroma and taste, as well as various biologically active compounds including probiotic factors, when fermented with lactic acid bacteria (LAB). However, at present, few studies on the dynamics of flavors in tea soup at different fermentation stages were conducted. In this study, the composition of monosaccharides, aromatic components, free amino acids, and organic acids were measured, when the black tea beverages were fermented with Lactobacillus coryniformis FZU63 which was isolated from Chinese traditional kimchi. The results indicated that monosaccharides including glucose, fructose, mannose and xylose in black tea beverages are the main carbon sources for fermentation. In addition, the abundance of aromatic compounds in black tea soup are increased significantly at different fermentation stages, which endow the fermented black tea soup with fruit aroma on the basis of flowery and nutty aroma. Moreover, some bitter amino acids are reduced, whereas the content of sweet and tasty amino acids is elevated. Furthermore, the levels of lactic acid, malic acid, citric acid and other organic acids are accumulated during the fermentation. Additionally, sensory evaluation displays that black tea beverage is acquired with comprehensive high-quality after being fermented for 48 h. This study provides a theoretical basis to steer and control the flavor formation and quality of the fermented tea beverages during LAB fermentation.
Tea/chemistry* ; Beverages/microbiology* ; Camellia sinensis ; Fermentation ; Acids ; Amino Acids ; Glucose

Objective:To explore the safety and efficacy of adenosine triphosphate (ATP) in terminating paro-xysmal supraventricular tachycardia (PSVT) in children and the correlation between its efficacy, age and dose.Methods:A retrospective analysis was performed on the clinical data, efficacy and adverse effects of intravenous ATP in 120 children who had received ATP emergency cardioversion among 1 488 children with PSVT hospitalized in the Department of Pediatric Cardiology, Heart Center, First Hospital of Tsinghua University from September 2014 to November 2019.There were 80 boys and 40 girls with the age of (3.50±3.66) years (25 d-15 years). As for the group comparison, the measurement data was subject to the independent samples t test and Mann- Whitney U test; the enumeration data was subject to χ2 test. Results:Among the 120 children with PSVT, there were 42 cases (35.0%) <1 year old, and 24 cases(20.0%) combined with congenital heart disease.There were 8.3% of them (10/120 cases) suffering from tachycardiomyopathy (TCM) secondary to PSVT, whose LVEF increased from (32.70±11.69)% to (40.50±11.63)% after successful control of PSVT ( t=-3.647, P=0.005). The complete termination of PSVT by intravenous ATP was achieved in 53 of 120 cases (44.2%). ATP was given at 0.3 mg/kg, 0.2 mg/kg and 0.1 mg/kg in dose, and the significant effective rate was 56.5%(13/23 cases), 36.4%(32/88 cases) and 0, respectively, which showed that there was a significant difference in the therapeutic effect between different dose groups ( χ2=10.058, P=0.007). There was a significant difference regarding the complete termination rate between children <1 year old and those ≥1 year old [31.0%(13/42 cases) vs.51.3%(40/78 cases), χ2=4.575, P=0.032]. For refractory PSVT, the intravenous ATP was performed based on the absence of cardioversion with continuous pumping of other antiarrhythmic drugs, which achieved a significantly complete termination rate of 55.6% (10/18 cases). The rate of ATP adverse reactions was 2.5%(3/120 cases), presented with sinus arrest in children >1 year old with the dose of 0.2-0.3 mg/kg. Conclusions:It was relatively safe and effective to terminate PSVT in children with ATP, which was related to dose and age.For refractory PSVT, ATP can be intravenously pushed on the basis of continuous pumping of other antiarrhythmic drugs, which can achieve a higher complete termination rate.

Objective:To identify the risk factors for cardiac events like recurrent syncope and fatal events in children with long QT syndrome (LQTS).Methods:A retrospective review involving 69 children with LQTS with the age of (7.6±4.2) years (43 male patients, 26 female patients) admitted in the Heart Center, Division of Pediatric Cardiology, First Hospital of Tsinghua University from August 2013 to March 2019 was conducted.Medical history, surface electrocardiogram, Doppler echocardiography and screening results of pathogenic genes of each patient were analyzed.Patients were divided into cardiac event group (32 cases) and non-cardiac event group (37 cases) according to the presence or absence of cardiac events like syncope or sudden death.Differences between 2 groups were compared using the independent sample Student′s t test and Chi- square test. Results:There were 32 cases among 69 children (46.4%) had recurrent syncope, involving 2 deaths, 14 cases among 69 children (20.3%) had a positive family history and 8 cases among 69 children (11.6%) had family history of sudden death.There were 52 cases among 69 children (75.4%) had arrhythmias.Among them, 32 patients (46.4%) with ventricular arrhythmia, including 11 cases (15.9%) with torsades de pointes (TdP). Ten LQTS-associated pathogenic or pathogenic pathologic mutations were found in 53 cases among 69 children (76.8%). Children with cardiac events had a younger mean age of onset [(4.7±4.1) years vs.(7.4±3.7) years, t=-2.856, P=0.006], a longer mean corrected QT (QTc) [(529±66) ms vs.(478±52) ms, t=3.537, P=0.001] and a higher incidence of TdP (34.4% vs.0%, P<0.001) compared with those who did not have cardiac events.Pathogenic mutations of KCNQ1 and KCNH2 were more frequent in children with cardiac events (62.5% vs.18.9%, χ2=14.178, P=0.001). Conclusions:Children with LQTS are prone to cardiac events.Children with a younger onset age, a longer QTc duration, malignant ventricular tachycardia and mutations of the KCNQ1 and KCNH2 genes are more frequently complicated by cardiac events.

