When is the best time and grade to start ruxolitinib in corticosteroid-refractory acute graft-versus-host-disease: A multi-center research.

OBJECTIVE: Ruxolitinib was recently approved to treat corticosteroid-resistant acute graft-versus-host disease (GvHD). However, it is unknown as to whether starting ruxolitinib at a lower versus higher acute GvHD grade or earlier versus later affected outcomes. This study identified the impact of starting acute GvHD grade and start time after declaring corticosteroid resistance and the effect on complete and overall response rates to ruxolitinib therapy. METHODS: Retrospective, observational multi-center study. We divided cohorts into starting ruxolitinib ≤ 7 days (N = 45) versus at > 7 days after declaring corticosteroid resistance (N = 24). RESULTS: In ≤ 7 days cohort complete response (CR) rates at day 28 were 69% (54, 81%) versus 25% (11, 47%; p = .001) in > 7 days cohort, and overall response (OR) rates were 91% (78, 96%) versus 80% (48, 92%; p = .25). CONCLUSIONS: Our data suggest that starting ruxolitinib in ≤ 7 days of declaring corticosteroid failure regardless of G vHD grade improves complete response rate but not OR rates. Starting ruxolitinib at grade I and within 7 days may get a more significant response.

Efficacy and safety of generic pomalidomide plus low-dose dexamethasone in relapsed or refractory multiple myeloma: a multicenter, open-label, single-arm trial.

This multicenter, open-label, single-arm trial (ClinicalTrials.gov, NCT05236621) was conducted to confirm the efficacy and safety of generic pomalidomide plus dexamethasone in Chinese patients with relapsed or refractory multiple myeloma (RRMM). Total 79 eligible RRMM patients were planned to be included. Patients were treated with generic pomalidomide (4 mg daily on days 1-21, orally) and low-dose dexamethasone (40 mg/day on days 1, 8, 15, and 22, orally; 20 mg for patients aged > 75 years) in 28-day cycles until disease progression with a maximum treatment duration of 2 years. The primary endpoint is the overall response rate (ORR) assessed by the independent review committee per the 2016 International Myeloma Working Group guidelines. A total of 85 eligible patients were included in this study from 32 centers in China, with a median age of 62.0 (range, 39-76) years, a median prior line of therapy of 4 (range, 1-16), and 41.2% patients with high-risk cytogenetics. The ORR was 38.8% (95% confidence interval (CI), 28.44-50.01). The disease control rate was 67.1% (95% CI, 56.02-76.87), meanwhile, the median progression-free survival was 5.55 months (95% CI, 3.68-7.52). Among the treatment-related adverse events (TRAEs), infective pneumonia (17.6%) was the most frequent non-hematologic adverse event, while a decrease in neutrophil count (52.9%) was the most common grade ≥ 3 TRAE. The study results indicated that the generic pomalidomide demonstrated consistent efficacy and a safety profile similar to the branded pomalidomide when combined with low-dose dexamethasone in Chinese RRMM patients.Registration number ClinicalTrials.gov NCT05236621, retrospectively registered on February 11, 2022.

Analysis of Pathogenic Bacteria Distribution and Related Factors in Recurrent Acute Cholangitis.

Background: To evaluate the risk factors and prognosis of patients with acute cholangitis recurrence. Methods: A total of 503 patients with acute cholangitis admitted to the First Affiliated Hospital of Chongqing Medical University between July 2013 and January 2022 were included in this retrospective observational study, who were followed up for 360 days and divided into relapse group and non-recurrence group according to the recurrence of acute cholangitis. Risk factors and prognosis of patients with acute cholangitis recurrence were analyzed by univariate, multivariate analyses and proportional hazards model. Results: A total of 161 patients with recurrent acute cholangitis were identified. Recurrent acute cholangitis usually occurred within 125 days; Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecalis, and Enterococcus faecium was the most common positive record both in blood and bile culture. In the multivariate analysis, abdominal pain (OR = 2.448, 95% CI = 1.196-5.010, P = 0.014), bile stones (OR = 2.429, 95% CI = 1.024-5.762, P = 0.044), diabetes (OR = 1.790, 95% CI = 1.007-3.182, P = 0.047), pathogen (OR = 3.305, 95% CI = 1.932-5.654, P<0.001), and chronic kidney disease (OR = 2.500, 95% CI = 1.197-5.221, P = 0.015) may be ascertained as the risk factors of acute cholangitis recurrence. The recurrence of acute cholangitis was identified as an independent risk factor for patient death (HR = 4.524, 95% CI = 1.426-14.357, P = 0.010) by Cox proportional-hazards regression. Conclusion: Abdominal pain, bile stones, diabetes and chronic kidney disease may be risk factors of acute cholangitis recurrence. Patients with recurrent acute cholangitis have poor prognosis and high mortality. Early control of recurrent risk factors and active intervention are beneficial to high-risk patients.

