OBJECTIVE: To investigate the role of MK2 inhibitor MMI-0100 on inflammatory response after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and related mechanisms. METHODS: An allo-HSCT mouse model was established. Recipient rats were randomly divided into BMT+NaCl group and BMT+MMI-0100 group, and were injected with NaCl and MMI-0100 every day after transplantation, respectively. Samples of the two groups were collected on d 7 and 14, femur paraffin sections were stained with HE, and pathological changes in the bone marrow cavity were observed under the light microscope. The gene and protein expression levels of pro-inflammatory cytokines IL-1β and IL-18 were detected by qPCR and Western blot. Macrophage typing was detected by flow cytometry. The expression levels of NLRP3 and Caspase-1 were detected by Western blot. RESULTS: Inflammatory cell infiltration in the bone marrow cavity was significantly reduced in the BMT+MMI-0100 group. Western blot results showed that the protein expression levels of IL-1β and IL-18 in the BMT+MMI-0100 group were decreased compared to the BMT+NaCl group on day 7 and day 14 (all P <0.01). The qPCR results showed that compared to the BMT+NaCl group, the IL-18 gene expression levels in the BMT+MMI-0100 group were significantly reduced on day 7 and day 14 (both P <0.01). In the BMT+MMI-0100 group, the expression level of IL-1β gene decreased on day 7 (P <0.05), but increased and was higher than that in the BMT+NaCl group on day 14 (P <0.05). Flow cytometry results showed that the expression of M1 macrophages and M1/M2 ratio decreased in the BMT+MMI-0100 group compared to BMT+NaCl group (all P <0.05). Western blot results showed that the protein expression levels of NLRP3 and Caspase-1 in the BMT+MMI-0100 group were lower than those in the BMT+NaCl group (all P <0.05). CONCLUSION MMI-0100 can ameliorate bone marrow inflammatory injury after allo-HSCT and may act by reducing NLRP3 expression to promote M2 polarization.
Animals ; Interleukin-1beta/metabolism* ; Rats ; Interleukin-18/metabolism* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammation ; Bone Marrow/pathology* ; Protein Serine-Threonine Kinases/metabolism* ; Intracellular Signaling Peptides and Proteins/antagonists & inhibitors* ; Caspase 1/metabolism* ; Macrophages ; Transplantation, Homologous

Bone Transplantation/adverse effects* ; Transplantation, Autologous/adverse effects*

OBJECTIVE: To detect the expression level of HK2 gene in the bone marrow of newly diagnosed patients with acute myeloid leukemia (AML) and investigate its influence on the clinical characteristics and prognosis. METHODS: The expression level of HK2 gene in the bone marrow of 90 newly diagnosed patients with AML that accompanying clinical characteristics and survival status were detected by RT-qPCR, and compared with 18 allogeneic hematopoietic stem cell transplantation (allo-HSCT) donors. The Chi-square test, Kaplan-Meier survival analysis, and Cox proportional hazards regression model were used to analyze the correlation of HK2 expression level with clinical characteristics and prognosis. RESULTS: Compared with allo-HSCT donors, the HK2 expression was significantly increased in newly diagnosed AML patients (P <0.01). Compared with patients with total response (OR, complete response + complete response with incomplete hematologic recovery) after 2 courses of induction chemotherapy, the expression of HK2 in patients without OR was significantly increased (P <0.05). There was a significant difference in the relative expression of HK2 between patients with and without OR after 2 courses of induction therapy (P <0.001). The median survival time of patients with high expression of HK2 was significantly shorter than that of patients with low expression of HK2 (P <0.05). The multivariate Cox proportional hazards regression analysis showed that prognostic stratification, the expression level of HK2, and whether two courses of induction therapy achieved OR were independent factors affecting the prognosis of AML patients (P <0.05). CONCLUSIONS Compared with allo-HSCT donors, the expression level of HK2 gene is increased in the bone marrow of newly diagnosed AML patients. The prognosis of patients with high expression of HK2 is poor. The expression level of HK2 is an independent factor affecting the prognosis of AML patients.
Humans ; Bone Marrow ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Leukemia, Myeloid, Acute/therapy* ; Prognosis ; Retrospective Studies ; Transplantation, Homologous/adverse effects*

