[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.

[Mechanism of piRNA in bisphenol A-promoted invasion and migration of prostate cancer cells].

Objective: To investigate the regulatory mechanisms of piwi-interacting RNA (piRNA) in bisphenol A (BPA)-induced prostate cancer cell invasion and migration. Methods: The Cancer Genome Atlas (TCGA) data was used to analyze and screen for piRNAs with significantly increased expression in prostate cancer tissues. PC-3 cells were treated with different concentrations of BPA for 12, 24, and 48 h, respectively, and the 20% inhibitory concentration (IC20) was measured using a CCK-8 assay. The expression levels of piRNAs before and after BPA treatment were determined by reverse transcription-quantitative PCR. Target genes regulated by BPA and associated with prostate cancer were screened in the Comparative Toxicogenomics Database (CTD). Dual-luciferase reporter gene assay was performed to verify the relationship between piRNA and target genes, and the expression change of the piRNA target gene was detected by Western blotting. Cell migration and invasion assays were used to determine the effects of piRNA on the malignant phenotype of prostate cancer cells. Results: After treatment of PC-3 cells with 160 µmol/L BPA, the expression of piR-sno48 was most significantly increased (P<0.05). Transfection of piR-sno48 antagomir resulted in decreased expression of endogenous piR-sno48 and a significant increase in the expression of its target gene GSTP1 (P<0.05). However, the expression of GSTP1 did not change significantly in BPA-treated PC-3 cells after transfection with piR-sno48 antagomir (P>0.05). The dual-luciferase reporter gene confirmed that piR-sno48 inhibited the expression of GSTP1 by forming an inversely complementary sequence with the 3'-UTR of GSTP1. The Transwell assay results showed that treatment with BPA significantly increased the invasion and migration ability of prostate cancer cells (P<0.01), whereas piR-sno48 antagonists significantly inhibited the effects above (P<0.01). Conclusion: BPA promotes the invasion and migration of prostate cancer cells by upregulating the expression of piR-sno48 and suppressing the expression of GSTP1. Interfering with the expression of endogenous piR-sno48 may inhibit the malignant phenotype of prostate cancer cells caused by BPA.

[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.

[Efficacy and safety of secondary allogeneic hematopoietic stem cell transplantation in 70 patients with recurrent hematologic malignancies after transplantation].

Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.

[Clinical analysis of the usefulness of letermovir for prevention of cytomegalovirus infection after haploidentical hematopoietic stem cell transplantation].

Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ2=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ2=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.

[Dynamic monitoring of plasma Epstein-Barr Virus DNA load can predict the occurrence of lymphoproliferative disorders after haploidentical hematopoietic stem cell transplantation].

Objective: To determine the optimal cutoff value of Epstein-Barr virus (EBV) DNA load that can assist in the diagnosis of post-transplant lymphoproliferative disease (PTLD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The data of patients with EBV infection after haplo-HSCT from January to December 2016 were retrospectively analyzed. Through constructing the receiver operating characteristic (ROC) curve and calculating the Youden index to determine the cutoff value of EBV-DNA load and its duration of diagnostic significance for PTLD. Results: A total of 94 patients were included, of whom 20 (21.3% ) developed PTLD, with a median onset time of 56 (40-309) d after transplantation. The median EBV value at the time of diagnosis of PTLD was 70,400 (1,710-1,370,000) copies/ml, and the median duration of EBV viremia was 23.5 (4-490) d. Binary logistic regression was used to analyze the peak EBV-DNA load (the EBV-DNA load at the time of diagnosis in the PTLD group) and duration of EBV viremia between the PTLD and non-PTLD groups. The results showed that the difference between the two groups was statistically significant (P=0.018 and P=0.001) . The ROC curve was constructed to calculate the Youden index, and it was concluded that the EBV-DNA load ≥ 41 850 copies/ml after allogeneic hematopoietic stem cell transplantation had diagnostic significance for PTLD (AUC=0.847) , and the sensitivity and specificity were 0.611 and 0.932, respectively. The duration of EBV viremia of ≥20.5 d had diagnostic significance for PTLD (AUC=0.833) , with a sensitivity and specificity of 0.778 and 0.795, respectively. Conclusion: Dynamic monitoring of EBV load in high-risk patients with PTLD after haplo-HSCT and attention to its duration have important clinical significance, which can help clinically predict the occurrence of PTLD in advance and take early intervention measures.

