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Background: Aim was to compare histological diagnosis of differently stained endometrial tissue on chromohysteroscopy.Methods: A total of 80 patients diagnosed with AUB and satisfying the study design were included in the study. Hysteroscopy followed by chromohysteroscopy was done using 1% methylene blue. Staining patterns were observed and guided biopsies were taken from differently stained areas and sent for histopathology.Results: On chromohysteroscopy, out of the 80 participants, 53 (66.3%) had focal staining and 27 (33.7%) had diffuse staining. The overall sensitivity, specificity, PPV and NPV of TVS in diagnosing uterine abnormalities was 51.7%, 45.1%, 34.9%, 62.2% respectively. The overall sensitivity, specificity, PPV and NPV for hysteroscopy were 96.6%, 41.2%, 48.3%, 95.5% respectively. The indices for chromohysteroscopy were as follows: sensitivity-69% for focal and 31% for diffuse staining, specificity-49.0% for focal staining and 69.7% for diffuse staining, PPV-43.5% for focal and 33.3% for diffuse staining, NPV-73.5% for focal staining and 62.3% for diffuse staining.Conclusions: The idea of staining of endometrium and taking a guided biopsy is exciting and is undoubtedly, better than a blind sampling. However, subjecting all the patient of AUB to chromohysteroscopy in order to find a major histopathological difference is questionable and needs larger trials to reach to concrete decision.
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Acute fatty liver of pregnancy (AFLP) is a condition that occurs during the third trimester of pregnancy, typically manifesting around 36 weeks of gestation. It represents a critical obstetric emergency with considerable neonatal mortality. To manage AFLP disease, a multidisciplinary approach is essential which helps meaningfully in the improvement of its prognosis during the post-partum period. Historically, it was considered a fatal disease for both mother and fetus. Nowadays, the prognosis is improved by rapid diagnosis, early delivery and administration of treatment. We reported three cases of Moroccan women diagnosed with AFLP in our hospital who received a multi-disciplinary care with good prognosis. The first and third parturient gave birth by vaginal delivery and the second one by caesarean section.
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Objective:To explore the antitumor effect of ADU-S100/doxorubicin in situ vaccine on diffuse large B-cell lymphoma (DLBCL) and its mechanism.Methods:The 6-week-old female BALB/c mice were selected, and the bilateral murine subcutaneous B-cell lymphoma model was established with murine B-cell lymphoma A20 cells. The subcutaneous tumor-bearing mice were randomly divided into untreated group (without treatment), ADU-S100 in situ vaccine treatment group (intratumoral injection of interferon gene stimulating factor agonist ADU-S100), doxorubicin in situ vaccine treatment group (intratumoral injection of doxorubicin), and ADU-S100/doxorubicin in situ vaccine treatment group (intratumoral injection of ADU-S100 and doxorubicin) by using random number table method, with 5 mice in each group. The right tumors of the bilateral subcutaneous tumor-bearing mice were defined as proximal tumors, and the left tumors of the bilateral subcutaneous tumor-bearing mice were defined as distal tumors. Only the proximal tumors were treated via the intratumoral route, and the distal tumors were not treated. On day 23 after tumor inoculation, the percentages of CD11c + dendritic cells (DC), CD8 + CD11c + DC and CD80 + CD11c + DC in the spleen of mice in each group were detected by flow cytometry. The splenocytes of mice in each group were stimulated with A20 tumor cell lysate in vitro, the percentages of 5'-ethynyl-2'-deoxyuridine-positive (EdU +) cells and tumor necrosis factor-α-positive (TNF-α +) cells in CD8 + T cells in each in situ vaccine treatment group were detected by flow cytometry, and the killing effect of cytotoxic T lymphocyte (CTL) in each group was measured by using the lactate dehydrogenase (LDH) cytotoxicity assay kit. The mice treated with ADU-S100/doxorubicin in situ vaccine were intraperitoneally injected with anti-mouse CD8α (clone 53-6.7) mAb or isotype control on days 7, 12 and 17 after tumor inoculation to eliminate CD8 + cells. On day 23 after tumor inoculation, the proximal and distal tumor volumes of mice in the ADU-S100/doxorubicin in situ vaccine combined with anti-mouse CD8α (clone 53-6.7) mAb or isotype control treatment group were measured, the percentages of CD8 + T cells and CD8 + CD11c + DC in the spleen of tumor-bearing mice in these two groups were detected by flow cytometry, and the infiltration of CD8 + T cells in the tumor tissues from these two groups was detected by immunohistochemistry (IHC) staining. Results:On days 11, 14, 17, 20 and 23 after tumor inoculation, the proximal and distal tumor volumes of mice in each treated group were lower than those in the untreated group (all P < 0.05). The proportions of CD11c + DC in the spleen of the untreated group, ADU-S100 in situ vaccine treatment group, doxorubicin in situ vaccine treatment group and ADU-S100/doxorubicin in situ vaccine treatment group were (4.92±0.63)%, (7.54±0.84)%, (7.45±0.86)% and (11.63±0.85)%, respectively, and the difference was statistically significant ( F = 72.30, P < 0.001); the proportions of CD8 + CD11c + DC were (1.36±0.34)%, (4.02±0.43)%, (4.22±0.61)% and (6.11±0.73)%, respectively, and the difference was statistically significant ( F = 76.09, P < 0.001); the proportions of CD80 + CD11c + DC were (0.51±0.24)%, (1.69±0.23)%, (1.82±0.25)% and (4.09±0.39)%, respectively, and the difference was statistically significant ( F = 167.40, P < 0.001). The CTL responses and the proportion of EdU + cells and TNF-α + cells in CD8 + T cells in each in situ vaccine treatment group were higher than those in the untreated group (all P < 0.05). Furthermore, the enhanced CTL responses and the increased proportion of EdU + cells and TNF-α + cells in CD8 + T cells were observed in the ADU-S100/doxorubicin in situ vaccine treatment group as compared to the ADU-S100 in situ vaccine treatment group and doxorubicin in situ vaccine treatment group (all P < 0.05). The proportions of CD8 + T cells and CD8 + CD11c + DC in the spleen of mice treated with ADU-S100/doxorubicin in situ vaccine and anti-mouse CD8α mAb were lower than those in ADU-S100/doxorubicin in situ vaccine and isotype control group (both P < 0.05) and both proximal and distal tumor volumes of mice treated with ADU-S100/doxorubicin in situ vaccine and anti-mouse CD8α mAb were larger than those in ADU-S100/doxorubicin in situ vaccine and isotype control group (both P < 0.05). Conclusions:ADU-S100/doxorubicin in situ vaccine can induce profound regression of proximal tumors in bilateral murine subcutaneous B-cell lymphoma model and generate systemic immune responses capable of partially inhibiting distant tumor growth, and the antitumor efficacy of ADU-S100/doxorubicin in situ vaccine may require CD8 + CD11c + DC-mediated CD8 + T cell immune responses.
