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 explore the feasibility of using two-dimensional speckle tracking echocardiography for measuring right ventricular strain and function in healthy adults, and to analyze the impact of age and gender.Methods:This study is a cross-sectional study. Healthy adults who underwent physical examination in the Physical Examination Center of Beijing Hospital from January 1, 2020 to January 1, 2021 were included. Two researchers independently measured various right ventricular longitudinal strain indices using the Echopac software, including (global longitudinal strain (GLS), apical longitudinal strain (ALS), midventricle longitudinal strain (MLS), basal longitudinal strain (BLS), free wall GLS (FWGLS), free wall ALS (FWALS), free wall MLS (FWMLS) and free wall BLS (FWBLS)) as well as tricuspid annular plane systolic excursion (TAPSE) and right ventricle-fraction of area change (RVFAC). The above indicators were taken as the average of two physicians. The consistency of the measurements by two physicians was evaluated by the within-group correlation coefficient ( ICC). Results:A total of 233 subjects were included, including 137 males, aged (58.5±14.2) years. ICC values was all above 0.8 with excellent agreement. The values of FWGLS and GLS in healthy adults were -26.63% and -21.89%, respectively. There was no statistically significant difference in TAPSE ((2.06±0.41)cm vs. (2.10±0.39)cm, P=0.510) and RVFAC ((51.17±9.91)% vs. (50.89±8.65)%, P=0.826) between males and females. The values of various right ventricular long axis strain indicators (GLS, ALS, MLS, BLS, FWGLS, FWMLS, FWMLS, FWBLS) in females aged 18 to 40 and 41 to 65 years were higher than those in males of the same age (all P<0.05), while there was no statistically significant difference in the values of various right ventricular long axis strain indicators between the sexes in subjects aged 65 years and above (all P>0.05). In females, the right ventricular GLS, ALS, MLS, FWGLS, FWALS, FWMLS, and FWBLS values in the groups aged 18 to 40 and 41 to 65 years were significantly higher than those in the group aged 65 years and above (all P<0.05). In contrast, no significant differences were found in these indices among different age groups in males (all P>0.05). Conclusions:Using two-dimensional speckle tracking technology in echocardiography to measure right ventricular strain indicators is feasible and highly reproducible. Gender and age have an impact on right ventricular strain indicators.

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.

Objective:To explore indications for replantation of proximal proper digital artery and establishing extrinsic arterial perfusion pressure in the treatment of special type of severed digits with avulsion over 12.0 hours of warm ischemia, and to analyse the factors that affected the survival rate of the replanted digits.Methods:From September 2014 to January 2022, 8 patients with severed digits and prolonged warm ischemia were treated by transposition of adjacent digital artery together with the technique of extrinsic arterial perfusion pressure in the Department of Wrist and Hand Surgery, the Orthopaedic Hospital in Sichuan Province. During the operation, the defected proximal proper digital artery was reconstructed and repaired with vein graft, one side of the digital artery was repaired with an inverted "Y" vein graft, and one side of "Y" vein was bridged and anastomosed to repair the original digital artery. On the other side, the adjacent proximal proper digital arteries were transpositioned and anastomosed to gain an extrinsic arterial perfusion pressure, which increased the distal haemodynamic and reconstituted the blood supply. Of the 8 patients (9 severed digits) : 1 had severed index and middle fingers, 2 had severed index fingers, 4 had severed thumbs and 1 had severed little finger. All the patients were males, aged 16-63 years old, at 37.6 years old in average. Warm ischemia time of the severed digits were 12.3-20.6 hours, with 17.4 hours in average. The survival rate of replanted digits was observed after surgery. Postoperative follow-ups were conducted through telephone or WeChat reviews.Results:Follow-up time was 6-26 months, at 8.3 months in average. Retrospective analysis was performed. Vascular compromises occurred in 3 patients 4 digits (arterial insufficiency in 1 digit, venous congestion in 3 digits), skin necrosis occurred in 1 patient (1 digit) and digit necrosis in 1 patient (1 digit). Overall, 8 of the 9 replanted digits survived. According to the Replantation Function Evaluation Standard of Hand Surgery Association of Chinese Medical Association, the digit function after replantation was evaluated at excellent in 6 digits, good in 1 digit and poor in 1 digit.Conclusion:For a severed digit with an ischemia time over 12.0 hours, the survival rate can be improved by transposition of an adjacent digital artery to provided extrinsic arterial perfusion pressure.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Liddle syndrome and Gordon syndrome are two rare single-gene inherited hypertension diseases. In patients≤40 years, the prevalence of Liddle syndrome is about 1% and Gordon syndrome is uncertain all over the word, for which is often misdiagnosed and mistreated. The therapies of those diseases are targeted at gene mutation sites, as well as combined with modified lifestyle, and can achieve satisfactory diseases control. This paper reports a patient who is diagnosed with Liddle syndrome and Gordon syndrome at the same time. We aimed to consolidate and improve the diagnosis and accurate treatment of those two diseases by sharing, studying and discussing together with clinical doctors.

