[Clinical application of split liver transplantation: a single center report of 203 cases].

Objective: To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application. Methods: This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis. Results: The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group (χ2=5.560,P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group (χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion: SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

[Clinical and biological features and prognosis of patients with leukemic non-nodal mantle cell lymphoma].

Objective: To investigate the clinical, biological and prognostic characteristics of leukemic non-nodal mantle cell lymphoma (nnMCL). Methods: The clinical data of 14 patients with nnMCL and 238 patients with classical mantle cell lymphoma (cMCL) in Blood Diseases Hospital, Chinese Academy of Medical Sciences from November 2000 to October 2020 were retrospectively analyzed. Among the 14 patients with nnMCL, there were 9 males and 5 females, with the age [M (Q1, Q3)] of 57.5 (52.3, 67.0) years. Among the 238 patients with cMCL, there were 187 males and 51 females, with the age of 58.0 (51.0, 65.3) years. The clinical and biological characteristics of the two groups were recorded and compared. Follow-up and efficacy evaluation were conducted by re-examination during hospital stay and telephone follow-up and so on. Results: The proportion of CD200 expression in nnMCL patients was 8/14, which was higher than that in cMCL patients [14.6% (19/130)] (P=0.001). The proportion of CD23 expression in nnMCL patients was 8/14, which was higher than that in cMCL patients [13.5% (23/171)] (P<0.001). The proportion of CD5 expression in nnMCL patients was 10/14, which was lower than that in cMCL patients [97.4% (184/189)] (P=0.001). The proportion of CD38 expression in nnMCL patients was 4/14, which was lower than that in cMCL patients [69.6% (112/161)] (P=0.005). The expression proportion of sex-determining region of Y chromosome-related high-mobility-group box 11 (SOX11) in nnMCL patients was 1/5, which was lower than that in cMCL patients [77.9% (60/77)] (P=0.014). The proportion of immunoglobulin heavy chain variable region (IGHV) mutations in nnMCL patients was 11/11, which was higher than that in cMCL patients [26.0% (13/50)] (P<0.001). As of April 11, 2021, the follow-up time for nnMCL and cMCL patients was 31 (8-89) months and 48 (0-195) months, respectively. Among the 14 nnMCL patients, 6 patients were still under observation, and 8 patients were treated. The overall response rate (ORR) was 8/8, including 4 patients with complete remission and 4 patients with partial response. The median overall survival and median progression-free survival were not reached in nnMCL patients. In the cMCL group, 50.0% (112/224) patients achieved a complete response, 24.6% (55/224) patients achieved a partial response, and ORR was 74.6% (167/224). There was no statistically significant difference in ORR between the two groups (P=0.205). Conclusions: nnMCL patients have an indolent progression, with higher expression rates of CD23 and CD200 and lower expression rates of SOX11, CD5 and CD38. Most patients have IGHV mutations, with a relatively good prognosis, and"watch and wait"approach is an optional treatment.

[Clinical efficacy of split liver transplantation in the treatment of children with biliary atresia].