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Objective:To investigate the clinical efficacy and safety of ZR2 (zevalin + lenalidomide + rituximab) regimen in the treatment of elderly patients with diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was conducted. The clinical data of 16 elderly (>65 years old) non-germinal center B-cell-like DLBCL patients treated with ZR2 regimen at the Taixing People's Hospital from January 2021 to March 2023 were retrospectively analyzed. The efficacy, adverse reactions and prognosis of patients were observed.Results:Of the 16 patients, 11 were male and 5 were female, with the age [ M ( Q1, Q3)] of 76 years old (70 years old, 78 years old), and 10 cases were Ann Arbor stage Ⅲ-Ⅳ. Among the 16 patients, 9 achieved complete remission, 4 patients achieved partial remission. All 16 patients experienced varying degrees of reversible bone marrow suppression, grade Ⅲ-Ⅳ hematologic adverse reactions included neutropenia (7 cases) and thrombocytopenia (2 cases), and the bone marrow hematopoiesis recovered after treatment with granulocyte colony-stimulating factor and thrombopoietin. The main ≥grade Ⅱ non-hematologic adverse reactions were gastrointestinal reactions (5 cases), liver function abnormalities (3 cases) and peripheral neuropathy (2 cases), which were improved after the appropriate treatment. Two patients discontinued the treatment of this regimen due to disease progression, and 1 patient died from complications after 2 cycles of treatment. No deep vein thrombosis, cardiac toxicity or renal toxicity occurred during the treatment process. Conclusions:The ZR2 regimen is effective in the treatment of elderly DLBCL patients with tolerable adverse reactions.
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Objective:To investigate the level of serum lipoprotein a [Lp (a)] in patients with diffuse large B-cell lymphoma (DLBCL) and its clinical significance.Methods:A retrospective cohort study was performed. The clinical data of 87 patients with DLBCL who were treated at Changshu No.2 People's Hospital from January 2017 to June 2022 (the newly treated DLBCL group) were retrospectively analyzed, and 78 healthy physical examination subjects were selected as the control group. The level of Lp(a) in the two groups and the level of Lp(a) in DLBCL patients achieving different therapeutic effects after treatment were compared. The receiver operating characteristic (ROC) curve was used to analyze the efficacy of serum Lp(a) in predicting the therapeutic effect of DLBCL patients, and the area under the curve (AUC) was calculated to determine the optimal critical value. Based on the optimal critical value, patients with DLBCL were divided into low Lp(a) group and high Lp(a) group, and the clinicopathological characteristics of DLBCL patients with different Lp(a) levels were compared. Cox proportional hazards model was used to analyze the factors affecting the prognosis of DLBCL patients. Kaplan-Meier method was used to compare the relapse-free survival (RFS) and overall survival (OS) of DLBCL patients with different Lp(a) levels.Results:The level of Lp (a) in the newly treated DLBCL group was higher than that in the control group[ (0.24±0.09) g/L vs. (0.09±0.06) g/L], and the difference was statistically significant ( t = 3.61, P = 0.019). Among 87 patients, 54 achieved complete remission (CR), 23 achieved partial remission (PR), and 10 achieved progression of the disease (PD). The Lp (a) levels of patients achieving CR, PR, and PD were (0.09±0.09) g/L, (0.12±0.08) g/L, and (0.25±0.15) g/L, respectively. The Lp (a) levels in patients achieving CR and PR were lower than those in the newly treated DLBCL patients [(0.24±0.09) g/L], and the differences were statistically significant (all P < 0.05). There was no statistically significant difference in the Lp (a) levels between patients achieving PD and the newly treated DLBCL patients ( P > 0.05). The ROC curve results showed that the optimal critical value of serum Lp (a) in predicting the efficacy of DLBCL patients was 0.25 g/L, AUC was 0.776 (95% CI: 0.676-0.876, P < 0.05), and its sensitivity and specificity was 66.67%, 82.76%, respectively. According to the optimal critical value of Lp (a) (0.25 g/L), patients were divided into the low Lp (a) group (≤ 0.25 g/L) (57 cases) and the high Lp (a) group (>0.25 g/L) (30 cases). The proportion of patients with lactate dehydrogenase level >227 U/L, Ann Arbor stage Ⅲ-Ⅳ, and extranodal organ involvement >1 in the high Lp (a) group was higher than that in the low Lp (a) group, and the differences were statistically significant (all P < 0.05). Cox multivariate analysis results showed that Ann Arbor stage Ⅲ-Ⅳ, international prognostic index (IPI) score 3-5, and Lp (a)>0.25 g/L were independent risk factors for OS in DLBCL patients (all P < 0.05); Ann Arbor stage Ⅲ-Ⅳ and IPI score 3-5 were independent risk factors for RFS in DLBCL patients (all P < 0.05). The median OS in the low Lp (a) group was not reached; the median OS of the high Lp (a) group was 21 months, and there was a statistically significant difference in OS between the two groups ( P = 0.001). The median RFS time was not reached in the low Lp (a) group and the high Lp (a) group; and there was no statistically significant difference in RFS between the two groups ( P = 0.102) . Conclusions:Lp(a) level of DLBCL patients is increased, and Lp(a) could be a factor influencing the prognosis of DLBCL.