OBJECTIVE: To explore clinical effect of attaching locking plate with bone grafting based on retaining the original intramedullary nail in treating non-union after intramedullary nail fixation of long shaft fractures of lower limbs. METHODS: A retrospective study was conducted on 20 patients treated with non-union fractures after intramedullary nailing of long shaft fractures of lower limbs from June 2015 to June 2020. All patients were treated with the original intramedullary nailing and bone grafting from the iliac bone, and were underwent open reduction plate internal fixation and bone grafting for old fractures. Among them, 14 were males and 6 were females, aged from 35 to 56 years old with an average of (42.2±9.6) years old. Nine patients were femoral shaft fracture and 11 patients were tibial shaft fracture. According to characteristics of fracture end nonunion, 6 patients were stable/atrophic, 9 patients were unstable/large, and 5 patients were unstable/atrophic. The nonunion time ranged from 8 to 12 months with an average of(9.8±2.0) months after the initial surgery. Visual analogue scale (VAS), knee range of motion, bone healing time, complications and fracture-end healing were recorded before and at the latest follow-up. RESULTS: All patients were followed up for 18 to 48 months with an average of (36.3±10.5) months. The incision of all patients were healed at stageⅠwithout complications such as infection or internal fixation ruptur. Healing time of femur and tibia was (8.5±2.6) months and (9.5±2.2) months. Knee joint motion increased from preoperative (101.05±8.98) ° to postoperative (139.35±8.78) ° at the latest follow-up (t=-12.845, P<0.001). VAS decreased from preoperative (5.15±1.72) to postoperative (0.75±0.96) at the latest follow-up (t=11.186, P<0.001). CONCLUSION On the basis of retaining the original intramedullary nail, the addition of locking plate internal fixation and autogenous iliac bone grafting have advantages of simple operation, less trauma, fewer complications and high fracture healing rate. It is one of the effective surgical schemes for the treatment of nonunion after intramedullary nail fixation of long bone fracture of lower extremity.
Male ; Female ; Humans ; Adult ; Middle Aged ; Bone Transplantation ; Retrospective Studies ; Bone Plates ; Fracture Fixation, Intramedullary/adverse effects* ; Femoral Fractures/complications* ; Lower Extremity ; Fractures, Ununited/surgery* ; Fracture Healing ; Tibial Fractures/complications* ; Bone Nails ; Treatment Outcome

Acromioclavicular joint (ACJ) injury is a common shoulder injury. There are various techniques of ACJ reconstruction. Superficial infection after ACJ reconstruction is not an uncommon complication. However, osteomyelitis post ACJ reconstruction has never been highlighted as a possible complication. Our patient is a 31-year-old male who sustained a Rockwood 5 ACJ dislocation and had anatomical ACJ reconstruction with autogenous gracilis and semitendinosus graft. Our technique involved the anatomical reconstruction of the ACJ and the coracoclavicular ligament with the usage of two bioscrews and the temporary stabilisation of the ACJ with two k-wires. As in any orthopaedic surgery, infection is often disastrous especially when the surgery involves implants. It can be disastrous with high morbidity to the patient as well as a costly complication to treat. Therefore, we wish to highlight this case as despite its rarity, osteomyelitis can be devastating to the patient and should be prevented if possible.
Acromioclavicular Joint ; injuries ; surgery ; Adult ; Anti-Bacterial Agents ; administration & dosage ; Bone Screws ; adverse effects ; Bone Wires ; adverse effects ; Gracilis Muscle ; transplantation ; Hamstring Muscles ; transplantation ; Humans ; Joint Dislocations ; surgery ; Male ; Orthopedic Procedures ; adverse effects ; methods ; Osteomyelitis ; etiology ; prevention & control ; therapy ; Postoperative Complications ; etiology ; prevention & control ; therapy ; Prognosis ; Reconstructive Surgical Procedures ; adverse effects ; methods

BackgroundMineral and bone disorder is one of the severe complications in kidney transplant recipients (KTRs). Previous studies showed that bisphosphonates had favorable effects on bone mineral density (BMD). We sought to compare different bisphosphonate regimens and rank their strategies.

