[Association between long-term exposure to ambient ozone and sperm quality in Shandong Province].

Objective: To evaluate the association between long-term exposure to ambient ozone (O3) and sperm quality. Methods: From January 1, 2014, to December 31, 2019, healthy sperm donors were recruited through the Human Sperm Bank of Shandong University Affiliated Reproductive Hospital. A total of 37 977 sperm donation data from 2 971 healthy volunteers were analyzed. The average annual O3 concentration (0.01°× 0.01°) was matched according to household address. A multivariate mixed-effect model was used to analyze the exposure-response relationship between the average O3 exposure concentration and sperm quality in the previous year, with each donor as a random intercept. All results were presented as % changes with 95% confidence intervals (CIs) for all sperm parameters associated with 10 µg/m3 increases in O3. The effects of individual characteristics on the association between O3 and sperm quality were evaluated by stratified analysis. Results: The average O3 concentration in the year before semen collection was (107.09±7.50) µg/m3. Each 10 µg/m3 increase in O3 was associated with declined sperm concentration (-3.12%, 95%CI:-4.55%, -1.67%), total sperm count (-5.21%, 95%CI:-7.28%, -3.09%), total sperm motility (-1.49%, 95%CI:-2.37%, -0.61%), progressive motility (-2.53%, 95%CI:-3.78%, -1.26%), total motile sperm count (-5.82%, 95%CI:-8.17%, -3.41%), and progressively motile sperm count (-6.22%, 95%CI:-8.73%, -3.64%). Men aged 30 and above, obese, and with lower education levels might be more susceptible to the influence of O3 on sperm quality, but the difference was not statistically significant (P>0.05). Conclusion: Long-term exposure to O3 in Shandong Province is associated with a decrease in sperm quality.

Sacubitril/valsartan and cardiovascular biomarkers among patients with recent COVID-19 infection: The PARACOR-19 randomized clinical trial.

AIMS: The PARACOR-19 randomized controlled trial (RCT) was designed to examine the effects of sacubitril/valsartan on markers of cardiac injury, inflammation, structure, and function among patients who have recovered from acute coronavirus disease 2019 (COVID-19) infection. METHODS AND RESULTS: PARACOR-19 was a single-centre, double-blind RCT of patients with cardiovascular risk factors and a history of COVID-19 infection 4-16 weeks prior to enrolment. Patients were randomized to sacubitril/valsartan (titrated to the maximum dose of 97/103 mg twice daily) versus matching placebo. Co-primary endpoints were change from baseline to 12 weeks in high-sensitivity cardiac troponin T (hs-cTnT) and soluble ST2 (sST2). Exploratory endpoints included change from baseline to 12 weeks in additional circulating biomarkers. Overall, 42 patients were randomized between August 2021 and March 2023 (n = 20 sacubitril/valsartan, n = 22 placebo). Median (25th-75th) time from COVID-19 diagnosis to enrolment was 67 (48-80) days. Median age was 67 (62-71) years, 48% were female, and 91% were White. Compared with placebo, sacubitril/valsartan did not have a significant effect on the co-primary endpoints of change from baseline in hs-TnT and sST2 (all p ≥ 0.29). In exploratory analyses, sacubitril/valsartan led to a 46% greater reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and 51% greater reduction in C-terminal telopeptide of collagen type I (CITP). Permanent drug discontinuation occurred in four patients in the sacubitril/valsartan group and three patients in the placebo group. There were no deaths and one patient was hospitalized in each group. CONCLUSION: In this pilot RCT of patients who recovered from acute COVID-19, sacubitril/valsartan did not lower hs-cTnT or sST2 compared with placebo. Exploratory analyses suggested potential benefits of sacubitril/valsartan on cardiac wall stress and collagen turnover as measured by NT-proBNP and CITP. Sacubitril/valsartan was well tolerated. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04883528.

[The effect of glucose-6-phosphate dehydrogenase deficiency on allogeneic hematopoietic stem cell transplantation in patients with hematological disorders].

