Association of radiotherapy for prostate cancer and second primary colorectal cancer: a US population-based analysis.

BACKGROUND: Radiotherapy (RT) is a common treatment for prostate cancer, yet the risk of second primary colorectal cancer (SPCRC) in patients with prostate cancer undergoing RT has not been adequately studied. METHODS: This study employed a population-based cohort design using the US Surveillance, Epidemiology, and End Results (SEER) database to identify individuals diagnosed between January 1975 and December 2015. The cumulative incidence of SPCRC was estimated using Fine-Gray competing risk regression. Poisson regression analysis was used to estimate the risk associated with RT. Survival outcomes of patients with SPCRC were evaluated using the Kaplan-Meier method. RESULTS: A total of 287,607 patients diagnosed with prostate cancer were identified. The cumulative incidences were higher in patients who did not receive RT (2.00%) compared to those who underwent RT (2.47%) after 25 years. After adjustment for multiple variables, RT was associated with an increased risk of developing combined SPCRC (adjusted HR 1.590). Additionally, the overall survival was significantly lower in patients who developed colorectal cancer after receiving RT as compared to those who did not receive RT. CONCLUSION: These findings underscore the need for diligent long-term monitoring and effective management strategies to detect SPCRC in patients treated with RT for prostate cancer.

[The efficacy and safety of daratumumab in relapsed and refractory multiple myeloma].

Objective: To investigate the efficacy and safety of daratumumab in relapsed and refractory multiple myeloma (RRMM). Methods: The efficacy and adverse events (AEs) of daratumumab based regimens were retrospectively analyzed in 37 patients with RRMM from Peking University People's Hospital, Beijing Hospital and Fu Xing Hospital affiliated to Capital Medical University in China. The deadline for inclusion was December, 2019. Results: Among the 37 patients, 35 patients were available for response evaluation. The overall response rate (ORR) was 68.6%, which was better in patients receiving 16 mg/kg daratumumab than in those with fixed doses of 800 mg daratumumab [ORR: 78.3%(18/23) vs. 40.0%(4/10)]. The percentage of infusion related reactions of daratumumab was 27.0%(10/37). The most common hematological AEs were lymphocytopenia and thrombocytopenia, with the incidences of grade 3 or more severe 59.5%(22/37) and 43.2%(16/37) respectively. Pulmonary infections(37.8%, 14/37) were the most common non-hematological AEs. One patient with positive hepatitis B surface antigen (HBsAg) and two patients dependent on dialysis were safely treated with daratumumab. Conclusion: Daratumumab is highly effective in relapsed and refractory multiple myeloma. Adverse reactions are mild and well tolerable.

Molecular Recalibration of PD-1+ Antigen-Specific T Cells from Blood and Liver.

Checkpoint inhibitors and adoptive cell therapy provide promising options for treating solid cancers such as HBV-related HCC, but they have limitations. We tested the potential to combine advantages of each approach, genetically reprogramming T cells specific for viral tumor antigens to overcome exhaustion by down-modulating the co-inhibitory receptor PD-1. We developed a novel lentiviral transduction protocol to achieve preferential targeting of endogenous or TCR-redirected, antigen-specific CD8 T cells for shRNA knockdown of PD-1 and tested functional consequences for antitumor immunity. Antigen-specific and intrahepatic CD8 T cells transduced with lentiviral (LV)-shPD-1 consistently had a marked reduction in PD-1 compared to those transduced with a control lentiviral vector. PD-1 knockdown of human T cells rescued antitumor effector function and promoted killing of hepatoma cells in a 3D microdevice recapitulating the pro-inflammatory PD-L1hi liver microenvironment. However, upon repetitive stimulation, PD-1 knockdown drove T cell senescence and induction of other co-inhibitory pathways. We provide the proof of principle that T cells with endogenous or genetically engineered specificity for HBV-associated HCC viral antigens can be targeted for functional genetic editing. We show that PD-1 knockdown enhances immediate tumor killing but is limited by compensatory engagement of alternative co-inhibitory and senescence program upon repetitive stimulation.

[Application of adaptive statistical iterative reconstruction veo and 80 kv in renal computed tomography angiography].

