Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

To determine whether the microRNAs (miRNAs) contained in cancer-derived microvesicles (MVs) mirror those of the parental tumor cells, we compared the miRNA expression profiles of MVs derived from their parental hepatocellular carcinoma (HCC) cells. The presence and levels of 888 miRNAs from SMMC-7721 cells and MVs were detected by Agilent miRNA microarray analysis. Four selected miRNAs were verified by real time qRT-PCR. Furthermore, the genes of the miRNAs were bioinformatically identified to explore potential roles of the miRNAs in HCC microenvironment. Our results showed that miRNAs expression profiles of MVs derived from HCC were significantly changed. Of all the miRNAs tested, 148 miRNAs were co-expressed in MVs and SMMC-7721 cells, only 121 and 15 miRNAs were detected in MVs and SMMC-7721 cells, respectively. Among the 148 co-expressing miRNAs, 48 miRNAs had the similar expression level and 6 of them were supposed to be oncogenic or suppressive miRNAs. According to the target prediction by Quantile Algorithm method, these miRNAs may regulate 3831 genes which were closely related to cell cycle, apoptosis and oncogenesis, and 78 were known tumor suppressors or oncogenes. Gene ontology (GO) analysis indicated that 3831 genes were mainly associated with nucleic acid binding, cell death, cell adhesion. MVs containing miRNAs, released into the HCC microenvironment, bear the characteristic miRNAs of the original cells and might participate in cancer progression.
Carcinoma, Hepatocellular ; genetics ; Cell Line, Tumor ; Cell Transformation, Neoplastic ; genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; genetics ; Humans ; Liver Neoplasms ; genetics ; MicroRNAs ; genetics ; Neoplasm Proteins ; genetics ; RNA, Neoplasm ; genetics ; Transport Vesicles ; genetics

A female patient diagnosed with acute myelocytic leukemia M5a (AML-M5a) relapsed 986 days after her allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from an unrelated male donor with matched human leukocyte antigen (HLA). Three re-induction chemotherapies were administered, and partial remission was achieved. The patient was given repetitive infusion of cytokine-induced killer (CIK) cells expanded from recipient peripheral mononuclear cells of full donor chimerism due to loss of contact of quondam donor for donor lymphocyte infusion (DLI) and rejection of second transplantation. The patient achieved complete cytogenetical remission. This strategy might overcome the obstacle of donor unavailability and present an appealing new therapeutic alternative to donor-recruited adoptive immunotherapy for relapsed disease at post-transplantation.
Adult ; Cytokine-Induced Killer Cells ; transplantation ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia ; therapy

OBJECTIVETo analysis the clinic and genotype in two Chinese patients with Dyskeratosis congenita (DC).

METHODSThe two patients were characterized by mucocutaneous abnormalities (abnormal nails, lacey reticular pigmentation, and oral leukoplakia), bone marrow failure. They were diagnosed with DC. DC genes were amplified by polymerase chain reaction (PCR), including DKC1, TERT, TERC, TINF2, NOP10, NHP2, then DNA sequencing was performed for abnormal exons.

RESULTSAn abnormal peak was found in exon 6 of TINF2 gene of the two patients. DNA sequencing showed a 845G→A transition in TINF2 gene in the two patients.

CONCLUSIONWe should think about DC if the young patients with mucocutaneous abnormalities and marrow failure. TINF2 c.845G→A(R282H) does exist in the two patients. It is reported in China for the first time.

Base Sequence ; Child, Preschool ; DNA Mutational Analysis ; Dyskeratosis Congenita ; diagnosis ; genetics ; Exons ; Female ; Humans ; Infant ; Male ; Telomere-Binding Proteins ; genetics

Cell-Derived Microparticles ; Disease Progression ; Humans ; Leukemia ; pathology

