Uterine Artery Embolization with Small-Sized Particles for the Treatment of Symptomatic Adenomyosis: A 42-Month Clinical Follow-Up.

PURPOSE: To assess the long-term outcome of performing uterine artery embolization (UAE) using small particles in women with symptomatic adenomyosis (AD). METHODS: Twenty-seven consecutive women (median age 42 years, range 29-53 years) with AD, in eight cases AD combined with fibroids, who underwent UAE between February 2015 and January 2019, were retrospectively analyzed. The embolization was performed using small-sized polyvinyl alcohol particles (100 µm and 300 µm). The patients completed the Uterine Fibroid Symptom and Quality of Life questionnaire at baseline and at a 42-month follow-up (range 24-71). The junction zone (JZ) thickness and uterine volume were also calculated at baseline and at a three-month follow-up. RESULTS: The total symptom severity score (SSS) decreased from a median of 59 (range 34-78) at baseline to a median of 9 (range 3-47) at the end of this study; the health-related quality of life score (HRQOL) increased from a median of 38 (range 23-49) at baseline to a median of 84 (range 46-97) at 42 months. Twenty of the 27 patients were asymptomatic. The clinical response of the remaining seven women was little improvement in their symptoms, and one of the seven women underwent a hysterectomy at 35 months. Twenty-six of the 27 (96%) patients had a preserved uterus at the 42-month follow-up. There was no difference after UAE in SSS, HRQOL, junction zone (JZ) thickness, and uterus volume between patients with pure AD and those with AD combined with fibroids (p = 0.729, 0.710, 0.973, and > 0.99). There was no difference in the JZ thickness and uterus volume at baseline between the asymptomatic women and the women with an insufficient response (p = 0.854 and 0.253), and there were no major complications afterwards. CONCLUSION: From the long-term follow-ups, it could be seen that UAE using small particles is safe and effective in treating AD, especially in preserving the uterus. There is no relationship between the clinical outcomes and the initial presence of AD, with or without fibroids, and the JZ thickness at baseline does not seem to be a predictor for the long-term outcome of UAE.

Clinical benefit of COX-2 inhibitors in the adjuvant chemotherapy of advanced non-small cell lung cancer: A systematic review and meta-analysis.

BACKGROUND: Lung cancer is a major cause of death among patients, and non-small cell lung cancer (NSCLC) accounts for more than 80% of all lung cancers in many countries. AIM: To evaluate the clinical benefit (CB) of COX-2 inhibitors in patients with advanced NSCLC using systematic review. METHODS: We searched the six electronic databases up until December 9, 2019 for studies that examined the efficacy and safety of the addition of COX-2 inhibitors to chemotherapy for NSCLC. Overall survival (OS), progression free survival (PFS), 1-year survival rate (SR), overall response rate (ORR), CB, complete response (CR), partial response (PR), stable disease (SD), and toxicities were measured with more than one outcome as their endpoints. Fixed and random effects models were used to calculate risk estimates in a meta-analysis. Potential publication bias was calculated using Egger's linear regression test. Data analysis was performed using R software. RESULTS: The COX-2 inhibitors combined with chemotherapy were not found to be more effective than chemotherapy alone in OS, progression free survival, 1-year SR, CB, CR, and SD. However, there was a difference in overall response rate for patients with advanced NSCLC. In a subgroup analysis, significantly increased ORR results were found for celecoxib, rofecoxib, first-line treatment, and PR. For adverse events, the increase in COX-2 inhibitor was positively correlated with the increase in grade 3 and 4 toxicity of leukopenia, thrombocytopenia, and cardiovascular events. CONCLUSION: COX-2 inhibitor combined with chemotherapy increased the total effective rate of advanced NSCLC with the possible increased risk of blood toxicity and cardiovascular events and had no effect on survival index.

Combined intravenous and intra-articular tranexamic acid administration in total knee arthroplasty for preventing blood loss and hyperfibrinolysis: A randomized controlled trial.