Objectives: To determine the effect of glucose-6-phosphate-dehydrogenase (G6PD) deficiency on patients' complications and prognosis following allogeneic stem cell hematopoietic transplantation (allo-HSCT) . Methods: 7 patients with G6PD deficiency (study group) who underwent allo-HSCT at Peking University People's Hospital from March 2015 to January 2021 were selected as the study group, and thirty-five patients who underwent allo-HSCT during the same period but did not have G6PD deficiency were randomly selected as the control group in a 1∶5 ratio. Gender, age, underlying diseases, and donors were balanced between the two groups. Collect clinical data from two patient groups and perform a retrospective nested case-control study. Results: The study group consisted of six male patients and one female patient, with a median age of 37 (range, 2-45) years old. The underlying hematologic diseases included acute myeloid leukemia (n=3), acute lymphocytic leukemia (n=2), and severe aplastic anemia (n=2). All 7 G6PD deficiency patients achieved engraftment of neutrophils within 28 days of allo-HSCT, while the engraftment rate of neutrophils was 94.5% in the control group. The median days of platelet engraftment were 21 (6-64) d and 14 (7-70) d (P=0.113). The incidence rates of secondary poor graft function in the study group and control group were 42.9% (3/7) and 8.6% (3/35), respectively (P=0.036). The CMV infection rates were 71.4% (5/7) and 31.4% (11/35), respectively (P=0.049). The incidence rates of hemorrhagic cystitis were 57.1% (4/7) and 8.6% (3/35), respectively (P=0.005), while the bacterial infection rates were 100% (7/7) and 77.1% (27/35), respectively (P=0.070). The infection rates of EBV were 14.3% (1/7) and 14.3% (5/35), respectively (P=1.000), while the incidence of fungal infection was 14.3% (1/7) and 25.7% (9/35), respectively (P=0.497). The rates of post-transplant lymphoproliferative disease (PTLD) were 0% and 5.7%, respectively (P=0.387) . Conclusions: The findings of this study indicate that blood disease patients with G6PD deficiency can tolerate conventional allo-HSCT pretreatment regimens, and granulocytes and platelets can be implanted successfully. However, after transplantation, patients should exercise caution to avoid viral infection, complications of hemorrhagic cystitis, and secondary poor graft function.

[Analysis of related factors influencing the detection rate of mosaic embryo and the pregnancy outcomes with mosaic embryo transfers].

Objective: To explore the related factors influencing the detection rate of mosaic embryo and the pregnancy outcomes of mosaic embryo transfer in preimplantation genetic testing for aneuploidy (PGT-A) based on next generation sequencing (NGS) technology. Methods: A retrospective study was performed to analyze the clinical data of patients in 745 PGT-A cycles from January 2019 to May 2023 at Chongqing Health Center for Women and Children, including 2 850 blastocysts. The biopsy cells were tested using NGS technology, and the embryos were divided into three groups based on the test results, namely euploid embryos, aneuploid embryos and mosaic embryos. The influence of population characteristics and laboratory-related parameters on the detection rate of mosaic embryo were analyzed, and the pregnancy outcomes of 98 mosaic embryo transfer cycles and 486 euploid embryo transfer cycles were compared during the same period, including clinical pregnancy rate and live birth rate. Results: Among the embryos tested (n=2 850), the number and proportion of euploid embryos, aneuploid embryos and mosaic embryos were 1 489 (52.2%, 1 489/2 850), 917 (32.2%, 917/2 850) and 444 (15.6%, 444/2 850), respectively. Among mosaic embryos, 245 (55.2%, 245/444) were segmental mosaic embryos, 118 (26.6%, 118/444) were whole-chromosome mosaic embryos, and 81 (18.2%, 81/444) were complex mosaic embryos. NGS technology was performed in 4 genetic testing institutions and the detection rate of mosaic embryo fluctuated from 13.5% to 27.0%. The distributions of female age, level of anti-Müllerian hormone, PGT-A indications, ovulation-inducing treatments, gonadotropin (Gn) dosage, Gn days, inner cell mass grade, trophectoderm cell grade, genetic testing institutions and developmental stage of blastocyst were significantly different among the three groups (all P<0.05). Multi-factor analysis showed that the trophectoderm cell grade and genetic testing institutions were significantly related to the detection rate of mosaic embryo; compared with the trophectoderm cell graded as A, the detection rate of mosaic embryo was significantly increased in the trophectoderm cell graded as B-(OR=1.59, 95%CI: 1.04-2.44, P=0.033); compared with genetic testing institution a, the detection rate of mosaic embryo was significantly higher (OR=2.89, 95%CI: 2.10-3.98, P<0.001) in the testing institution c. The clinical pregnancy rate and live birth rate with mosaic embryos transfer were significantly lower than those of euploid embryos transfer (clinical pregnancy rate: 51.0% vs 65.2%, P=0.008; live birth rate: 39.4% vs 53.2%, P=0.017). After adjustment for age, PGT-A indications, trophectoderm cell grade and days of embryo culture in vitro, the clinical pregnancy rate and live birth rate with mosaic embryos transfer were significantly lower than those of euploid embryos transfer (clinical pregnancy rate: OR=0.52, 95%CI: 0.32-0.83, P=0.007; live birth rate: OR=0.50, 95%CI: 0.31-0.83, P=0.007). Conclusions: The trophectoderm cell grade and genetic testing institutions are related to the detection rate of mosaic embryo. Compared with euploid embryos transfer, the clinical pregnancy rate and live birth rate with mosaic embryos transfer are significantly reduced. For infertile couple without euploid embryos, transplantable mosaic embryos could be recommended according to the mosaic ratio and mosaic type in genetic counseling to obtain the optimal pregnancy outcome.