Construction of a prognostic model of acute myeloid leukemia associated with immunogenic cell death.

BACKGROUND: Immunogenic cell death (ICD)is a kind of regulatory cell death, which causes a series of antigen-specific adaptive immune responses by generating and emitting some danger signals or damage-associated molecular patterns (DAMPs). At present, little is known about the prognostic value of ICD and its related processes in acute myeloid leukemia (AML). The aim of the study was to explore the relationship between ICD and tumor immune microenvironment changes in AML. RESEARCH DESIGN & METHODS: In the study, AML samples were divided into two groups by consensus clustering analysis, and then gene enrichment analysis and GSEA analysis were performed on the ICD high expression group. Furthermore, CIBERSORT was used to analyze the tumor microenvironment and immune characteristics of AML. Finally, a prognostic model related to ICD was constructed by using univariate and multivariate regression analysis. RESULTS: ICD was divided into two groups according to the level of ICD gene expression. The ICD high expression group was associated with good clinical results and high levels of immune cell infiltration. CONCLUSIONS: The study constructed and verified the prognostic characteristics of AML related to ICD, which has important value in predicting the overall survival time of AML patients.

Addition of ruxolitinib in Graft-versus-Host disease prophylaxis for pediatric ß-Thalassemia major patients after allogeneic stem cell transplantation: A retrospective cohort study.

BACKGROUND: To evaluate the effect of addition of ruxolitinib in Graft-versus-Host Disease (GVHD) prophylaxis on pediatric patients with ß-thalassemia major after allogeneic hematopoietic stem cell transplantation(HSCT). METHODS: This retrospective study reviewed 49 consecutive ß-thalassemia major pediatric patients who underwent HSCT from unrelated or haploidentical donors from February 2018 to October 2022. All transplantation recipients received cyclosporine A (CsA), mycophenolate mofetil (MMF), and short-term methotrexate (MTX) as GVHD prophylaxis; while 27 of them in the ruxolitinib group had added ruxolitinib oral to GVHD prophylaxis regimen at 2.5 mg twice daily once successful engraftment after January 2020. RESULTS: The outcome showed that the ruxolitinib group had a lower cumulative incidence than the control group regardless of acute GVHD (22.2% vs.40.9%; p = .153) or chronic GVHD (18.5% vs.40.9%; p = .072); especially, the incidence of grade III-IV acute GVHD was reported significantly less frequently in ruxolitinib group than that of the control group (0 vs. 27.3%, p = .005). No significant difference was detected between the two groups in EBV (Epstein-Barr virus)/CMV (cytomegalovirus) reactivation and BKV (BK virus) infection (p = .703, 1.000, and .436, respectively). Twenty-six patients (96.3%) in the ruxolitinib group were alive, while two patients (9.1%) in the control group died of intestinal acute GVHD. The 2-year overall survival (OS) and thalassemia-free survival (TFS) were both 96.296% in the ruxolitinib group, while both 90.909% in the control group. CONCLUSION: This study reveals that ruxolitinib prophylaxis is a promising option to decrease the incidence of grade III-IV acute GVHD in pediatric patients with ß-thalassemia major.

Recombinant human thrombopoietin (rhTPO) of different dosing regimens for refractory/relapsed primary immune thrombocytopenia: a multicenter, randomized controlled trial and pharmacokinetics study.