BACKGROUND: Total knee arthroplasty (TKA) is a surgical procedure to replace the weight-bearing surfaces of the knee joint to relieve pain and disability. However, blood loss and fibrinolytic activity, accounting for a poor prognosis following TKA operation, were relieved by fibrinolytic inhibitor tranexamic acid (TXA). For a better application of TXA function, we explored the effect of intravenous injection (IV) of TXA combined with intra-articular injection (IA) of TXA in patients after TKA. METHODS: Patients admitted from Weifang People's Hospital from January 2015 to December 2016 who received TKA were injected with 20 mg/kg TXA by IV before TKA (n = 50), 3.0 g TXA by IA after TKA (n = 50), or combination of 20 mg/kg TXA by IV before TKA and 3.0 g TXA by IA after TKA (n = 50). Knee function was assessed using HSS, KSS, NASS, and ROM. In addition, the total blood loss (TBL), hidden blood loss (HBL), maximum hemoglobin (Hb) drop, fibrinolytic activity, as well as incidence of thromboembolism were measured. The patients were followed up for 6 months. The deadline for follow-up was June 2017 and the incidence of thromboembolism events within 6 months after operation was counted. RESULTS: HSS, KSS, NASS scores, and ROM were elevated after patients receiving TKA. Patients received IV plus IA TXA has decreased TBL, HBL, and maximum Hb drop than those received IV TXA-alone and IA TXA-alone, with reductions in FDP and D-dimer, indicating that IV plus IA TXA injection is superior to prevent blood loss and hyperfibrinolysis during TKA. Age, sex, type of femoral prosthesis, and the injection method of TXA were risk factors for HBL of patients after receiving TKA. CONCLUSIONS: The aforementioned results demonstrate that TKA is an effective surgery, and IV plus IA TXA injection functions more effectively in reducing blood loss and fibrinolytic activity in patients, which is a clinical factor of occult hemorrhage.

Rivaroxaban improves hidden blood loss, blood transfusion rate and reduces swelling of the knee joint in knee osteoarthritis patients after total knee replacement.

Osteoarthritis (OA) is the third most common diagnosis made by general practitioners in older patients. The purpose of the current study is to investigate effects rivaroxaban had on both hidden blood loss and blood transfusion rate (BTR) in patients with knee OA (KOA) after going through a total knee replacement (TKR).Between the time periods of December 2011 up until January 2015, a total of 235 patients underwent TKR and were selected to be assigned to either the rivaroxaban or nonanticoagulant groups. Coagulation function indexes before surgery and following administration of rivaroxaban, total blood loss, hidden blood loss, dominant blood loss, blood transfusion volume, hemoglobin reduction, degree of postoperative pain (visual analogue scale), the degree of knee swelling, and range of motion following surgery were all recorded. Hospital for special surgery (HSS) scores offered an objective evaluation for the knee joint functions before surgery at the intervals of 2 weeks and after surgery at intervals of 3 months, 6 months, 12 months, and 24 months.Patients in the rivaroxaban group had shown a higher hidden blood loss, as well as a higher BTR, compared to those involved in the nonanticoagulant group. BTR was found to have been 49.59% in the rivaroxaban group, and 35.09% for the nonanticoagulant group. Patients in the rivaroxaban group had lower degrees of knee swelling than those involved in the nonanticoagulant group. There was no deep vein thrombosis (DVT) detected in the rivaroxaban group, whereas 5 DVT cases were detected in the nonanticoagulant group. In the rivaroxaban group, the HSS scores of the knee joint functions were remarkably higher at the 2-week mark in succession to the surgery than those involved with the nonanticoagulant group.This overall data demonstrated that KOA patients after TKR had presented with a higher hidden blood loss, BRT, and lower swelling degrees of the knee joint after being treated by the rivaroxaban.

[Pattern recognition of decorative papers with different visual characteristics using visible spectroscopy coupled with principal component analysis (PCA)].

As one of the most important decorative materials for the modern household products, decorative papers impregnated with melamine not only have better decorative performance, but also could greatly improve the surface properties of materials. However, the appearance quality (such as color-difference evaluation and control) of decorative papers, as an important index for the surface quality of decorative paper, has been a puzzle for manufacturers and consumers. Nowadays, human eye is used to discriminate whether there exist color difference in the factory, which is not only of low efficiency but also prone to bring subjective error. Thus, it is of great significance to find an effective method in order to realize the fast recognition and classification of the decorative papers. In the present study, the visible spectroscopy coupled with principal component analysis (PCA) was used for the pattern recognition of decorative papers with different visual characteristics to investigate the feasibility of visible spectroscopy to rapidly recognize the types of decorative papers. The results showed that the correlation between visible spectroscopy and visual characteristics (L*, a* and b*) was significant, and the correlation coefficients wereup to 0.85 and some was even more than 0. 99, which might suggest that the visible spectroscopy reflected some information about visual characteristics on the surface of decorative papers. When using the visible spectroscopy coupled with PCA to recognize the types of decorative papers, the accuracy reached 94%-100%, which might suggest that the visible spectroscopy was a very potential new method for the rapid, objective and accurate recognition of decorative papers with different visual characteristics.

