A decade of insight: bibliometric analysis of gut microbiota's role in osteoporosis (2014-2024).

Purpose: Osteoporosis represents a profound challenge to public health, underscoring the critical need to dissect its complex etiology and identify viable targets for intervention. Within this context, the gut microbiota has emerged as a focal point of research due to its profound influence on bone metabolism. Despite this growing interest, the literature has yet to see a bibliometric study addressing the gut microbiota's contribution to both the development and management of osteoporosis. This study aims to fill this gap through an exhaustive bibliometric analysis. Our objective is to uncover current research hotspots, delineate key themes, and identify future research trends. In doing so, we hope to provide direction for future studies and the development of innovative treatment methods. Methods: Relevant publications in this field were retrieved from the Web of Science Core Collection database. We used VOSviewer, CiteSpace, an online analysis platform and the R package "Bibliometrix" for bibliometric analysis. Results: A total of 529 publications (including 351 articles and 178 reviews) from 61 countries, 881 institutions, were included in this study. China leads in publication volume and boast the highest cumulative citation. Shanghai Jiao Tong University and Southern Medical University are the leading research institutions in this field. Nutrients contributed the largest number of articles, and J Bone Miner Res is the most co-cited journal. Of the 3,166 scholars who participated in the study, Ohlsson C had the largest number of articles. Li YJ is the most co-cited author. "Probiotics" and "inflammation" are the keywords in the research. Conclusion: This is the first bibliometric analysis of gut microbiota in osteoporosis. We explored current research status in recent years and identified frontiers and hot spots in this research field. We investigate the impact of gut microbiome dysregulation and its associated inflammation on OP progression, a topic that has garnered international research interest in recent years. Additionally, our study delves into the potential of fecal microbiota transplantation or specific dietary interventions as promising avenues for future research, which can provide reference for the researchers who focus on this research filed.

Successful outcome of neoadjuvant PD-1 blockade, VEGFR-2 inhibitor plus chemotherapy for potentially unresectable esophagogastric junctional squamous cell carcinoma: a case report.

Background: Esophagogastric junctional squamous cell carcinoma (EJSCC) is quite rare among all gastric carcinoma, its potential resectable rate is low due to the late diagnosis. Recently, programmed death-1 (PD-1) blockade combined with anti-angiogenesis have gained accumulated clinical experiences in treating solid tumors. This is the first reported case with EJSCC who achieved a partial remission (PR) after neoadjuvant PD-1 blockade, vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitor plus chemotherapy. Case Description: We present an EJSCC case treated with novel neoadjuvant treatment. A 64-year-old Chinese male had the symptom of chocking for 3 months. An enhanced abdominal computed tomography (CT) scan found a locally advanced, potentially unresectable esophagogastric junctional (EGJ) mass, and the preoperative immunohistochemistry result exhibited a highly positive programmed death-ligand 1 (PD-L1) expression, so the patient received three courses of neoadjuvant camrelizumab (200 mg/day), apatinib (750 mg/day), albumin paclitaxel (200 mg/day) and nedaplatin (70 mg/day), he was well tolerant without any adverse event, and he underwent radical surgery after a significant tumor shrinkage. The patient recovered well after surgery, and he has received four cycles of camrelizumab and apatinib as maintenance treatment. There is no recurrence 7 months after surgery. Conclusions: PD-1 blockade, VEGFR-2 inhibitor plus chemotherapy is effective and safe for the patient with EJSCC.

The role of mitochondrial fission factor in podocyte injury in diabetic nephropathy.

Diabetic nephropathy (DN) is one of the most important complications of diabetes mellitus (DM) and has become the second cause of end-stage renal disease (ESRD). This study intends to investigate the molecular mechanism of increased mitochondrial fission in podocytes under the effect of high glucose (HG), and to preliminarily study the role of mitochondrial fission factor (MFF)-mediated mitochondrial fission in podocyte injury of DN. In vitro studies, we found that HG induced increased mitochondrial fission and podocyte damage. At the same time MFF mRNA and protein levels was increased, suggesting that MFF was transcriptional upregulated under HG conditions. Consistent with this, in vivo studies found that mitochondrial fission was also significantly increased in podocytes of diabetic nephropathy mice, and MFF expression was up-regulated. Therefore, our study proves that mitochondrial fission increases in podocytes under DM both in vitro and in vivo, and the up-regulation of MFF expression may be one of the reasons for the increase of mitochondrial fission. After inhibiting the expression of MFF, the survival rate of podocytes was significantly decreased under HG conditions, suggesting that MFF may play a protective role in podocyte injury in DN.