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Objective:To investigate the clinicopathological features, mutation, therapeutic efficacy and the factors influencing the prognosis of patients with cardiac diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 11 cardiac DLBCL patients in Ruijin Hospital of Shanghai Jiao Tong University School of Medicine from January 2016 to October 2020 were retrospectively analyzed. NovaSeq sequencing platform was used to detect gene mutations in 5 patients, and bioinformatics analysis of sequencing data was conducted through public database to identify the mutation sites of pathogenic genes. Kaplan-Meier method was used to analyze the progression-free survival (PFS) and the overall survival (OS). Univariate Cox proportional risk model was used to analyze the influencing factors of prognosis.Results:Among 11 patients with cardiac DLBCL, 5 were male and 6 were female. The age [ M ( Q1, Q3)] was 61 years (45 years, 70 years). All 11 patients were non-germinal center B-cell (non-GCB) type. There were 2 primary cases and 9 secondary cases; 9 cases with Ann Arbor stage of Ⅲ-Ⅳ, 10 cases with increased lactate dehydrogenase (LDH) and 9 cases with international prognostic index (IPI) score equal to or higher than 3 scores. Among 11 patients, 9 cases received a first-line treatment based on the R-CHOP (rituximab, cyclophosphamide, epirubicin/doxorubicin hydrochloride liposomes, vincristine and prednisone) regimen, of which 8 patients achieved complete remission (CR), and 1 patient achieved stable disease (SD); 1 patient received IR2 (ibrutinib + rituximab + lenalidomide) treatment regimen and achieved SD, and 1 patient received supportive treatment only and achieved progression of the disease. The follow-up time was 39.9 months (25.6 months, 57.3 months). The 3-year PFS rate and 3-year OS rate of 11 patients was 54.5%, 77.9 %, respectively. Univariate Cox regression analysis showed that gender, B symptoms, Ann Arbor stage, LDH level, number of extranodal lesions, IPI score were not correlated with PFS and OS of patients (all P > 0.05). Among 5 cases undergoing gene detection, KMT2D mutations and PIM1 mutations were detected in 2 cases,respectively. Interestingly, KMT2D mutations were only found in secondary cardiac DLBCL patients (2/3), while PIM1 mutations were only detected in primary cardiac DLBCL patients (2/2). Conclusions:Most cardiac DLBCL patients are non-GCB type and have advanced clinical stage, while may benefit from R-CHOP treatment regimen. PIM1 and KMT2D are the commonly mutated genes in cardiac DLBCL.
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Objective:To investigate the predictive value of controlling nutritional status (CONUT) score in the prognosis of patients with advanced diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 654 patients newly diagnosed with advanced DLBCL diagnosed in 7 medical centers in Huaihai Lymphoma Working Group from October 2009 to January 2022 were retrospectively collected. All the patients received rituximab-based immune chemotherapy regimens. The patients were randomly assigned to the training set (458 cases) and the validation set (196 cases) in a 7:3 ratio. The clinicopathological data of patients were collected, and the CONUT score was calculated based on albumin, lymphocyte count, and total cholesterol. The optimal critical value of CONUT scote was determined by using MaxStat method. Kaplan-Meier method was used to draw survival curves; Cox proportional hazards model was used to make univariate analysis and multivariate analysis on the factors influencing overall survival (OS). The efficacy of CONUT score in combination with the International prognostic index (IPI) and an enhanced IPI (NCCN-IPI) in predicting OS was evaluated by using receiver operating characteristic (ROC) curves.Results:The median follow-up time of 654 patients was 38.1 months (95% CI: 35.3 months- 40.9 months), and the 5-year OS rate was 49.2%. According to the MaxStat method, the optimal critical value for CONUT score was determined to be 6 points. All the patients were classified into the normal nutritional status group (CONUT score ≤ 6 points, 489 cases) and the poor nutritional status group (CONUT score > 6 points, 165 cases). The results of the multivariate analysis showed that CONUT score > 6 points, male, lactate dehydrogenase >240 U/L, high white blood cell count, low hemoglobin level and age > 60 years were independent risk factors for OS of patients with advanced DLBCL (all P < 0.05). Patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group in the overall cohort of advanced DLBCL. Subgroup analysis revealed that among patients with Eastern Cooperative Oncology Group-performance status (ECOG PS) score < 2 points, IPI low-intermediate risk, IPI intermediate-high risk, NCCN-IPI low-intermediate risk, and NCCN-IPI intermediate-high risk, the patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group (CONUT score ≤ 6 points) (all P < 0.05). Conclusions:CONUT score has a certain value in the assessment of the prognosis of patients with advanced DLBCL, and its predictive efficacy is further improved when combined with IPI and NCCN-IPI.