[Impact of SARS-CoV-2 infection on graft composition and early transplant outcomes following allogeneic hematopoietic stem cell transplantation].

Objective: To assess the feasibility of using donors with novel coronavirus disease 2019 (COVID-19) for allogeneic hematopoietic stem cell transplantation (allo-HSCT) when there are no other available donors and allo-HSCT cannot be delayed or discontinued. Methods: Seventy-one patients with malignant hematological diseases undergoing allo-HSCT between December 8, 2022, and January 10, 2023, were included. Of these, 16 received grafts from donors with mild COVID-19 (D-COVID(+) group) and 55 received grafts from donors without COVID-19 (D-COVID(-) group). The graft compositions were compared between the two groups. Engraftment, acute graft-versus-host disease (aGVHD), overall survival (OS), and relapse were also evaluated. Results: There were no serious side effects or adverse events in the D-COVID(+) group. The mononuclear cell dose and CD34(+) cell dose were comparable between the two groups, and no additional apheresis was required. There were no significant differences in the lymphocyte, monocyte, and T-cell subset doses between the two groups. The median natural killer cell dose in the D-COVID(+) group was significantly higher than that in the D-COVID(-) group (0.69×10(8)/kg vs. 0.53×10(8)/kg, P=0.031). The median follow-up time was 72 (33-104) days. All patients achieved primary engraftment. The 60-day platelet engraftment rates in the D-COVID(+) and D-COVID(-) groups were 100% and (96.4±0.2) %, respectively (P=0.568). There were no significant differences in neutrophil (P=0.309) and platelet (P=0.544) engraftment times. The cumulative incidence of grade 2-4 aGVHD was (37.5±1.6) % vs. (16.4±0.3) % (P=0.062), and of grade 3-4 aGVHD was 25.0% ±1.3% vs. 9.1% ±0.2% (P=0.095) in the D-COVID(+) and D-COVID(-) groups, respectively. The probabilities of 60-day OS were 100% and 98.1% ±1.8% (P=0.522) in the D-COVID(+) and D-COVID(-) groups, respectively. There was no relapse of primary disease during the study period. Conclusion: When allo-HSCT cannot be delayed or discontinued and no other donor is available, a donor with mild COVID-19 should be considered if tolerable. Larger sample sizes and longer follow-up periods are required to validate these results.

[Relationship between treatment and prognosis in patients with late-onset severe pneumonia after allogeneic hematopoietic stem cell transplantation].

OBJECTIVE: To explore the relationship between drug treatment and outcomes in patients with late-onset severe pneumonia (LOSP) after allogeneic stem cell transplantation (allo-SCT). METHODS: We retrospectively analyzed the effects of the initiation time of treatment drugs, especially antiviral drugs and glucocorticoids on the clinical outcomes in 82 patients between January 2016 and August 2021 who developed LOSP after allo-SCT in Peking University People's Hospital. Univariate analysis was performed by Mann-Whitney U test and χ2 test, and multivariate analysis was performed by Logistic regression. When multiple groups (n>2) were involved in the χ2 test, Bonferroni correction was used for the level of significance test. RESULTS: Of all 82 patients in this study, the median onset time of LOSP was 220 d (93-813 d) after transplantation, and the 60-day survival rate was 58.5% (48/82). The median improvement time of the survival patients was 18 d (7-44 d), while the median death time of the died patients was 22 d (2-53 d). Multivariate analysis showed that the initiation time of antiviral drugs from the onset of LOSP (< 10 d vs. ≥10 d, P=0.012), and the initiation time of glucocorticoids from antiviral drugs (< 10 d vs. ≥10 d, P=0.027) were the factors affecting the final outcome of the patients with LOSP at the end of 60 d. According to the above results, LOSP patients were divided into four subgroups: group A (antiviral drugs < 10 d, glucocorticoids ≥10 d), group B (antiviral drugs < 10 d, glucocorticoids < 10 d), group C (antiviral drugs ≥10 d, glucocorticoids ≥10 d) and group D (antiviral drugs ≥10 d, glucocorticoids < 10 d), the 60-day survival rates were 91.7%, 56.8%, 50.0% and 21.4%, respectively. CONCLUSION: Our study demonstrated that in patients who developed LOSP after allo-SCT, the initiation time of antiviral drugs and glucocorticoids were associated with the prognosis of LOSP, and the survival rate was highest in patients who received antiviral drugs early and glucocorticoids later. It suggested that for patients with LOSP of unknown etiology should be highly suspicious of the possibility of a secondary hyperimmune response to viral infection.

