Objective To study the effects of Trichinella spiralis (T.spiralis) infection on mice with oxazolone (OXZ)-induced colitis and the possible immunologic mechanism.Methods Female BALB/c mice at age 6-8 weeks were randomly divided into four groups (A to D).Each mouse in groups B and D was infected with T.spiralis strains.Twenty-one days after T.spiralis infection,the mice in groups A and B were treated with 50％ ethanol solution,while those in groups C and D were treated with OXZ to induce the murine model of colitis.Several parameters including survival rate,disease activity index (DAI),macroscopic damage and histological score,myeloperoxidase (MPO) activity and the expression of cytokines (IFN-γ,IL-4 and IL-10) in colonic and splenic tissues at mRNA and protein levels were measured 3 and 7 days after modeling.Results No significant differences in the survival rate,DAI score,macroscopic damage score,histological score,MPO activity were observed between mice from groups C and D (P＞0.05).Pre-exposing the mice to T.spiralis strains neither alleviated the mucosal damages nor aggravated the condition of colitis.Compared with group C,the expression of IFN-γ on the third day and the expression of IFN-γ,IL-4 and IL-10 on the seventh day at mRNA and protein levels in colon and spleen tissues were significantly increased in mice treated with T.spiralis and OXZ (P＜0.05).The expression of IL-10 at transcriptional level in spleen tissues on the third day was higher than that of group C (P＜0.05).The expression of IL-4 and IL-10 at protein level in colon tissues on the third day were significantly up-regulated as compared with those of group C (P＜0.05).Conclusion The severity of OXZ-induced colitis in the murine model was neither alleviated nor aggravated by pre-exposing the mice to T.spiralis strains.High doses of IL-10 not only weakened the regulatory effects on Th2 responses,but also induced the production of proinflammatory cytokines,resulting in a new drift of Th1/Th2 without aggravating Th2 responses.Further investigation on the mechanism of T.spiralis-induced over-expression of IL-10 should be conducted,which might increase the practicability of using T.spiralis strains against OXZ-induced colitis.

Objectives: To compare the efficacy and safety of Chinese generic imatinib with branded imatinib as frontline therapy in adults with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) (Frontline group) , and to explore the efficacy and safety of Chinese generic imatinib in CML-CP patients switching from branded imatinib (Switching group) . Methods: Frontline group: Data of adults with newly diagnosed CML-CP receiving Chinese generic imatinib (Xinwei^®) or branded imatinib (Glivec^®) between October 2013 and August 2018 were retrospectively collected and analyzed. Switching group: Data of adults diagnosed with CML-CP who received branded imatinib and then switched to Chinese generic imatinib after achieving at least complete cytogenetic response (CCyR) were retrospectively collected and analyzed. Results: Frontline group: In total, 409 adult patients receiving Chinese generic imatinib (n=201) or Glivec (n=208) were included in this study. Median age was 42 years (range, 18-83 years) . Comparison of baseline showed significant difference on demographic characteristics among two cohorts: lower education level (P<0.001) , and divorced or widowed status (P=0.004) and rural household registration (P<0.001) were more common in the generic imatinib cohort than those in the Glivec cohort. There was no significant difference on age, gender, Sokal risk score, WBC and HGB between the 2 cohorts. With a median follow-up of 25 months (range, 3-62 months) , there was no significant difference on the 3-year cumulative incidence of achieving CCyR (97.5% vs 94.5%, P=0.592) , major molecular response (MMR) (84.3% vs 93.1%, P=0.208) , molecular response^4.0 (MR^4.0) (42.7% vs 41.7%, P=0.277) , molecular response^4.5 (MR^4.5) (25.4% vs 33.0%, P=0.306) as well as the 3-year probabilities of failure free survival (FFS) (76.7% vs 81.0%, P=0.448) , progression free survival (PFS) (91.8% vs 96.3%, P=0.325) and overall survival (OS) (95.8% vs 98.5%, P=0.167) between the generic and branded imatinib cohorts. Multivariate analysis showed the type of imatinib was not associated with treatment responses and outcomes. The incidences of adverse effects were comparable in the 2 cohorts. Switching group: In total, 39 patients switching from branded imatinib to Chinese generic imatinib after achieving at least CCyR were included in this study. Median age was 42 years (range, 23-80 years) . With a median follow-up of 39 months (range, 6-63 months) , molecular responses were maintained in 23 (58.9%) patients and improved in 12 (39.8%) patients. Adverse effects were tolerable. Conclusion Demographic characteristics might influence the choice of the type of TKI used in CML-CP patients. There was a comparable efficacy and safety between the Chinese generic imatinib and the branded imatinib in adults with newly diagnosed CML-CP under standard management and closely monitoring. Patients could safely switch from the branded imatinib to the Chinese generic imatinib.