Metastasis of Sarcomatoid Malignant Mesothelioma With p16/CDKN2A Deletion Manifested as a Subcutaneous Mass in the Back: A Case Report and Review of Literature.

Sarcomatoid malignant mesothelioma (MM) is a rare and aggressive disease, and its diagnosis is challenging. A 60-year-old man presented with a recurrent subcutaneous mass in his right back after the initial resection. A chest computed tomography (CT) scan found right pleural thickening, nodular pleural thickening, pleural effusion, mediastinal, and right infraclavicular lymph nodes enlargement, which indicated a right pleura MM. Immunohistochemical stains of the resected mass showed sarcomatous atypical spindle cells, which were positive for pan-CKs (clone Anti-cytokeratin cocktail AE1/AE3), cytokeratin 5/6 (CK5/6), Wilm's tumor 1, podoplanin, vimentin and programmed death-ligand 1 (PD-L1), and negative for Napsin A, thyroid transcription factor 1, CDX 2, calretinin and desmin, and fluorescent in situ hybridization detected homozygous p16/cyclin-dependent kinase inhibitor 2A (p16/CDKN2A) deletion. The association of the chest CT features and the pathological assessment confirmed metastatic MM in the subcutaneous layer of the back. Moreover, positron emission tomography-CT showed multiple metastases in his brain. He developed massive right pleural effusion and chest tightness soon, and the mass kept growing despite local and systemic treatments. The patient die of pulmonary failure in 3 months.

Root Anatomy and Root Canal Morphology of Maxillary Second Permanent Molars in a Chongqing Population: A Cone-Beam Computed Tomography Study.

BACKGROUND To investigate variations in the anatomy of root canals in permanent second molars of the upper jaw in a population in Chongqing, China, using cone-beam computed tomography (CBCT). MATERIAL AND METHODS CBCT imaging data of 400 second permanent molars of the upper jaws of 200 patients were retrospectively reviewed. Patients' gender, age, numbers of roots and canals, root fusion of permanent second molars of the maxilla on both sides, and morphological categories of root canals of mesiobuccal roots were recorded. The distances from the apices of the distobuccal and mesiobuccal roots to the buccal bone plate were measured. RESULTS Of the 400 permanent second maxillary molars, 312 (78.0%) had three roots and 247 (61.75%) had three canals. Fused roots were observed in 126 (31.5%) teeth; of these, 67 (53.2%) had three canals and 44 (34.9%) had two canals. Morphologically, 297 (74.25%), 29 (7.25%), nine (2.25%) and 65 (16.25%) teeth had type I, II, III, and IV mesiobuccal root canals, respectively, with 103 (25.75%) having secondary mesiobuccal canals. The distances from the apices of the mesiobuccal, distobuccal, and single buccal roots to the surface of the buccal osseous lamella were 7.34±1.89 mm, 6.26±1.74 mm, and 8.60±2.56 mm, respectively. CONCLUSIONS The root form and canal shape of permanent second molars of the upper jaw varied greatly among the population of Chongqing, China. CBCT is a valuable method for assessing the complex anatomic morphology of teeth.

Comparative study of micro-transplantation from HLA fully mismatched unrelated and partly matched related donors in acute myeloid leukemia.

Micro-transplantation (MST) by chemotherapy, combined with granulocyte colony-stimulating factor-mobilized peripheral blood stem cell (GPBSC) infusion, from an HLA partial matched related donor has shown some encouraging effective therapy for acute myeloid leukemia (AML). However, the outcome of human leukocyte antigen (HLA) fully mismatched unrelated donor-derived MST in such patients is still unknown. In the present study, we compared the efficacy of HLA fully mismatched unrelated donor-derived MST, and partly matched related donor-derived MST, in AML of 126 patients from two centers in China, These patients, aged 16 to 65 years, were given three or four courses of MST, which consisted of a high dosage cytarabine followed by GPBSC from unrelated donor or related donor. There was a statistically significant difference in 3-year leukemia-free survival (LFS) and 3-year overall survival (OS) between the unrelated and the related group. The non-treatment-related mortality (NRM) rates of patients, and other adverse complications, were no different in the two groups. In conclusion, unrelated donor-derived MST is believed to be a safe treatment, with efficacy similar to or higher than related donor-derived MST. This result provides support for the potential of MST for expanding the donor selection. However, the specific mechanism of action needs further study.