Personalised follow-up and management schema for patients with screen-detected pulmonary nodules: A dynamic modelling study.

BACKGROUND: Selecting the time target for follow-up testing in lung cancer screening is challenging. We aim to devise dynamic, personalized lung cancer screening schema for patients with pulmonary nodules detected through low-dose computed tomography. METHODS: We developed and validated dynamic models using data of pulmonary nodule patients (aged 55-74 years) from the National Lung Screening Trial. We predicted patient-specific risk profiles at baseline (R0) and updated the risk evaluation results in repeated screening rounds (R1 and R2). We used risk cutoffs to optimize time-dependent sensitivity at an early decision point (3 months) and time-dependent specificity at a late decision point (1 year). RESULTS: In validation, area under receiver operating characteristic curve for predicting 12-month lung cancer onset was 0.867 (95 % confidence interval: 0.827-0.894) and 0.807 (0.765-0.948) at R0 and R1-R2, respectively. The personalized schema, compared with National Comprehensive Cancer Network (NCCN) guideline and Lung-RADS, yielded lower rates of delayed diagnosis (1.7% vs. 1.7% vs. 6.9 %) and over-testing (4.9% vs. 5.6% vs. 5.6 %) at R0, and lower rates of delayed diagnosis (0.0% vs. 18.2% vs. 18.2 %) and over-testing (2.6% vs. 8.3% vs. 7.3 %) at R2. Earlier test recommendation among cancer patients was more frequent using the personalized schema (vs. NCCN: 29.8% vs. 20.9 %, p = 0.0065; vs. Lung-RADS: 33.2% vs. 22.8 %, p = 0.0025), especially for women, patients aged ≥65 years, and part-solid or non-solid nodules. CONCLUSIONS: The personalized schema is easy-to-implement and more accurate compared with rule-based protocols. The results highlight value of personalized approaches in realizing efficient nodule management.

Targets and treatments in primary CNS lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare and highly aggressive lymphoma entirely localized in the central nervous system or vitreoretinal space. PCNSL generally initially responds to methotrexate-containing chemotherapy regimens, but progressive or relapsing disease is common, and the prognosis is poor for relapsed or refractory (R/R) patients. PCNSL is often characterized by activation of nuclear factor kappa B (NF-κB) due to mutations in the B-cell receptor (BCR) or toll-like receptor (TLR) pathways, as well as immune evasion. Targeted treatments that inhibit key PCNSL mechanisms and pathways are being evaluated; inhibition of Bruton's tyrosine kinase (BTK) downstream of BCR activation has demonstrated promising results in treating R/R disease. This review will summarize the evidence and potential for targeted therapeutic agents to improve treatment outcomes in PCNSL. This includes immunotherapeutic and immunomodulatory approaches and inhibitors of the key pathways driving PCNSL, such as aberrant BCR and TLR signaling.

[Effect of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients underwent haploidentical stem cell transplantation].