[Research advances on microchimerism].

The microchimerism is a status of the microcell or DNA of an individual in another one with genetic differences. Taking an overall view about the discovery and research of the microchimerism, it was found that although the study of the microchimerism emphasizes the formation, origin, distribution, type, relationship to disease and several other aspects, the objects of the study are always the microchimerism that obtained naturally. As it is known to all, the microchimerism can also be produced in some clinical treatment, such as in the transplant and transfusion, but compared with the microchimerism gained naturally, obviously, the study for the iatrogenic microchimerism formed in the treatment is not elaborate enough. The curative effect of micro transplantation, a new technique for leukemia treatment, is obvious, but its mechanism is unclear, whether that is related to microchimerism still needs further research. This review summarizes the study history and perspective of the microchimerism so as to provide some ideas for studying the action mechanism of microchimerism in micro transplantation.

[Establishment and identification of a H-2 completely mismatched microtransplantation model of leukemia mouse].

This study was purposed to establish and identify a H-2 completely mismatched microtransplantation model of leukemia mouse. The recipients were female BALB/c mice, while donors were male C57BL/6J mice. Recipients were inoculated intravenously with 1×10(6) of WEHI-3 cells, a cell line of myelomonocytic leukemia. Donors received 100 µg/kg G-CSF mobilization through hypodermic injection, every 12 hours, and it last 5 days. Chemotherapy regimens was MA (mitoxantrone+cytarabine), and it last 4 days. Recipients were given chemotherapy conditioning without GVHD prophylaxis after inoculation of leukemic cells for 2 days, and within 8 hours after last chemotherapy received donor mobilized spleen mononuclear cells (sMNC). The number of sMNC was (3, 6, 12) ×10(7), respectively. The early death rate, recovery level of WBC in peripheral blood and leukemia load were compared between chemotherapy and microtransplantation groups. The donor chimerism was detected by RT-PCR. From the clinical manifestation and pathological features, the GVHD in recipients was evaluated. The results showed that the early mortality in chemotherapy group was 25%, meanwhile those in the (3, 6, 12)×10(7) groups were 16.67%, 8.33%, 8.33%, respectively. The(3, 6)×10(7) groups has a stronger hematopoietic recovery capability than that in chemotherapy and 12×10(7) groups (P < 0.05) . There were more leukemic cells in chemotherapy mice than that in microtransplantation mice (P < 0.01) , and (12, 6)×10(7) groups had lower leukemia load than that in 3×10(7) group (P < 0.05) . No signs of GVHD were observed in microtransplantation mice. The donor microchimerism could be discovered at eraly 2 weeks after donor cell transfusion. It is concluded that a H-2 completely mismatched microtransplantation model of leukemia mouse has been successfully established, and it will provide a experimental base for studying microtransplantation in clinic.

HLA-mismatched stem-cell microtransplantation as postremission therapy for acute myeloid leukemia: long-term follow-up.

PURPOSE: Despite best current therapies, approximately half of patients with acute myeloid leukemia in first complete remission (AML-CR1) with no HLA-identical donors experience relapse. Whether HLA-mismatched stem-cell microtransplantation as a novel postremission therapy in these patients will improve survival and avoid graft-versus-host disease (GVHD) is still unknown. PATIENTS AND METHODS: One hundred one patients with AML-CR1 (9 to 65 years old) from four treatment centers received programmed infusions of G-CSF-mobilized HLA-mismatched donor peripheral-blood stem cells after each of three cycles of high-dose cytarabine conditioning without GVHD prophylaxis. Donor chimerism and microchimerism and WT1+CD8+ T cells were analyzed. RESULTS: The 6-year leukemia-free survival (LFS) and overall survival (OS) rates were 84.4% and 89.5%, respectively, in the low-risk group, which were similar to the rates in the intermediate-risk group (59.2% and 65.2%, respectively; P=.272 and P=.308). The 6-year LFS and OS were 76.4% and 82.1%, respectively, in patients who received a high dose of donor CD3+ T cells (≥1.1×10(8)/kg) in each infusion, which were significantly higher than the LFS and OS in patients who received a lower dose (<1.1×10(8)/kg) of donor CD3+ T cells (49.5% and 55.3%, respectively; P=.091 and P=.041). No GVHD was observed in any of the patients. Donor microchimerism (2 to 1,020 days) was detected in 20 of the 23 female patients who were available for Y chromosome analysis. A significant increase in WT1+CD8+ T cells (from 0.2% to 4.56%) was observed in 33 of 39 patients with positive HLA-A*02:01 antigen by a pentamer analysis. CONCLUSION: Microtransplantation as a postremission therapy may improve outcomes and avoid GVHD in patients with AML-CR1.