Recombinant human TPO (rhTPO) is effective for refractory/relapsed primary immune thrombocytopenia (ITP), but optimal dosing regimen remains elusive. In this multicenter, randomized, controlled trial, a total of 282 adult ITP patients (mean age 47.3 years; 82 men) with a platelet count ≤30 × 109/L or >30 × 109/L with active bleeding randomly received a once daily (QD) subcutaneous injection of 7500 U (n = 64) or 15000 U rhTPO for 14 injections, or 15000 U or 30000 U rhTPO once every other day (QOD) for 7 injections. The primary outcomes included change from baseline in platelet count and total response rate (TRR) on day 14. On day 14, the median increase of platelet count from baseline was the highest in the 15000-U QD group (167.5 × 109/L, interquartile range [IQR] 23.0-295.0 × 109/L), followed by the 30000-U QOD group (57.5 × 109/L, IQR 9.0-190.0 × 109/L) (ANCOVA P < .001; P = .266 with baseline count as a covariate). The TRR on day 14 was also the highest in the 15000-U QD group (63.2%), followed by the 30000-U QOD group (59.7%). The rate of grade 3 and above adverse events did not differ among the four groups. There were no new safety concerns. All 4 regimens are safe and well-tolerated. The 30000-U QOD regimen is practically indistinguishable in efficacy to the 15000-U QD regimen.

What is the context? Relative thrombopoietin deficiency is implicated in primary immune thrombocytopenia (ITP), which is characterized by increased platelet destruction and impaired megakaryopoiesis.Patients who are innately unresponsive to or have relapsed after glucocorticoid treatment have limited treatment options.Recombinant human thrombopoietin (rhTPO) improves treatment response of primary ITP patients when added to high-dose dexamethasone.What is new? This trial sought to identify an optimal dosing regimen of rhTPO for patients who had failed or relapsed after glucocorticoid therapy.Of the 4 regimens, once daily 15000 U rhTPO for 14 injections yielded the greatest median increase in platelet count (167.5 × 10⁹/L) from baseline and attained the highest total response rate on day 14 (63.2%).30000 U rhTPO once every other day for 7 injections was effective in rapidly increasing platelet counts in the first 7 days.All 4 regimens were safe and well-tolerated.What is the impact? The 30000 U rhTPO once every other day regimen may offer an effective and safe regimen with less frequent injections, but future trials with longer follow-up are needed.

The novel HLA-DPB1*1352:01 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-DPB1*1352:01 differs from HLA-DPB1*02:01:02:01 by one nucleotide in exon 4.

Azaphilones from the Endophyte Diaporthe sp. and Their Toxicity.

Chemotherapy and targeted therapies are increasingly used as conventional means to control tumor growth and prolong survival. Patient treated with anti-neoplastic agents experience severe side effects, especially those cytotoxic chemotherapies. Exploring chemo agents with less side effects is the hot spot of anticancer research. In this study, three azaphilone derivatives (chaetoviridin A (1), chaetoviridin E (2) and chaetomugilin D (3)) were isolated from the endophyte of the plant Anoectochilus roxburghii (Wall.) Lindl, their structures were elucidated by NMR. The toxicity of these compounds was evaluated by zebrafish model. The results show that these compounds had no toxicity against zebrafish. These compounds may act as safe anticancer drug leads according to this result. These three azaphilone derivatives were first time reported isolated from Diaporthe species which mainly used to isolate from Chaetomium species.

[The Clinical Observation with Ruxolitinib as Graft-Versus-Host Disease Prophylaxis for Children with Thalassemia after Unrelated or Haploidentical Allo-Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To retrospectively analyze the efficacy and safety of ruxolitinib therapy for children with thalassemia after unrelated or haploidentical stem cell transplantation. METHODS: From March 2020 to March 2021, 22 patients received successfully allogeneic hematopoietic stem cell transplantation in the Zhongshan Hospital of Xiamen University, from +30 to 100 days,those patients received ruxolitinib therapy (2.5 mg, twice daily) and all adverse reactions were observed, include aGVHD, cGVHD, CMV and EBV infection. RESULTS: 22 patients underwent allogeneic stem cell transplantation, 5 patients were diagnosed as aGVHD, 3 patients had grade I－II skin GVHD and 2 patients had grade II intestinal GVHD, those patients were cured. All patients were followed up for more than 21 weeks, 4 cases developed cGVHD, including 3 cases of localized liver GVHD and 1 case of pulmonary GVHD, those were relieved after active treatment. 8 patients had elevated EBV copies (>3×103/ml), and 3 patients had increased CMV copies, the patients recovered after immunosuppressant and antiviral treatment. There was no CMV infection and EBV related post-transplantant lymphoproliferative disorders(PTLD), and no transplant related deaths. CONCLUSION: Ruxolitinib can effectively reduce the incidence and severity of GVHD without affecting the hematopoietic recovery, and improve the survival status of thalassemia children after transplantation.