Objective: To explore the application of adaptive statistical iterative reconstruction Veo (ASIR-V) and 80 kV in renal computed tomography angiography(CTA). Methods: Eighty patients with renal computed tomography angiography were prospectively collected from April 2018 to July 2018 in the Affiliated Hospital of Shaanxi University of Chinese Medicine and randomly divided into group A and group B. The patients in group A adopted tube voltage 120 kV and contrast agent concentration 600 mgI/kg and reconstructed with filtered back projection (FBP), while the patients in group B were scanned with tube voltage 80 kV and contrast agent concentration 350 mgI/kg and reconstructed with FBP and ASIR-V from 10% to 100% with 10% interval. The CT values and standard deviation (SD) of the right renal artery, left renal artery were measured respectively to calculate the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR).The image quality of renal CTA was subjectively scored by two experienced radiologists blindly using a 5-point criteria.The contrast agent,CT volume dose index(CTDI(vol)) and dose length product(DLP) in both groups were recorded and the effective radiation dose(ED) was calculated. Results: The ED ((2.11±0.19)mSv) and contrast agent ((21.9±3.0)g) in group B were 65.1% (P<0.05) and 42.2% (P<0.05) lower than those in group A ((6.04±1.89)mSv and (38.0±3.8)g).With the increase of ASIR-V percentage in group B, CT values showed no significant difference, SD values gradually decreased, SNR values and CNR values gradually increased.The CT values with different reconstruction algorithm showed no statistically significant difference (all P>0.05) between group A and group B. The SD values with 40%ASIR-V to 100%ASIR-V reconstruction in group B were significantly lower than those of group A (all P<0.05).The SNR values with 50% ASIR-V to 100% ASIR-V reconstruction and CNR values with 70%ASIR-V to 100%ASIR-V were significantly higher than those of group A(all P<0.5).Two radiologists had excellent consistency in subjective scores of image quality for renal CTA(all kappa>0.75, P<0.05). The subjective scores with 60% ASIR-V to 90% ASIR-V in group B were significantly higher than those in group A (P<0.05), of which 70%ASIR-V reconstruction achieved the highest subjective score for renal CTA. Conclusion: ASIR-V and 80 kV can significantly reduce radiation dose (about 65.1%) and contrast agent (about 42.2%) in renal CTA, ASIR-V reconstruction can significantly improve the image quality of renal CTA, of which 70% ASIR-V reconstruction achieved the best image quality in 80 kV renal CTA.

Association of the programmed cell death-1 PD1.5 C>T polymorphism with cervical cancer risk in a Chinese population.

The association of the programmed cell death-1 PD1.5 C>T polymorphism with cervical cancer risk has not been investigated. In this hospital-based case-control study, we analyzed 256 patients with cervical cancer and 250 healthy controls. Pearson chi-square test was used to examine differences in the distribution of genotypes between cases and controls. Association between the polymorphism and the susceptibility to cervical cancer was evaluated using unconditional logistic regression analysis. This revealed that the frequencies of the three genotypes (CC, CT, and TT) in cervical cancer cases and controls were 17.58, 65.23, and 17.19% and 24.80, 40.40, and 34.80%, respectively; the difference between the two groups was significant (P < 0.001). We found that the CT genotype was significantly associated with increased cervical cancer risk (adjusted OR = 2.18; 95%CI = 1.37-6.11; P = 0.009). Moreover, there was significant association between PD-1.5 C/T polymorphism and susceptibility to cervical cancer under dominant model (OR = 1.27, 95%CI = 1.01-2.15, P = 0.047). We conclude that the PD-1.5 C/T polymorphism may be associated with increased risk of cervical cancer. The study also highlights the importance of conducting genetic association studies in different ethnic populations.

[Characterization of mutational pattern in patients with Ph negative myeloproliferative neoplasms].