Factors aggravating acne vulgaris during the COVID-19 pandemic in China: a web-based cross-sectional survey.

OBJECTIVE: Acne vulgaris is a common skin disease worldwide. Throughout the COVID-19 pandemic, many patients with acne complained of worsening symptoms. This investigation was designed to survey the impact of COVID-19 regulations on acne and guide patients with acne on symptom management during the pandemic. MATERIALS AND METHODS: From April 7th to April 21st, 2020, an anonymous, self-completed, web-based questionnaire was distributed to patients previously diagnosed with acne (via the Chinese internet medical software). Information collected included patients' mask-wearing routines and behavioral factors including dietary habits, sleep habits, facial hygiene, and make-up use habits. RESULTS: 508 qualified questionnaire responses were collected. During the COVID-19 outbreak in China, there was an overall worsening of patients' acne symptoms (152, 29.9%). Behaviors including intake of sweets (34.9% vs. 16.0%, p<0.01), dairy consumption (32.9% vs. 23.3%, p<0.05), greasy (19.1% vs. 11.2%, p<0.05) and spicy food intake (30.3% vs. 14.3%, p<0.01) and mask-wearing frequency (>28 hours per week) (25.0% vs. 15.3%, p<0.05) presented a statistically significant difference between the acne aggravated and non-aggravated groups. Longtime mask-wearing (>28 hours per week), rather than the mask type, was significantly associated with acne symptom deterioration during the COVID-19 outbreak (odds ratio [OR]: 2.164; 95% confidence interval [CI]: 1.232-3.801). CONCLUSIONS: Besides the well-known risk factors, such as sweets intake, dairy consumption, and greasy and spicy food intake, wearing masks appears to trigger or aggravate acne during the COVID-19 pandemic. Limiting overall mask-wearing time may help to manage acne.

[A retrospective comparative study of haplotype hematopoietic stem cell transplantation and human leukocyte antigen-matched sibling donor hematopoietic stem cell transplantation in the treatment of acute B-lymphocyte leukemia].