Objective: To investigate the effects of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients with haploidentical stem cell transplantation (haplo-SCT). Methods: Fifteen consecutive patients who received haplo-SCT and pre-transplant donor specific anti-human leukocyte antigen (HLA) antibody (DSA) positive [mean fluorescence intensity (MFI)≥2 000] in the Institute of Hematological Diseases from November 2021 to March 2023 were retrospectively recruited into the desensitized group. There were 4 males and 11 females, with a median age [M(Q1, Q3)] of 48 (37, 59) years. All patients were desensitized with sirolimus combined with anti-CD20 monoclonal antibody. The non-desensitized group included 29 patients with haplo-SCT who had not received desensitization treatment from August 2012 to June 2016. There were 12 males and 17 females with a median age of 42 (26, 50) years. Up to October 1, 2023, the median follow-up time was 13 (9, 18) months in the study group and 23 (14, 29) months in the control group. The changes of MFI before and after desensitization treatment and the prognosis of patients in the desensitized group were compared, including the incidence of primary implantation failure (pGF), neutrophil implantation time, platelet implantation time, grade Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) and chronic GVHD incidence, non-recurrence related mortality, event-free survival rate, disease-free survival rate and overall survival rate. The survival curve was drawn by Kaplan-Meier method, and the survival rate between groups was compared with Log-rank test. Results: After desensitization treatment, the level of DSA MFI in the desensitized group decreased from 8 879 (7 544, 11 495) to 3 781 (1 638, 4 165) after desensitization treatment (P<0.01). All of the patients achieved hematopoietic recovery, and the median time for neutrophil and platelet engraftment were 14 (11, 15) and 20 (18, 25) days, respectively. The incidence of pGF in the desensitized group was 0, which was lower than that in the non-desensitized group (34.5%, 10/29) (P=0.011). The expected 1-year disease-free survival rate and overall survival rate in the desensitized group were 100% (15/15) and 100% (15/15) respectively, while those in the non-desensitized group were 75.9% (22/29) and 75.9% (22/29) respectively, the difference was not statistically significant (both P>0.05). The one-year event-free survival rate in the desensitized group was expected to be 100% (15/15), which was higher than that in the non-desensitized group (51.3%, 15/29) (P=0.002). Conclusion: Sirolimus combined with anti-CD20 monoclonal antibody desensitization therapy can reduce the DSA level of haplo-SCT recipients, promote hematopoietic engraftment after transplantation, and avoid the occurrence of pGF after transplantation.

[Clinical features and risk factors for invasive fungal sinusitis after allogeneic hematopoietic stem cell transplantation].

Objective: To analyze the clinical characteristics and outcomes of patients with invasive fungal sinusitis (invasive fungal rhinosinusitis, IFR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and explored the risk factors for IFR after allo-HSCT. Methods: Nineteen patients with IFR after allo-HSCT at Peking University People's Hospital from January 2012 to December 2021 were selected as the study group, and 95 patients without IFR after allo-HSCT during this period were randomly selected as the control group (1:5 ratio) . Results: Nineteen patients, including 10 males and 9 females, had IFR after allo-HSCT. The median age was 36 (10-59) years. The median IFR onset time was 68 (9-880) days after allo-HSCT. There were seven patients with acute myeloid leukemia, five with acute lymphoblastic leukemia, two with myelodysplastic syndrome, two with chronic myeloid leukemia, one with acute mixed-cell leukemia, one with multiple myeloma, and one with T-lymphoblastic lymph node tumor. There were 13 confirmed cases and 6 clinically diagnosed cases. The responsible fungus was Mucor in two cases, Rhizopus in four, Aspergillus in four, and Candida in three. Five patients received combined treatment comprising amphotericin B and posaconazole, one patient received combined treatment comprising voriconazole and posaconazole, nine patients received voriconazole, and four patients received amphotericin B. In addition to antifungal treatment, 10 patients underwent surgery. After antifungal treatment and surgery, 15 patients achieved a response, including 13 patients with a complete response and 2 patients with a partial response. Multivariate analysis revealed that neutropenia before transplantation (P=0.021) , hemorrhagic cystitis after transplantation (P=0.012) , delayed platelet engraftment (P=0.008) , and lower transplant mononuclear cell count (P=0.012) were independent risk factors for IFR after allo-HSCT. The 5-year overall survival rates in the IFR and control groups after transplantation were 29.00%±0.12% and 91.00%±0.03%, respectively (P<0.01) . Conclusion: Although IFR is rare, it is associated with poor outcomes in patients undergoing allo-HSCT. The combination of antifungal treatment and surgery might be effective.

[Research progress on HEG1 in cardiovascular generation and tumor development].

Heart development protein with EGF-like domains 1 (HEG1) is a novel mucin-like membrane protein with a long O-glycosylation region and EGF domain. HEG1 plays critical roles in embryo development and cardiogenesis, and is closely related to the occurrence and progression of malignant tumors. Here this article demonstrates the research progress on HEG1 in cardiovascular formation and tumor development in recent years, to inspire new ideas for the pathogenesis, diagnosis and treatment of related diseases.