HLA-Mismatched Microtransplant in Older Patients Newly Diagnosed With Acute Myeloid Leukemia: Results From the Microtransplantation Interest Group.

IMPORTANCE: The outcome of older patients with acute myeloid leukemia (AML) remains unsatisfactory. Recent studies have shown that HLA-mismatched microtransplant could improve outcomes in such patients. OBJECTIVE: To evaluate outcomes in different age groups among older patients with newly diagnosed AML who receive HLA-mismatched microtransplant. DESIGN, SETTING, AND PARTICIPANTS: This multicenter clinical study included 185 patients with de novo AML at 12 centers in China, the United States, and Spain in the Microtransplantation Interest Group. Patients were divided into the following 4 age groups: 60 to 64 years, 65 to 69 years, 70 to 74 years, and 75 to 85 years. The study period was May 1, 2006, to July 31, 2015. EXPOSURES: Induction chemotherapy and postremission therapy with cytarabine hydrochloride with or without anthracycline, followed by highly HLA-mismatched related or fully mismatched unrelated donor cell infusion. No graft-vs-host disease prophylaxis was used. MAIN OUTCOMES AND MEASURES: The primary end point of the study was to evaluate the complete remission rates, leukemia-free survival, and overall survival in different age groups. Additional end points of the study included hematopoietic recovery, graft-vs-host disease, relapse rate, nonrelapse mortality, and other treatment-related toxicities. RESULTS: Among 185 patients, the median age was 67 years (range, 60-85 years), and 75 (40.5%) were female. The denominators in adjusted percentages in overall survival, leukemia-free survival, relapse, and nonrelapse mortality are not the sample proportions of observations. The overall complete remission rate was not significantly different among the 4 age groups (75.4% [52 of 69], 70.2% [33 of 47], 79.1% [34 of 43], and 73.1% [19 of 26). The 1-year overall survival rates were 87.7%, 85.8%, and 77.8% in the first 3 age groups, which were much higher than the rate in the fourth age group (51.7%) (P = .004, P = .008, and P = .04, respectively). The 2-year overall survival rates were 63.7% and 66.8% in the first 2 age groups, which were higher than the rates in the last 2 age groups (34.2% and 14.8%) (P = .02, P = .03, P < .001, and P < .001, respectively). The 1-year cumulative incidences of nonrelapse mortality were 10.2%, 0%, 3.4%, and 26.0% in the 4 age groups and 8.1% in all patients. The median times to neutrophil and platelet recovery were 12 days and 14 days after induction chemotherapy, respectively. Five patients had full or mixed donor engraftment, and 30.8% (8 of 26) of patients demonstrated donor microchimerism. Two patients (1.1%) developed severe acute graft-vs-host disease. CONCLUSIONS AND RELEVANCE: Microtransplant achieved a high complete remission rate in AML patients aged 60 to 85 years and higher 1-year overall survival in those aged 60 to 74 years.

[Biological characteristics of Microvesicles Derived from Bone Marrow Mesenchymal Stem Cells and Their Capacities Supporting ex vivo Expansion of Hematopoietic Stem Cells].