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Objective:To explore the efficacy and safety of tislelizumab combined with zanubrutinib in the treatment of refractory diffuse large B-cell lymphoma (DLBCL).Methods:A prospective observational study was conducted. A total of 10 patients with refractory DLBCL admitted to Beijing Chaoyang District Third Ring Cancer Hospital, a specialist medical consortium of Cancer Hospital Chinese Academy of Medical Sciences from November 2020 to February 2023 were prospectively collected. All the 10 refractory DLBCL patients at least received first-line systemic therapy containing rituximab; and they were given tislelizumab 200 mg, intravenous infusion, on day 1 and zanubrutinib 160 mg, orally, twice a day, day 1-day 21, with 21 days as 1 cycle; 6 patients received second-line therapy and 4 patients received ≥ third-line therapy. Subsequent regimens were added with rituximab (375 mg/m 2, intravenous infusion on day 1). The primary endpoint will be reached 12 months after enrollment if there was no disease progression or other events that were scheduled to withdraw from the study. The therapeutic efficacy was summarized at the end of the follow-up in March 2023. Kaplan-Meier method was used to make survival analysis and the adverse reactions were summed up. Results:There were 6 males and 4 females, all at stage Ⅲ-Ⅳ; and age [ M ( Q1, Q3)] was 55 years (50 years, 69 years). All 10 patients completed 90 cycles of treatment with tislelizumab and zanubrutinib, with the cycle number of 8 cycles (2 cycles, 24 cycles). The follow-up time was 19 months (11 months, 28 months); 4 cases achieved complete remission, 3 cases achieved partial remission and 1 case had the stable disease. The progression-free survival was 8.5 months (1.3 months, 27.0 months); the median remission duration time and median overall survival time were not reached. Treatment-related adverse reactions included 2 cases of neutropenia, 1 case of anemia, and 1 case of elevated alanine aminotransferase and aspartate aminotransferase, all of which were grade 1-2. Conclusions:Tislelizumab combined with zanubrutinib has good clinical efficacy and safety in the treatment of refractory DLBCL.
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Objective To evaluate the regulatory effect of the adaptor related protein complex 2 subunit μ1(AP2M1)on proliferation and invasion of diffuse large B-cell lymphoma(DLBCL).Methods Human diffuse large B-cell lymphoma cell line OCI-LY8 was aliquoted into control group,NC-shRNA group,AP2M1-shRNA group,NC-LV group,and AP2M1-LV group.Lipofectamine 2000 was used for cell transfection.Cell proliferation was detected by tetramethylazolium salt(MTT)method,apoptosis was detected by flow cytometry and cell migration and invasion were detected by Transwell assay.The protein expression of AP2M1,epidermal growth factor receptor(EGFR),p-phosphatidylinositol 3 kinase(PI3K),PI3K,p-protein kinase B(Akt)and AKT was detec-ted by Western blot.Results Compared with control group,the relative expression of AP2M1 mRNA and protein in the AP2M1-shRNA group was decreased(P＜0.05).The relative cell viability was increased(P＜0.05).The cell apoptosis rate was decreased(P＜0.05).The counting number of migrating and invading cells was in-creased(P＜0.05).The relative expression level of EGFR protein and the phosphorylation level of PI3K and AKT were increased(P＜0.05).Compared with Control group,the expression of AP2M1 mRNA and protein relative ex-pression level in AP2M1-LV group was increased(P＜0.05).The relative cell viability was decreased(P＜0.05).The cell apoptosis rate was increased(P＜0.05).The number of migrating and invading cells was decreased(P＜0.05).The relative expression level of EGFR protein and the phosphorylation level of PI3K and AKT were all decreased(P＜0.05).Conclusions The over-expression of AP2M1 partially inhibits the proliferation and invasion of DLBCL cells by inhibiting the EGFR/PI3K/AKT signaling pathway.
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Objective To analyze micronutrient levels in three types of female patients with diffuse hair loss.Methods The clinical data of 299 female patients with diffuse alopecia from January 2018 to June 2021 in the Department of Dermatology of Daping Hospital were analyzed retrospectively.Results The level of serum 25-hydroxyvitamin D in patients with diffuse alopecia was significantly lower than that in the control group,and had no impact to the type of diffuse alopecia.The concentration of serum zinc in patients with diffuse alopecia areata was also significantly lower than that in the control group.When ferritin≤50 ng/mol was taken as the threshold of iron deficiency and 25-hydroxyvitamin D≤20 ng/mol,as the indicator level of serum 25-hydroxyvitamin D deficiency,the proportion of serum 25-hydroxyvitamin D and serum ferritin deficiency in all the three types of diffuse hair loss patients was higher than that in the control group(P＜0.05).So,lack of iron and serum 25-hydroxyvitamin D were belived to be related to the occurrence of diffuse alopecia of women.Conclusions Iron metabolism disorder and se-rum 25-hydroxyvitamin D level play a key role in female diffuse alopecia,while the effects of copper and zinc on hair growth and hair loss cycle are not well identified yet.
