ObjectiveTo observe the morphological and functional changes of retinal degeneration in mice with CLN7 neuronal ceroid-lipofuscinosis, and the therapeutic effects of glial cell derived neurotrophic factor (GDNF) and/or ciliary neurotrophic factor (CNTF) based on neural stem cells (NSC) on mouse photoreceptor cells. MethodsA total of 100 CLN7 mice aged 14 days were randomly divided into the experimental group and the control group, with 80 and 20 mice respectively. Twenty C57BL/6J mice aged 14 days were assigned as wild-type group (WT group). Mice in control group and WT group did not receive any interventions. At 2, 4, and 6 months of age, immunohistochemical staining was conducted to examine alterations in the distribution and quantity of cones, rod-bipolar cells, and cone-bipolar cells within the retinal of mice while electroretinography (ERG) examination was utilized to record scotopic a and b-waves and photopic b-wave amplitudes. At 14 days of age, the mice in the experimental group were intravitreally injected with 2 μl of CNTF-NSC, GDNF-NSC, and a 1:1 cell mixture of CNTF-NSC and GDNF-NSC (GDNF/CNTF-NSC). Those mice were then subdivided into the CNTF-NSC group, the GDNF-NSC group, and the GDNF/CNTF-NSC group accordingly. The contralateral eyes of the mice were injected with 2 μl of control NSC without neurotrophic factor (NTF) as their own control group. At 2 and 4 months of age, the rows of photoreceptor cells in mice was observed by immunohistochemical staining while ERG was performed to record amplitudes. At 4 months of age, the differentiation of grafted NSC and the expression of NTF were observed. Statistical comparisons between the groups were performed using a two-way ANOVA. ResultsCompared with WT group, the density of cones in the peripheral region of the control group at 2, 4 and 6 months of age (F=285.10), rod-bipolar cell density in central and peripheral retina (F=823.20, 346.20), cone-bipolar cell density (F=356.30, 210.60) and the scotopic amplitude of a and b waves (F=1 911.00, 387.10) in central and peripheral retina were significantly decreased, with statistical significance (P＜0.05). At the age of 4 and 6 months, the density of retinal cone cells (F=127.30) and b-wave photopic amplitude (F=51.13) in the control group were significantly decreased, and the difference was statistically significant (P＜0.05). Immunofluorescence microscopy showed that the NSC transplanted in the experimental group preferentially differentiated into astrocytes, and stably expressed CNTF and GDNF at high levels. Comparison of retinal photoreceptor nucleus lines in different treatment subgroups of the experimental group at different ages: CNTF-NSC group, at 2 months of age: the whole, central and peripheral regions were significantly different (F=31.73, 75.06, 75.06; P＜0.05); 4 months of age: The difference between the whole area and the peripheral region was statistically significant (F=12.27, 12.27; P＜0.05). GDNF/CNTF-NSC group, 2 and 4 months of age: the whole (F=27.26, 27.26) and the peripheral area (F=16.01, 13.55) were significantly different (P＜0.05). In GDNF-NSC group, there was no statistical significance at all in the whole, central and peripheral areas at different months of age (F=0.00, 0.01, 0.02; P＞0.05). ConclusionsCLN7 neuronal ceroid-lipofuscinosis mice exhibit progressively increasing degenerative alterations in photoreceptor cells and bipolar cells with age growing, aligning with both morphological and functional observations. Intravitreal administration of stem cell-based CNTF as well as GDNF/CNTF show therapeutic potential in rescuing photoreceptor cells. Nevertheless, the combined application of GDNF/CNTF-NSC do not demonstrate the anticipated synergistic protective effect. GDNF has no therapeutic effect on the retinal morphology and function in CLN7 neuronal ceroid-lipofuscinosis mice.
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.