Objective: To compare the clinical efficacy of split liver transplantation (SLT) and living donor liver transplantation(LDLT) in the treatment of children with biliary atresia. Methods: The clinical data of 64 children with biliary atresia who underwent SLT and 44 children who underwent LDLT from June 2017 to May 2022 at Liver Surgery & Liver Transplantation Center,the Third Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. Among the children who received SLT, there were 40 males and 24 females. The median age at transplantation was 8 months (range:4 to 168 months). Among the patients who received LDLT, there were 24 males and 20 females. The age at transplantation ranged from 4 to 24 months,with a median age of 7 months. Sixty-four children with biliary atresia were divided into two groups according to the SLT operation time: 32 cases in the early SLT group(June 2017 to January 2019) and 32 cases in the technically mature SLT group (February 2019 to May 2022). Rank sum test or t test was used to compare the recovery of liver function between the LDLT group and the SLT group,and between the early SLT group and the technically mature SLT group. The incidence of postoperative complications was compared by χ2 test or Fisher exact probability method. Kaplan-Meier method and Log-rank test were used for survival analysis. Results: The cold ischemia time(M (IQR)) (218 (65) minutes), intraoperative blood loss(175 (100) ml) and graft-to-recipient body weight ratio (3.0±0.7) in the LDLT group were lower than those in the SLT group(500 (130) minutes, 200 (250) ml, 3.4±0.8) (Z=-8.064,Z=-2.969, t=-2.048, all P<0.05). The cold ischemia time(457(158)minutes) and total hospital stay ((37.4±22.4)days) in the technically mature SLT group were lower than those in the early SLT group(510(60)minutes, (53.0±39.0)days).The differences were statistically significant (Z=-2.132, t=1.934, both P<0.05).The liver function indexes of LDLT group and SLT group showed unimodal changes within 1 week after operation. The peak values of ALT, AST, prothrombin time, activeated partial thromboplasting time, international normalized ratio, fibrinogen and creatinine all appeared at 1 day after operation, and the peak value of prothrombin activity appeared at 3 days after operation. All indicators returned to normal at 7 days after operation. The 1-,2-,and 3-year overall survival rates were 95.5% in LDLT group and 93.5% in the technically mature SLT group, and the difference was not statistically significant. The 1-,2-,and 3-year overall survival rates were 90.2% in the early SLT group and 93.5% in the technically mature SLT group, and there was no significant difference between the two groups(P>0.05). The main complications of the early SLT group were surgery-related complications(28.1%,9/32), and the main complications of the technically mature SLT group were non-surgery-related complications(21.9%,7/32). There were 5 deaths in the SLT group,including 4 in the early SLT group and 1 in the technically mature SLT group. Conclusion: The survival rate of SLT in the treatment of biliary atresia is comparable to that of LDLT.

[Liver transplantation for polycystic liver disease: 11 cases report and literature review].

Objective: To explore the indications and safety of orthopedic liver transplantation for polycystic liver disease (PLD). Methods: Data of 11 patients with PLD who underwent orthotopic liver transplantation between 2004 and 2013 was retrospectively analyzed. Demographic, clinical and follow-up data were collected for statistical analysis. The survival rate was calculated by Kaplan-Meier method. Results: Over a period of 10 years, the patients received modified piggyback orthopedic liver transplantation (n=9) or combined liver-kidney transplantation (n=2) for PLD. The recipients' median age was 56 years. Seven patients were classified as Gigot type Ⅱ PLD, and four were classified as Gigot type Ⅲ PLD. Eight patients had severe decreased mobility (Eastern Cooperative Oncology Group, ECOG≥3). Only three cases were Child-Pguh Class C patients and the model for end-stage liver disease (MELD) score was>20. The mean hospitalization duration was (45.4±15.3) days, and the mean length of stay in intensive care unit was (4.1±1.9) days. The perioperative mortality was 18.2% and morbidity of complications was 63.6%. The median follow-up period was 111 months. Two patients died of severe complications after combined liver-kidney transplantation. One patient died of ischemia cholangitis during follow-up. The actuarial 1-, 5-and 10-year survival rate during the follow-up period was 82.2%, 81.8%, and 65.5%, respectively. Conclusions: Liver transplantation is the only curative and safe procedure for PLD, and it provides a good long-term prognosis and high quality of life for PLD patients. Liver transplantation could be a primary option in treating progressive or advanced PLD.

[Diagnosis and treatment understanding of Waldenström macroglobulinemia in China: a cross-sectional study].

