ObjectiveTo review the osteoclasts (OC) function beyond bone resorption. MethodsThe related literature on OC function beyond bone resorption was reviewed, analyzed, and summarized. ResultsOC control the bone formation through releasing of matrix-derived growth factors, bidirectional cell-to-cell signals, and secreting OC-coupling factors, and play an important role in the niche formation, hematopoietic stem cells mobilization, and maintenance of its quantity and function;besides, OCs also regulate angiogenesis. ConclusionThese discoveries greatly enrich the current knowledge of OC function and open up an all-new research domain. However, the exact regulatory mechanism of OC affecting the hematopoiesis is still lack in-depth understood. Additionally, it remains to be elucidated how OC-coupling factors act on osteoblast lineage differentiation and how OC-induced angiogenesis participates in physiological and pathological processes. Unclosing the underlying mechanisms will facilitate providing scientific therapeutic strategies for treatment of many OC-related diseases.
ObjectiveTo observe the clinical features of cytomegalovirus (CMV) retinitis (CMVR)-related uveitis after hematopoietic stem cell transplantation (HSCT).MethodsA retrospective clinical study. From October 2015 to May 2020, 14 cases of 21 eyes of CMVR patients with CMVR after HSCT confirmed by the ophthalmological examination of The First Affiliated Hospital of Soochow University were included in the study. Among them, there were 5 males with 8 eyes and 9 females with 13 eyes. The average age was 35.12±12.24 years old. All the affected eyes were examined by slit lamp microscope combined with front lens and fundus color photography. At the same time, fluorescein fundus angiography (FFA) was performed to examine 10 eyes of 5 cases; 3 cases of 3 eyes were examined for inflammatory cytokines in aqueous humor. All eyes received intravitreal injection of ganciclovir; patients with a history of systemic CMV infection received intravenous infusion of ganciclovir/foscarnet. The retinal lesions in the eye were completely resolved or the aqueous CMV-DNA was negative as a cure for CMVR. The uveitis symptoms, signs, FFA manifestations and the test results of inflammatory factors in aqueous humor before and after the CMVR cure was observed. The follow-up time after CMVR was cured was 3-42 months, and the average follow-up time was 14.28±13.12 months.ResultsAll eyes with CMVR were diagnosed with retrocorneal dust and/or stellate keratic precipitates (KP), anterior chamber flare and cells, and varying degrees of vitreous flocculent opacity; the retina was typical of a mixture of hemorrhage and yellow-white necrosis like "scrambled eggs with tomatoes". After CMVR was cured, there were 16 eyes (71.4%, 10/14) in 10 cases with KP, anterior chamber flare, cell and vitreous opacity. FFA examination revealed that the majority of retinal leakage during the active period of CMVR was necrotic foci and surrounding tissues; after CMVR was cured, the majority of retinal leakage was the retina and blood vessels in the non-necrotic area. The test results of inflammatory factors in aqueous humor showed that interleukin (IL)-6, IL-8, and vascular endothelial cell adhesion molecules were significantly increased in the active phase of CMVR; after 3 months of CMVR cured, inflammatory factors did not increase significantly.ConclusionCMVR-associated uveitis after HSCT show as chronic panuveitis, with no obvious eye congestion, KP, anterior chamber flare, cell and vitreous opacity, and retinal vessel leakage which could exist for a long time (＞3 months).