Objective To assess the effectiveness and safety of autologous stem cell transplantation after high-dose chemotherapy in first-line treatment of follicular lymphoma. Method Randomized controlled trials (RCTs) of autologous stem cell transplantation after high-dose chemotherapy in first-line treatment of follicular lymphoma were collected from MEDLINE (1990-2009), EMBASE (1990-2009), OVID (1990-2009), and the Cochrane Library (Issue 2, 2009), and the proceedings of ASH were searched manually. The methodological quality of included studies was evaluated, and data analysis was performed with software STATA 10.0 and RevMan 4.3. Result A total of 4 RCTs involving 941 patients were included. The results of meta-analysis showed that overall survival rate (HR=0.82, 95%CI 0.49 to 1.15), event-free survival rate (HR=0.35, 95%CI 0.24 to 0.47), total remission rate (RR=0.35, 95%CI 0.96 to 1.30), and secondary malignant tumor incidence rate (RR=1.68, 95%CI 0.47 to 6.07). Conclusion According to the present evidences, autologous stem cell transplantation after high-dose chemotherapy can not improve overall survival rate and total remission rate, but can improve event-free survival rate, and do not increase secondary malignant tumor incidence rate. However, more high-quality, multiple-center, large-sample randomized controlled trials are required.
ObjectiveTo observe the protective effect of human umbilical cord blood stem cells (hUCBSC) transplantation on retinal ganglion cells (RGC) after optic nerve injury. Method48 adult Sprague-Dawley rats were randomly divided into group A and B, therefore 24 rats in each group. Calibrated optic nerve crush injury model was induced in the left eyes, the right eyes served as a control. Medicine was injected at seventh day after optic nerve injury. PBS was injected into the eyes of Group A rats by peribulbar injection. The hUCBSCs were injected into the eyes of Group B rats by peribulbar injection. Seven days before sacrifice, 5% fluorogold was injected into superior colliculi bilaterally. At 7, 14, 21, 28 days after labeled, retinal flat mounts were observed under fluorescence microscope and optical microscope to investigate the morphological and RGC changes in density during retinal degeneration. ResultsThe RGC number showed a tendency to decline gradually along with increases of the time in two groups, but the trend of decrease of Group B was evidently slower than that of Group A. The RGC number of the injury eye were less than the control eye in Group A and B (t=3.24, 3.15; P < 0.05). At 7, 14, 21, 28 days after labeled, the RGC number (t=4.78, 4.70, 3.98, 3.27; P < 0.05) and labeled RGC rate (t=4.39, 4.21, 4.36, 5.07; P < 0.05) in group B were more than those in group A. After optic nerve injury, there was karyopycnosis on ganglion cell layer of retina, thinning on each layer of retina, derangement of cell and decrease in RGC. There was different degree of the above change in different time after optic nerve injury. There were the swelling, the hemorrhage, derangement of spongiocyte and the denaturation like vacuole in the spot of optic nerve injury. Moreover, they were aggravating with increases of the time after optic nerve injury. There was no pathological changes in normal eyes. ConclusionThe hUCBSC can increase the survival rate of the RGC and can rescue and(or) restore the injujed RGC after transplanted into body of optic nerve crush rat model by peribulbar injection.
Objective To systematically review the survival outcome and safety of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for β-thalassemia. Methods The PubMed, EMbase, CNKI, WanFang Data and CBM databases were electronically searched to collect studies on haplo-HSCT for β-thalassemia from January 1, 2017 to December 31, 2021. Two reviewers independently screened the literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using RevMan 5.4.1 software and Stata 16.0 software. Results A total of 6 case-series studies involving 286 patients were included. The results of meta-analysis indicated that overall survival (OS) and thalassemia-free survival (TFS) for β-thalassemia patients undergoing haplo-HSCT were 92.5% (95%CI 86.1% to 96.1%) and 88.5% (95%CI 74.6% to 95.3%), the incidence of Ⅲ-Ⅳ degree acute graft versus host disease (Ⅲ-Ⅳ aGvHD) and chronic graft versus host disease (cGvHD) were 11.5% (95%CI 6.5% to 20.0%) and 23.1% (95%CI 12.3% to 39.8%), and the transplantation related mortality was 6.5% (95%CI 3.8% to 10.7%). Conclusion Relevant clinical studies published in the past 5 years provide the latest information and progress of haplo-HSCT for β-thalassemia. At present, great efficacy has been shown in NF-14-TM therapeutic regimen, but the long-term efficacy remains unclear. Due to the limited quality and quantity of the included studies, more high-quality evidence from long-term comparative studies is still needed.