MethodsWe searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to April 01, 2017, for randomized controlled trials (RCTs) comparing bisphosphonate treatments in adult KTRs. The primary outcome was BMD change. We executed the tool recommended by the Cochrane Collaboration to evaluate the risk of bias. We performed pairwise meta-analyses using random effects models and network meta-analysis (NMA) using Bayesian models and assessed the quality of evidence.

ResultsA total of 21 RCTs (1332 participants) comparing 6 bisphosphonate regimens were included. All bisphosphonates showed a significantly increased percentage change in BMD at the lumbar spine compared to calcium except clodronate. Pamidronate with calcium and Vitamin D analogs showed improved BMD in comparison to clodronate with calcium (mean difference [MD], 9.84; 95% credibility interval [CrI], 1.06-19.70). The combination of calcium and Vitamin D analogs had a significantly lower influence than adding either pamidronate or alendronate (MD, 6.34; 95% CrI, 2.59-11.01 and MD, 6.16; 95% CrI, 0.54-13.24, respectively). In terms of percentage BMD change at the femoral neck, both pamidronate and ibandronate combined with calcium demonstrated a remarkable gain compared with calcium (MD, 7.02; 95% CrI, 0.30-13.29 and MD, 7.30; 95% CrI, 0.32-14.22, respectively). The combination of ibandronate with calcium displayed a significant increase in absolute BMD compared to any other treatments and was ranked best.

ConclusionsOur NMA suggested that new-generation bisphosphonates such as ibandronate were more favorable in KTRs to improve BMD. However, the conclusion should be treated with caution due to indirect comparisons.

Bone Density ; drug effects ; Diphosphonates ; adverse effects ; therapeutic use ; Female ; Humans ; Kidney Transplantation ; adverse effects ; Male ; Osteoporosis ; prevention & control ; Randomized Controlled Trials as Topic

No abstract available.
Adult ; Bone Marrow/*pathology ; Fatal Outcome ; Graft vs Host Disease/etiology ; High-Throughput Nucleotide Sequencing ; Humans ; Liver Cirrhosis/pathology/*therapy ; *Liver Transplantation/adverse effects ; Microsatellite Repeats ; Middle Aged ; Polymerase Chain Reaction ; *Polymorphism, Single Nucleotide ; Transplantation Chimera/*genetics

Severe graft-versus-host disease (GVHD) is an often lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT). The safety of clinical-grade mesenchymal stem cells (MSCs) has been validated, but mixed results have been obtained due to heterogeneity of the MSCs. In this phase I study, the safety of bone marrow-derived homogeneous clonal MSCs (cMSCs) isolated by a new subfractionation culturing method was evaluated. cMSCs were produced in a GMP facility and intravenously administered to patients who had refractory GVHD to standard treatment resulting after allogeneic HSCT for hematologic malignancies. After administration of a single dose (1x10(6) cells/kg), 11 patients were evaluated for cMSC treatment safety and efficacy. During the trial, nine patients had 85 total adverse events and the rate of serious adverse events was 27.3% (3/11 patients). The only one adverse drug reaction related to cMSC administration was grade 2 myalgia in one patient. Treatment response was observed in four patients: one with acute GVHD (partial response) and three with chronic GVHD. The other chronic patients maintained stable disease during the observation period. This study demonstrates single cMSC infusion to have an acceptable safety profile and promising efficacy, suggesting that we can proceed with the next stage of the clinical trial.
Bone Marrow ; Drug-Related Side Effects and Adverse Reactions ; Graft vs Host Disease* ; Hematologic Neoplasms ; Hematopoietic Stem Cell Transplantation ; Humans ; Mesenchymal Stromal Cells* ; Myalgia ; Population Characteristics