OBJECTIVE: To explore the biological characteristics of microvesicles(MV) derived from bone marrow mesenchymal stem cells (BM-MSC) and their capability supporting ex vivo expansion of hematopoietic stem cells(HSC). METHODS: The MV from cultured BM-MSC supernatant were isolated by multi-step differential velocity contrifugation; the morphological characteristics of MV were observed by electron microscopy with negative staining of samples; the protein level in MV was detected by using Micro-BCA method; the surface markers on MV were analyzed by flow cytometry. The peripheral blood HSC(PB-HSC) were isolated after culture and mobilization; the experiment was diveded into 2 group: in MV group, the 10 mg/L MV was given, while in control group, the same volume of PBS was given; the change of PB-HSC count was observed by cell counting; the change of surface markers on PB-HSC was detected dynamically by flow cytometry; the cell colony culture was used to determin the function change of PB-HSC after co-culture with MV. RESULTS: MSC-MVs are 20-100 nm circular vesicles under electron microscope. About 10 µg protein could be extracted from every 1×106 MSC. The flow cytometry showed that CD63 and CD44 were positive with a rate of 96.0% and 50.2%, while the HLA-DR, CD34, CD29 and CD73 etc were negative. When being co-cultured with GPBMNC for 2 days, the cell number of MV groups was 1.49±0.15 times of the control group (P>0.05). When being co-cultured for 4 days, the cell number of MV groups was 2.20±0.24 times of the control group(P<0.05). The CD34+ cell number of MV groups was 1.76±0.30 times the control group after culture for 2 day and 1.95±0.20 times after culture for 4 day. CONCLUSION: The MV has been successfully extracted from MSC culture supernatant by multi-step differential velocity centrifugation. MSC-MV can promote HSC expansion in vitro.

[Biological Characteristics of Microvesicles Secreted by Human Peripheral Blood Hematopoietic Stem Cells].

OBJECTIVE: To investigate the effects of microvesicles(MV) isolated from human peripheral blood hematopoietic stem cells(PB-HSC) on immune regulation and hematopoiesis. METHODS: PB-HSCs were separated by density-gradient centrifugation and cultrued. The supernatants of PB-HSC at 48 h were harvested for isolation and purification of MV by using ultracentrifugation. The electron microscopy was used to observe the morphology of MV. The protein level in MV was quantified through bicinchoninic acid(BCA) protein assay. Flow cytometry was used to detect the immunophenotype of MV. Human peripheral blood mononuclear cells(PB-MNC) were isolated from healthy donor and treated with isolated MV. After being co-cultured for 12 h, confocal microscopy was used to observe the action mode of MV on PB-MNC. After being co-cultured for 48 h, the levels of IL-2, IL-6, IL-8, IL-10, IFN-γ and TNF-α were detected by ELISA. Flow cytometry was used to detect the changes of T cell subsets and the activation of T cell subsets as well as intracellular cytokine staining after co-culture for 48 h. The methylcellulose was used to assess the hematopoiesis-supportive function of MV as well as co-cultured supernatants. RESULTS: The eletron microscopy revealed that MV were elliptical membrane vesicles. The protein amount in MV ranges from 29 to 110 µg. Flow cytometry showed that MV expressed mix markers on the surface, especially highly expressed MV specific marker CD63(85.86%) and hematopoietic stem cell marker CD34(33.52%). After being co-cultured for 12 h, confocal microscopy showed that MV were merged with PB-MNC. After being co-cultured for 48 h, ELISA showed that the secretion of cytokines IL-6,IL-8, IL-10 as well as TNF-α was increased while the level of IL-2 and IFN-γ was not changed much. The results of flow cytometry showed that there was no significant change in T cell subsets and T cell activation. Staining of intracellular factor showed that IL-8 was increased significantly in CD11c+ cells. The colony-forming experiments revealed that MV and the co-cultured supernatants could facilitate the colony formation. CONCLUSION: MV isolated from PB-HSC have immune-regulatery function and can prornote hematopoiesis.

[Effect of Infusion of Recipient Spleen Cells at Different Time after Murine Haploidentical Hematopoietic Stem Cell Transplantation on Graft Versus Host Disease].

OBJECTIVE: To explore the effect of infusing G-CSF mobilized recipient spleen cells at different time after haploidentical stem cell transplantation(HSCT) on graft-versus-host disease (GVHD) in mice and its possible mechanism. METHODS: Forty mice after HSCT were randomly divided into 4 groups (n=10): GVHD positive control group (control group), 1st d recipient cell infusion group after transplantation (+1 d group), 4th d recipient cell infusion group after transplantation(+4 d group), 7th d recipient cell infusion group after transplantation(+7 d group). The mice in control group were injected the normal saline of same equivalent with experimental group which were given the same amount of G-CSF-mobilized recipient spleen cells. The general manifestation and pathological change of GVHD were observed. The expression changes of CD3+CD4+, CD3+CD8+ cell subsets and FasL in peripheral blood were detected by flow cytometry. RESULTS: The incidence of GVHD was significantly decreased in +4 d group and the median survival time was longer than 60 days, which was significantly higher than that of control group (24 d), +1 d group (21 d), +7 d group (28 d). (P<0.01, P<0.01, P<0.01). The Fasl expression of peripheral blood T lymphocytes in +4 d group were significantly lower than that in the other 3 groups(P<0.05). CONCLUSION: The +4 d infusion of G-CSF mobilized recipient spleen cells on 4th day after haploidentical HSC transplantation can inhibit the expression of FasL in donor T lymphocytes, and significantly reduce the incidence of GVHD.