Objective: To investigate whether haplotype hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of pre transplant minimal residual disease (Pre-MRD) positive acute B lymphoblastic leukemia (B-ALL) compared with HLA- matched sibling donor transplantation (MSDT) . Methods: A total of 998 patients with B-ALL in complete remission pre-HSCT who either received haplo-HSCT (n=788) or underwent MSDT (n=210) were retrospectively analyzed. The pre-transplantation leukemia burden was evaluated according to Pre-MRD determinedusing multiparameter flow cytometry (MFC) . Results: Of these patients, 997 (99.9% ) achieved sustained, full donor chimerism. The 100-day cumulative incidences of neutrophil engraftment, platelet engraftment, and grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) were 99.9% (997/998) , 95.3% (951/998) , and 26.6% (95% CI 23.8% -29.4% ) , respectively. The 3-year cumulative incidence of total chronic GVHD was 49.1% (95% CI 45.7% -52.4% ) . The 3-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) of the 998 cases were 17.3% (95% CI 15.0% -19.7% ) and 13.8% (95% CI 11.6% -16.0% ) , respectively. The 3-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 69.1% (95% CI 66.1% -72.1% ) and 73.0% (95% CI 70.2% -75.8% ) , respectively. In the total patient group, cases with positive Pre-MRD (n=282) experienced significantly higher CIR than that of subjects with negative Pre-MRD [n=716, 31.6% (95% CI 25.8% -37.5% ) vs 14.3% (95% CI 11.4% -17.2% ) , P<0.001]. For patients in the positive Pre-MRD subgroup, cases treated with haplo-HSCT (n=219) had a lower 3-year CIR than that of cases who underwent MSDT [n=63, 27.2% (95% CI 21.0% -33.4% ) vs 47.0% (95% CI 33.8% -60.2% ) , P=0.002]. The total 998 cases were classified as five subgroups, including cases with negative Pre-MRD group (n=716) , cases with Pre-MRD<0.01% group (n=46) , cases with Pre-MRD 0.01% -<0.1% group (n=117) , cases with Pre-MRD 0.1% -<1% group (n=87) , and cases with Pre-MRD≥1% group (n=32) . For subjects in the Pre-MRD<0.01% group, haplo-HSCT (n=40) had a lower CIR than that of MSDT [n=6, 10.0% (95% CI 0.4% -19.6% ) vs 32.3% (95% CI 0% -69.9% ) , P=0.017]. For patients in the Pre-MRD 0.01% -<0.1% group, haplo-HSCT (n=81) also had a lower 3-year CIR than that of MSDT [n=36, 20.4% (95% CI 10.4% -30.4% ) vs 47.0% (95% CI 29.2% -64.8% ) , P=0.004]. In the other three subgroups, the 3-year CIR was comparable between patients who underwent haplo-HSCT and those received MSDT. A subgroup analysis of patients with Pre-MRD<0.1% (n=163) was performed, the results showed that cases received haplo-HSCT (n=121) experienced lower 3-year CIR [16.0% (95% CI 9.4% -22.7% ) vs 40.5% (95% CI 25.2% -55.8% ) , P<0.001], better 3-year LFS [78.2% (95% CI 70.6% -85.8% ) vs 47.6% (95% CI 32.2% -63.0% ) , P<0.001] and OS [80.5% (95% CI 73.1% -87.9% ) vs 54.6% (95% CI 39.2% -70.0% ) , P<0.001] than those of MSDT (n=42) , but comparable in 3-year NRM [5.8% (95% CI 1.6% -10.0% ) vs 11.9% (95% CI 2.0% -21.8% ) , P=0.188]. Multivariate analysis showed that haplo-HSCT was associated with lower CIR (HR=0.248, 95% CI 0.131-0.472, P<0.001) , and superior LFS (HR=0.275, 95% CI 0.157-0.483, P<0.001) and OS (HR=0.286, 95% CI 0.159-0.513, P<0.001) . Conclusion: Haplo HSCT has a survival advantage over MSDT in the treatment of B-ALL patients with pre MRD<0.1% .

[BK virus encephalitis in children with hematopoietic stem cell transplantation].

Objective: To explore the morbidity, mortality, median onset time, clinical characteristics, diagnosis, treatment, and outcome of BK virus (BKV) central nervous system infection in children with allogeneic hematopoietic stem cell transplantation (allo-HSCT) , and improve the understanding, clinical diagnosis, and treatment of the disease. Methods: Seven hundred and nine children who received haploid HSCT treatment in Peking University People's Hospital from January 1, 2015 to December 31, 2020 were reviewed. Fourteen patients were diagnosed with BKV central nervous system infection, and their clinical characteristics, treatment process, and prognosis were analyzed. Results: The incidence of BKV central nervous system infection was 1.97% (14 cases) , mostly in men (12 cases) , with a median age of 11 years old and median onset time of 55 d. Additionally, most of the cases showed disturbance of consciousness and seizures (seven cases) . Furthermore, 14 cases were treated with acyclovir and ganciclovir alone or with gamma globulin. Nine cases were cured, of which one died of viral encephalitis and four of other diseases, with a mortality rate of 35.7%. Conclusion: Individuals with central nervous system involvement by BKV infection, usually show signs and symptoms of acute encephalitis, with some cases being accompanied by meningeal involvement. Although BKV encephalitis was diagnosed and actively treated with drugs, many patients still died of multiple organ failure or other complications. Therefore, when there are neurological symptoms and hemorrhagic cystitis in patients with allo-HSCT, it is necessary to be highly vigilant against BKV central nervous system infection. This helps to make clear diagnosis and treatment quickly; thus, improving the survival rate and quality of life of patients with HSCT.

[Ovarian Sertoli-Leydig cell tumors: DICER1 hotspot mutations and associated clinicopathological features].