OBJECTIVE: To observe the repairing effects of bone marrow transplantation with nerve tissue committed stem cell (NTCSCs) on experimental rats with injury of noise-induced hearing loss. METHOD: Guinea pigs were randomly divided into control group, noise exposure group and the transplanting group. A week after white noise exposure of 110 dB, NTCSCs and PBS were injected into guinea pigs of the noise exposure group and the transplanting group respectively. One week after noise exposure to four weeks continuous administration. ABR thresholds were measured respectively prior to the experiment, 1 week post-noise,1, 2 and 4 weeks post-drugs, The changes of cochlea hair cells were also observed by a scan electron microscope (SEM). RESULT: The ABR threshold shifts in the transplanting group were significantly fewer than that in the noise exposure group. SEM showed that hear hair of the inner and outer hair cells in noise exposure group displayed mess, fusion and imperfections. In the transplanting treatment group, the hair cells displayed slight pathological changes, there wasn't significant differents comparied with normal group. The number of OHCs were relatively stable in the normal group, while the obvious OHC loss was observed in other groups. There was significant difference among the three groups, however, the OHC loss in the transplanting group was no significantly different to that in the noise exposure (P > 0.05). CONCLUSION The bone marrow NTCSCs which had been transplanted to rat cochlea could reduce the damage of the noise on the hair cell, and thus played a role in repairing the damage of auditory nerve.
Animals ; Bone Marrow Cells ; Bone Marrow Transplantation ; Cochlea ; Guinea Pigs ; Hair Cells, Auditory, Outer ; pathology ; ultrastructure ; Hearing Loss, Noise-Induced ; therapy ; Noise ; adverse effects ; Rats ; Stem Cell Transplantation

BACKGROUNDThe effects of donor characteristics on CD34(+) cell dose remain controversial. Recently, we developed a novel haploidentical transplant protocol, in which mixture allografts of granulocyte colony-stimulating factor (G-CSF)-primed bone marrow (G-BM) and G-CSF-mobilized peripheral blood (G-PB) were used. The aim of this study was to investigate the effects of donor characteristics on CD34(+) cell dose in mixture allografts of G-BM and G-PB.

METHODSA total of 162 healthy adult donors, who underwent bone marrow harvest and peripheral blood collection between January 2009 and November 2010 in Peking University People's Hospital, were prospectively investigated. G-CSF was administered subcutaneously at a dose of 5 µg/kg once a day for 5-6 consecutive days. Bone marrow and peripheral blood stem cells were harvested on the fourth day and fifth day, respectively. A final total CD34(+) cell dose less than 2×10(6) cells/kg recipient body weight was considered a poor mobilization.

RESULTSOf the 162 donors, 31 (19.1%) did not attain this threshold. The obtained median CD34(+) cell doses in bone marrow, peripheral blood, and mixture allografts were 0.83×10(6)/kg, 2.40×10(6)/kg, and 3.47×10(6)/kg, respectively. Multiple regression analysis showed that donor age had a significant negative effect on CD34(+) cell dose in either G-BM, or G-PB, or mixture allografts of G-BM and G-PB. And a 1-year increase in age was associated with a 5.6% decrease in the odds of achieving mobilization cutoff. No significant correlation was found for donor gender, body mass index (BMI), and weight.

CONCLUSIONDonor age is the only factor among the four parameters, including age, gender, weight, and BMI, that influence CD34(+) cell dose in mixture allografts of G-BM and G-PB, and younger donors should be chosen to obtain sufficient CD34(+) cells for transplantation.

Adolescent ; Adult ; Aged ; Allografts ; Antigens, CD34 ; metabolism ; Bone Marrow ; Bone Marrow Transplantation ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; metabolism ; Hematopoietic Stem Cell Mobilization ; adverse effects ; Humans ; Male ; Middle Aged ; Prospective Studies ; Tissue Donors ; Young Adult