Objective: To conduct a nationwide physician survey to better understand clinicians' disease awareness, treatment patterns, and experience of Waldenström macroglobulinemia (WM) in China. Methods: This cross-sectional study was conducted from February 2022 to July 2022 by recruiting clinicians with WM treatment experience from hematology, hematology-oncology, and oncology departments throughout China. Quantitative surveys were designed based on the qualitative interviews. Results: The study included 415 clinicians from 219 hospitals spread across thirty-three cities and twenty-two provinces. As for diagnosis, the laboratory tests prescribed by physicians for suspected WM patients were relatively consistent (92% -99% recommendation for laboratory, 79% -95% recommendation for pathology, 96% recommendation for gene testing, and 63% -83% recommendation for imaging examination). However, from a physician's perspective, there was 22% misdiagnosis occurred in clinical practice. The rate of misdiagnosis was higher in lower-level hospitals than in tertiary grade A hospitals (29% vs 21%, P<0.001). The main reasons for misdiagnosis were that WM was easily confused with other diseases, and physicians lacked the necessary knowledge to make an accurate diagnosis. In terms of gene testing in clinical practice, 96% of participating physicians believed that WM patients would require gene testing for MYD88 and CXCR4 mutations because the results of gene testing would aid in confirming diagnosis and treatment options. In terms of treatment, 55% of physicians thought that the most important goal was to achieve remission, while 54% and 51% of physicians wanted to improve laboratory and/or examination results and extend overall survival time, respectively. Among patients with treatment indications, physicians estimated that approximately 21% of them refused to receive treatment, mainly owing to a lack of affordable care and disease awareness. When selecting the most appropriate treatment regimens, physicians would consider patient affordability (63% ), comorbidity (61% ), and risk level (54% ). Regimens containing Bruton tyrosine kinase inhibitor (BTKi) were most widely recommended for both treatment-naïve and relapsed/refractory patients (94% for all patients, 95% for treatment-naïve patients, and 75% for relapsed/refractory patients), and most physicians recommended Ibrutinib (84% ). For those patients who received treatment, physicians reported that approximately 23% of patients did not comply with the treatment regimen due to a lack of affordability and disease awareness. Furthermore, 66% of physicians believe that in the future, increasing disease awareness and improving diagnosis rates is critical. Conclusions: This study is the first national physician survey of WM conducted in China. It systematically describes the issues that exist in WM diagnosis and treatment in China, such as a high rate of misdiagnosis, limited access to gene testing and new drugs, and poor patient adherence to treatment. Chinese doctors believe that improving doctors' and patients' understanding of WM is one of the most urgent issues that must be addressed right now.

Gene expression profile and enrichment pathways in different stages of bladder cancer.

Bladder cancer is a highly heterogeneous neoplasm. We examined the gene expression profile in 3 bladder cancer stages (Ta, T1, T2) using expression microarray analysis of 40 bladder tumors. Differentially expressed genes were found by the t-test, with <0.005 as the significance threshold. KEGG pathway-enrichment analysis was used to study the signaling pathways of the genes. We found 36 genes that could be used as molecular markers for predicting the transition from Ta-T1 to T1-T2. Among these, 11 overlapped between Ta-T1 and T1-T2 stages. Six genes were down-regulated at the Ta-T1 stage, but were up-regulated at the T1-T2 stage (ANXA5, ATP6V1B2, CTGF, GEM, IL13RA1, and LCP1); 5 genes were up-regulated at the Ta-T1 stage, but down-regulated at the T1-T2 stage (ACPP, GNL1, RIPK1, RAPGEF3, and ZER1). Another 25 genes changed relative expression levels at the T1-T2 stage. These genes (including COL1A1, COL1A2, FN1, ITGA5, LGALS1, SPP1, VIM, POSTN, and COL18A1) may be involved in bladder cancer progression by affecting extracellular matrix-receptor interaction and focal adhesion. The cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and calcium-signaling pathway were associated with bladder cancer progression at both the Ta-T1 and T1-T2 stages.

[Clinical characteristics of 11 patients with chronic lymphocytic leukemia with t (14;19) (q32;q13)].

Objective: To analyze the clinicopathological characteristics of 11 cases of chronic lymphocytic leukemia (CLL) with t (14;19) (q32;q13) . Methods: The case data of 11 patients with CLL with t (14;19) (q32;q13) in the chromosome karyotype analysis results of the Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 1, 2018, to July 30, 2022, were retrospectively analyzed. Results: In all 11 patients, t (14;19) (q32;q13) involved IGH::BCL3 gene rearrangement, and most of them were accompanied by +12 or complex karyotype. An immunophenotypic score of 4-5 was found in 7 patients and 3 in 4 cases. We demonstrated that CLLs with t (14;19) (q32;q13) had a mutational pattern with recurrent mutations in NOTCH1 (3/7), FBXW7 (3/7), and KMT2D (2/7). The very-high-risk, high-risk, intermediate-risk, and low-risk groups consisted of 1, 1, 6, and 3 cases, respectively. Two patients died, 8 survived, and 2 were lost in follow-up. Four patients had disease progression or relapse during treatment. The median time to the first therapy was 1 month. Conclusion: t (14;19) (q32;q13), involving IGH::BCL3 gene rearrangement, is a rare recurrent cytogenetic abnormality in CLL, which is associated with a poor prognosis.