OBJECTIVE: To characterize the molecular profile in patients with Ph negative myeloproliferative neoplasms (MPN) by exploring 49 gene mutations. METHODS: Targeted gene sequencing were performed to analyze 49 MPN-associated genes in 51 patients with Ph negative MPN, of which CARL (exon 9), NPM1 (exon 12) and CEBPA (TAD, BZIP domains) were investigated by using Sanger sequencing simultaneously, while FLT3-ITD was assessed by PCR method. RESULTS: Mutations were detected in 73.5% (36/49) of genes, and the mutational rates of JAK2-V617F, CALR (exon 9) and MPL were 60.8%(31/51), 7.8%(4/51) and 7.8%(4/51) respectively, whereas the mutational rates of ASXL1, SETBP1, and SF3B1 were around 10%. In addition, 96.1% (49/51) of patients harbored at least one mutation, and more than half of the patients (52.9%, 27/51) possessed 3 or 4 gene mutations. The amount of gene mutations was significantly higher in patients with JAK2-V617F mutation than those without JAK2-V617F or CALR (exon 9) mutation (P<0.05). The last finding was that there was no statistically significant difference in the amount of mutations among four MPN subtypes (PV, ET, PMF, and MPN-U). CONCLUSION: Most patients with Ph negative MPN possesses three or more gene mutations, with various mutational profiles.

[Effect of JAZF1 over-expression on high-fat diet-induced non-alcoholic fatty liver disease].

Objective: To investigate the effects of juxtaposed with another zinc finger gene 1 (JAZF1) over-expression on the levels of pro-inflammatory cytokines in high-fat diet (HFD)-induced mouse fatty liver and its associated mechanisms. Methods: Twenty male C57BL/6J (3 weeks old) and 10 male JAZF1 transgenic (JAZF1-Tg) mice were randomly divided into three groups: wide-type with normal diet (NF group,n= 10), wide-type with high-fat diet (HF group,n= 10), and JAZF1-Tg with high-fat diet (HJ group,n= 10). All mice were fed with the corresponding diet for 12 weeks, and their food consumption and body weight were measured periodically. After 12 weeks, fasting blood glucose (FBG), insulin (INS), total cholesterol (TC), triglyceride (TG), free fatty acids (FFA), and alanine aminotransferase (ALT) in the blood and liver tissue from each group were measured. TG concentration in liver tissue was determined using an enzymatic assay, and the mRNA expression of tumor necrosis factor-α(TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) in the liver was measured by RT-PCR. In addition, the expression of p-JNK/JNK, p-p-38 MAPK/p-38 MAPK, p-ERK/ERK, IκBα, andß-actin (reference) in the liver was determined using Western blot.. Results: (1) Body weight, FBG, INS, TC, and ALT were significantly reduced in the HJ group compared with those of the HF group (31.19±0.81 vs 36.07±1.43, 6.94±0.32 vs 8.14±0.36, 31.09±2.12 vs 45.21±3.34, 3.05±0.07 vs 3.81±0.08, 54.75±4.92 vs 68.09±5.15, respectively;P< 0.05). There were no significant differences in TG and FFA between the HJ and HF groups (0.72±0.05 vs 0.81±0.03, 0.81±0.4 vs 0.87±0.03; bothP> 0.05). (2) There was no significant difference in liver TG concentration between the HJ and HF groups (35.49±3.17 vs 38.26±3.59,P> 0.05). (3) Compared with the HF group, the HJ group had significantly reduced mRNA expression of TNF-α, MCP-1, and IL-8 (2.54TNF-αvs 8.64±0.73, 1.19±0.73,vs 3.93±0.18, 5.09±0.48 vs 9.09±0.89; allP< 0.01), significantly reduced protein expression of p-JNK and p-p-38 MAPK (0.92±0.06 vs 1.51±0.01, 1.07±0.04 vs 1.45±0.04; bothP< 0.01), and significantly increased protein expression of IκBα(0.99±0.06 vs 0.79±0.05,P< 0.01) in liver tissue. However, no significant difference was observed in the p-ERK level between the HJ and HF groups (P> 0.05). Conclusion: Upregulation of JAZF1 expression can significantly inhibit the expression of TNF-α, MCP-1, and IL-8 in the liver of mice on HFD. This attenuation may be closely associated with the reduced activation of the JNK, p-38 MAPK, and NF-κB pathways.

The novel HLA-B*48:19 allele, identified by sequence-based typing in a Chinese individual.

HLA-B*48:19 differs from HLA-B*48:01:01 exon 3 2 nt at position 195 and 196 (C→T and T→G).

Characterization of a novel allele, HLA-B*15:139.