Bioinformatics Analysis of the Key Genes and Pathways in Multiple Myeloma.

Objective: To study the differentially expressed genes between multiple myeloma and healthy whole blood samples by bioinformatics analysis, find out the key genes involved in the occurrence, development and prognosis of multiple myeloma, and analyze and predict their functions. Methods: The gene chip data GSE146649 was downloaded from the GEO expression database. The gene chip data GSE146649 was analyzed by R language to obtain the genes with different expression in multiple myeloma and healthy samples, and the cluster analysis heat map was constructed. At the same time, the protein-protein interaction (PPI) networks of these DEGs were established by STRING and Cytoscape software. The gene co-expression module was constructed by weighted correlation network analysis (WGCNA). The hub genes were identified from key gene and central gene. TCGA database was used to analyze the expression of differentially expressed genes in patients with multiple myeloma. Finally, the expression level of TNFSF11 in whole blood samples from patients with multiple myeloma was analyzed by RT qPCR. Results: We identified four genes (TNFSF11, FGF2, SGMS2, IGFBP7) as hub genes of multiple myeloma. Then, TCGA database was used to analyze the survival of TNFSF11, FGF2, SGMS2 and IGFBP7 in patients with multiple myeloma. Finally, the expression level of TNFSF11 in whole blood samples from patients with multiple myeloma was analyzed by RT qPCR. Conclusion: The study suggests that TNFSF11, FGF2, SGMS2 and IGFBP7 are important research targets to explore the pathogenesis, diagnosis and treatment of multiple myeloma.

Primary isolated central nervous system acute lymphoblastic leukemia with BCR-ABL1 rearrangement: A case report.

BACKGROUND: BCR-ABL1 fusion gene is associated with a poor prognosis and a high incidence in central nervous system (CNS) leukemia. CNS invasion which detected at the initial diagnosis is commonly with bone marrow infiltration. It is uncommon for the leukemia cells to be located primarily in the CNS without bone marrow involvement. CASE SUMMARY: We here report the rare initial presentation of CNS-restricted BCR-ABL-positive acute lymphoblastic leukemia in a 30-year-old female patient who clinically manifested with leukemic meningitis, with no involvement in peripheral blood or bone marrow. Identification of abnormal phenotypes of blast cells, and BCR-ABL1 rearrangement in the cerebrospinal fluid alone established the diagnosis of primary CNS-isolated acute lymphocytic leukemia. The patient received a combination of intrathecal therapy and high-dose chemotherapy. But the benefits of the treatments were short-lived and she experienced recurrence. CONCLUSION: Flow cytometry in combination with molecular genetic analysis improved diagnostic accuracy. New approaches that may enhance the efficacy of the existing therapies and cure CNS leukemia are required.

Clinical Characteristics and Outcome Analysis for HLA Loss Patients Following Partially Mismatched Related Donor Transplantation Using HLA Chimerism for Loss of Heterozygosity Analysis by Next-Generation Sequencing.

Genomic loss of mismatched human leukocyte antigen (HLA loss) is one of the most vital immune escape mechanisms of leukemic cells after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the methods currently used for HLA loss analysis have some shortcomings. Limited literature has been published, especially in lymphoid malignancies. This study aims to evaluate the incidences, risk factors of HLA loss, and clinical outcomes of HLA loss patients. In all, 160 patients undergoing partially mismatched related donor (MMRD) transplantation from 18 centers in China were selected for HLA loss analysis with the next-generation sequencing (NGS)-based method, which was validated by HLA-KMR. Variables of the prognostic risk factors for HLA loss or HLA loss-related relapse were identified with the logistic regression or the Fine and Gray regression model. An HLA loss detection system, HLA-CLN [HLA chimerism for loss of heterozygosity (LOH) analysis by NGS], was successfully developed. Forty (25.0%) patients with HLA loss were reported, including 27 with myeloid and 13 with lymphoid malignancies. Surprisingly, 6 of those 40 patients did not relapse. The 2-year cumulative incidences of HLA loss (22.7% vs 22.0%, P = 0.731) and HLA loss-related relapse (18.4% vs 20.0%, P = 0.616) were similar between patients with myeloid and lymphoid malignancies. The number of HLA mismatches (5/10 vs <5/10) was significantly associated with HLA loss in the whole cohort [odds ratio (OR): 3.15, P = 0.021] and patients with myeloid malignancies (OR: 3.94, P = 0.021). A higher refined-disease risk index (OR: 6.91, P = 0.033) and donor-recipient ABO incompatibility (OR: 4.58, P = 0.057) contributed to HLA loss in lymphoid malignancies. To sum up, HLA-CLN could overcome the limitations of HLA-KMR and achieve a better HLA coverage for more patients. The clinical characteristics and outcomes were similar in patients with HLA loss between myeloid and lymphoid malignancies. In addition, the results suggested that a patient with HLA loss might not always relapse.