[Efficacy and safety of programmed death-1 inhibitor in the treatment of relapsed/refractory classical Hodgkin's lymphoma].

Objective: This retrospective, single-center study aimed to evaluate the efficacy and safety of programmed death-1 (PD-1) inhibitors, either as monotherapy or in combination with chemotherapy, in the management of relapse/refractory classical Hodgkin's lymphoma (R/R cHL) . Methods: A total of 35 patients with R/R cHL who received treatment at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from September 2016 to December 2020 were enrolled in this study. Among them, 17 patients received PD-1 inhibitor monotherapy (PD-1 inhibitor group), while 18 patients received a combination of PD-1 inhibitor and chemotherapy (PD-1 inhibitor + chemotherapy group). Clinical data and follow-up information were retrospectively analyzed, and survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards model. Results: The median age of the 35 patients with R/R cHL was 29 years (range: 11-61 years), with 54.3% being male. According to the Ann Arbor staging system, 62.9% of patients presented with advanced (stage Ⅲ/Ⅳ) disease, and 48.6% had extranodal involvement. Before PD-1 inhibitor therapy, the median number of prior lines of therapy was 2 (range: 1-3). Objective responses were observed in 28 patients, including 22 complete response (CR) cases, resulting in an overall response rate (ORR) of 80.0% and a CR rate of 62.9%. Specifically, the ORR and CR rates were 64.7% and 58.8%, respectively, in the PD-1 inhibitor group and 94.4% and 66.7%, respectively, in the PD-1 inhibitor + chemotherapy group. Among the 18 patients who underwent sequential autologous hematopoietic stem cell transplantation (auto-HSCT) [13 CR and five partial response (PR) cases], eight patients received PD-1 inhibitor therapy after auto-HSCT as consolidation therapy. All patients maintained a CR status after transplantation, and they exhibited significantly improved progression-free survival (PFS) rates compared with those who did not undergo sequential auto-HSCT (4-year PFS rates: 100% vs 53.5% ; P=0.041). The incidence of immune-related adverse events was 29%, with only one patient experiencing grade≥3 adverse reactions, which indicated a favorable safety profile for the treatment approach. Conclusions: PD-1 inhibitor monotherapy demonstrates notable efficacy and sustained response in patients with R/R cHL. PD-1 inhibitors combined with chemotherapy significantly improve response rates. Additionally, for salvage therapy-sensitive patients, consolidation treatment with PD-1 inhibitors after auto-HSCT exhibits the potential for prolonging PFS.

[Current status of diagnosis and treatment of chronic lymphocytic leukemia in China: A national multicenter survey research].

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.

Observation of reactor electron antineutrinos disappearance in the RENO experiment.

The RENO experiment has observed the disappearance of reactor electron antineutrinos, consistent with neutrino oscillations, with a significance of 4.9 standard deviations. Antineutrinos from six 2.8 GW(th) reactors at the Yonggwang Nuclear Power Plant in Korea, are detected by two identical detectors located at 294 and 1383 m, respectively, from the reactor array center. In the 229 d data-taking period between 11 August 2011 and 26 March 2012, the far (near) detector observed 17102 (154088) electron antineutrino candidate events with a background fraction of 5.5% (2.7%). The ratio of observed to expected numbers of antineutrinos in the far detector is 0.920±0.009(stat)±0.014(syst). From this deficit, we determine sin(2)2θ(13)=0.113±0.013(stat)±0.019(syst) based on a rate-only analysis.

Assessment of boreal forest historical C dynamics in the Yukon River Basin: relative roles of warming and fire regime change.