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Purpose To explore the clinicopathological features and molecular characteristics of primary CD5+diffuse large B cell lymphoma(DLBCL).Methods Immunohisto-chemistry and next-generation sequencing(NGS)were used to compare the pathological features,immunophenotypes,and mo-lecular characteristics between primary CD5+DLBCL and CD5-DLBCL,and to analyze their relationship with prognosis and clinical characteristics of patients.Results Among 311 DLBCL patients,there were 46 cases(14.7％)of CD5+DLBCL.There were no statistically significant differences in patient gen-der,clinical staging,international prognostic index between CD5+DLBCL and CD5-DLBCL,and between CD5+DLBCL with and without MYD88 L265P mutation(P＞0.05).Immuno-phenotypically,the overexpression of BCL2(69.5％vs 49.4％,P=0.003)and the co-expression of BCL2 and C-MYC(26％vs 14％,P=0.04)were higher in the CD5+DLBCL group than those in the CD5-DLBCL group;the expression of C-MYC(53％vs 20％),BCL6(93.3％vs 61.3％),Ki67(93.3％vs 64.5％),and co-expression(46.7％vs 20.8％)were higher in the CD5+with MYD88 L265P mutation group than those in the CD5+without MYD88 L265P mutation group(P＜0.05).Survival analysis showed that the disease progres-sion-free survival time of patients in the CD5+DLBCL group tended to be shorter than that of patients in the CD5-DLBCL group(P=0.09).Furthermore,the disease progression-free survival time of patients in the CD5+without MYD88 L265P mutation group was significantly longer than that of patients in the CD5+with MYD88 L265P mutation group(P=0.04).NGS detection found differences in the distribution of accompan-ying mutated genes between CD5+DLBCL and CD5-DLBCL groups.ConclusionCD5 expression and CD5+with MYD88 L265P mutation may be potential indicators of poor prognosis in DLBCL patients.
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Purpose To investigate the effect of MYD88 gene overexpression on the proliferation and apoptosis of human diffuse large B cell lymphoma(DLBCL)cells,and to prelimi-narily explore the mechanism of MYD88 gene action.Methods PEGFP-C2-MYD88 overexpressing MYD88 L265P gene was transfected into DLBCL cells by plasmid transfection.The exper-iment was divided into blank control group,negative control group and MYD88 L265P overexpression group.The fluores-cence expression of MYD88 L265P after overexpression was ob-served under inverted fluorescence microscope.RT-PCR and Western blot were used to detect the mRNA and protein expres-sion of MYD88 L265P,IRAK4,NF-κB and BCL2 in DLBCL cells before and after overexpression of MYD88 L265.CCK8 method was used to detect DLBCL cells proliferation and Ho-echst staining was used to detect DLBCL cells apoptosis.Re-sults After overexpression of MYD88 L265P,compared with the blank control group(0.670 4±0.017 5)and the negative control group(0.715 3±0.019 6),the MYD88L265P overex-pression group(1.157 2±0.010 2)increased significantly,with statistical significance(all P＜0.05).After overexpression of MYD88 L265P,compared with the blank control group(0.69 ±0.04)and the negative control group(0.81±0.07),the MYD88L265P overexpression group(0.48±0.05)was signifi-cantly decreased,with statistical significance(all P＜0.05).After overexpression of MYD88 L265P,compared with the blank control group(mRNA:1.0158±0.0115,0.987 3±0.010 2,1.007 6±0.015 3,protein:0.183 4±0.058 9,0.096 8± 0.015 7,0.147 5±0.0418)and negative control group(mR-NA:0.9132±0.0098,1.0032±0.0156,0.9327± 0.011 2,protein:0.187 9±0.042 3,0.088 9±0.0513,0.134 8±0.050 1),the mRNA(3.243 2±0.013 6,2.976 6 ±0.0213,1.585 9±0.019 8)and protein expressions(0.452 7±0.052 4,0.218 9±0.047 5,0.301 4±0.059 8)of IRAK4,NF-κB and anti-apoptosis protein BCL2 in MYD88L265P overexpression group were significantly increased,which was statistically significant(all P＜0.05).Conclusion After overexpression of MYD88 L265P,the apoptosis rate of DLBCL cells decreased and the cell proliferation rate increased.The mechanism may be related to the mutation of MYD88 L265P gene,activation and amplification of NF-κB pathway,and pro-motion of the overexpression of antiapoptotic protein BCL2.
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Purpose To explore the molecular features of diffuse large B-cell lymphoma(DLBCL)with high expression of MYC.Methods The clinical data of 45 cases of DLBCL were collected.Immunohistochemical EnVision method was used to classify the patients into the group with high expression of MYC and the group with low expression of MYC.All samples were subjected to DNA targeted sequencing and molecular typing was performed using the LymphGen online tool.Cellular origin was determined by using the Lymph2Cx method.The correlation be-tween MYC overexpression and clinicopathological parameters was analyzed by the x2 test and Fisher precise test.Survival curves were drawn and survival-related factors were analyzed u-sing Cox univariate and multivariate regression.ResultsCases were classified into DLBCL with high expression of MYC(n=17)and DLBCL with low expression of MYC(n=28).Com-pared to the group with low expression of MYC,the group with high expression of MYC had more PIM1,MYD88,CD79B,CD58 and PRDM1 mutations(76.5％vs 28.6％,70.6％vs 32.1％,58.8％vs28.6％,29.4％vs3.6％,29.4％vs 3.6％,P＜0.05),MCD were more frequently found(58.8％vs 10.7％,P=0.001),GCB were rarely found(17.6％vs 50.0％,P=0.030).Overall survival was significantly shorter in DLBCL with high expression of MYC(P＜0.05).Cox multi-factorial analysis showed that age was an independent prognostic factor for DLBCL(P＜0.05).Conclusion Patients with high expression of MYC were frequently characterized as MCD and ABC,and PIM1,MYD88,CD79B,CD58 and PRDM1 muta-tions were common.Patients with high expression of MYC had a poorer prognosis.