Objective:To explore the risk factors for atrial fibrillation(AF)in elderly Chinese patients with severe valvular heart disease(VHD).Methods:This was a cross-sectional study and consecutively enrolled 978 elderly patients with severe VHD diagnosed in 18 Class A tertiary hospitals across the country from September 2021 to March 2022, including 322(32.9%)patients with concurrent AF.Clinical and echocardiographic data were collected to analyze the risk factors for AF.Results:Among VHD patients, compared with the non-AF group, the AF group was older, had a higher female ratio, higher diastolic blood pressure, higher proportions with cerebrovascular disease and chronic kidney disease, lower serum low density lipoprotein cholesterol and higher serum creatinine, amino-terminal A-type natriuretion peptide and glycosylated hemoglobin.As for echocardiographic parameters, the left atrial diameter was larger, the left ventricular end-diastolic diameter, interventricular septum thickness, and left ventricular posterior wall thickness were smaller in the AF group than in the non-AF group.All of the differences were statistically significant(all P<0.05). The results of multivariate Logistic regression analysis showed that the left atrial anteroposterior diameter increased( OR=1.166, P<0.01), the left ventricular end-diastolic diameter decreased( OR=0.929, P<0.01), and advanced age( OR=1.051, P<0.05)was an independent risk factor for elderly VHD patients with concurrent AF. Conclusions:In elderly patients with severe VHD, advanced age, an increased left atrial anteroposterior diameter, and a decreased left ventricular end-diastolic diameter were independently associated with AF.Therefore, evaluation of cardiac structure and regular follow-up should be performed in elderly patients with severe VHD for early intervention to reduce the incidence of AF.

Objective:To investigate the diagnostic value of independent and combined subtests of the psychometric hepatic encephalopathy score (PHES) in mild hepatic encephalopathy(MHE) of patients with liver cirrhosis, so as to optimize the PHES.Methods:This was a prospective, multicenter and real-world study which was sponsored by the National Clinical Research Center of Infectious Diseases and the Portal Hypertension Consortium. Twenty-six hospitals from 13 provinces, autonomous regions and municipalities countrywide participated in this study, induding Tianjin Third Central Hospital, the Fourth People′s Hospital of Qinghai Province, the Second Affiliated Hospital of Baotou Medical College, the Third People′s Hospital of Taiyuan, the Fifth Medical Center of PLA General Hospital and so on. From October 2021 to February 2022, outpatients and hospitalized patients with liver cirrhosis and no obvious hepatic encephalopathy were consecutively enrolled. All patients received 5 PHES subjects in the same order: number connection test(NCT)-A, NCT-B, digit symbol test(DST), line tracing test(LTT) and serial dotting test(SDT), and the scores were calculated. The total score of PHES <-4 was taken as the cut-off value for diagnosing MHE. Compare the differences in each subtest between MHE group and non-MHE group. Receiver operating characteristic curve(ROC) and area under the curve(AUC) was performed to assess the diagnostic value of independent and combined subtests in MHE. Mann-Whitney U test and DeLong test were used for statistical analysis. Results:A total of 581 patients with liver cirrhosis were enrolled, 457 were diagnosed as MHE, and the incidence of MHE was 78.7%. The results of NCT-A, NCT-B, SDT, LTT, DST of MHE group were 60.00 s(47.01 s, 88.00 s), 90.45 s(69.32 s, 125.35 s), 74.00 s(57.65 s, 96.60 s), 74.72(60.00, 98.61) and 27.00(20.00, 36.00), respectively. Compared those of non-MHE group(34.00 s(29.15 s, 44.48 s), 50.00 s(40.98 s, 60.77 s), 50.00 s(41.07 s, 63.03 s), 46.23(38.55, 59.42) and 42.00(34.00, 50.75)), the differences were statistically significant( Z=12.37, 12.98, 9.83, 11.56, 10.66; all P<0.001). The AUC(95% confidence interval(95% CI)) of subtests of PHES NCT-B, NCT-A, LTT, DST and SDT alone in MHE diagnosis were 0.880(0.849 to 0.910), 0.862(0.828 to 0.896), 0.838(0.799 to 0.877), 0.812(0.772 to 0.851) and 0.788(0.743 to 0.832), respectively. The combination of 2 PHES subtests significantly increased the diagnostic efficacy. Among them the diagnostic efficacy of the combination of NCT-B and LTT was the best, the AUC(95% CI) was 0.924(0.902 to 0.947), the specificity was 91.9% and the sensitivity was 79.2%, which was better than a single PHES subtest (NCT-A, NCT-B, SDT, LTT and DST) and the combination of NCT-A and DST(AUC was 0.879, 95% CI0.847 to 0.910) which was recommended by guidelines on the management of hepatic encephalopathy in cirrhosis, the differences were statistically significant ( Z=3.78, 3.83, 5.57, 5.51, 5.38, 2.93; all P<0.01). Furthermore, compared between the combination of NCT-B and LTT and the combination of 3 subests of PHES, only the diagnostic efficacy of combination of NCT-B, LTT and SDT (AUC was 0.936, 95% CI 0.916 to 0.956) was better than that of the combination of NCT-B and LTT, the difference was statistically significant( Z=2.32, P=0.020). Conclusion:Based on the diagnostic efficacy and clinical feasibility of PHES subtests and their combinations, the combination of NCT-B and LTT is recommended for the diagnosis of MHE.