Carbon (C) dynamics of boreal forest ecosystems have substantial implications for efforts to mitigate the rise of atmospheric CO2 and may be substantially influenced by warming and changing wildfire regimes. In this study we applied a large-scale ecosystem model that included dynamics of organic soil horizons and soil organic matter characteristics of multiple pools to assess forest C stock changes of the Yukon River Basin (YRB) in Alaska, USA, and Canada from 1960 through 2006, a period characterized by substantial climate warming and increases in wildfire. The model was calibrated for major forests with data from long-term research sites and evaluated using a forest inventory database. The regional assessment indicates that forest vegetation C storage increased by 46 Tg C, but that total soil C storage did not change appreciably during this period. However, further analysis suggests that C has been continuously lost from the mineral soil horizon since warming began in the 1970s, but has increased in the amorphous organic soil horizon. Based on a factorial experiment, soil C stocks would have increased by 158 Tg C if the YRB had not undergone warming and changes in fire regime. The analysis also identified that warming and changes in fire regime were approximately equivalent in their effects on soil C storage, and interactions between these two suggests that the loss of organic horizon thickness associated with increases in wildfire made deeper soil C stocks more vulnerable to loss via decomposition. Subbasin analyses indicate that C stock changes were primarily sensitive to the fraction of burned forest area within each subbasin and that boreal forest ecosystems in the YRB are currently transitioning from being sinks to sources at -0.7% annual area burned. We conclude that it is important for international mitigation efforts focused on controlling atmospheric CO2 to consider how climate warming and changes in fire regime may concurrently affect the CO2 sink strength of boreal forests. It is also important for large-scale biogeochemical and earth system models to include organic soil dynamics in applications to assess regional C dynamics of boreal forests responding to warming and changes in fire regime.

Association of p53 Arg72Pro and MDM2 SNP309 polymorphisms with glioma.

Epidemiological studies of the association of variants p53 Arg72Pro and MDM2 single-nucleotide polymorphism 309 (SNP309) with glioma risk have produced inconsistent results. The aim of the current study was to evaluate the association of these 2 variants with glioma susceptibility using a meta-analysis approach. For p53 Arg72Pro, 10 case-control studies including 2587 glioma patients and 4061 unrelated controls were identified. The pooled odds ratios (ORs) for Arg/Pro heterozygotes and Pro/Pro homozygotes were 1.08 [95% confidence interval (95%CI) = 0.85-1.37] and 1.08 (95%CI = 0.85-1.36), respectively, when compared to Arg/Arg carriers. Under the dominant effect model, Pro allele carriers also showed no significantly elevated glioma risk (pooled OR = 1.11, 95%CI = 0.90-1.38), and similar results were found under the recessive-effect model (pooled OR = 1.17, 95%CI = 0.85-1.61). For variant MDM2 SNP309, 3 case-control studies including 606 cases and 309 controls were identified. A marginal association with glioma risk was found for heterozygous G/T carriers (pooled OR = 1.95, 95%CI = 1.00- 3.81), whereas homozygous G/G carriers showed an increased but not significantly elevated risk of glioma (pooled OR = 2.14, 95%CI = 0.71-6.45) compared with that of T/T homozygotes. We also found no significant association between the MDM2 SNP309 polymorphism and glioma risk (pooled OR = 1.86, 95%CI = 0.94-3.67 and pooled OR = 1.25, 95%CI = 0.62-2.56, respectively) under the dominant and recessive models. Taken together, the current data suggested that the 2 polymorphisms may not contribute to glioma susceptibility.

[Dose-enhanced immunochemotherapy followed by first-line autologous peripheral blood stem cell transplantation for young patients with high-risk aggressive B-cell lymphoma: an efficacy and prognostic factor analysis].