Objective:To explore the efficacy and safety of BCL-2 inhibitor-based treatment in patients with relapsed/refractory t (11; 14) primary systemic light chain amyloidosis.Methods:This was a retrospective case series study. Ten patients with relapsed/refractory t(11;14) primary systemic light chain amyloidosis who had all received treatment with a combination regimen including the BCL-2 inhibitor venetoclax from January 2018 to November 2022 at the Hematology Department of Peking University People′s Hospital were included. Adverse events, and hematological and organ responses were evaluated.Results:The median age of the ten enrolled patients was 59 (range 41-78) years, and the male to female ratio was 8∶2. Except for one patient, a very good partial or better response was achieved in 8/9 patients and one patient obtained a partial response. The overall response rate was 100%. The median time to achieve a hematological response was 60 (range 24-236) days. At least one organ response was observed in 7/9 patients. With a median follow-up of 18 months, one patient experienced hematological progression and one patient died. Grade 3 adverse events included lymphocytopenia (3 cases), anemia (1 case), diarrhea (1 case), and appendicitis (1 case). One patient died of pulmonary fungal infection two months after completion of treatment, which was not excluded as being treatment related.Conclusion:A combination regimen including BCL-2 inhibitors in patients with relapsed/refractory t(11;14) primary systemic light chain amyloidosis is a potentially safe and effective treatment option that warrants further investigation.

Objective To explore the incidence and severity of hepatic adverse events (AEs) and identify factors associated with hepatic AEs in patients with chronic myeloid leukemia (CML) in chronic phase (CP) treated with tyrosine kinase inhibitors (TKIs).Methods Liver biochemistry parameters [including ALT(alanine aminotransferase),AST(aspartate aminotransferase),ALP(alkaline phosphatase),and TBil(total bilirubin)] during the first 6 months on imatinib (Gleevec(R)),dasatinib (Sprycel(R)) or nilotinib (Tasigna(R)) in CML-CP patients were collected and analyzed retrospectively.Results A total of 436 patients were enrolled in this study,including 271 with imatinib,58 with dasatinib,and 107 with nilotinib.The incidences of any abnormality of liver injury were 21.8％(59/271),15.5％(9/58) and 32.7％(35/107) in the imatinib,dasatinib and nilotinib groups,respectively.Most of the hepatic AEs were CTCAE grade 1 or 2 and mild or moderate liver injury except 1.9％ of TBil CTCAE grade 3 in the nilotinib group.Multivariate analyses showed nilotinib [OR=2.9(1.3-6.6),P=0.012;OR=4.4(1.2-15.6),P=0.023] and male gender [OR=2.3(1.4-3.9),P=0.002;OR=3.0(1.2-7.6),P=0.018] were significantly associated with moderate liver impairment.Conclusions TKIs including imatinib,dasatinib and nilotinib were well tolerated with mild to moderate hepatic AEs in CML-CP patients.Nilotinib and male sex were associated with occurrence of liver biochemistry abnormalities and moderate hepatic injury.