The novel allele HLA-B*15:139 was closest to HLA-B*15:02,*15:18, with a single-nucleotide mismatch in exon 2.

The role of lymphocyte count in the early diagnosis of surgical site infection following posterior lumbar fusion.

OBJECTIVE: This study aimed to explore the early diagnostic value of lymphocyte count in the early diagnosis of surgical site infection (SSI) following posterior lumbar fusion. PATIENTS AND METHODS: In this study, we retrospectively analyzed the data from a total of 37 patients with lumbar SSI from Guizhou  Province Orthopaedic Hospital and Nanyang Central Hospital, 2008.1-2018.11, and 104 patients without SSI. We analyzed the C-reactive protein (CRP) level, white blood cell count (WBC) and differential count before instrumented lumbar fusion at 3 and 7 days postoperatively. The significance of the differences was evaluated by one-way ANOVA, followed by Fisher's test. The parameters mentioned above were analyzed on postoperative days 3 and 7 using the receiver operating characteristic curve and the area under the curve (AUC). Furthermore, the analyses were conducted by SPSS 22.0 software. RESULTS: The lymphocyte count in the SSI group on postoperative day 3 was significantly lower than that in the no-SSI group after surgery (p=0.000). According to the ROC curve analysis of related parameters on postoperative day 3, the AUC value of lymphocytes (0.840) was significantly larger than the AUC value of C-reactive protein (0.749). CONCLUSIONS: The lymphocyte count and C-reactive protein level on postoperative day 3 are reliable predictors of infection.

[Molecular features of 109 patients with chronic myelomonocytic leukemia in a single center].

Objective: To explore the molecular features of chronic myelomonocytic leukemia (CMML) . Methods: According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Results: Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (OR=4.129, 95% CI 1.481-11.510, Q=0.007) and TET2 (OR=5.276, 95% CI 1.979-14.065, Q=0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (OR=0.174, 95% CI 0.038-0.791, Q=0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old vs 47 years old, P<0.001), white blood cell count (15.9×10(9)/L vs 4.4×10(9)/L, P<0.001), proportion of monocytes (21.5% vs 15%, P=0.001), and hemoglobin level (86 g/L vs 74 g/L, P=0.014). TET2 mutations (P=0.021) and SRSF2 mutations (P=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (P<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. Conclusion: According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.

[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.

[Genomics of next generation sequencing in pediatric B-acute lymphoblastic leukemia and its impact on minimal residual disease].

Objective: To describe the gene mutation profile of newly diagnosed pediatric B-acute lymphoblastic leukemia (B-ALL) and analyze its effect on minimal residual disease (MRD). Methods: A total of 506 newly diagnosed B-ALL children treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from September 2018 to July 2021 were enrolled in this retrospective cohort study. The enrolled children were divided into MRD ≥1.00% group and <1.00% group according to MRD results on the 19th day since chemotherapy, and MRD ≥0.01% group and <0.01% group according to MRD results on the 46th day. Clinical characteristics and gene mutations of two groups were compared. Comparisons between groups were performed with chi-square test or Fisher's exact test. Independent risk factors of MRD results on the 19th day and the 46th day were analyzed by Logistic regression model. Results: Among all 506 patients, there were 318 males and 188 females. On the 19th day, there were 114 patients in the MRD ≥1.00% group and 392 patients in the MRD <1.00% group. On the 46th day, there were 76 patients in the MRD ≥0.01% group and 430 patients in the MRD <0.01% group. A total of 187 gene mutations were detected in 487 (96.2%) of 506 children. The most common gene mutations were signal transduction-related KRAS gene mutations in 111 cases (22.8%) and NRAS gene mutations in 99 cases (20.3%). Multivariate analysis showed that PTPN11 (OR=1.92, 95%CI 1.00-3.63), KMT2A (OR=3.51, 95%CI 1.07-11.50) gene mutations and TEL-AML1 (OR=0.48, 95%CI 0.27-0.87), BCR-ABL1 (OR=0.27, 95%CI 0.08-0.92) fusion genes and age >10 years (OR=1.91, 95%CI 1.12-3.24) were independent influencing factors for MRD ≥1.00% on the 19th day. BCORL1 (OR=2.96, 95%CI 1.18-7.44), JAK2 (OR=2.99, 95%CI 1.07-8.42) and JAK3 (OR=4.83, 95%CI 1.50-15.60) gene mutations and TEL-AML1 (OR=0.43, 95%CI 0.21-0.87) fusion gene were independent influencing factors for MRD ≥0.01% on the 46th day. Conclusions: Children with B-ALL are prone to genetic mutations, with abnormalities in the RAS signaling pathway being the most common. Signal transduction related PTPN11, JAK2 and JAK3 gene mutations, epigenetic related KMT2A gene mutation and transcription factor related BCORL1 gene mutation are independent risk factors for MRD.