ObjectivesTo systematically review the efficacy and safety of palifermin on oral mucositis (OM) and acute graft versus host disease (aGVHD) for hematological malignancy patients undergoing hematopoietic stem cell transplantation (HSCT).MethodsPubMed, The Cochrane Library, Web of Science, EMbase, Clinicaltrials.gov, CNKI and WanFang Data databases were electronically searched to collect randomized controlled trials (RCTs) of the efficacy of palifermin on OM and aGVHD for hematological malignancy patients undergoing HSCT from inception to September 30th, 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 7 RCTs involving 904 patients were included. The results of meta-analysis showed that: palifermin could reduce the duration of OM grade 2 to 4 (MD=−4.21, 95%CI −7.83 to −0.58, P=0.02), OM grade 3 to 4 (MD=−2.54, 95%CI −4.61 to −0.46, P=0.02) significantly for hematological malignancy patients undergoing HSCT. However, no significant difference was found in the prevalence of aGVHD grade 2 to 4 (RR=1.29, 95%CI 0.95 to 1.75, P=0.11), aGVHD grade 3 to 4 (RR=0.99, 95%CI 0.55 to 1.77, P=0.97), OM grade 2 to 4 (RR=0.86, 95%CI 0.72 to 1.03, P=0.11) and OM grade 3 to 4 (RR=0.82, 95%CI 0.65 to 1.03, P=0.08) between palifermin group and placebo group. The prevalence of paresthesia (RR=4.24, 95%CI 1.24 to 14.56, P=0.02) and erythema (RR=1.49, 95%CI 1.06 to 2.09, P=0.02) were significantly higher in palifermin group.ConclusionsThe durations of OM grade 2 to 4, 3 to 4 are significantly reduce in patients receiving palifermin compared with those receiving a placebo, however, no statistically significant difference are found in the incidence of aGVHD grade 2 to 4, 3 to 4, OM grade 2 to 4, 3 to 4. Parethesia and erythema are more prevalent among patients using palifermin. Therefore, advantages and disadvantages of palifermin should be considered when used in clinical.
Abstract:Objective To investigate the pattern and affecting factors of hematopoietic stem cell mobilization after off-pump coronary artery bypass grafting（OPCAB）. Methods Fifty-five patients of coronary artery disease without acute myocardial infarction （AMI） who underwent selective OPCAB were chosen for this study. Four ml blood sample was taken at 30 min before operation, and 6, 12, 24, 48, 72 and 120 h after operation. The hematopoietic stem cell count was made by flow cytometer with CD34 and CD45 double antibody. The serum myoeardium enzyme and troponin T （cTnT） were measured at the same time. Results The hematopoietic stem cell count was 0. 13%±0. 12% of all nucleated cells in the peripheral blood circulation before operation. It increased significantly witha peak value at 24 halter OPCAB（0.34%±0.20%）. It turned back to pre-operativelevelat 120h after operation. Smoking, hyperlipemia and diabetes mellitus had no effect on hematopoietic stem cell mobilization. But hypertension could reduce its mobilization significantly. The hematopoietic stem cell count was positively correlated with creatine kinase （CK）, creatine kinase-MB isoenzyme （CK-MB）, lactate de hydrogenase （LDH） and cTnT （r=0. 692,P=0. 000; r=0. 558, P=0. 000; r=0. 447, P=0. 000 and r=0. 401, P=0. 004, respectively） 24h after OPCAB. Conclusion Hematopoietic stem cells mobilize rapidly and temporarily after OPCAB. Myocardial injury and CABG risk factors take part in hematopoietic stem cell mobilization.
【Abstract】Objective To give a summary of the current researches on hematopoietic stem cell niche. Methods Through extensive reviewing the related domestic and abroad literatures, the present summary reviews the components of hematopoietic stem cell niche, related cell factors and related cell signaling pathway participating in regulation of hematopoietic stem cell. Results The activities of hematopoietic stem cells are regulated by the niche (microenvironment), which is composed of hematopoietic stem cell and its surrounding cells. The regulation cannot be completed through one signaling pathway. Also, the self-renewal and differentiation of hematopoietic stem cell cannot be completed only through osteoblastic cells. Conclusion The niche regulates hematopoietic stem cells by different ways. With study in-depth, we will comprehensively understand the nature of stem cells and the study will provide a broader space to stem cell-based therapy.
Cytomegalovirus (CMV) retinitis (CMVR) is a common opportunistic infection of the eye after allogeneic hematopoietic stem cell transplantation in patients with hematological diseases. It often occurs within 3 months after the operation, with CMV activation and high blood CMV peaks. It often occurs on patients with long-term CMV viremia, human leukocyte antigen incompatible transplantation, unrelated donor transplantation, haploid transplantation, childhood hematopoietic stem cell transplantation, delayed lymphocyte engraftment, acute and chronic graft-versus-host disease after surgery. The visual prognosis of patients is related to the area of CMVR lesions on the retina, the number of quadrants involved, whether the macula is involved, and the CMV load of the vitreous body is involved, and it is not related to whether the Epstein-Barr virus infection is combined with blood and vitreous humor. The incidence of CMVR is increasing year by year. It is helpful that paying attention to systemic risk factors and epidemiology can provide more effective guidance for ophthalmologists during diagnosis and treatment, help patients improve the prognosis of vision, and reduce or even avoid the occurrence of blindness caused by CMVR.