Objective: To explore age-related clinical characteristics, early responses and outcomes in non-senile adults with de novo acute myeloid leukemia (AML). Methods: Data of consecutive cases of 18-65 years adults with de novo AML (non-acute promyelocytic leukemia) were reviewed retrospectively. Clinical characteristics at diagnosis, early responses and outcomes across different age groups of patients were analyzed. Results: 1 097 patients were enrolled. 591 (53.9%) were male. Median age was 42 years. Increasing age was significantly associated with decreasing WBC count (P=0.003), increasing PLT count (P=0.034), lower blast proportions in bone marrow (P=0.021). The incidence of NPM1⁺/FLT3-ITD^- increased with age (P<0.001). Multivariate analyses showed that increasing age was associated with low probabilities of achieving morphologic leukemia free state (MLFS) (P=0.053) and complete remission (CR) (P=0.004) and poor overall survival (OS) (P=0.070) in the whole patients population. However, increasing age was not associated with low MLFS rate and poor OS, except low CR rate (P=0.075) in those receiving standard induction regimen instead of low-intensity regimen. Conclusions There were significant differences on clinical characteristics, cytogenetics and molecular genetics across different age groups in non-senile adults with de novo AML. In the patients receiving standard induction regimen, age was not associated with MLFS rate and OS.

Objective:To summarize the clinical manifestations and prognostic factors of patients with hepatic amyloidosis in a single center.Methods:The clinical data of 28 primary systemic light chain amyloidosis cases with liver involvement in our center from October 2012 to January 2023 were retrospectively analyzed. The main clinical manifestations and prognostic factors were studied. Statistical analysis were performed using the χ 2 test, Fisher's exact test, Wilcoxon rank test, or Kaplan-Meier survival curve log-rank test according to the different data. Results:The main clinical manifestations of patients with liver involvement were abdominal distension, hepatomegaly, and edema. CD56 and chemokine receptor 4 protein expression accounted for 52% (13/25) and 56% (14/25). 64.3% (9/14) patients were combined with t (11,14), and 21.4% (3/14) patients were positive for 1q21 (+), and no patients were detected with del(17p). Univariate analysis showed that Mayo 2004 and 2012 stages and total bilirubin (TBil) ≥34.2 μmol/L were associated with progression-free survival and overall survival. The median progression-free survival and overall survival were significantly inferior in patients with TBil≥34.2μmol/L group (0.178 years, 0.195 years) than with the TBil<34.2μmol/L group (0.750 years, 3.586 years) ( P ?

Objective:To analyze the effect and safety of plerixafor combined with G-CSF mobilization in plasma cell disease.Methods:The clinical baseline data, success rate of collection, and adverse reactions of consecutive cases of plasma cell disease were analyzed retrospectively, where the patients received plerixafor combined with G-CSF for autologous hematopoietic stem cell mobilization in Peking University People's Hospital from January 2018 to December 2019.Results:Forty-nine patients with plasma disease were included, of which 39 (79.6% ) were multiple myeloma, 8 (16.3% ) were amyloidosis, and 2 (4.1% ) were monoclonal gammopathy of renal significance. A total of 16 patients (32.7% ) had renal insufficiency, and 7 patients (14.3% ) had previous collection failure. The median times of apheresis was 1 (1-3) , median days of apheresis was 2 (1-3) days, 47 patients (95.9% ) were successfully collected for once, and the success rate of collection for twice was 100% after using plerixafor for mobilization. In 16 patients with renal insufficiency, collection was successful in 5 patients (31.3% ) on the first day, while aphresis was required in 8 patients (50% ) on the second day and 3 (18.8% ) on the third day. The main adverse reactions were fatigue, insomnia, abdominal pain, diarrhea, dizziness, and arthralgia. A total of 37 patients underwent autologous hematopoietic stem cell transplantation with 11 (8-13) days for neutrophil engraftment, and 11 (9-26) days for platelet engraftment.Conclusions:Plerixafor combined with G-CSF has a high success rate in mobilizaion of autologous hematopoietic stem cells in patients with plasma cell disease with minimum side effects, even in patients with renal insufficiency.