In order to investigate the molecular mechanisms of SARI expression regulation in chronic myeloid leukemia (CML), 46 patients with CML and 40 healthy volunteers were recruited in this study. SARI expression in the peripheral blood mononuclear cells (PBMNC) of CML patients and healthy volunteers was assayed by using real-time quantitative PCR. K562 cells were in vitro incubated with the BCR-ABL inhibitor STI571 (imatinib) at 37°C and 5% CO2 for 24 hours, then SARI expression was detected by using real-time quantitative PCR. All experiments were repeated three times. The results showed that as compared with healthy volunteers, the expression of SARI mRNA in PBMNC of CML patients presented a lower level (p < 0.001). After exposure of K562 cells to STI571 (2.5 µmol/L) for 24 hours, the SARI expression was higher than that in K562 cells treated without STI571 (p < 0.001). It is concluded that the suppression of SARI expression is involved in CML pathogenesis, and BCR-ABL mediates the down-regulation of SARI mRNA expression in K562 cells. These findings suggest a new orientation for gene therapy in CML patients.
Basic-Leucine Zipper Transcription Factors ; genetics ; Benzamides ; Fusion Proteins, bcr-abl ; antagonists & inhibitors ; Gene Expression Regulation, Leukemic ; drug effects ; Humans ; Imatinib Mesylate ; K562 Cells ; Piperazines ; pharmacology ; Pyrimidines ; pharmacology ; Tumor Suppressor Proteins ; genetics

The aim of this study was to investigate the apoptosis-inducing effect of cinnamic aldehyde (CA) on chronic myeloid leukemic (CML) cells and its mechanism. K562 cells and primary bone marrow mononuclear cells (MNC) from patients with CML were treated by various concentrations of CA. Flow cytometry was employed to measure the apoptosis of K562 cells and primary CML bone marrow MNC. Western blot was used to determine the expression of C-MYC and the phosphorylation of CrkL in K562 cells, and real-time polymerase chain reaction (real-time PCR) was used to quantify the expression of BCR-ABL mRNA in K562 cells. The results indicated that CA induced the apoptosis of K562 cells in a time- and dose-dependent manner. CA induced apoptosis of CML MNC dose-dependently. CA inhibited the expression of BCR-ABL mRNA and C-MYC, reduced CrkL phosphorylation levels in K562 cells. It is concluded that CA induces apoptosis of CML cells in vitro. Down-regulation of the expression and function of BCR-ABL may be one of its most important anti-leukemia mechanisms.
Acrolein ; analogs & derivatives ; pharmacology ; Apoptosis ; drug effects ; Fusion Proteins, bcr-abl ; metabolism ; Gene Expression Regulation, Leukemic ; Humans ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; metabolism ; pathology

In order to investigate the effect of PP2A activator and PP2A inhibitor on proliferation of HL-60 cells and analyze the changes of PP2A activity in patients with acute myeloid leukemia (AML), HL-60 cells were treated with FTY720 alone or in combination with okadaic acid (OA) for 24 hours in culture. Cell proliferation was assayed with CCK8 kit. In addition, 20 AML patients including de novo AML and relapsed AML were enrolled in this study. The activity of PP2A in the peripheral blood mononuclear cells of patients was assayed with a PP2A Immunoprecipitation Phosphatase Assay Kit, the data were analyzed by software SPSS 16.0. The results indicated that as compared with control group, the proliferation of cells in FTY720 group was obviously inhibited (p < 0.05). The proliferation of cells in FTY720 + OA group was slightly inhibited as compared with the control group, there was no statistical difference (p > 0.05), but there was significant difference between the FTY720 + OA and FTY720 groups (p < 0.05). The activity of PP2A in AML patients (453.67 ± 102.52 pmol phosphate) was obviously lower than that in the normal controls (673.29 ± 96.32 pmol phosphate), there was significant difference between them (p < 0.01). It is concluded that the activation or inhibition of PP2A can affect the proliferation of HL-60 cells in vitro. Compared with healthy individuals, the activity of PP2A in AML patients is obviously lower. PP2A protein playing a key role in the occurrence and development of AML may be valuable for the diagnosis and treatment of AML.
Adult ; Aged ; Apoptosis ; Case-Control Studies ; Cell Proliferation ; drug effects ; Enzyme Activators ; pharmacology ; Enzyme Inhibitors ; pharmacology ; Female ; Fingolimod Hydrochloride ; HL-60 Cells ; Humans ; Leukemia, Myeloid, Acute ; metabolism ; Male ; Middle Aged ; Okadaic Acid ; pharmacology ; Propylene Glycols ; pharmacology ; Protein Phosphatase 2 ; antagonists & inhibitors ; metabolism ; Sphingosine ; analogs & derivatives ; pharmacology ; Young Adult

