BACKGROUND:Human mesenchymal stem cells derived from Wharton's jelly(WJCs)display the characteristics of MSCs as defined by the International Society for Cellular Therapy.They can be differentiated into bone,cartilage,adipose,muscle,and neural cells.They can also support the expansion of other stem cells,be weli-tolerated by the immune system,and have the ability to home to tumors.OBJECTIVE:To investigate biological changes of WJCs and brain tumor stem cells(BTSCs)co-cultured in vitro.METHODS:WJCs cultured by situ cultivation and BTSCs used enzyme digestion way respectively,and gathering the 3rd passage of WJCs though subculturing as well as BTSCs.Two kinds of cells co-cultured in 24-well plates in serum-free medium (SFM)without any growth factor.3 and 7 days after co-cultured respectively,CD133 expression of suspension cells in the 24-well plates were identified by flow cytometry,and immunofluorescence was performed for Nestin and glial fibrillary acidic protein (GFAP)expression of adherent cells.Co-culture supernatant(CCS)re-suspended 3~(rd) passage of BTSCs and cultured into 96-well plates at day 3,which were used to determine the difference in cell growth curve in both groups using a microplate reader.RESULTS AND CONCLUSION:With the cocultivation days increasing,the phenomenon that tumor sphere cells began to be decomposed,adherent and differentiated observed by an inverted microscope.BTSCs in the co-cultured group expressed GFAP and Nestin when adherent and differentiated.The higher degree of malignant brain tumor tissue used in culturing BTSCs was,the higher expression of CD133 in BTSCs was.CD 133~+ in BTSCs declined when co-cultured with WJCs.Growth curve of brain tumor stem cells cultured in CCS compared with in SFM at day 3,which indicates that the proliferation of BTSCs inhibited obviously.Results indicated that CD 133~+ expression and proliferative capacity of BTSCs went down and BTSCs underwent differentiation during the co-culture in vitro.

BACKGROUND:Bone marrow mesenchymal stem cells have low immunogenicity and immunomodulatory effect,but there are seldom reports concerning the immunomodulatory effect of Wharton's jelly-derived mesenchymal stem cells of human umbilical cord and its mechanims.OBJECTIVE:To investigate the immunomodulatory effects and mechanisms of Wharton's jelly-derived mesenchymal stem cells of human umbilical cord on varient peripheral blood T lymphocytes.METHODS:Mesenchymal stem cells were isolateded from Wharton's jelly of human umbilical cord by tissue culture.T lymphocytes from human peripheral blood were stimulated by phytohemagglutinin and co-cultured with umbilical cord Wharton's jelly-derived mesenchymal stem cells and umbilical cord Wharton's jelly-derived mesenchymal stem cells supernatant respectively to measure A value following 72 hours of coculture using multifunctional microplate reader.Expression of cytokines including transforming growth factor-beta 1(TGF-β1)and interferon-y(IFN-γ)was evaluated by enzyme-labeled immunosorbent assay.RESULTS AND CONCLUSION:Wharton's jelly-derived mesenchymal stem cells could inhibite the proliferation of T lymphocytes induced by phytohemagglutinin.The proliferation inhibition rate was 56%(P＜0.01).Wharton's jelly-derived mesenchymal stem cells supernatant also had inhibitory effects on proliferation of T lymphocytes induced by phytohemagglutinin,in a dose-dependent fashion.The proliferation inhibition rates were 8.3% and 27% respectively in the 50% Wharton's jelly-derived mesenchymal stem cells supernatant and 100% Wharton's jelly-derived mesenchymal stem cells supematant groups(P＜0.05).Wharton's jelly-derived mesenchymal stem cells significantly decreased γ-interferon secrted from T-lymphocytes(P＜0.05).The secretion of TGF-β1 was lower in the coculture of Wharton's jelly-derived mesenchymal stem cells and T lymphocytes group than Wharton's jelly-derived mesenchymal stem cells alone group(P＜0.05).These indicated that Wharton's jelly-derived mesenchymal stem cells and Wharton's jelly-derived mesenchymal stem cells supernatant have inhibitory effects on proliferation of T lymphocytes induced by phytohemagglutinin.The mechanims may be associated with cell contant and inhibition of v-interferon secrted from T-lymphocytes.

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 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.

Objective To investigate the prevalence and influencing factors associated with frailty among institutional older adults and to provide evidence for intervention study.Methods A total of 237 older adults living in four welfare homes from Chengdu in Sichuan Province were recruited by convenience sampling.A cross-sectional survey was conducted,and frailty was assessed by the frailty phenotype;general information was collected by selfmade general information questionnaire;functional capacity was assessed by Barthel questionnaire;depressive status was assessed by GDS-15;cognitive function was assessed by clock drawing test and nutritional status was assessed by short form mini nutritional scale questionnaire (MNA-SF).Results The reported rate of frailty was 55.69％ among institutional older adults,and 44.31％ reported no frailty;grip weakness (207,87.3％),slow walking speed (172,72.6％) and low physical activity(131,55.3％) were the main frailty problems.Univariate analysis showed that the elderly'frailty conditions were different in the pre-retirement occupations,smoking,alcohol consumption,physical exercise,chronic diseases,medication,acute events (last year),self-reported health,using assisted walking devices,ability of daily life,depression,cognitive ability and nutritional status,and the differences were statistically significant(P＜0.05).Conclusion The status of frailty is not optimistic among institutional older adults and many factors are associated with frailty.Healthcare providers should pay more attention to the frailty issue and take timely intervention strategies to prevent or delay the frailty.

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 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 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.

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.