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Objective·To analyze the clinicopathologic characteristics,gene mutation profile,and prognostic factors of thyroid diffuse large B-cell lymphoma(DLBCL).Methods·From November 2003 to December 2021,a total of 66 patients with thyroid DLBCL[23 cases(34.8%)with primary thyroid DLBCL,and 43 cases(65.2%)with secondary thyroid DLBCL]admitted to Ruijin Hospital,Shanghai Jiao Tong University School of Medicine were retrospectively analyzed for their clinicopathological data,survival and prognostic factors.Gene mutation profiles were evaluated by targeted sequencing(55 lymphoma-related genes)in 40 patients.Results·Compared to primary thyroid DLBCL,secondary thyroid DLBCL had advanced ratio of Ann Arbor stage Ⅲ?Ⅳ(P=0.000),elevated serum lactate dehydrogenase(LDH)(P=0.043),number of affected extranodal involvement≥2(P=0.000),non-germinal center B cell(non-GCB)(P=0.030),BCL-2/MYC double expression(DE)(P=0.026),and international prognostic index(IPI)3?5-scores(P=0.000).The proportion of patients who underwent thyroid surgery(P=0.012)was lower than that of patients with primary thyroid DLBCL.The complete remission(CR)rate in primary thyroid DLBCL patients was higher than that in secondary thyroid DLBCL patients(P=0.039).Fifty-five patients(83%)received rituximab combined with cyclophosphamide,doxorubicin,vincristine,and prednisone(R-CHOP)-based first-line regimen.The estimated 5-year progression free survival(PFS)rate of primary thyroid DLBCL patients was 95.0%,higher than the 49.7%of the secondary patients(P=0.010).Univariate analysis showed that Ann Arbor Ⅲ?Ⅳ(HR=4.411,95%CI 1.373?14.170),elevated LDH(HR=5.500,95%CI 1.519?19.911),non-GCB(HR= 5.291,95%CI 1.667?16.788),and DE(HR=6.178,95%CI 1.813?21.058)were adverse prognostic factors of PFS in patients with thyroid DLBCL.Ann Arbor Ⅲ?Ⅳ(HR=7.088,95%CI 0.827?60.717),elevated LDH(HR=6.982,95%CI 0.809?60.266),and DE(HR=18.079,95%CI 1.837?177.923)were adverse prognostic factors of overall survival(OS).Multivariate analysis showed that Ann Arbor Ⅲ?Ⅳ(HR=4.693,95%CI 1.218?18.081)and elevated LDH(HR=5.058,95%CI 1.166?21.941)were independent adverse prognostic factors of PFS in patients with thyroid DLBCL.Targeted sequencing data showed mutation frequency>20%in TET2(n=14,35%),KMT2D(n=13,32%),TP53(n=11,28%),GNA13(n=10,25%),KMT2C(n=9,22%),and TP53 were adverse prognostic factors of PFS in patients with thyroid DLBCL(P=0.000).Conclusion·Patients with primary thyroid DLBCL have better PFS and OS than those with secondary thyroid DLBCL.Ann Arbor Ⅲ?Ⅳ,elevated LDH,non-GCB,and DE(MYC and BCL2)are adverse prognostic factors in thyroid DLBCL.TET2,KMT2D,TP53,GNA13,and KMT2C are commonly highly mutated genes in thyroid DLBCL,and the prognosis of patients with TP53 mutations is poor.
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Objective To investigate the expression of zinc finger protein 382(ZNF382)in diffuse large B-cell lymphoma(DLBCL)tissue and its relationship with clinical pathological characteristics and prognosis of DLBCL patients.Methods A total of 57 DLBCL patients admitted to the Department of Hematology,Luoyang Central Hospital from January 2014 to December 2018 were selected as the research subjects.The biopsy pathological specimens and clinical data of DLBCL patients were collected;another 20 patients of reactive proliferative lymph node tissue preserved in the Department of Pathology,Luoyang Central Hospital were taken as the control group.The expression of ZNF382 in DLBCL tissue and reactive proliferative lymph node tissue was detected by En vision two-step method.The difference of ZNF382 expression was compared between DLBCL tissue and reactive proliferative lymph node tissue.The correlations of ZNF382 expression with the clinical features such as age,gender,primary tumor site,Ann Arbor stage,international prognostic index(IPI)score,Hans typing,B-symptoms,bone marrow infiltration,giant masses,Eastern Cooperative Oncology Group(ECOG)score,β2-microglobulin(β2-MG),serum lactate dehydrogenase(LDH),Ki67,and chemotherapy regimen of DLBCL patients were analyzed by univariate analysis;the survival curve was drawed by Kaplan Meier method,and the univariate and multivariate survival analysis were performed by log-rank tests and Cox proportional risk regression models.Results The expression level of ZNF382 in DLBCL tissue was significantly lower than that in reactive proliferative lymph node tissue(Z=-5.056,P＜0.01).The expression level of ZNF382 was correlated with IPI score,Ann Arbor stage,Hans typing,B-symptoms,bone marrow infiltration and giant masses of DLBCL patients(P＜0.05);the expression level of ZNF382 was not associated to gender,age,primary site,ECOG score,β2-MG,serum LDH,Ki67,and whether the chemotherapy regimen combined with rituximab or not of DLBCL patients(P＞0.05).Among the 57 DLBCL patients,the treatment was effective in 36 patients(63.20％)and ineffective in 21 patients(36.80％);the expression level of ZNF382 in tumor tissue of DLBCL patients with effective treatment was significantly higher than that of DLBCL patients with ineffective treatment(Z=-2.895,P＜0.05).The 2-year event free survival rate of DLBCL patients in the ZNF382 high expression group was significantly higher than that in the ZNF382 low expression group(x2=17.955,P＜0.001).The results of univariate survival analysis showed that female,primary lymph nodes,B-symptoms,bone marrow infiltration,giant masses,IPI score≥3,elevated β2-MG,Ki67＞70％,non-germinal center B-cell-like lymphoma,Ann Arbor stageⅢ-Ⅳ and low expression of ZNF382 were risk factors for poor prognosis in DLBCL patients(P＜0.05).The results of multivariate analysis showed that primary lymph nodes,Ann Arbor stage Ⅲ-Ⅳ and low expression of ZNF382 were independent influencing factors for poor prognosis in DLBCL patients(P＜0.05).Conclusion ZNF382 protein is low expressed in the tumor tissues of DLBCL patients,which is closely related to the occurrence,development and prognosis of DLBCL;and it can be used as an indicator for evaluating the prognosis of DLBCL.