[Establishment of Mouse Model of H-2 Haploidentical Hematopoietic Stem Cell Transplantation from Double Donors].

OBJECTIVE: To establish a new mouse model of H-2 haploidentical stem cell transplantation from double donors (DHSCT) and compare with conventional haploidentical hematopoietic stem cell transplantation (HSCT) so as to alleviate transplant-related complications. METHODS: The recipients CB6F1 of conventional HSCT group were pretreated by 8 Gy total body irradiation(TBI), and received 3×107 donor (male C57) spleen mononuclear cells (spMNC) mobilized by G-CSF within 2 hours after TBI. Recipients CB6F1 of D-HSCT groups accepted 2 Gy TBI, and received total 12×107 spMNC mobilized by G-CSF from 2 donors within 2 hours after TBI, each donor donated 6×107 cells. According to the different strains and sex of donors, DHSCT were divided into 3 groups: in group A, the stem cells were from male C57 and female BALB/c; in group B, stem cells were from male C57 and male BALB/c, while the stem cells in group C were from male C57 and male C3H. Hematopoietic reconstruction, engraftment, GVHD and survival were observed among these 4 groups. RESULTS: The nadir of white blood cell count after conventional HSCT were lower than 1×109/L and lasted for 3 to 5 days, while not less than 3×109/L after D-HSCT among either group A, B or C. The complete chimerism (CC) in conventional HSCT group was achieved quickly within only 1 week in peripheral blood. Mixed chimerism (MC) in peripheral blood was found within the first week after DHSCT among either group A, B or C, and transformed into stable CC within the second week eventually. Both GVHD morbidity and mortality of conventional HSCT were 100% at 34th day after transplantation.Among DHSCT groups,the overall GVHD morbidity and mortality at 34th day after transplant were 49.6% and 50%(P<0.01,P<0.05), respectively,and 60.4% and 81.2% at 50th day after transplant. Overall survival of 50 days was 50.9% that indicated a long survival in such mice DHSCT. The differences of hematopoietic reconstruction, donor cell engraftment, GVHD incidence, GVHD mortality and OS were not statistically significant among group A, B and C(P>0.05). CONCLUSION: A new mouse model of H-2 haploidentical peripheral blood stem cell transplantation from double donors (DHSCT) has been successfully established by reducing conditioning intensity and increasing graft cell numbers from double haploidentical donors without GVHD prophylaxis. DHSCT successfully achieved stable complete chimerism, less GVHD morbidity and mortality and longer OS without hematopoietic suppression. This study provides experimental evidence for clinical application of HLA haploidentical peripheral blood stem cell transplantation from double donors.

Preparation of micro-porous bioceramic containing silicon-substituted hydroxyapatite and beta-tricalcium phosphate.

Dimensional instability caused by sintering shrinkage is an inevitable drawback for conventional processing of hydroxyapatite (HA). A new preparation method for biphasic calcium phosphates was developed to increase micro pores and biodegradation without significant dimensional change. Powder pressed HA discs, under 100MPa, were immersed in a colloidal mixture of tetraethoxysilane (TEOS) and ammonium hydroxide for 10min, followed by drying, and then were sintered at 900°C, 1050°C, and 1200°C, respectively. Comparing with pure HA discs, the newly prepared product sintered up to 1200°C contained silicon substituted HA, beta-tricalcium phosphate, and calcium silicate with better micro-porosity, high specific surface area, less sintering shrinkage and the strength maintained. The cytocompatibility test demonstrated a better viability for D1 mice stem cells cultured on TEOS treated HA for 14days compared to the pure HA. This simple TEOS sol-gel pretreatment has the potential to be applied to any existing manufacturing process of HA scaffold for better control of sintering shrinkage, create micropores, and increase biodegradation.