ObjectiveTo observe aqueous cytomegalovirus (CMV) DNA load in patients with cytomegalovirus retinitis (CMVR) after allogeneic hematopoietic stem cell transplantation (Allo-HSCT), and to explore influencing factors for transient elevation of CMV-DNA load during the treatment. MethodsA retrospective study. From January 2016 to July 2020, 28 eyes of 19 patients with CMVR after Allo-HSCT diagnosed in the Department of Ophthalmology of Peking University People's Hospital were included in the study. Among them, there were 8 males with 12 eyes, 11 females with 16 eyes; the mean age was 28 years; 10 patients were unilateral and 9 patients were bilateral. During the course of treatment and follow-up, the blood CMV-DNA remained negative. All patients were treated with intravitreal injection of 60 mg/ml ganciclovir 0.05 ml (containing ganciclovir 3 mg), twice a week for two weeks in induction phase and weekly injection in maintenance phase. Aqueous humor sample was collected during injection of ganciclovir (IVG) and CMV-DNA load was determined by real-time quantitative polymerase chain reaction. Intravitreal treatment was terminated if aqueous CMV-DNA load turned negative after the fourth or later intravitreal injection. The patients were followed up every 2 weeks for at least 6 months. Serum CMV-DNA was negative in all patients during treatment and follow-up. All the eyes were divided into continuous decline group and non-continuous decline group depending on whether there was transient elevation of aqueous CMV-DNA load, and data between two groups were compared. Pearson linear regression analysis was used to analyze the correlation between aqueous CMV-DNA load and injection times or treatment duration. ResultsAt the end of treatment, the median number of IVG in the affected eye was 7 (4, 9). The results of correlation analysis showed that the aqueous humor CMV-DNA load of the affected eye was related to the number of treatments [R2=0.385, P＜0.000 1, B=－0.237 log10 copies/(ml · time)], and the duration of treatment [R2=0.394, P <0.000 1, B=－0.301 log10 copies/(ml · week)] were negatively correlated. Among the 28 eyes, 13 eyes (46.4%, 13/28) in the continuous decline group and 15 eyes (53.6%, 15/28) in the non-sustained decline group. Baseline visual acuity (t=－1.223), intraocular pressure (t=1.538), aqueous humor CMV-DNA load (t=－0.109), retinitis lesion area (Z=－0.308) in the continuous decline group and the non-continuous decline group), the number of quadrants involved (Z=－0.024) and whether the macula was involved (Z=－1.826), combined with anterior segment inflammation (Z =－0.499), combined with high intraocular pressure (Z=－1.342), terminal visual acuity (t =－0.845), intraocular pressure (t=－0.068), total IVG times (Z=0.907), age (Z=－0.832), gender composition (Z=－1.074), etc. The difference was not statistically significant (P＞0.05). ConclusionThe CMV-DNA load in aqueous humor decreases by about 50% every week during the treatment of CMVR eyes after Allo-HSCT; the transient increase in the CMV-DNA load in the aqueous humor during treatment does not affect the treatment process and clinical prognosis.
Objective To review the research progress of osteoblasts in the hematopoietic microenvironment of bone marrow and regulatory pathways and mechanisms. Methods The advances in the osteoblasts as crucial components for hematopoietic microenvironment in bone marrow, regulation to osteoblasts and hematopoietic stem cells(HSCs), and correlative singal pathways and mechanisms were introduced based on the recent related literature. Results Evidence indicates that osteoblasts are crucial components of the hematopoietic microenvironments in adult bone marrow. The osteoblasts maintainthe quiescence of primitive HSCs by the signaling receptorsligands, secreted cell factors and celladhesion molecules and by regulating other cells in the niche. The quiescent primitive HSCs persist stem cell characteristic which has unlimited selfrenewal and multipotent differentiation potential. Conclusion The further understanding of the relationship between osteoblasts and hematopoietic microenvironment should lead to development of new strategies directed toward clinical therapeutics of HSCs transplantation.