Hyperviscosity Syndrome Induced Bilateral Visual and Auditory Impairment in Therapy Resistant Waldenström Macroglobulinemia with MYD88 and CXCR4 Mutations.

Hyperviscosity syndrome (HVS) is an emergent complication of Waldenström macroglobulinemia (WM) characterized by visual, neurologic, and rarely auditory impairment. We report a 69-year-old female with MYD88 and CXCR4-mutant WM who developed HVS resulting in bilateral blindness and deafness associated with neurologic manifestations including confusion, severe generalized weakness, and imbalance. Ophthalmologic evaluation revealed bilateral central retinal vein occlusion (CRVO), diffuse retinal hemorrhages, macular edema, and serous macular detachments (SMD). Magnetic resonance imaging of the brain showed bleeding in the inner ears. Management was challenging as her WM was resistant to systemic therapies including bendamustine + rituximab (BR) and rituximab + bortezomib + dexamethasone (RVD). Bruton's tyrosine kinase inhibitors could not be used initially due to ongoing lower gastrointestinal bleeding. She required five total sessions of plasma exchange and was finally initiated on zanubrutinib, achieving a partial response. She also received intravitreal bevacizumab with rapid resolution of the retinal hemorrhages but with little improvement of the SMD. She had partial restoration of her hearing in the right ear and only slight improvement in her bilateral visual deficits. The management of HVS in frail, elderly patients with therapy-resistant WM can be challenging. In these cases, plasma exchange is required until an effective systemic therapy can be safely instituted. Genomic profiling is important in the management of WM as it can predict treatment resistance and guide therapeutic decisions.

[Effect of recombinant human thrombin for hemostasis in liver resection: a randomized controlled phase â ¢ clinical trial].

Objective: To evaluate the hemostatic efficacy, safety and immunogenicity of recombinant human thrombin in the treatment of liver wounds that still ooze after conventional surgical hemostasis. Methods: A multicenter, stratified randomized, double-blind, placebo-controlled phase Ⅲ trial with a planned enrollment of 510 subjects at 33 centers, with a 2∶1 randomization to the thrombin group versus the placebo group. An interim analysis will be conducted after approximately 70% of the subjects have completed the observation period. The primary efficacy endpoint was the rate of hemostasis within 6 minutes at the point of bleeding that could be evaluated. Safety analysis was performed one month after surgery, and the positive rates of anti-drug antibody (ADA) and neutralizing antibody were evaluated. Results: At the interim analysis, a total of 348 subjects had been randomized and received the study drug (215 were male and 133 were female). They were aged 19-69 (52.9±10.9)years. Among them, 232 were in the thrombin group and 116 were in the placebo group, with balanced and comparable demographics and baseline characteristics between the two groups. The hemostasis rate at 6 minutes was 71.6% (95%CI:65.75%-77.36%) in the thrombin group and 44.0% (95%CI: 34.93%-53.00%) in the placebo group, respectively (P<0.001). No grade≥3 drug-related adverse events and no drug-related deaths were reported from the study.No recombinant human thrombin-induced immunologically-enhanced ADA or immunologically-induced ADA was detected after topical use in subjects. Conclusion: Recombinant human thrombin has shown significant hemostatic efficacy and good safety in controlling bleeding during liver resection surgery, while also demonstrating low immunogenicity characteristics.

Acquired Factor VII Deficiency Associated With Chronic Myeloid Leukemia Blast Crisis.

Factor VII (FVII) is an important, vitamin K-dependent clotting factor. Acquired FVII deficiency is a rare entity that is associated with serious bleeding complications. We report a case of acquired FVII deficiency in a patient with recurrent chronic myeloid leukemia in blast crisis who developed bilateral retinal hemorrhages. The coagulopathy was corrected with the initiation of chemotherapy and subsequent reduction in peripheral blast count.

IRAK-4 inhibition: emavusertib for the treatment of lymphoid and myeloid malignancies.