The long-term outcome of reduced-intensity allogeneic stem cell transplantation from a matched related or unrelated donor, or haploidentical family donor in patients with leukemia: a retrospective analysis of data from the China RIC Cooperative Group.

This study compared 6-year follow-up data from patients undergoing reduced-intensity conditioning (RIC) transplantation with an HLA-matched related donor (MRD), an HLA-matched unrelated donor (MUD), or an HLA-haploidentical donor (HID) for leukemia. Four hundred and twenty-seven patients from the China RIC Cooperative Group were enrolled, including 301 in the MRD, 79 in the HID, and 47 in the MUD groups. The conditioning regimen involved fludarabine combined with anti-lymphocyte globulin and cyclophosphamide. Graft-versus-host disease (GVHD) prophylaxis was administered using cyclosporin A (CsA) and mycophenolate mofetil (MMF). Four hundred and nineteen patients achieved stable donor chimerism. The incidence of stage II-IV acute GVHD in the HID group was 44.3 %, significantly higher than that in the MRD (23.6 %) and MUD (19.1 %) groups. The 1-year transplantation-related mortality (TRM) rates were 44.3, 17.6, and 21.3, respectively. Event-free survival (EFS) at 6 years in the HID group was 36.7 %, significantly lower than that of the MRD and MUD groups (59.1 and 66.0 %, P < 0.001 and P = 0.001, respectively). For advanced leukemia, the relapse rate of the HID group was 18.5 %, lower than that of the MRD group (37.5 %, P = 0.05), but the EFS at 6 years was 31.7 and 30.4 % (P > 0.05), respectively. RIC transplantation with MRD and MUD had similar outcome in leukemia which is better than that with HID. RIC transplantation with HID had lower relapsed with higher TRM and GVHD rate, particularly in advanced leukemias. RIC transplantation with MRD and MUD had similar outcomes in leukemia and they were better than those with HID. RIC transplantation with HID had a lower relapse rate but higher TRM and GVHD rates, particularly in cases of advanced leukemia.

[Features of Immunophenotypes and Characteristics of Molecular Biology and Cellular Genetics of AML Patients with CD4 and CD7 Expression].

OBJECTIVE: To explore the features of immunophenotypes and the characteristics of molecular biology and cellular genetics of AML patients with CD7 and CD4 expression. METHODS: The immunophenotypical markers of AML cells were detected by multiple parameter flow cytometry; the expression of WT1, MDK, ETO, PML-RaRa and BCR-ABL were detected by RT-PCR; and cellular features were analyzed by R-band in 304 patients. The patients were divided into three groups according to their immunophenotypes: AML with CD7 expression (CD7 group), AML with CD4 expression(CD4 group) and AML without CD7 and CD4 expression (common AML group). RESULTS: The expression rate and level of HLA-DR in CD7 group were higher than those in the common AML group, and the expression rate of CD33 and CD34 was higher than that in the other two groups. The expression rate and level of CD15, CD64 in the CD4 group were higher than those in the other 2 groups, and the expression rate and level of CD33 were higher than those in the common AML group. WT1 expression in the CD7 group was lower than that in the common AML group. PML-RaRa was not detected in the CD7 group. AML with co-expression of CD4 or CD7 showed more normal karyotype. (15;17) was not found in AML with CD7 expression. CONCLUSION: AML cells with CD7 expression originate from precursor cells and are blocked in the early phase of hematological development; AML cells with CD4 expression originate from more mature stage of hematological devevelopment and with CD33, CD64 and CD15 high expression; AML cells with CD7 and CD4 expression are characterized by no-specific change of cellular genetics. According to the expression level and intesity of CD4 and CD7, and together with other specific lineage markers, the MRD in AML patients can be quantitatively detected.

A Study of Human Leukocyte Antigen Mismatched Cellular Therapy (Stem Cell Microtransplantation) in High-Risk Myelodysplastic Syndrome or Transformed Acute Myelogenous Leukemia.