[Clinical manifestations and gene analysis of 18 cases of hereditary protein S deficiency].

Objective: To analyze the clinical manifestations and molecular pathogenesis of 18 patients with inherited protein S (PS) deficiency. Methods: Eighteen patients with inherited PS deficiency who were admitted to the Institute of Hematology & Blood Diseases Hospital from June 2016 to February 2019 were analyzed: activity of protein C (PC) and antithrombin (AT) , PS activity were measured for phenotype diagnosis; high throughput sequencing (HTS) was used for screening of coagulation disease-related genes; Sanger sequencing was used to confirm candidate variants; Swiss-model was used for three-dimensional structure analysis. Results: The PS:C of 18 patients ranged from 12.5 to 48.2 U/dL. Among them, 16 cases developed deep vein thrombosis, including 2 cases each with mesenteric vein thrombosis and cerebral infarction, and 1 case each with pulmonary embolism and deep vein thrombosis during pregnancy. A total of 16 PROS1 gene mutations were detected, and 5 nonsense mutations (c.134_162del/p.Leu45*, c.847G>T/p.Glu283*, c.995_996delAT/p.Tyr332*, c.1359G> A/p.Trp453*, c.1474C>T/p.Gln492*) , 2 frameshift mutations (c.1460delG/p.Gla487Valfs*9 and c.1747_1750delAATC/p.Asn583Wfs*9) and 1 large fragment deletion (exon9 deletion) were reported for the first time. In addition, the PS:C of the deep vein thrombosis during pregnancy case was 55.2 U/dL carrying PROC gene c.565C>T/p.Arg189Trp mutation. Conclusion: The newly discovered gene mutations enriched the PROS1 gene mutation spectrum which associated with inherited PS deficiency.

[Clinical and laboratory features compared between JAK2 exon12 and JAK2 V617F mutated polycythemia vera].

Objective: To compare clinical and laboratory features between JAK2 exon12 and JAK2 V617F mutated polycythemia vera (PV) . Method: We collected data from 570 consecutive newly-diagnosed subjects with PV and JAK2 mutation, and compared clinical and laboratory features between patients with JAK2 exon12 and JAK2 V617F mutation. Results: 543 (95.3%) subjects harboured JAK2 V617F mutation (JAK2 V617F cohort) , 24 (4.2%) harboured JAK2 exon12 mutations (JAK2 exon12 cohort) , and 3 (0.5%) harboured JAK2 exon12 and JAK2 V617F mutations. The mutations in JAK2 exon12 including deletion (n=10, 37.0%) , deletion accompanied insertion (n=10, 37.0%) , and missense mutations (n=7, 25.9%) . Comparing with JAK2 V617F cohort, subjects in JAK2 exon12 cohort were younger [median age 50 (20-73) years versus 59 (25-91) years, P=0.040], had higher RBC counts [8.19 (5.88-10.94) ×10(12)/L versus 7.14 (4.11-10.64) ×10(12)/L, P<0.001] and hematocrit [64.1% (53.7-79.0%) versus 59.6% (47.2%-77.1%) , P=0.001], but lower WBC counts [8.29 (3.2-18.99) ×10(9)/L versus 12.91 (3.24-38.3) ×10(9)/L, P<0.001], platelet counts [313 (83-1433) ×10(9)/L versus 470 (61-2169) ×10(9)/L, P<0.001] and epoetin [0.70 (0.06-3.27) versus 1.14 (0.01-10.16) IU/L, P=0.002] levels. We reviewed bone marrow histology at diagnosis in 20 subjects with each type of mutation matched for age and sex. Subjects with JAK2 exon12 mutations had fewer loose megakaryocyte cluster (40% versus 80%, P=0.022) compared with subjects with JAK2 V617F. The median follow-ups were 30 months (range 4-83) and 37 months (range 1-84) for cohorts with JAK2 V617F and JAK2 exon12, respectively. There was no difference in overall survival (P=0.422) and thrombosis-free survival (P=0.900) . Conclusions: Compared with patients with JAK2 V617F mutation, patients with JAK2 exon12 mutation were younger, and had more obvious erythrocytosis and less loose cluster of megakaryocytes.