The expression of immunological markers of one hematopoietic lineage on the abnormal cells of another lineage (cross-lineage expression) is a known feature of leukemia. The present study was aimed to investigate the cross-lineage expression in ALL cells. The cross-lineage expression in ALL cells from 505 patients was detected by flow cytometry using 23 monoclonal antibodies (McAbs) in triple staining combinations. The results showed that in whole ALL, the expression of myeloid antigens occurred in 56.4% of the cases, and CD13 was the most frequently expressed myeloid marker (32.7%) followed by CD33 (29.5%), CD15 (19.2%) and CD11b (7.7%). CD13/CD33 expressions were more frequent in CD34(+) cases than in CD34(-) cases. In B-ALL, T-cell antigen CD4, CD5, CD7 and CD2 were found in 27 (6.3%), 12 (2.8%), 8 (1.9%), and 6 (1.4%) cases respectively, and CD7(+), CD2(+) and CD4(+) cases commonly expressed CD13/CD33. In T-ALL, B-cell antigen cCD79a, CD19 and CD22 were found in 6 (8.1%), 5 (6.8%), and 2 (2.8%) cases respectively, and all of CD19(+) and CD22(+) cases were all accompanied with CD13/CD33. It is concluded that cross-lineage expression in ALL mostly exists in the immature stages, ALL cells more frequently express phenotypes B(+)M(+), T(+)M(+) and occasionally B(+)T(+)M(+), but B(+)T(+)M(-) phenotype is extremely rare.
Adolescent ; Adult ; Aged ; Antigens, CD ; metabolism ; Child ; Child, Preschool ; Female ; Flow Cytometry ; methods ; Humans ; Immunophenotyping ; Infant ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; immunology ; metabolism ; Young Adult

Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease of transformed hematopoietic progenitor cells. The expressions of JunB and CDH13 (cadherin-13) gene as tumor suppressor gene were inactivated by promoter methylation in CML patients. This study was purposed to investigate the methylation difference of JunB and CDH13 gene promoter and the expression levels of JunB and CDH13 gene in CD34(+)CD38(-) cells in CML patients vs normal individuals. CD34(+)CD38(-) cells from 8 cases of CML and 5 normal individuals were selected by flow cytometry. The methylation status of JunB and CDH13 genes were detected by MS-PCR in selected CD34(+)CD38(-) cells. The expression levels of JunB and CDH13 gene was detected with real time polymerase chain reaction (RT-PCR). The results showed that no methylation of JunB and CDH13 gene was detected in CD34(+)CD38(-) cells of 5 normal individuals. Methylations of JunB and CDH13 promoter were found in 87.5% (7/8) and 50% (4/8) CML CD34(+)CD38(-) cells, percentages of which were significantly higher than those in normal individuals. The difference was statistically significant (p < 0.05). The relative expression levels of JunB and CDH13 mRNA in CD34(+)CD38(-) cells of CML patients were significantly lower than those in normal individuals (2(-DeltaDeltaCT) were 1/5.21 and 1/10.63 respectively). It is concluded that the high methylation of JunB and CDH13 gene promoter occurs in CD34(+)CD38(-) cells of CML patients, their mRNA expression level is significantly lower, thus the methylation of JunB and CDH13 gene promoter probably plays a role in the pathogenesis of CML and may have clinical significance in predicting prognosis of CML.
ADP-ribosyl Cyclase 1 ; immunology ; Adult ; Aged ; Antigens, CD34 ; immunology ; Cadherins ; genetics ; DNA Methylation ; Female ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; Male ; Middle Aged ; Promoter Regions, Genetic ; Proto-Oncogene Proteins c-jun ; genetics