Several studies have identified mutations in the MYD88L265P gene as a key driver mutation in several B-cell lymphomas. B-cell lymphomas that harbor the MYD88L265P mutation form a complex with phosphorylated Bruton's tyrosine kinase (BTK) and are responsive to BTK inhibition. However, BTK inhibition in B-cell lymphomas rarely results in a complete response and most patients experience eventual disease relapse. Persistent survival signaling though downstream molecules such as interleukin 1 receptor-associated kinase 4 (IRAK-4), an integral part of the "myddosome" complex, has been shown to be constitutively active in B-cell lymphoma patients treated with BTK inhibitors. Emerging evidence is demonstrating the therapeutic benefit of IRAK-4 inhibition in B-cell lymphomas, along with possibly reversing BTK inhibitor resistance. While MYD88 gene mutations are not present in myeloid malignancies, downstream overexpression of the oncogenic long form of IRAK-4 has been found in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), particularly in AML and MDS that harbor mutations in splicing factors U2AF1 and SF3B1. These data suggest that the anti-leukemic activity of IRAK-4 inhibition can be exploited in relapsed/refractory (R/R) AML/MDS. In this review article, we discuss the currently available pre-clinical and clinical data of emavusertib, a selective, orally bioavailable IRAK-4 inhibitor in the treatment of R/R B-cell lymphomas and myeloid malignancies.

[Prognostic analysis of patients with acute leukemia and central nervous system involvement undergoing allogeneic hematopoietic stem cell transplantation].

Objective: To investigate the potential of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in mitigating the adverse prognosis associated with central nervous system leukemia (CNSL) and to assess the significance of prophylactic intrathecal injection. Methods: A retrospective cohort analysis was conducted involving 30 patients with acute leukemia who had a history of CNSL who underwent allo-HSCT at Peking University People's Hospital between September 2012 and March 2018 (referred to as the CNSL-positive group). In addition, 90 patients with acute leukemia were selected from the same period who underwent allo-HSCT without a history of CNSL (referred to as the CNSL-negative group) and a rigorous 1∶3 matching was performed based on disease type, disease status, and transplantation type to form the control group. The prognosis between the two groups was compared using Kaplan-Meier analysis and the high-risk factors for CNSL relapse post-transplant were identified through Cox proportional-hazards model. Results: The median age of patients in the CNSL-negative group was significantly higher than that of patients in the CNSL-positive group (32 years vs. 24 years, P=0.014). No significant differences were observed in baseline data, including sex, disease type, disease status at transplantation, donor-recipient relationship, and human leukocyte antigen consistency between the two groups. The median follow-up time was 568 days (range: 21-1 852 days). The 4-year cumulative incidence of relapse (71.4%±20.9% vs. 29.3%±11.5%, P=0.005) and the cumulative incidence of CNSL post-transplant (33.6%±9.2% vs. 1.2%±1.2%, P<0.001) were significantly higher in the CNSL-positive group than in the CNSL-negative group. Furthermore, the 4-year leukemia-free survival rate in the CNSL-positive group was significantly lower than that in the CNSL-negative group (23.1%±17.0% vs. 71.5%±11.6%, P<0.001). However, no significant differences were observed in the 4-year cumulative transplant-related mortality and overall survival rates between the two groups (both P>0.05). Multivariate analysis revealed that a history of CNSL before transplantation (HR=25.050, 95%CI 3.072-204.300, P=0.003) was identified as high-risk factors for CNSL relapse post-transplant. Conversely, haploidentical transplantation was associated with a reduced risk of CNSL relapse post-transplant (HR=0.260, 95%CI 0.073-0.900, P=0.034). Within the CNSL-positive group, seven patients received prophylactic intrathecal therapy after transplantation, and their CNSL relapse rate was significantly lower than that of the 23 patients who did not receive intrathecal therapy after transplantation (0/7 vs. 9/23, P=0.048). Conclusions: Patients with a history of CNSL have a higher risk of relapse and experience poorer leukemia-free survival following transplantation. The use of prophylactic intrathecal injection shows promise in mitigating CNSL relapse rates, although further validation through prospective studies is necessary to substantiate these observations.

90Yttrium Ibritumomab Tiuxetan (Zevalin) for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Report of 5 Cases.

Radioimmunotherapy (RIT) with radio-labeled monoclonal antibodies to CD20 produces a high response rate in patients with low-grade B-cell lymphomas. The use of this modality in patients with chronic lymphocytic leukemia (CLL) has been sporadic in clinical trials and was hampered by the extensive marrow involvement seen commonly in patients with CLL, which would produce a high risk for marrow aplasia after treatment with RIT. Herein, we report our experience with RIT in 5 patients with CLL or SLL showing short-lived responses and significant myelosuppression. After 90Y-ibritumomab tiuxetan treatment, the median time to relapse was 65 days, and no cases of MDS or AML were observed during follow-up. All patients experienced grade ≥3 thrombocytopenia and neutropenia, with median durations of 39.5 days and 107 days, respectively.