[Effect of G-CSF on murine thymocyte emigration and cell cycle alteration after a sublethal dose of irradiation].

This study was aimed to investigate the effect of recombinant human granulocyte colony-stimulating factor(G-CSF) on murine thymocyte emigration and cell cycle alteration after a sublethal dose of gamma-irradiation. Female BALB/c mice were given 6.0 Gy γ-ray total body irradiation and then randomly divided into G-CSF and control groups. Mice in the G-CSF group were injected recombinant human G-CSF 100 µg/(kg·d) subcutaneously once daily for 14 consecutive days and mice in the control group were given the same volume of phosphate buffered solution. Thymocyte cycle alteration and the proportion of apoptosis cells were detected by flow cytometry within 72 hours after irradiation. Real-time PCR was used for detection and quantitation of murine T cell receptor rearrangement excision circles (sjTREC) of the thymic cells at 30 and 60 day after the irradiation. The results showed that at 6 hour after irradiation G-CSF could significantly increase the thymic cells in G(0)/G(1) phase, G-CSF vs control: (82.0 ± 5.0)% vs (75.9 ± 2.8)% (p < 0.05), and decrease the thymic cells in S phase, G-CSF vs control: (10.2 ± 4.8)% vs (15.7 ± 2.3)% (p < 0.05), but G-CSF seemed have no evident effects on the percentage of thymic cells in G(2)/M phase. G-CSF could also protect thymocytes from apoptosis at 6 hour and 12 hour after irradiation the percentages of apoptosis cells in G-CSF group were (11.5 ± 2.4)% and (15.5 ± 3.3)%, respectively, which were significantly lower than that of the control group (16.5 ± 2.2)% and (22.6 ± 0.7)%, respectively (p < 0.05). The sjTREC copy amount was conspicuously higher in G-CSF group than that in the control at 30 day after irradiation (p < 0.01), but the preponderance disappeared 60 days later. It is concluded that G-CSF has a positive effect on the thymic cell cycle alteration to protect thymocytes from apoptosis and enhance the recent thymocyte emigration, which may contribute to the central immune reconstitution after irradiation.

[Expression of NOV and BNIP3 gene in mouse myelomonocytic leukemia and its significance].

This study was aimed to investigate the expression level of NOV and BNIP3 mRNA in mice myelomonocytic leukemia (AML-M(4)) and its significance. The mice were inoculated intravenously with myelomonocytic leukemia cells of WEHI-3, and divided randomly into chemotherapy group and control (untreated) group. Bone marrow samples were then collected from both groups at different times. The NOV and BNIP3 mRNA expression were detected by TaqMan quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), and the relationship between these expression levels and clinical significance in leukemia incidence and progression were analyzed with ß-actin as the housekeeping gene. The results showed that the mean values of NOV and BNIP3 increased gradually from 2 weeks after inoculation and achieved highest level at death in control group. Expression level of NOV increased from 1.85E-05 before inoculation to 3.57E-02 at death (p < 0.05), and BNIP3 from 3.44E-03 to 3.48E-02. While 2 gene expression in the chemotherapy group decreased quickly to 2.51E-05 and 1.58E-03 (p < 0.05) respectively after chemotherapy, which were close to the level before inoculation (p > 0.05). The 2 gene expressions again rose at relapse, and difference of expression level between 2 group at death were no statistically significant (p > 0.05). It is concluded that the expression of NOV and BNIP3 in leukemia AML-M(4) is significantly higher than that in normal controls, of which high level expression is an important factor in the development of leukemia. Close relation between the therapeutic effect and expression level of these two genes suggests the great value in prognostic evaluation and MRD detection.

[Relationship between WT1-specific T-cell subsets and graft-versus-host disease after nonmyeloablative allogeneic transplantation].