Objective: This study aimed to determine the efficacy of dose-enhanced immunochemotherapy followed by autologous peripheral blood stem cell transplantation (ASCT) in young patients with newly diagnosed high-risk aggressive B-cell lymphoma. Methods: A retrospective study was conducted to examine the clinical and survival data of young patients with high-risk aggressive B-cell lymphoma who received dose-enhanced immunochemotherapy and ASCT as first-line treatment between January 2011 and December 2018 in Blood Diseases Hospital. Results: A total of 63 patients were included in the study. The median age range was 40 (14-63) years old. In terms of the induction therapy regimen, 52 cases received R-DA-EP (D) OCH, and the remaining 11 received R-HyperCVAD/R-MA. Sixteen (25.4% ) patients achieved partial response in the mid-term efficacy assessment, and ten of them were evaluated as complete response after transplantation. The median follow-up was 50 (8-112) months, and the 3-year progression-free survival (PFS) rate and overall survival (OS) rate were (83.9±4.7) % and (90.4±3.7) % , respectively. Univariate analysis demonstrated that age-adjusted international prognostic index ≥2 scores was a negative prognostic factor for OS (P=0.039) , and bone marrow involvement (BMI) was an adverse prognostic factor for OS (P<0.001) and PFS (P=0.001) . However, multivariate analysis confirmed that BMI was the only independent negative predictor of OS (P=0.016) and PFS (P=0.001) . Conclusions: The use of dose-enhanced immunochemotherapy in combination with ASCT as first-line therapy in the treatment of young, high-risk aggressive B-cell lymphoma results in good long-term outcomes, and BMI remains an adverse prognostic factor.

[Large B-cell lymphoma with IRF4 rearrangement: six case reports and a literature review].

Objective: To study the clinical, histopathological, and genetic features of large B-cell lymphoma (LBCL) with IRF4 rearrangement. Methods: Six patients presenting at our center between December 2017 and October 2021 were evaluated by pathological examination, fluorescence in situ hybridization, and next-generation sequencing. The relevant literature was reviewed. Results: ①The study sample included three males and three females with a median age of 33 years. Three tumors were in the tonsils, two in the lymphoid nodes, and one in the dorsal lump. All patients were treated using the RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, prednisone) regimen. All of them were alive at the time of follow-up in November 2021. ②Microscopic examination showed an entirely follicular pattern in one case and an entirely diffused pattern in 5 cases. The tumor cells were medium to large, and most of the lesions were dilatative with brisk mitotic activity (n=five cases) and no starry sky pattern (n=6 cases) . ③Four cases exhibited a GCB phenotype, and the other two exhibited a non-GCB phenotype. All of the cases were positive for CD20, PAX-5, MUM, and BCL6, and negative for CD5. Moreover, CD10, BCL2, and c-MYC were positive in 4, 3, and 2 cases, respectively.④IRF4 gene rearrangement was identified in all cases, BCL6 gene rearrangement was detected in 5 cases, and 2 cases were positive. BCL2 and MYC gene rearrangement were performed in 5 cases, all negative. ⑤Three paraffin tissue samples were used for next-generation sequencing, and lymphoma-related gene mutations such as IRF4, TP53, IGLL5, and MYD88 were detected in 3 cases. Conclusions: LBCL with IRF4 rearrangement is a rare entity with unique clinical, pathological, and genetic characteristics. This entity's pathogenesis, treatment options, and long-term prognosis still need to be explored further.

[Clinical and biological characteristics of non-IgM lymphoplasmacytic lymphoma].

Objective: The study aims to explore the clinical and biological characteristics of patients with non-IgM lymphoplasmacytic lymphoma (LPL) . Methods: The clinical data of 340 patients with LPL admitted to the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College were collected retrospectively, including 23 cases of the non-IgM LPL and 317 cases of the Waldenström's macroglobulinemia (WM) , from July 1993 to August 2020. The clinical and biological characteristics of the two groups were compared. Results: Among 23 patients with the non-IgM type LPL, two patients secreted monoclonal IgA, 14 patients secreted monoclonal IgG, and seven patients did not secrete monoclonal immunoglobulin. The median age of the non-IgM LPL and WM were both 62 (35-81) years old. Compared with the WM group, the proportion of women (56.5% vs 27.3%, P=0.007) , the proportion of splenomegaly (60.1% vs 43.8%, P=0.100) , and the proportion of extranodal invasion (21.7% vs 12.3%, P=0.672) in non-IgM LPL group were higher. Eighteen patients were tested for MYD88 gene mutation, and the overall mutation rate of MYD88 was 55.6%. In the non-IgM LPL group, a total of 17 patients received treatment, which had a comparable proportion (94.4% vs 92.7%, P=0.488) to the WM group. Sixteen patients were evaluated for efficacy, and the overall remission rate of the first-line treatment was 87.5%. The median follow-up time was 33.9 (3.5-125.1) months, and the median PFS and OS were both not reached. The 3-year PFS and OS rates were 71.4% and 68.9%, respectively. In the WM group, the median PFS was 66.2 months and the median OS was 78.1 months. Compared with the WM group, in the non-IgM group no significant differences in PFS (P=0.340) and OS (P=0.544) were seen. Conclusion: The clinical and biological characteristics of the non-IgM LPL and WM patients were similar. However, the proportion of women and extranodal involvement were higher in the non-IgM LPL group. The survival and prognosis of the non-IgM LPL patients were similar to those of the WM patients.