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Objective To investigate the factors that lead to diffuse chorioretinal atrophy(DCA)in patients with high myopia(HM)and to establish a prediction model.Methods In this retrospective case-control study,a total of 169 HM patients(338 eyes)admitted to the Department of Ophthalmology,Harbin 242 Hospital from October 2018 to October 2022 were selected.All patients underwent comprehensive ophthalmic examination at the time of inclusion.The incidence of DCA was evaluated according to the International Photographic Classification and Grading System for myopic maculopa-thy,and the risk factors of DCA in HM patients were analyzed by multivariate Logistic regression.The predictive model of DCA in HM patients was established by the receiver operating characteristic curve(ROC)based on risk factors,and the calibration degree of the predictive model was tested by Hosmer-Lemeshow(H-L).Results Among the 169 patients,34 patients were divided into the DCA group,and 135 patients were divided into the non-DCA group;there were statistically significant differences in age and gender distribution between the two groups(both P＜0.05).The axial length(AL),pat-tern standard deviation(PSD),positive rate of carbonic anhydrase 2(CAII)antibody in the DCA group were higher than those in the non-DCA group,while the best corrected visual acuity(BCVA),mean defect(MD)of the visual field,spheri-cal equivalent(SE),deep retinal microvessel density(MVD)and serum 25-hydroxyvitamin D[25(OH)D]were lower than those in the non-DCA group(all P＜0.05).Older age,longer AL and positive CAII antibody were the risk factors for DCA in HM patients(all P＜0.05),while greater deep retinal MVD and higher 25(OH)D were the protective factors(both P＜0.05).ROC analysis showed that the area under the curve of the prediction model for DCA in HM patients was 0.864(95％CI:0.802-0.911,P＜0.001),and the sensitivity and specificity were 85.29％and 88.15％,respectively.According to the H-L test,the prediction model for DCA in HM patients was relatively consistent with the actual results(P＞0.05).Con-clusion The occurrence of DCA in HM patients is affected by age,AL,CAII antibody,deep retinal MVD and 25(OH)D level,and a prediction model established based on the above factors can predict the risk of DCA well.
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Purpose To investigate the predictive value of 18F-FDG PET/CT radiomic features before treatment for progression free survival(PFS)and overall survival(OS)in diffuse large B-cell lymphoma(DLBCL).Materials and Methods A total of 135 patients with pathologically proven DLBCL in Chinese PLA General Hospital from January 2016 to December 2018 and 18F-FDG PET/CT imaging prior to treatment were retrospectively collected.Patients were randomly divided into training set and test set using 8∶2,and then the training set was divided into training set and verification set using 8∶2 to construct the model.Semi-automatically delineated patients'lymphoma lesions as regions of interest and extracted the features.Univariate COX and least absolute shrinkage and selection operator regression were used to screen the features,and the non-zero radiomic features were obtained and the weight coefficients were used to calculate the Radscore value of each patient,and the predictive value of Radscore on PFS and OS was analyzed.Three models were established using traditional prognostic indicators(metabolic parameters and clinical factors),Radscore and combination.C-index,time-dependent area under the curve and decision curve were used to evaluate the model prediction efficiency.Finally,based on the optimal model,a column diagram was drawn,and the calibration curve was used to verify the efficiency of the column diagram.Results The combined model predicted PFS and OS at 3 and 5 years better than the traditional prognostic index model and Radscore model(Z=0.962 1-2.253 9,all P<0.05).Decision curve showed that the combined model achieved the greatest clinical net benefit.The calibration curve showed that the predicted values of the nomogram were in good agreement with the observed values.Conclusion Radscore is an independent prognostic factor for survival in DLBCL patients.The combined model has great application value in guiding the formulation of clinical individualized treatment plan.