OBJECTIVE: To explore the relationship between WT1-induced T-cell subsets and graft-versus-host disease (GVHD) after nonmyeloablative allogeneic hematopoietic stem cell transplantation (NST). METHODS: Peripheral blood mononucleated cells (PBMCs) from 19 patients who expressed WT1 and developed GVHD after NST were simulated by WT1126-134 peptide in vitro, and proportions of WT1-induced-T-cell subsets (Tc1, Tc2, Th1, Th2 cells) before and after transplant were detected by intracellular cytokine staining (ICCS) assay. WT1-specific CD8(+) CTLs of 14 patients with HLA-A*0201 were detected by HLA-A*0201/WT1 pentamer. RESULTS: (1) 17 of 19 patients developed GVHD, among whom proportions of Tc1 and Th1 cells, achieved peak value in 16 patients at occurrence of GVHD (P = 0.039); (2) The peak proportions of Tc1 and Th1 cells in patients with aGVHD above grade II were higher than those with grade I, but being no statistical difference (P = 0.900 and P = 0.140, respectively); (3) The peak proportion of Th1 cells (P = 0.004), but not Tc1 cells (P = 0.060) in patients with extensive cGVHD was significantly higher than that in patients with limited one; (4) Proportions of Tc1, Th1 and WT1(+)CD8(+)CTL in patients without GVHD were similar to those in patients with Grade I aGVHD, but lower than those in aGVHD above grade II. CONCLUSION: GVHD promotes the generation of WT1-induced GVL effect, and the intensity of the latter maybe correlated with the intensity of GVHD, especially cGVHD. Th1 cells play a more important role in the enhancement of WT1-induced GVL effect in extensive cGVHD patient than in limited cGVHD patients.

Infusion of HLA-mismatched peripheral blood stem cells improves the outcome of chemotherapy for acute myeloid leukemia in elderly patients.

Treatment outcome of acute myeloid leukemia (AML) in elderly patients remains unsatisfactory. It has been shown that the infusion of granulocyte colony-stimulating factor-mobilized donor peripheral blood stem cells (G-PBSCs) can enhance graft-versus-leukemia effects and speed hematopoietic recovery. Fifty-eight AML patients aged 60-88 years were randomly assigned to receive induction chemotherapy with cytarabine and mitoxantrone (control group; n = 28) or it plus human leukocyte antigen-mismatched G-PBSCs (G-PBSC group; n = 30). Patients who achieved complete remission received another 2 cycles of postremission therapy with intermediate-dose cytarabine or it plus G-PBSCs. The complete remission rate was significantly higher in the G-PBSC group than in the control group (80.0% vs 42.8%; P = .006). The median recovery times of neutrophils and platelets were 11 days and 14.5 days, respectively, in the G-PBSC group and 16 days and 20 days, respectively, in the control group after chemotherapy. The 2-year probability of disease-free survival was significantly higher in the G-PBSC group than in the control group (38.9% vs 10.0%; P = .01). No graft-versus-host disease was observed in any patient. Persistent donor microchimerism was successfully detected in all of the 4 female patients. These results indicate that G-PBSCs in combination with conventional chemotherapy may provide a promising treatment method for AML in elderly patients.

[Application of HLA-A*0201/WT1 pentamer combined with intracellular IFNgamma+ staining in detecting circulating WT1 specific T cells in leukemia].

This study was purposed to investigate the value of combination of pentamer and intracellular IFNgamma staining in the qualitative and quantitative detection of circulating antigen-specific T cells. WT1 expressions in 14 HLA-A*0201+ patients and their matched donors were detected by RT-PCR, and circulating WT1 specific T cells were assayed by HLA-A*0201/WT1 pentamer combined with intracellular IFNgamma+ staining. The results showed that the low level of WT1 expression was found only in 2 cases out of 14 donors, but different levels of WT1 expression could be observed in all leukemic patients. The WT1+CD8+ CTL and WT1+IFNgamma+ cells did not detected in all 14 donors, but WT1+CD8+ CTL cells in 2 patients and WT1+IFNgamma+ cells in 3 patients could be detected before transplantation respectively, there was no significant difference between them, while the WT1+CD8+ CTL cells and WT1+IFNgamma+ cells both could be detected in all 14 patients after transplantation, the positive detection rate after transplantation was obviously higher than that before transplantation. The WT1+CD8+ and WT1+ IFNgamma+ cells could be detected within 30 days after transplantation, but the positive detection rate of WT1+IFNgamma+ cells was higher than that of WT1+CD8+ CTL cells (p=0.014). The median peak value of WT1+CD8+ CTL cells was 0.18% in 14 patients, and the median peak value of WT1+IFNgamma+ cells was 0.83% in 14 patients, the later was significantly higher than former. The median peak time of WT1+CD8+ CTL cells was 75 days after transplantation, while the WT1+IFNgamma+ cells was 105 days after transplantation, there was no significant difference between them. It is concluded that pentamer and intracellular IFNgamma staining may effectively detect circulating WT1 specific T cells in leukemic patients, and the combination of these two methods profit to the exact qualitation and quantitation of circulating antigen-specific T cells.