[Clinical features and outcomes of newly diagnosed follicular lymphoma concurrent with diffuse large B-cell lymphoma component].

Objective: To explore the clinical features and survival of newly diagnosed follicular lymphoma (FL) patients with diffuse large B-cell lymphoma (DLBCL) component. Methods: 1845 newly diagnosed FL patients aged ≥ 18 years with grades 1-3a in 11 medical centers in China from 2000 to 2020 were included, and patients with DLBCL component were screened. The clinical data and survival data of the patients were retrospectively analyzed, and the prognostic factors were screened by univariate and multivariate analysis. Results: 146 patients (7.9% ) with newly diagnosed FL had DLBCL component. The median age was 56 (25-83) years, 79 males (54.1% ) . The pathology of 127 patients showed the proportion of DLBCL component. Patients were divided into two groups according to whether the proportion of DLBCL component was ≥ 50% . The study found that patients with DLBCL component ≥ 50% had higher grade 3 ratio (94.3% vs 91.9% , P=0.010) , Ki-67 index ≥ 70% ratio (58.5% vs 32.9% , P=0.013) and PET-CT SUVmax ≥ 13 ratio (72.4% vs 46.3% , P=0.030) than patients with DLBCL component<50% . All patients received CHOP or CHOP like ± rituximab chemotherapy. The overall response rate (ORR) was 88.2% , and the complete response (CR) rate was 76.4% . In the groups with different proportions of DLBCL component, there was no significant difference in the remission rate after induction treatment and the incidence of disease progression within 2 years after initiation of treatment (POD24) (P<0.05) . The overall estimated 5-year progression free survival (PFS) rate was 58.9% , and the 5-year overall survival (OS) rate was 90.4% . The 5-year OS rate of POD24 patients was lower than that of non POD24 patients (70.3% vs 98.5% , P<0.001) . Compared with non maintenance treatment of rituximab, maintenance treatment of rituximab could not benefit the 5-year PFS rate (57.7% vs 58.8% , P=0.543) , and the 5-year OS rate had a benefit trend, but the difference was not statistically significant (100% vs 87.8% , P=0.082) . Multivariate analysis showed that failure to reach CR after induction treatment was an independent risk factor for PFS (P=0.006) , while LDH higher than normal was an independent risk factor for OS (P=0.031) . Conclusion: FL patients with DLBCL component ≥50% have more invasive clinical and pathological features. CHOP/CHOP like ± rituximab regimen can improve the clinical efficacy of patients. Rituximab maintenance therapy can not benefit the PFS and OS of patients. Failure to reach CR after induction therapy was the independent unfavorable factor for PFS.

The role of liver transplantation for intrahepatic cholangiocarcinoma: a single-center experience.

BACKGROUND/AIM: Intrahepatic cholangiocarcinoma (ICC) is not a widely accepted indication for liver transplantation (LT). The present study describes our institutional experience with patients who underwent transplantation for ICC. METHODS: A retrospective analysis was performed on 11 consecutive patients with ICC who underwent LT between October 2003 and November 2008 at our institution. RESULTS: At a median patient follow-up interval of 10 months (2-56), the median survival time was 9 months (2.5-53). The perioperative mortality and the recurrence rate were 0 and 45.5%, respectively. Five patients are currently alive 10, 12, 41, 51 and 53 months after LT, respectively. One patient died 3 months after LT as a result of bile leak and toxic shock, and 5 patients died of tumor recurrences at 2.5, 8, 8, 9 and 10 months post-LT, respectively. The 1-, 2-, 3- and 4-year disease-free survival rates and overall survival rates of all the patients were 51.9, 51.9, 51.9 and 51.9%, and 50.5, 50.5, 50.5 and 50.5%, respectively. CONCLUSION: With better and strict patient selection, the prognosis of LT for ICC could be improved. ICC patients with lymph node involvement, vascular or bile duct invasion are contraindicated for LT.