Objective: To investigate DICER1 hotspot mutations in ovarian Sertoli-Leydig cell tumor (SLCT) and its associated clinicopathological features. Methods: Forty-three SLCTs and 40 other sex cord-stromal tumors (SCSTs) diagnosed between 2010 and 2017 at Fudan University Shanghai Cancer Center were examined for somatic DICER1 hotspot mutations by Sanger sequencing. The associations between mutation status and clinicopathological features, including patient age, tumor differentiation and recurrence, were analyzed. Results: Somatic DICER1 mutations were found in 51% (22/43) of SLCTs, while none in the other 40 SCSTs. The most common mutation of DICER1 was p.D1709N in exon 24 (41%, 9/22) and the second most common mutation of DICER1 was p.E1813K in exon 25 (14%, 3/22). A novel frameshift mutation (c.5464delG, p.M1837fs*16) was identified in one SLCT with microcystic pattern. Mutations were more likely to occur in patients under forty years of age (P=0.046), whereas no significant associations were found between DICER1 mutations and clinical symptoms, morphology or tumor recurrence. Conclusions: Somatic DCIER1 hotspot mutations are specifically found in SLCT and may serve as an ancillary marker in differential diagnosis of SLCT from other SCST. The mutations occur more often in young patients (<40 years old). Additional studies are warranted to examine the associations between DICER1 mutations and clinicopathological features and prognosis of SLCT.

The use of a single ammonium acidic salt towards simple green co-precipitation synthesis for Mn4+-activated fluorides.

Herein, a simple green co-precipitation route for Mn4+-activated fluorides has been realized via individually using the aqueous acidic salt NH4HF2 as a solvent. The systematic explorations of ionization, erosion, solvent concentration, solvency on reactants, and reaction with an extra weak acid disclosed that the near-saturated aqueous NH4HF2, ionizing into abundant HF2-, H+, and F- ions, exhibited large dissolving capacity and good stabilization on Mn4+ without obvious toxicity. The green synthesized example of Cs2GeF6:Mn4+ emitted a typical narrow band red light at 633 nm with normal optimal doping at ∼8 at%. Compared with its contrast prepared from the HF system, it experienced only ∼10% reduction in quantum efficiency and slight emission attenuation below 150 °C as the more humidity-sensitive weaker acid surface aroused lattice thermal vibration. The further action as red component fabricated a high-quality warm white light-emitting diode (W-LED) with a high color rendering index (Ra ∼ 91), high luminous efficacy (∼149 lm W-1), low correlated color temperature (∼3211 K), and good color stability against the operating environment. Combined with the universal synthesis of A2XF6:Mn4+ (A = K, Rb, Cs; X = Si, Ge), our findings can probably open up a simple and feasible green synthetic strategy for efficient Mn4+-doped fluorides using acidic salts.

[Invasive breast lobular carcinoma with extracellular mucin: a clinicopathological analysis].

Objective: To study the clinicopathological features of invasive lobular carcinoma (ILC) of the breast with extracellular mucin and outcomes of patients. Method: Clinicopathological features and clinical follow-up (39-123 months and a median follow-up of 55 months) of seven ILC with extracellular mucin were obtained. Hematoxylin-and-eosin (H&E) and immunohistochemistry (IHC) stained sections were reviewed, and fluorescence in situ hybridization (FISH) assay was performed for tumors with HER2 IHC 2+. Patient prognosis was analyzed and literatures related to ILC with extracellular mucin were reviewed. Results: All seven patients were female, aged from 43 to 73 years (median age, 55 years). The tumors ranged in size from 1 to 5 cm (median size 2 cm). All seven cases were of histological grade 2. Most areas of the tumors presented with the morphology of classic ILC, and variable amount of extracellular mucin were observed focally. In six cases, part of the tumor cells contained intracellular mucin, and the nucleus were pushed to one side of the cells, creating the impression of signet-ring cells. Two patients had lymph node metastases at diagnosis, and developed liver and bone metastases at 38th and 48th month, respectively, after surgery, and died at 48th and 123th month, respectively. While the other five patients, except one lost to follow-up, had been disease-free during the follow-up period. IHC results showed estrogen receptor (ER) and progesterone receptor (PR) positivity in 7/7 and 6/7 cases, respectively. Tumors of six patients were HER2 IHC 0/1+. The remaining one was HER2 IHC 2+, while FISH assay revealed HER2 gene amplification in that tumor. The proportion of cases with HER2-positivity was 1/7. The proliferation index Ki-67 ranged from less than 5% to 30%, and Ki-67 less than or equal to 10% were in 5/7 cases. According to the 2013 St. Gallen International Expert Consensus on breast cancer, all tumors were of luminal types; of those, two were luminal A and five were luminal B. Conclusions: ILC with extracellular mucin tends to occur in women over 50 years old. All tumors in the study are grade 2 classic ILC, with signet-ring cells as a common feature. All seven tumors are classified as luminal types, with luminal B as the main molecular subtype.