[Overexpression of Nei endonuclease VIII-like protein 3 in hepatocellular carcinoma indicates increased levels of immune infiltration and an unfavorable prognosis].

Objective: To evaluate the role and molecular mechanism of Nei endonuclease VIII-like protein 3 (NEIL3) in hepatocellular carcinoma (HCC) through The Cancer Genome Atlas database. Methods: RNA sequencing of HCC samples was the first step in determining the level of gene NEIL3 expression in normal tissues and tumors. Then, NEIL3 was used for the Gene Ontology, the Kyoto Encyclopedia of Genes and Genomes, gene enrichment analysis, immune cell infiltration analysis. The samples were divided into high and low expression groups according to the median expression level of NEIL3 in liver cancer tissues. Logistic regression analysis, Kaplan-Meier analysis, univariate and multivariate Cox regression analysis, and a nomogram prognostic model were used to explore the clinical and prognostic significance of NEIL3 in HCC. Results: Compared with normal samples, NEIL3 was highly expressed in most malignant tumors, including HCC (P < 0.05). High expression of NEIL3 was related to cell cycle, DNA replication, and cell receptor pathways. In addition, the high expression of NEIL3 was significantly positively correlated with T-helper 2 lymphocytes and infiltration levels (R = 0.670, P < 0.001). Compared with the NEIL3 low expression group, the NEIL3 high expression group had a higher level of Th2 cell infiltration in tumor tissues (P < 0.001). Logistic regression analysis showed that NEIL3 overexpression was associated with high T stage, high pathological stage, high tissue grade, AFP > 400 µg/L and vascular invasion of HCC. The Kaplan-Meier analysis results showed that overall survival [hazard ratio (HR) = 2.53, P < 0.001)], disease-specific survival (HR = 2.52, P < 0.001), and progression-free interval (HR = 1.82, P < 0.001) in patients with HCC with high NEIL3 expression were unfavorable. Cox regression analysis results showed that high NEIL3 expression was an independent risk factor for an unfavorable prognosis in HCC patients (P = 0.002). The nomogram and calibration chart further demonstrated that high NEIL3 expression was one of the risk factors for an unfavorable prognosis in HCC patients. Conclusion: Elevated expression of NEIL3 is associated with an unfavorable prognosis and an increased proportion of immune cells in HCC, and it is likely to be used as a potential biomarker for evaluating the prognosis and immune infiltration level.

[Safety and survival analysis of haplo-identical hematopoietic stem cell transplantation in patients with severe aplastic anemia who had previous failure to antithymoglobulin treatment].

Objective: To investigate the safety and efficacy of haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) conditioning with the same dosage form of antithymoglobulin (ATG) in patients with severe aplastic anemia (SAA) failure to ATG. Methods: This was a retrospective cohort study. A total of 65 patients with SAA who failed ATG treatment and received haplo-HSCT conditioning with the same dosage of ATG at the Institute of Hematology, Peking University People's Hospital between July 2008 and October 2020 were included as the ATG treatment failure group. An additional 65 SAA patients who applied ATG for the first time during haplo-HSCT were randomly selected by stratified sampling as the first-line haplo-HSCT group. Baseline clinical data and follow-up data of the two groups were collected. Conditioning-related toxicity within 10 days after ATG application and long-term prognosis were analyzed. The Kaplan-Meier was used to calculate the overall survival rate, and the Log-rank test was applied to compare the rates of the two groups. Results: In the ATG treatment failure group, there were 36 males and 29 females, and the age at the time of transplantation [M (Q1, Q3)] was 16 (8, 25) years. In the first-line haplo-HSCT group, there were 35 males and 30 females, with a median age of 17 (7, 26) years. Within 10 days of ATG application, the incidence of noninfectious fever, noninfectious diarrhea, and liver injury in the ATG treatment failure group was 78% (51 cases), 45% (29 cases), and 28% (18 cases), respectively, and in the first-line haplo-HSCT group was 74% (48 cases), 54% (35 cases), and 25% (16 cases), respectively; the difference between the two groups was not statistically significant for any of these three parameters (all P>0.05). For graft-versus-host disease (GVHD), there was no significant difference between the ATG treatment failure group and the first-line haplo-HSCT group in the development of 100 day Ⅱ to Ⅳ acute GVHD (29.51%±0.35% vs. 25.42%±0.33%), Ⅲ to Ⅳ acute GVHD (6.56%±0.10% vs. 6.78%±0.11%), and 3-year chronic GVHD (26.73%±0.36% vs. 21.15%±0.30%) (all P>0.05). Three-year overall survival (79.6%±5.1% vs. 84.6%±4.5%) and 3-year failure-free survival (79.6%±5.1% vs. 81.5%±4.8%) were also comparable between these two groups (both P>0.05). Conclusions: Compared with no exposure to ATG before HSCT, similar early adverse effects and comparable survival outcomes were achieved in patients with SAA who failed previous ATG treatment and received haplo-HSCT conditioning with the same dosage form of ATG. This might indicate that previous failure of ATG treatment does not significantly impact the efficacy and safety of salvaging haplo-HSCT in patients with SAA.