[Clinical analysis of fludarabine and cyclophosphamide combined with rituximab in the first-line treatment of 43 cases of chronic lymphoblastic leukemia].

Objective: To investigate the efficacy of fludarabine and cyclophosphamide combined with rituximab (FCR) in previously untreated patients with chronic lymphocytic leukemia (CLL) . Methods: The clinical data of 43 enrolled patients from May 2004 to December 2017 were analyzed the efficacy and survival results. Results: A total of 43 patients with 31 males and 12 females, and the median age was 58 years old (range 36 to72) before treatment. There were 8 patients with symptom B. The median number of peripheral blood lymphocyte was 26 (3-550) ×10(9)/L. IGHV unmutated was detected in 62.1% (18/29) patients, P53 deletion in 14% (6/43) patients, RB1 deletion in 18.6% (8/43) patients, Trisomy 12 in 25.6% (11/33) patients, ATM deletion in 16.7% (7/42) patients, respectively. The median number of treatment courses administered was 4 (range 2-6) . Twenty patients obtained CR (46.5%) , 18 patients obtained PR, 4 patients were SD, 1 patient was PD. The overall response rate (ORR) was 88.37%. Seven patients obtained MRD negative. After the median follow-up time of 51 (6-167) months, median PFS was 67 (29-105) months, median OS was not reach, 5-year PFS was (62.1±8.6) %, 10-year PFS was (31±14.3) %, 5-year OS was (70.5±8.3) %, and 10-year OS was (51.3±13.8) %. Less than 4 courses predicted adverse OS (P<0.05) . P53 deletion and less than 4 courses were associated with poor PFS (P<0.001) , and the prognostic value still remained after multivariate analysis[HR=7.65 (95%CI 1.74-33.60) , P=0.007; HR=3.75 (95%CI 1.19-11.80) , P=0.025]. Eighteen patients (41.9%) appeared grade 2-3 infection after chemotherapy, and 19 patients (44.2%) appeared grade 3-4 hematological adverse reactions. One patient (2.3%) was developed tumor lysis syndrome. All adverse reactions were controlled or recovered spontaneously. Conclusion: Previously untreated CLL patients treated with FCR had a high response rate and good survival rate, which is an important treatment choice for fit patients.

Herbaceous Dominant the Changes of Normalized Difference Vegetation Index in the Transition Zone Between Desert and Typical Steppe in Inner Mongolia, China.

Asymmetric responses of aboveground net primary productivity (ANPP) to precipitation were identified as a signal to predict ecosystem state shifts at temperate grassland zones in Inner Mongolia, China. However, mechanism studies were still lacking. This study hypothesized that the enhanced growth and newly emerged herbaceous after increased precipitation resulted in the highest asymmetry at the transition zone between desert and typical steppe. We monitored the responses of the normalized difference vegetation index (NDVI) of different species to precipitation events using un-manned aerial vehicle technology to test this hypothesis. NDVI and species richness were measured twice at fixed points in July and August with a time interval of 15 days. Results showed that: (1) From July to August, NDVI in the transition zone increased significantly after precipitation (P < 0.05), but NDVI in both the desert and typical steppe showed a non-significant change (P > 0.05). (2) In the transition zone, NDVI increases from the shrub and herbaceous contributed to 37 and 63% increases of the site NDVI, respectively. (3) There was a significant difference in species richness between July and August in the transition zone (P < 0.05), mainly caused by the herbaceous (Chenopodiaceae, Composite, Convolvulaceae, Gramineae, Leguminosae, and Liliaceae), which either emerged from soil or tillers growth from surviving plants. This study demonstrated that herbaceous dominant the changes of NDVI in the transition zone, which provides a scientific basis for the mechanism studies of ANPP asymmetric response to precipitation and warrants long-term measurements.