[Comparision of Allogeneic Hematopoietic Stem Cell Transplantation between Children with Thalassemia of Different Ages].

OBJECTIVE: To investigate the difference of therapeutic effects on children with thalassemia at different age after hematopoietic stem cell transplantation. METHODS: The clinical data of children with thalassemia treated in our hospital were retrospectively analyzed. The children were divided into 2-5 years old group and 6-12 years old group. The success rate of implantation, transplant-related mortality, GVHD incidence, and other transplant-related complications, as well as thalassemia-free survival (TFS) were compared between the two groups. RESULTS: The incidence of GVHD, hemorrhagic cystitis and severe oral mucositis after transplantation in the 2-5 years old group were significantly lower than those in the 6-12 years old group, while there was no statistically significant difference in the TFS between the two groups. CONCLUSION: Children in the low age (2-5 years old) group show fewer complications and higher quality of life after transplantation, therefore, stem cell transplantation at 2-5 years old is more conducive to rehabilitation of the children with thalassemia.

[The Clinical Efficacy of Haploidentical Hematopoietic Stem Cell Transplantation by Using Parental Donors in Patients with Thalassemia].

OBJECTIVE: To analyze the clinical efficacy of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) by using parental donors on thalassemia patients. METHODS: The 13 thalassemia patients treated by haplo-HSCT using parental donors in our hospital from July 1, 2016, to July 1, 2020 were retrospectively reviewed. Hematopoiesis reconstitution, the incidence of GVHD, infections and the long-term survival of the patients were analyzed. RESULTS: Twelve of the 13 patients were successfully implanted, the success rate of implantation was 92.3%. The median time of neutrophil and platelet engraftment was 12.5 days (range, 9-22 days) and 21 days (range,12-34 days), respectively. One patient achieved primary graft failure. Three (25%) patients developed to acute GVHD (aGVHD) and achieved complete remission after treatment. Chronic GVHD developed in three (25%) patients, one of them was extensive and under treatment, while one patient developed to severe bacterial infection (7.7%). CMV viremia was diagnosed in two patients (15.4%). There were no patients developed to CMV disease. Three (23.1%) patients achieved EB viremia after transplantation, one of them developed to EBV-related lymphocytic proliferative disease, while there were no patients showed invasive fungal infection. At the last follow-up, all patients survived, twelve of them were free from transfusion dependency. There were no transplant-related deaths. Projected overall and thalassemia-free survival at three years was 100% and 92.3%, respectively. CONCLUSION: The transplant protocol of haplo-HSCT by using parental donors in patients with thalassemia has reliable source of donors, high incidence of successful implantation and low incidence of GVHD, which can be used as an effective way to increase the source of donors in children with thalassemia.

Tocilizumab combined with ruxolitinib in the treatment of children with steroid resistant graft versus host disease after hematopoietic stem cell transplantation: report of 6 cases.

Six children with steroid resistant graft versus host disease (GVHD) after hematopoietic stem cell transplantation admitted in the hospital, including 4 cases of acute GVHD and 2 cases of chronic GVHD. Among the 4 acute GVHD cases, the main manifestations were large area rash and fever in 2 cases, and abdominal pain and diarrhea in 2 cases. In 2 chronic GVHD cases, one presented lichenoid dermatosis, and the other showed repeated oral ulcers with difficult mouth opening. Patients received tocilizumab (8 mg/kg per dose every 3 weeks) and ruxolitinib (5-10 mg/d, 28 d), at least 2 courses were completed. All patients had complete responses (100%), and 5 patients responded after completion of two treatment courses, with the median time of remission was 26.7 d. The median follow-up period was 11 (7-25) months, and no severe treatment-related adverse reactions were observed.