[Expression of SMARCA4(BRG1) and SMARCB1(INI1) in dedifferentiated and undifferentiated endometrial carcinomas and their correlations with clinicopathological features].

Objective: To investigate the expression of SMARCA4 (BRG1) and SMARCB1 (INI-1) protein in endometrial dedifferentiated carcinoma (DDC) and undifferentiated carcinoma (UDC), and their correlation with clinicopathologic features. Methods: Clinicopathological information was gathered for 26 cases of DDC and UDC and consulting hospitals from January, 2006 to December, 2018 in Fudan University Shanghai Cancer Center, including 10 cases of DDC and 16 cases of UDC. Morphologic features and diagnosis were reviewed by two pathologists. Immunohistochemistry for expression of BRG1 and INI1 protein was performed. The correlations with clinicopathologic features were analyzed. Results: BRG1 and INI1 loss were present in 14 of 26 cases of DDC/UDC, including 12 BRG1-deficient cases and 2 INI1-deficient cases, respectively. Six cases demonstrated variable amounts of rhabdoid cells in 14 BRG1/INI1-deficient cases, and only 1 case showed rhabdoid cells in the 12 intact expression cases. However, there was no significantly statistical difference (P=0.060). Age, invasive depth, lymph node status and FIGO stage were not associated with the expression of the BRG1 and INI1 (P=0.437, P=0.672, P=0.242, P=0.348). Remarkably, the BGR1/INI1-deficient patients had worse survival than those with intact expression (4.7 vs. 22.9, P=0.033). Conclusion: BRG1/INI1-deficient is observed in approximately half of DDC and UDC. Identification of these tumors is clinically relevant due to their more aggressive behavior and poor prognosis. Hence, BRG1 and INI1 immunohistochemical stains should be performed for DDC and UDC in order to help the pathologists to distinguish these tumors from other carcinomas, and to predict the clinical prognosis.

[Clinicopathological study of BCOR rearrangement in high grade endometrial stromal sarcoma].

Objective: To investigate clinicopathological, cytogenetic features and differential diagnoses of high grade endometrial stromal sarcoma (HGESS) with BCOR gene rearrangement. Methods: Five cases of HGESS with BCOR rearrangement were collected from consultant files (2016-2018) at Fudan University Shanghai Cancer Center. Interphase FISH was performed using a dual color break-apart probe. The clinical data, histologic features and immunohistochemical findings were reviewed. Results: All 5 cases occurred in adult women with a median age of 48 (range, 45-55) years. Abdominal pain and abnormal vaginal bleeding were the most common symptoms. Microscopically, the tumors showed mainly tongue-like and/or intersecting myometrial invasion. Stromal myxoid matrix and/or collagen plaques were prominent in all the cases. Most tumors consisted of uniform, haphazard fascicles of short spindle cells with mild to moderate nuclear atypia. Mitotic figures and necrosis were easily identified. Significant nuclear pleomorphism was not seen. Most tumors were rich in thick-walled small vessels. Prominent perivascular tumor cell whorling seen in conventional low-grade endometrial stromal sarcoma was not seen. All tumors expressed CD10 with only focal or absent desmin, SMA and/or h-caldesmon staining. ER or PR expression was seen in 4 tumors and 1 tumor showed both marker expression. Diffuse cyclin D1 was present in 2 tumors. BCOR immunoreactivity was present with strong staining in 3 cases and moderate staining in 1 case respectively. Ki-67 index ranged from 10% to 30%. Fluorescence in situ hybridization confirmed chromosomal aberration of BCOR gene in all tumors, that were previously diagnosed as myxoid leiomyosarcoma (2 cases), spindle cell uterine sarcoma (2 cases) and low-grade endometrial stromal sarcoma (1 case). Limited follow-up information revealed that 3/5 patients developed tumor recurrence, metastasis or death within one year. Conclusion: BCOR rearranged HGESS has distinct morphological features and aggressive clinical behavior. In the presence of significant overlapping morphologic features between BCOR rearranged HGESS and other myxoid uterine mesenchymal tumors, especially myxoid leiomyosarcoma, molecular analysis is essential for accurate diagnoses.