UNLABELLED: The treatment outcomes of myelodysplastic syndrome (MDS) and transformed acute myelogenous leukemia (tAML) remain very unsatisfactory. We designed a combination of human leukocyte antigen (HLA)-mismatched hematopoietic stem cell microtransplantation (MST) with chemotherapy for patients with MDS and tAML and evaluated its effects and toxicity. Patients were between 13 and 79 years old. Patients with MDS (n=21) were given HLA-mismatched MST combined with decitabine and cytarabine; patients with tAML (n=22) were given HLA-mismatched MST combined with decitabine and cytarabine, and also mitoxantrone. Patients in complete remission (CR) also received MST plus decitabine and medium-dose cytarabine chemotherapy without graft-versus-host disease (GVHD) prophylaxis. The overall response rate of the patients with MDS was significantly higher than that of those with tAML (81% vs. 50%; p=.03). The CR rates were 52.4% and 36.4% in the two groups, respectively. There was no difference in the cytogenetic CR rate between the MDS and tAML groups (85.7% vs. 70%, respectively; p=.7). The 24-month overall survival of the patients with MDS was significantly higher than that of the patients with tAML (84.7% and 34.1%, respectively; p=.003). The median recovery times of neutrophils and platelets were, respectively, 14 and 17 days in the patients with MDS, and 16 and 19 days in those with tAML. The treatment-related mortality rates were 4.8% and 18.2%, respectively, in the MDS and tAML groups (p=.34). No GVHD was observed in any patient. Microtransplantation combined with decitabine and chemotherapy may provide a novel, effective, and safe treatment for high-risk MDS and tAML. SIGNIFICANCE: Microtransplantation (MST) refers to regular chemotherapy combined with granulocyte colony-stimulating factor-mobilized peripheral blood stem cell infusion of human leukocyte antigen-mismatched donor cells without using immunosuppressive agents. It aims to support hematopoietic recovery and perform graft-versus-leukemia (GVL) effects but differs from traditional allogeneic stem cell transplantation because the rate of donor cell chimerism is low and there is and no graft-versus-host disease (GVHD) risk. Thus, a trial was designed to evaluate the safety and efficacy of MST in patients with myelodysplastic syndrome and those with transformed acute myelogenous leukemia. Higher complete remission and cytogenetic complete response rates were observed, and the treatment improved disease progress-free survival, sped hematopoietic recovery, and avoided GVHD.

[Clinical Analysis of 4 AML Patients Aged Over 80 Years Treated with Chemotherapy Combined with Haploidentical Hematopoietic Stem Cell Infusion].

OBJECTIVE: To investigate the efficacy and safety of MA (mitoxantrone and cytarabine) regimen chemotherapy combined with granulocyte-colony stimulating factor (G-CSF)-mobilized family related HLA-haploidentical donor peripheral blood hematopoietic stem cell (G-PBHSC) infusion for the treatment of acute myeloid leukemia (AML) patients aged over 80 years. METHODS: Four elderly patients with AML were treated in Chinese Second Artillery General Hospital from August 2008 to September 2013. The proportion of male to female was 1 : 3 and the median age 83 (80-85) years. All patients received programmed infusions of G-PBHSC after MA regimen chemotherapy without graft-versus-host disease (GVHD) prophylaxis. After complete remission (CR), patients only received G-PBHSC infusion without chemotherapy. RESULTS: Three cases achieved CR and their disease free survival (DFS) time was 18, 8, 6 months, respectively. 1 case did not reach remission after 2 cycles chemotherapy. The median overall survival (OS) time was 10 (3-20) months. No GVHD was observed in any of the patients during treatment. Concludsion: The combination of chemotherapy and programmed haploidentical G-PBHSC infusion is an alternative approach for AML patients aged over 80 years.

Partial equilibrium approximations in apoptosis. II. The death-inducing signaling complex subsystem.

This paper is a continuation of our previous work (Huang and Yong, 2013) for simplifying the Fas signaling-induced apoptotic pathway identified by Hua et al. (2005) for human tumor T cells. The previous paper studied the downstream intracelluar-signaling subsystem, while the present one is concerned with the upstream death-inducing signaling complex (DISC) subsystem. Under the assumption that the bind of Fas-associated death domains and FLICE-inhibitory proteins to the DISC is much faster than that of the initiator procaspases, we greatly simplify the upstream subsystem from 35 reactions with 26 species to 6 reactions with 9 species by adopting the classical and recently justified partial equilibrium approximation method. Numerical simulations show that the simplified model is in an excellent agreement with the original model. Most importantly, the simplified model clearly reveals the key reactants and dominated pathways in the Fas signaling process, and thus provides new insights into the apoptosis.