Objective:To investigate clinical electrophysiological characteristics of idiopathic ventricular arrhythmias (VAs) and outcomes of radiofrequency catheter ablation (RFCA) in pediatric patients.Methods:A total of 328 consecutive pediatric patients with VAs and treated with RFCA in the First Hospital of Tsinghua University from January 2014 to December 2019 were recruited, involving 205 males and 123 females with the mean age of (7.8±3.9) years and the mean body weight of (32.8±17.7) kg.Their clinical electrophysiological characteristics, RFCA outcomes of different origins of VAs and complications were analyzed.Results:Among the 328 patients with the mean onset age of (5.4±4.1) years, 57.6% had frequent premature ventricular complex (PVC), 28.7% had paroxysmal ventricular tachycardia (VT) and 13.7% had incessant VT.A total of 38/328 cases (11.6%) VAs children were complicated with tachycardia-induced cardiomyopathy.Except for 13 cases of non-induced VAs, among 315 cases there were 152/328 cases (46.4%) originated from the ventricular outflow tract (including 46.1% of the origination of the right ventricular outflow tract septum, 27.6% of the origination of the left coronary cusp, 18.4% of the origination of the right coronary cusp, and 7.9% of the origination of the right ventricular outflow tract free wall), 55/328 cases (16.5%) originated from the tricuspid valve, 54/328 cases (17.4%) originated from the left posterior fascicle, 39/328 cases (11.9%) originated from the left posterior papillary muscle, 5/328 cases (1.5%) originated from multi-origin VAs, 3/328 cases (0.9%) originated from the left anterior fascicle, and 7/328 cases (2.1%) originated from other origins.Among 307/328 cases (93.6%) VAs patients receiving RFCA, 271/307 cases (88.3%) were instantly successful, 14/307 cases (4.6%) were effectively treated and 22/307 cases (7.2%) were invalid.During the follow-up time of 3 to 36 months, there were 42/271 cases (15.5%) recurrent cases.The mean radiation time and dose were (3.2±5.8) min, and (1.4±2.6) mGy, respectively.The mean dose-area product (DAP) was (384.2±42.6) mGy·cm 2.A total of 4/328 cases (1.2%) reported perioperative vascular complication.In 20 infant patients younger than 3 years, only 1 case was not induced during procedure of RFCA, and the remaining 19 cases were performed with RFCA, including 18/19 cases (94.7%) with an instant success and 4/18 (22.2%) recurrent cases during follow-up.There were 1/20 case (5.0%) had perioperative vascular complication caused by vascular puncture.No serious complications, such as myocardial perforation, cardiac tamponade and atrioventricular block were reported. Conclusions:The right ventricular outflow tract septum is the most common origin of the idiopathic VAs in pediatric patients.VAs originated from the ventricular outflow tract and tricuspid valve usually have an acceptable outcome following ablation.The recurrent rate is high following ablation in VAs cases originated from the left ventricular fascicle and posterior papillary muscle.RFCA is safe and effective for drug resistant or intolerant VAs in infants, but the surgical indications should be strictly mastered and operated by experienced pediatric electrophysiologists.The radiation dose of RFCA can be limited in a safe range under the guidance of the 3-dimensional mapping system.

Objective:To propose the application of recognizing bone species by touching blindly (ARBTB) and verify its application effect in human anatomy experimental courses.Methods:The study included experiment 1 and experiment 2, and the research objects were 60 students majoring in clinical medicine in Batch 2019 and 60 students majoring in preventive medicine in Batch 2018, respectively. The research objects in each experiment were randomized into mainstream teaching method group and ARBTB group, with 30 students in each group. In experiment 1, after students studying for the same hours, both of two groups carried out the same test, and then the average scores of the two groups were compared. In experiment 2, the average time spent by the two groups of students in osteology learning was compared.Results:In experiment 1, ARBTB group's average score of the test was significantly higher than that of the mainstream teaching group ( P<0.001). In experiment 2, the ARBTB group took much less time in osteology learning than the mainstream teaching group ( P<0.001). Conclusion:Compared with the mainstream teaching method, ARBTB is more effective in osteology learning, which is worth popularizing.