Objective:To investigate the clinicopathological features and misdiagnosis factors of ALK positive large B-cell lymphoma (ALK +LBCL). Methods:The clinicopathological data of 3 patients with ALK +LBCL in the Department of Pathology, the Affiliated Hospital of Xuzhou Medical University from 2010 to 2021 were collected retrospectively. Immunohistochemistry (IHC) was used for immunophenotyping, in-situ hybridization (ISH) for EBV-encoded RNA (EBER) detection, in-situ fluorescence hybridization (FISH, break-apart probes) for ALK, MYC, and CCND1 translocations. Next-generation sequencing (NGS) was used for the detection of gene fusions and mutations. And clinicopathological features and prognosis of patients were analyzed. Results:Among the 3 ALK +LBCL patients, there were 2 males and 1 female, aged 42, 59, and 39 years, respectively, none of which presented with B symptoms. Case 1 showed systemic lymphadenopathy with elevated serum EBV DNA loading, while cases 2 and 3 presented with extranodal lesions in the nasal and hard palate, respectively. Bone marrow biopsies were performed in cases 1 and 3, and neither showed involvement. Case 1 was at clinical stage Ⅲ while both cases 2 and 3 were at stage Ⅰ, and IPI score ranged 0-1 in all cases. The morphology of these cases was similar. The architecture was effaced by sheets of cohesive large cells growing in extensive infiltration and intra-sinus growth pattern. The neoplastic cells showed immunoblastic or plasmablastic morphology, and large anaplastic cells were easily found. The tumor cells expressed ALK protein cytoplasmically in almost all cells, with ALK gene translocations detected by FISH. Common B-cell and T-cell markers, including CD20, PAX5, CD19, CD2, CD3, CD5, CD7, CD43, CD56, and bcl-2, were negative, while plasmacytic differentiation markers, including CD138, CD38, and MUM1, were positive; CD22, BOB1 and OCT2 were variably expressed. CD10 was strongly expressed only in case 3. All cases were negative for bcl-6 but positive for CD4, perforin, CD30 (partial cells), pSTAT3 (diffusely), and MYC (40%-50%). The Ki-67 index was ranged 60%-70%. MYC translocation was not detected in any case by FISH. In case 1, EBER was strongly positive in>90% of tumor cells. Case 3 was diffusely positive for cyclin D1 but negative for SOX11 expression and CCND1 translocation. All cases harbored ALK fusion genes detected by NGS. In case 1, the fusion partner was TFG, which had not been reported in DLBCL, while in the other 2 cases, ALK fused with the CTCL gene, which was commonly seen in ALK +LBCL. Cases 1 and 3 were treated with ECHOP-based chemotherapy for six cycles and were followed up for 70 and 27 months, respectively, and both achieved complete remission. Conclusions:ALK +LBCL cases with diffuse EBER-positivity reported in this study show TGF as a new fusion partner of ALK in DLBCL, together with cyclin D1 expression. These rare cases are easily confused with EBV positive diffuse large B-cell lymphoma, not otherwise specified (EBV +DLBCL, NOS), cyclin D1 positive diffuse large B-cell lymphoma (cyclin D1 +DLBCL) and ALK positive anaplastic large cell lymphoma (ALK +ALCL), resulting in misdiagnosis. Being aware of these rare phenotypes is essential for pathologists to diagnose ALK+LBCL and guide appropriate treatment accurately.

Early phase trials refer to the early exploratory stage of transferring drug development into clinical trials. With China's strong encouragement for innovative drug research and development and enterprises vigorous investment, a large number of innovative drugs have entered early clinical trials. Early phase trials are generally based on innovative diagnosis and treatment mechanisms, pharmaceutical technology and drug delivery methods. Their research design are complex and diverse, and the new technology such as computer simulation are also widely used in the early phase trial process. These aspects are major challenges for the scientific and ethical review of early phase trials. Based on the characteristics of early phase trials, this article analyzes the ethical issues in early clinical trials such as risk uncertainty, therapeutic misunderstanding, subject compensation, breakthrough treatment, etc., and puts forward ethical countermeasures and suggestions.