[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.

[Risk factors for leukemia transformation in patients with myelodysplastic syndromes].

Objective: To explore the risk factors in leukemia transformation (LT) in those with myelodysplastic syndromes (MDS) . Methods: From January 2012 to December 2020,data on 320 patients with newly diagnosed primary MDS were gathered from the MDS center. The clinical features and molecular characteristics are explored. Additionally, a retrospective analysis of risk factors for the development of acute leukemia from MDS was done. Results: The median follow-up was13.6 (0.4-107.3) months. 23.4% (75/320) of the MDS patients had LT group. Significant differences between the LT group and non-LT group can be seen in age (P<0.001) , bone marrow blast percentage (P<0.001) , bone marrow fibrosis (P=0.046) , WHO classification (P<0.001) , IPSS-R (P<0.001) and IPSS-R karyotype group (P=0.001) . The median number of mutation of LT group was 1 (1, 3) , that in non-LT group was 1 (0, 2) ,which had a statistical difference (P=0.003) .At the time of the initial diagnosis of MDS, the LT group had higher rates of the TP53 mutation (P=0.034) , DNMT3A mutation (P=0.026) , NRAS mutation (P=0.027) and NPM1 mutation (P=0.017) . Compared with the mutations at first diagnosis and LT of six patients, the number of mutations increased and the variant allele frequencies (VAF) increased significantly in LT patients. Higher bone marrow blast percentage (Refer to <5% , 5% -10% : HR=4.587, 95% CI 2.214 to 9.504, P<0.001, >10% : HR=9.352, 95% CI 4.049 to 21.600, P<0.001) , IPSS-R cytogenetic risk groups (HR=2.603, 95% CI 1.229-5.511, P=0.012) , DNMT3A mutation (HR=4.507, 95% CI 1.889-10.753, P=0.001) , and NPM1 mutation (HR=3.341, 95% CI 1.164-9.591, P=0.025) were all independently associated with LT in MDS patients, according to results of multivariate Cox regression. Conclusion: Bone marrow blast percentage, IPSS-R cytogenetic risk groups, DNMT3A mutation, and NPM1 mutation are independent risk factors in LT for MDS patients.

[Overall survival and prognosis of patients with polycythemia vera: an analysis based on 906 patients from a single center].

Objective: To explore predictors of overall survival (OS) in Chinese patients with polycythemia vera (PV) . Methods: A total of 906 consecutive newly diagnosed patients with PV seen at the Blood Diseases Hospital, Chinese Academy of Medical Sciences, from June 2007 to February 2020 were included, and their data were collected. PV was diagnosed according to 2016 World Health Organization (WHO) diagnostic definitions. OS and prognostic factors were retrospectively analyzed. Results: Among the 906 patients, 439 were male (48.5%) and 467 were female (51.5%) . The median age was 57 years (range: 18-91 years) . 31.6% (276/874) of the patients had a thrombosis history at diagnosis, and 4.6% (25/541) of the patients had abnormal cytogenetics. The median follow-up was 54 months (95% confidence interval [CI] 8-130 months) . The 5- and 10-year cumulative deaths were 5.8% (95% CI 4.8%-6.7%) and 11.1% (95% CI 9.3%-12.9%) , respectively. Univariate analysis showed that age ≥60 years, thrombosis history, white blood cells (WBC) ≥15×10(9)/L, platelet (PLT) ≥450×10(9)/L, and platelet distribution width (PDW) ≥15 fl significantly correlated with worse OS, and palpable spleen correlated with better OS. Multivariate analysis showed that age ≥60 years (HR=4.3, 95% CI 2.1-9.2, P<0.001) and PDW ≥15 fl (HR=2.1, 95% CI 1.1-4.0, P=0.023) were independent prognostic factors for worse OS. The 5-year cumulative death for patients with PDW ≥15 fl or PDW<15 fl was 8.6% (95% CI 5.9%-11.3%) or 4.4% (95% CI 3.4%-5.4%) , respectively. The 5-year cumulative death for patients defined as low-, intermediate-, and high-risk patients by international working group score system for PV (IWG-PV) were 0.8% (95 CI 0.2%-1.4%) , 4.0% (95% CI 2.7%-5.3%) , and 12% (95% CI 9.6%-14.4%) , respectively, with a significant difference among the three cohorts (P<0.05) . PDW ≥ 15 fl significantly affected OS for intermediate- and high-risk patients (HR=2.3, 95% CI 1.2-4.2, P=0.009) defined by IWG-PV score system, but not for low-risk patients (HR=3.1, 95% CI 0.2-52.0, P=0.405) . Conclusions: Age ≥60 years and PDW ≥15 fl were independent prognostic factors for worse OS in PV. IWG-PV score system effectively predicted OS for Chinese patients with PV.