Objective:To explore the clinical characteristics, treatment patterns, and outcomes in newly diagnosed patients with chronic myeloid leukemia in the chronic phase (CML-CP) by age.Methods:Clinical data of consecutive ≥14 years old newly diagnosed CML-CP patients were retrospectively analyzed.Results:This study included 957 patients. Of the patients, 597 (62.4%) were male. The median age was 40 years (range, 14-83 years) . The patients were stratified into three age groups: <40 years ( n=470; 49.1%) , 40-59 years ( n=371; 38.8%) , and ≥60 years ( n=116; 12.1%) . The proportions of the patients who had splenomegaly ( P<0.001) , WBC ≥100 × 10 9/L ( P<0.001) , anemia ( P<0.001) , PLT<450 × 10 9/L ( P=0.022) , more blasts in the blood ( P=0.010) , and clonal chromosome abnormalities in Philadelphia chromosome-positive cells ( P=0.006) at diagnosis significantly decreased with age. However, the proportions of those with comorbidities ( P<0.001) , intermediate or high Sokal risk ( P<0.001) , and receiving imatinib as front-line therapy ( P<0.001) significantly increased with age. No significant differences in gender and the EUTOS Long-Term Survival risks were noted across the three age groups. The multivariate analysis showed that ≥60 years was an adverse predictor for overall survival. However, age was not significantly associated with tyrosine kinase inhibitor (TKI) therapy responses and other outcomes. The incidences of nonhematological toxicity were significantly increased with age during TKI therapy ( P<0.001) . However, those of hematological toxicity was similar across the three age groups. The proportions of the patients maintaining imatinib therapy ( P=0.026) and receiving low-dose TKI therapy ( P<0.001) significantly increased with age at the end of follow-up. Conclusions:Significant differences exist in clinical characteristics, TKI response, overall survival rates, and nonhematological toxicity among newly diagnosed CML-CP patients of different ages.

Objective: To explore Fertility and disease outcomes in patients with chronic myeloid leukemia (CML) . Methods: Clinical and fertility outcomes of male (from Jul. 1998 to Feb. 2018) and female CML (from Sep. 2009 to Feb. 2018) patients were retrospectively analyzed at Peking University People’s Hospital. Results: A total of 49 male CML patients and their spouses were enrolled. Before their spouses conceived, 34 patients were receiving tyrosine kinase inhibitor (TKI) imatinib, 9 with nilotinib, and 6 with dasatinib. At the time of conception, the median age of these male patients was 32 years (range, 25-48 years) , and the median TKI treatment duration was 36 months (range, 0.2-198 months) . One male patient having achieved complete hematologic response yet discontinuing TKI for a year developed a disease progression to blast crisis. The other 48 patients sustained stable disease. The total conception times were 61 and finally 55 infants were born including one with premature birth, two with low birth weight, and one with hypospadias receiving surgery. The other 18 female patients after pregnancy were enrolled. Two patients developed spontaneous abortions. Two received induced abortions. Fourteen gave birth to healthy infants without congenital malformation. The interval from diagnosis of CML to initiation of TKI was 4 months (range, 0.3-16 months) . During a median follow-up of 45 months (range from 7-114 months) , the estimated complete cytogenetic response (CCyR) rate, major molecular response (MMR) rate and molecular response^4.5 (MR^4.5) rate by 5 years were 88.9%, 85.3% and 35.1%, respectively. The estimated failure-free survival, progression-free survival and overall survival were 64.2%, 90.9% and 90.9%, respectively. All 14 babies developed as normal. Conclusions It seems that TKIs do not affect pregnancy outcome in the spouses of male CML patients, suggesting that withdrawal of TKIs is not necessary. Female CML patients have good pregnancy and disease outcomes in the TKI era.