The effect of bone cement on the curative effect of percutaneous kyphoplasty in the treatment of osteoporotic vertebral compression fracture.

BACKGROUND: To investigate the effect of bone cement on the curative effect of percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral compression fracture (OVCF). METHODS: A total of 323 patients with OVCF who underwent PKP in our hospital between January 2018 and June 2020 were enrolled. According to the viscosity and distribution of the bone cement, the patients were divided into a high viscosity (HV) group and a low viscosity (LV) group, and into a central distribution (central) group and a lateral distribution (lateral) group, and their baseline characteristics, perioperative parameters, efficacy indicators, and complications indicators were compared. RESULTS: In the HV group, the amount of bone cement injected and the number of patients with centrally distributed bone cement were significantly higher than those in the LV group, while the operation time and the number of patients with laterally distributed bone cement were significantly lower. Further, the bone cement viscosity in the central group was significantly higher than that in the lateral group. Before surgery, there were no significant differences between the groups in terms of the posterior back visual analog scale (VAS) score, Oswestry dysfunction index (ODI), Cobb angle, vertebral height, or anterior vertebral height (AVH) of the fractured vertebral body. However, after surgery, both the ODI and the Cobb angle were notably reduced and the AVH was increased in the HV group. Meanwhile, in the central group, the VAS, Cobb angle, and ODI were all dramatically reduced. CONCLUSIONS: Centrally distributed high-viscosity bone cement can reduce the Cobb angle and the incidence of bone cement leakage in patients with OVCF who undergo PKP, thereby improving the curative effect.

Polymyositis in a child with thalassemia after hematopoietic stem cell transplantation: A case report.

RATIONALE: Polymyositis (PM) is a rare neuromuscular phenotype of chronic graft-versus-host disease (cGVHD). Although glucocorticoids have been shown to be effective in the treatment of PM, most people experience poor treatment response and poor prognosis. PATIENT CONCERNS: A six-year-old boy with thalassemia received allogeneic hematopoietic stem cell transplantation (HSCT) and consequently developed sudden myasthenia of limbs 17 months after the transplant. DIAGNOSES: Medical history, current symptoms, laboratory examinations, and imaging findings of the patient indicated cGVHD complicated with PM. INTERVENTIONS: He was then given high-dose corticosteroid therapy, including tacrolimus, ruxolitinib, and rituximab. OUTCOMES: Twenty-three months after transplantation, creatine kinase levels returned to normal range, and the MRI showed that the original muscle edema signal was significantly improved. The patient's muscle weakness continued to improve, and his overall condition was good. LESSONS: This report suggests that glucocorticoids combined with immunosuppressants may be effective against polymyositis. Rituximab and ruxolitinib may be a good choice in treating polymyositis.

High-Throughput Human Telomere Length Analysis at the Single-Chromosome Level by FISH Coupled with Nano-Flow Cytometry.

Telomere length (TL) is a highly relevant biomarker for age-associated diseases and cancer, yet its clinical applications have been hindered by the inability of existing methods to rapidly measure the TL distribution and the percentage of chromosomes with critically short telomeres (CSTs, < 3 kb). Herein, we report the development of a high-throughput method to measure TL at the single-chromosome level. Metaphase chromosomes are isolated, hybridized with the Alexa Fluor 488-labeled telomeric peptide nucleic acid probe, and analyzed using a laboratory-built ultrasensitive nano-flow cytometer. The fluorescence intensity of individual chromosomes is converted to TL in kilobases upon external calibration. With an analysis rate of several thousand chromosomes per minute, a statistically robust TL distribution histogram is acquired in minutes, and the percentage of chromosomes with CSTs can be quickly assessed. By analyzing peripheral blood lymphocytes of 158 healthy donors, TL is found to shorten with age at a rate of 64 ± 3 bp/year and the percentage of chromosomes with CSTs increases with age at a rate of 0.32 ± 0.02%/year. Moreover, the data of 28 patients with chronic myeloid leukemia (CML) indicate that telomeres are significantly shorter at the time of diagnosis and the clinical phases of CML are closely associated with TL and the percentage of chromosomes with CSTs. This powerful tool could greatly deepen our understanding of telomere biology and improve the clinical utility of telomere biomarkers.