[Clinical and genetic analyses of hereditary factor â ¤ deficiency cases].

Objective: To analyze the clinical phenotype and molecular pathogenesis of nine patients with hereditary factor Ⅴ (FⅤ) deficiency. Methods: Nine patients with hereditary FⅤ deficiency who were admitted to the Institute of Hematology and Blood Diseases Hospital from April 1999 to September 2019 were analyzed. The activated partial thromboplastin time, prothrombin time, and FⅤ procoagulant activity (FⅤ∶C) were measured for phenotypic diagnosis. High-throughput sequencing was employed for the F5 gene mutation screening, Sanger sequencing was adopted to confirm candidate variants and parental carrying status, Swiss-model was used for three-dimensional structure analysis, and ClustalX v.2.1 was used for homologous analysis. Results: The FⅤ∶C of the nine patients ranged from 0.1 to 10.6. Among them, eight had a hemorrhage history, with kin/mucosal bleeding as the most common symptom (three cases, 37.5%) , whereas one case had no bleeding symptom. There were five homozygotes and four compound heterozygotes. A total of 12 pathogenic or likely pathogenic mutations were detected, of which c.6100C>A/p.Pro2034Thr, c.6575T>C/p.Phe2192Ser, c.1600_1601delinsTG/p. Gln534*, c.4713C>A/p.Tyr1571*, and c.952+5G>C were reported for the first time. Conclusion: The newly discovered gene mutations enriched the F5 gene mutation spectrum associated with hereditary FⅤ deficiency. High-throughput sequencing could be an effective method to detect F5 gene mutations.

MiR-587 acts as an oncogene in non-small-cell lung carcinoma via reducing CYLD expression.

OBJECTIVE: This study aims to explore the cancer-associated functions of microRNA-587 (miR-587) in the development of non-small-cell lung carcinoma (NSCLC) and the molecular mechanism. PATIENTS AND METHODS: Relative expression levels of miR-587 and CYLD in NSCLC samples were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Proliferative and migratory abilities in A549 and H1299 cells with overexpressed miR-587 were examined by Cell Counting Kit-8 (CCK-8) and transwell assay, respectively. The regulatory interaction between miR-587 and CYLD was determined by Dual-Luciferase reporter assay and Pearson correlation test. At last, the co-regulation of miR-587 and CYLD on NSCLC cell functions was assessed by rescue experiments. RESULTS: MiR-587 was upregulated in NSCLC samples and closely linked to tumor staging, whereas CYLD was downregulated and negatively correlated to that of miR-587. Survival analysis suggested that miR-587 was an unfavorable factor to the prognosis of NSCLC. Overexpression of miR-587 stimulated proliferative and migratory abilities in A549 and H1299 cells. CYLD was the downstream gene binding miR-587. Overexpression of CYLD could partially abolish the regulatory effects of overexpressed miR-587 on promoting proliferative and migratory abilities in NSCLC cells. CONCLUSIONS: MiR-587 stimulates proliferative and migratory abilities in NSCLC by downregulating CYLD, thus aggravating the progression of NSCLC.