[Erythrocytosis after hematopoietic stem cell transplantation: report of 3 cases and literature review].

This is a report of three cases of three male patients. One of the patients had myelodysplastic syndrome, and two had aplastic anemia; their ages were 28, 32, and 21 years old, respectively. Two patients underwent sibling allogeneic hematopoietic stem cell transplantation, and one underwent haploidentical hematopoietic stem cell transplantation. All the patients showed elevated hemoglobin and hematocrit at 6, 16, and 9 months after transplantation, with normal white blood cells and platelets and no splenomegaly. All causes of secondary polycythemia were ruled out. Bone marrow morphology showed no erythroid hyperplasia. The PCR result for BCR-ABL (P210, P230, P190, and variants) was negative, and there were no mutations at the amino acid site 617 of JAK2, exon 12 of JAK2, exon 9 of CALR, and amino acid site 515 of MPL. All three patients had hypertension. One patient was treated with amlodipine, and the other two patients were treated with angiotensin receptor blockers. The durations of erythrocytosis for these three patients were 6 years and 3 months, 4 years and 7 months, and 5 years and 3 months, respectively through December 2022. There was no tendency for spontaneous remission. Erythrocytosis after hematopoietic stem cell transplantation is a rare complication. Previous reports in the literature suggest that the mechanism of post-transplant erythrocytosis in recipients of allogeneic hematopoietic stem cell transplantation may be different from that of recipients of other transplants.

Quality of life assessment of patients after removal of late-onset infected mesh following open tension-free inguinal hernioplasty: 3-year follow-up.

PURPOSE: Open tension-free inguinal hernioplasty is one of the common surgical methods used today to treat inguinal hernias due to its simplicity and low recurrence rate. With the widespread use of tension-free inguinal hernia repair, the number of patients with mesh infections is gradually increasing. However, there is a lack of studies assessing the quality of life of patients after the removal of late-onset infected meshes in open inguinal hernias. The aim of this study was to analyse and assess the quality of life, pain severity and anxiety of patients after late-onset infection mesh removal following open inguinal hernioplasty. METHODS: Data from 105 patients admitted to our hospital from January 2014 to January 2019 who developed delayed mesh infection after open tension-free inguinal hernia repair were retrospectively analysed. 507 patients without mesh infection after open inguinal hernioplasty were included as cross-sectional controls. The baseline data of the two groups were matched for propensity score matching (PSM) with a caliper value of 0.05 and a matching ratio of 1:1. Patients are followed up by telephone or outpatient consultations for 3 years to assess quality of life, pain and anxiety after removal of the infected mesh. RESULTS: The 105 patients who developed late-onset mesh infection after inguinal hernia repair had a mean age of 64.07 ± 12.90 years and a mean body mass index (BMI) of 24.64 ± 2.67 (kg/m2). The mean follow-up time was 58 months and 10.5% (10/105) of the patients were lost to follow-up. At the 3-year follow-up there was one case of hernia recurrence and five cases of mesh reinfection. The patients' quality of life scores, pain scores and anxiety scores improved after surgery compared to the preoperative scores (all p < 0.01). CONCLUSION: Patients with late-onset mesh infection after inguinal hernioplasty showed an improvement in quality of life, pain and anxiety compared to preoperative after removal of the infected mesh. Mesh-plug have a higher risk of mesh infection due to their poor histocompatibility and tendency to crumple and shift.