A Kinetic Model for Cell Damage Caused by Oligomer Formation.

It is well known that the formation of amyloid fiber may cause invertible damage to cells, although the underlying mechanism has not been fully understood. In this article, a microscopic model considering the detailed processes of amyloid formation and cell damage is constructed based on four simple assumptions, one of which is that cell damage is raised by oligomers rather than mature fibrils. By taking the maximum entropy principle, this microscopic model in the form of infinite mass-action equations together with two reaction-convection partial differential equations (PDEs) has been greatly coarse-grained into a macroscopic system consisting of only five ordinary differential equations (ODEs). With this simple model, the effects of primary nucleation, elongation, fragmentation, and protein and seeds concentration on amyloid formation and cell damage have been extensively explored and compared with experiments. We hope that our results will provide new insights into the quantitative linkage between amyloid formation and cell damage.

[Efficacy of Nonmyeloablative Allogeneic Hematopoietic Stem Cells for 14 Case of Severe Acquired Aplastic Anemia].

OBJECTIVE: To investigate the therapeutic efficacy of nonmyeloablative allogeneic hematopoietic stem cells transplantation for severe acquired aplastic anemia (SAA). METHODS: Fourteen patients with severe acquired aplastic anemia received nonmyeloablative allogeneic hematopoietic stem cells transplantation from HLA matched sibling donors, among them 8 cases were dagnosed as SAA-I, 6 cases were diagnosed as SAA-II. The conditioning regimen consisted of fludarabine (FIUD), cyclophosphamide (CTX) and anti-thymocyte globulin (ATG/ALG). The prophylaxis for graft-versus-host disease (GVHD) was performed with cyclosporine (CsA) combined with mycophenolate mofetil (MMF) or tacrolimus (FK506). RESULTS: All the patients gained a quick successfully engraftment of donor hametopoietic cells. The mean recovery time for neutrophil and platelet was 9 d and 13 d respectively. All the patients have acquired a full donor chimerism before 14 d. There were only 2 cases of GVHD: one out of them was acute skin GVHD (grade I) at day 70 after transplantation and the other was chronic liver GVHD (grade I) in 1 years after transplantation, the GVHD more than degree II did not coccur in all patients, 9 patients with bacterial and fungal mixed infection and (or) virus infection were observed, and improved after anti-infection therapy. The median follow-up time were 54.5 months (ranged between 5-144 months), and 12 patients remain disease-free survival currently, only 2 patients died of fungal infectin. CONCLUSION: Transplantation of nonmyeloablative allogeneic hematopoietic stem cell is safe and effective for the treatment of severe acquired aplastic, but the prevention, treatment and monitoring of infection need to be enhance.

[Clinical analysis of lymphoblastic lymphoma/leukemia treated with Hyper-CVAD/MA regimen chemotherapy combined with haploidentical hematopoietic stem cell infusion].

This study was aimed to investigate the efficacy of Hyper-CVAD/MA regimen chemotherapy combined with haploidentical hematopoietic stem cell infusion for the treatment of lymphoblastic lymphoma/leukemia (LBL/ALL). Seven patients with LBL/ALL were treated in Second Artillery General Hospital from August 2009 to September 2012. All patients received programmed infusions of granulocyte-colony stimulating factor (G-CSF)-mobilized family related HLA-haploidentical donor peripheral blood hematopoietic stem cell (G-PBHSC) after each of cycle of Hyper-CVAD/MA regimen chemotherapy without graft-versus-host disease (GVHD) prophylaxis. A total of four cycles of therapy were planned. The interval between each cycle of treatment was 8 to 12 weeks. By April 2014, the median follow-up time was 41 (20-57) months. The results showed that the 7 patients totally received 30 cycles of treatment, and all patients achieved complete remission (CR). The patients were generally well-tolerated to therapy, and the most significant toxicities of grade 3 to 4 neutropenia and thrombocytopenia developed in nearly all of the patients after each course of the Hyper-CVAD/MA regimen. No GVHD was observed in any of the patients during treatment. Up to now, 5 patients were still alive, 2 patients were died of relapse. It is concluded that the combination of chemotherapy and programmed haploidentical G-PBHSC infusion is a promising approach to the treatment of LBL/ALL.