CT-scan based anatomical study as a guidance for infra-acetabular screw placement.

BACKGROUND: The infra-acetabular corridor is quite narrow, which makes a challenge for the orthopedists to insert the screw. This study aimed to explore the relationship between the infra-acetabular corridor diameter (IACD) and the minimum thickness of medial acetabular wall (MTMAW), and to clarify the way of screw placement. METHODS: The Computed tomography (CT) data of 100 normal adult pelvises (50 males and 50 females respectively) were collected and pelvis three-dimensional (3D) reconstruction was performed by using Mimics software and the 3D model was imported into Geomagic Studio software. The perspective of acetabulum was carried out orienting from iliopubic eminence to ischial tuberosity and the IACD was measured by placing virtual screws which was vertical to the corridor transverse section of "teardrop". The relationship between IACD and MTMAW was analyzed. When IACD was ≥5 mm, 3.5 mm all-in screws were placed. When IACD was < 5 mm, 3.5 mm in-out-in screws were placed. RESULTS: The IACD of males and females were (6.15 ± 1.24) mm and (5.42 ± 1.01) mm and the MTMAW in males and females were (4.40 ± 1.23) mm and (3.60 ± 0.81) mm respectively. The IACD and MTMAW in males were significantly wider than those of females (P < 0.05), and IACD was positively correlated with MTMAW (r = 0.859), the regression equation was IACD = 2.111 + 0.917 MTMAW. In the all-in screw group, 38 cases (76%) were males and 33 cases (66%) were females respectively. The entry point was located at posteromedial of the apex of iliopubic eminence, and the posterior distance and medial distance were (8.03 ± 2.01) mm and (8.49 ± 2.68) mm respectively in males. As for females, those were (8.68 ± 2.35) mm and (8.87 ± 2.79) mm respectively. In the in-out-in screw group, 12 cases (24%) were males and 17 cases (34%) were females, respectively. The posterior distance and medial distance between the entry point and the apex of iliopubic eminence were (10.49 ± 2.58) mm and (6.17 ± 1.84) mm respectively in males. As for females, those were (10.10 ± 2.63) mm and (6.63 ± 1.49) mm respectively. The angle between the infra-acetabular screw and the sagittal plane was medial inclination (0.42 ± 6.49) °in males, lateral inclination (8.09 ± 6.33) °in females, and the angle between the infra-acetabular screw and the coronal plane was posterior inclination (54.06 ± 7.37) °. CONCLUSIONS: The placement mode of the infra-acetabular screw (IAS) can be determined preoperatively by measuring the MTMAW in the CT axial layers. Compared with all-in screw, the in-out-in screw entry point was around 2 mm outwards and backwards, and closer to true pelvic rim.

[Plasma MiR-181b and MiR-194 As Biomarkers for Acute Graft- Versus-Host Disease and Significance of Their Changes].

OBJECTIVE: To investigate the clinical correlation of expression level changes of miR-181b and miR-194 to the pathogenesis of acute graft-versus-host disease (aGVHD), and determine plasma miR-181b and miR-194 as the potential biomarkers for aGVHD. METHODS: The plasma samples were collected from 31 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at before HSCT, 15 days after HSCT and onset of aGVHD. The expression levels of miR-181b and miR-194 were detected by quantitative real-time PCR. Receiver-operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to assess the sensitivity and specificity of miRNA biomarkers for the diagnosis of aGVHD. RESULTS: MiR-181b and miR-194 downregulated after treatment were significantly upregulated in the plasma at onset of aGVHD (P<0.05), and there was no significant difference in comparison with the level of before HSCT (P>0.05). The expressions of plasma miR-181b and miR-194 collected on day 15 after HSCT were significantly upregulated in the patients with aGVHD in comparison with non-GVHD patients (P<0.05). Moreover, these elevated miRNAs were detected before aGVHD. The AUC of miR-181b predicting aGVHD was 0.91±0.05 (specificity was 0.94, sensitivity was 0.69). The AUC of miR-194 predicting aGVHD was 0.91±0.06 (specificity was 0.94, sensitivity was 0.77). CONCLUSION: MiR-181b and miR-194 may serve as early biomarkers for the diagnosis and prognosis of aGVHD.