Objective To review the value of imaging assessment of stem cell transplantation in treatment for liver cirrhosis.Methods The related literatures in recent years were collected,and the applications of different radiological techniques and strategies of stem cell transplantation in treatment for liver cirrhosis were summarized.Results Stem cell transplantation in treatment for liver cirrhosis was feasible and effective. Radiological assessment could supply the prompt and accurate information for clinic to choose the proper therapeutic method.The curative effect could also be accurately assessed by radiological techniques.Conclusion Radiological examination is important for the assessment of stem cell transplantation in treatment for liver cirrhosis.
Objective To observe the effects of subretinal transplantation of rat mesenchymal stem cells (rMSCs) on Sodium Iodate (SI)induced retinal degeneration. Methods One hundred and twenty BrownNorway (BN) rats were divided into three groups including SI injection group,rMSCs transplantation group and normal control group, each with 40 rats. The retinal degeneration was induced by caudal vein injection of SI. The retinal pigment epithelium（RPE）and neural retinal were evaluated by ocular fundus photograph, fluorescein fundus angiography (FFA)，electroretinogram (ERG) and histological approach, and TUNEL（terminal deoxynucleotidyl transferasemediated dUTP nick end labeling ）. CMDiIprelabeled primary rMSCs were transplanted into the subretinal space of SIinduced rats. The survival, integration, and differentiation of rMSCs were observed between 14 day to 60 day after the transplantation.Results The rat retinal function was gradually reduced after14 days of SI injection, with a timedependent manner. After the RPE cells were damaged，the outer segments of photoreceptors became disrupted and shortened until karyopyknosis. The nuclear morphology and positive TUNEL labeling indicated that the death of photoreceptor cells was apoptosis. After rMSCs transplantation, CMDiI labeled donor cells were observed to be scattered in the subretinal space and expressed RPE cell markers. Average amplitude of b wave and Ops (oscillation potential) in ERG improved 27.80%,59.38% respectively after rMSCs transplantation.Conclusions Transplanted rMSCs can survive in subretinal space and differentiate into RPE.
ObjectiveTo analyze the efficacy and safety of various treatment strategies for patients with refractory/recurrent diffuse large B-cell lymphoma (r/r-DLBCL) by network meta-analysis. MethodsThe PubMed, EMbase and Cochrane Library databases were searched to collect randomized controlled trials (RCTs) and clinical controlled trials related to the objectives of the study from inception to November 16th, 2022. After two investigators independently screened the literature, extracted data and evaluated the risk of bias of the included studies, a network meta-analysis was performed using R 4.2.2 software. ResultsA total of 8 RCTs and 11 non-randomized controlled trials were included, involving 2 559 cases. The treatment regimen included chemotherapy, immunochemotherapy, chemotherapy combined with ADC, immunochemotherapy combined with ADC, ASCT based regimen, CAR-T based regimen, ASCT combined with CAR-T, immunomodulators, small molecule inhibitors, and rituximab combined with small molecule inhibitors. The ranking probability results showed that the top three complete remission (CR) rates among all schemes were ASCT combined with CAR-T, chemotherapy combined with ADC, and immune modulators; The top three overall response rates (ORR) were chemotherapy combined with ADC, ASCT combined with CAR-T, and ASCT. The CAR-T regimen had a higher rate of severe neutropenia; The severe thrombocytopenia rate of ASCT regimen was relatively high; There was no significant difference in the incidence of SAEs among the other options. ConclusionASCT combined with CAR-T and chemotherapy combined with ADC have the best therapeutic effects on r/r-DLBCL. However, the specific protocol to be adopted requires clinical doctors to combine actual conditions, comprehensively consider the efficacy and side effects, and develop personalized treatment strategies for r/r-DLBCL patients.
Ocular fundus diseases is a kind of ophthalmic diseases that occur in the vitreous, retina, choroid and optic nerve, including a series of pathophysiological changes such as inflammation, exudation and proliferation. Because of high morbidity and high blindness rate, ocular fundus diseases has been paid more and more attention from medical community. With the continuous deepening of research on its etiology, anatomy and pathological mechanism in recent years, clinicians have obtained more abundant treatment methods than in the past, and the medical treatment of ocular fundus diseases have made many phased progress. However, due to its wide spectrum of diseases and complex pathological mechanism, clinicians still need to further explore more effective treatment methods, and improve the effect of diagnosis and treatment to ocular fundus diseases.