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Objective:To investigate the changes of thyroid hormones and the flow velocity of superior thyroid artery in patients with Graves' disease and Hashimoto's thyrotoxicosis before and after treatment with methimazole.Methods:A case-control study was conducted to select 45 cases of Graves' disease and 45 cases of Hashimoto's thyroiditis from October 2021 to December 2022 in the Department of Endocrinology, North China University of Science and Technology Affiliated Hospital. The changes of thyroid hormone and blood flow velocity of superior thyroid artery in patients with Graves' disease and Hashimoto's thyroiditis before and after treatment with methimazole were analyzed. Measurement data satisfying normal distribution were expressed by xˉ±s, and the mean between two groups was compared by t test. Measurement data not satisfying normal distribution were expressed by M( Q1, Q3), and the median between two groups was compared by Wilcoxon rank sum test. χ 2 test was used to compare the constituent ratio of enumeration data among groups. Results:There was no significant difference in thyroid stimulating hormone (TSH) between the two groups before treatment, and there was no significant difference in TSH between the two groups after 1 month and 3 months of treatment (all P>0.05). The levels of free triiodothyronine (FT3) were (24.09±9.29) pmol/L and (17.41±9.36) pmol/L in Graves' disease group and Hashimoto's thyroiditis group respectively before treatment. FT4 were (60.23±20.82) and (43.47±21.71) pmol/L, respectively, and the peak stolie vloiy (PSV) were (69.53±5.70) and (52.65±4.64) cm/s, respectively in Graves' disease group and Hashimoto's thyroiditis group respectively before treatment. There were significant differences between the two groups ( t values wrere 3.39 and 3.74, Z=13.83, all P<0.001). The difference of FT3 between one month after treatment and before treatment was (-6.36±5.32) and (-12.64±9.08) pmol/L ( t=4.02, P<0.001) and the difference in FT3 between 3 months of treatment and before treatment was (-10.14±9.50) and (-17.80±11.17) pmol/L, respectively ( t=3.51, P<0.001) between the Graves disease group and the Hashimoto's thyroiditis group. The difference in FT4 between the Graves disease group and the Hashimoto's thyroiditis group after 1 month of treatment and before treatment was (-28.47±10.09) and (-20.57±14.48) pmol/L ( t=7.01, P<0.001), and the difference of FT4 was (-47.06±20.57) and (-30.17±20.54) pmol/L ( t=3.91, P<0.001) between the Graves disease group and the Hashimoto toxin group. The difference between one month after treatment and before treatment was (-13.10(-34.10,-2.60)) and (-10.50(-27.5,-0.20)) cm/s ( Z=2.63, P=0.009), respectively. The difference between 3 months and before treatment was (-31.40(-53.20,-12.70)) and (-19.90(-46.00,-4.70)cm/s ( Z=4.40, P<0.001)) between the Graves disease group and the Hashimoto's thyroiditis group, and the difference was statistically significant. Conclusion:Thyroid hormone levels were decreased after treatment with methimazole in patients with diffuse toxic goiter and Hashimoto toxemia, but the difference was not statistically significant. The PSV level of superior thyroid artery in patients with diffuse toxic goiter was significantly lower than that in patients with Hashimoto's thyrotoxicosis.
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ObjectiveTo observe the clinical effect of crocin tablets （CRO） combined with micropump infusion of doxorubicin in the prevention of acute cardiotoxicity in the patients with diffuse large B-cell lymphoma （DLBCL） and explore the related mechanism. MethodThe patients with DLBCL treated in the Huangshi Central Hospital from October 2022 to October 2023 were selected， and 92 patients who met the inclusion criteria were randomly assigned to a control group and an observation group at a ratio of 1∶1， with 46 patients in each group. The control group underwent conventional intravenous infusion of doxorubicin， and the observation group received CRO combined with micropump infusion of doxorubicin. The changes of abnormal ECG， myocardial injury markers， cardiac function indicators， oxidative stress， inflammatory mediators， and hemorheological indexes before and after chemotherapy were compared between the two groups. ResultThe incidence of abnormal ECG in the observation group was 23.91% （11/46）， which was lower than that （54.35%， 25/46） in the control group （χ2=8.944， P<0.01）. On day 8 after chemotherapy， the abnormal rates of creatine kinase-MB （CK-MB） and cardiac troponin I （cTnI） in the observation group were lower than those in the control group （χ2=4.423， 4.857， both P<0.05）. Compared with the control group after chemotherapy， the observation group showed lowered level of N-terminal pro-B-type natriuretic peptide， elevated left ventricular ejection fraction and levels of total antioxidant capacity and superoxide dismutase （P<0.01）， declined levels of interleukin-6 and tumor necrosis factor-α （P<0.01）， and decreased low whole blood viscosity， high whole blood viscosity， plasma viscosity， and fibrinogen （P<0.01）. ConclusionCRO combined with micropump infusion of doxorubicin can mitigate acute cardiotoxicity， reduce the incidence of abnormal ECG， protect cardiomyocytes， and improve the cardiac function by exerting the antioxidant and anti-inflammatory effects and improving blood flow.
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ObjectivesTo explore the effect of diffuse glioma with precentral-gyrus invasion on fMRI activation maps by grasping T-fMRI. MethodsA total of 56 diffuse glioma patients were divided into precentral-gyrus invasion （PGI： n=21） and precentral-gyrus non-invasion （PGNI： n=35） groups. Three statistical thresholds （P value： 10-4， P1； 10-6， P2； 10-8， P3） were set to obtain the activation maps accordingly （V1， V2 and V3）. The interhemispheric and bilateral precentral gyrus activation volumes ratios （IAVR and PAVR） were calculated， respectively. The activation volumes ［△V1=V1-V2； △V2=V2-V3； △Vn （ipsilateral）/△Vn’ （contralateral）， n=1， 2］ within two statistical thresholds and the corresponding interhemispheric ratio was further compared. In addition， the associations of tumor characteristics with IAVR and PAVR were analyzed. ResultsCompared with PGNI， PGI showed significantly decreased IAVR at p1， and the same trends of PAVR in PGI at P1 and P2 （P＜0.05）. However， neither IAVR nor PAVR showed significant differences at P3. PGI showed significantly lower ratios of △V1/△V1’ than PGNI （P=0.02）， except for △V2/△V2’. Additionally， within PGI， PAVR was negatively correlated with tumor volume （P=0.043）， and the distance from the tumor to the hand-knob was positively correlated with the IAVR and PAVR （P＜0.05）. ConclusionDiffuse glioma invading eloquent areas tended to affect interhemispheric asymmetry of activation at relatively lower statistical thresholds than diffuse glioma without invasion， rather than stricter statistical thresholds. Multiple ranges of statistical thresholds were recommended to analyze T-fMRI.