Publications by authors named "Gang An"

118 Publications

High incidence of MYD88 and KMT2D mutations in Chinese with chronic lymphocytic leukemia.

Leukemia 2021 Jan 22. Epub 2021 Jan 22.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Blood Diseases Hospital & Institute of Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41375-021-01124-5DOI Listing
January 2021

Multiple myeloma hinders erythropoiesis and causes anaemia owing to high levels of CCL3 in the bone marrow microenvironment.

Sci Rep 2020 11 25;10(1):20508. Epub 2020 Nov 25.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China.

Anaemia is the most common complication of myeloma and is associated with worse clinical outcomes. Although marrow replacement with myeloma cells is widely considered a mechanistic rationale for anaemia, the exact process has not been fully understood. Our large cohort of 1363 myeloma patients had more than 50% of patients with moderate or severe anaemia at the time of diagnosis. Anaemia positively correlated with myeloma cell infiltration in the bone marrow (BM) and worse patient outcomes. The quantity and erythroid differentiation of HSPCs were affected by myeloma cell infiltration in the BM. The master regulators of erythropoiesis, GATA1 and KLF1, were obviously downregulated in myeloma HSPCs. However, the gene encoding the chemokine CCL3 showed significantly upregulated expression. Elevated CCL3 in the BM plasma of myeloma further inhibited the erythropoiesis of HSPCs via activation of CCL3/CCR1/p38 signalling and suppressed GATA1 expression. Treatment with a CCR1 antagonist effectively recovered GATA1 expression and rescued erythropoiesis in HSPCs. Myeloma cell infiltration causes elevated expression of CCL3 in BM, which suppresses the erythropoiesis of HSPCs and results in anaemia by downregulating the level of GATA1 in HSPCs. Thus, our study indicates that targeting CCL3 would be a potential strategy against anaemia and improve the survival of myeloma patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-77450-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689499PMC
November 2020

VIS832, a novel CD138-targeting monoclonal antibody, potently induces killing of human multiple myeloma and further synergizes with IMiDs or bortezomib in vitro and in vivo.

Blood Cancer J 2020 11 2;10(11):110. Epub 2020 Nov 2.

Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Therapeutically targeting CD138, a define multiple myeloma (MM) antigen, is not yet approved for patients. We here developed and determined the preclinical efficacy of VIS832, a novel therapeutic monoclonal antibody (MoAb) with differentiated CD138 target binding to BB4 that is anti-CD138 MoAb scaffold for indatuximab ravtansine (BT062). VIS832 demonstrated enhanced CD138-binding avidity and significantly improved potency to kill MM cell lines and autologous patient MM cells regardless of resistance to current standard-of-care therapies, via robust antibody-dependent cellular cytotoxicity and phagocytosis mediated by NK and macrophage effector cells, respectively. Specifically, CD38-targeting daratumumab-resistant MM cells were highly susceptible to VIS832 which, unlike daratumumab, spares NK cells. Superior maximal cytolysis of VIS832 vs. daratumumab corresponded to higher CD138 vs. CD38 levels in MM cells. Furthermore, VIS832 acted synergistically with lenalidomide or bortezomib to deplete MM cells. Importantly, VIS832 at a sub-optimal dose inhibited disseminated MM1S tumors in vivo as monotherapy (P < 0.0001), and rapidly eradicated myeloma burden in all mice concomitantly receiving bortezomib, with 100% host survival. Taken together, these data strongly support clinical development of VIS832, alone and in combination, for the therapeutic treatment of MM in relapsed and refractory patients while pointing to its potential therapeutic use earlier in disease intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41408-020-00378-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643177PMC
November 2020

Age-associated changes in the circulating human antibody repertoire are upregulated in autoimmunity.

Immun Ageing 2020 6;17:28. Epub 2020 Oct 6.

HealthTell, 145 S. 79th St., Chandler, AZ 85226 USA.

Background: The immune system undergoes a myriad of changes with age. While it is known that antibody-secreting plasma and long-lived memory B cells change with age, it remains unclear how the binding profile of the circulating antibody repertoire is impacted.

Results: To understand humoral immunity changes with respect to age, we characterized serum antibody binding to high density peptide microarrays in a diverse cohort of 1675 donors. We discovered thousands of peptides that bind antibodies in age-dependent fashion, many of which contain di-serine motifs. Peptide binding profiles were aggregated into an "immune age" by a machine learning regression model that was highly correlated with chronological age. Applying this regression model to previously-unobserved donors, we found that a donor's predicted immune age is longitudinally consistent over years, suggesting it could be a robust long-term biomarker of humoral immune ageing. Finally, we assayed serum from donors with autoimmune disease and found a significant association between "accelerated immune ageing" and autoimmune disease activity.

Conclusions: The circulating antibody repertoire has increased binding to thousands of di-serine peptide containing peptides in older donors, which can be represented as an immune age. Increased immune age is associated with autoimmune disease, acute inflammatory disease severity, and may be a broadly relevant biomarker of immune function in health, disease, and therapeutic intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12979-020-00193-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539520PMC
October 2020

Primary Plasma Cell Leukemia: Real-World Retrospective Study of 46 Patients From a Single-Center Study in China.

Clin Lymphoma Myeloma Leuk 2020 10 27;20(10):e652-e659. Epub 2020 May 27.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. Electronic address:

Background: Primary plasma cell leukemia (PPCL) is a rare and aggressive plasma cell disorder. The use of novel agents, together with autologous stem cell transplantation, has improved survival outcome in PPCL. However, the prognosis is still very poor, and the optimal treatment remains an unmet clinical need.

Patients And Methods: We studied the efficacy and prognostic impact of novel agents in 46 patients with PPCL patients at the Blood Diseases Hospital in China. We examined the impact of clinical and laboratory features, as well as therapies (bortezomib- and/or immunomodulatory drug-based therapies, chemotherapy) on survival and extent of clinical response, including progression-free survival and overall survival (OS). Progression-free survival and OS were assessed by the Kaplan-Meier method, and survival distributions were compared by log-rank test.

Results: In our cohort of 46 PPCL patients, the median age at the time of diagnosis was 54 years. Overall response rate was 54% (25/46). The median (95% confidence interval) progression-free survival time was 6 (0-12.5) months, and OS time was 14 (4.6-23.4) months. The OS time was significantly longer in patients treated with bortezomib-based versus non-bortezomib-based therapies (median [95% confidence interval], 19 [9-28.9] vs. 5 [4-24] months; P = .019).

Conclusion: This large single-center study of PPCL supports the use of bortezomib-based therapies as frontline treatment in PPCL patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clml.2020.05.014DOI Listing
October 2020

Long-term remissions of young patients with high-risk follicular lymphoma after first-line autologous stem cell transplantation: Three case reports.

Medicine (Baltimore) 2020 May;99(22):e20395

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.

Rationale: Autologous stem cell transplantation (ASCT) is not routinely recommended as first-line choice for follicular lymphoma (FL). However, we actually have observed that young patients with extremely high-risk factors benefit from ASCT. This study aims to speculate the rationality of ASCT as first-line treatment, through 3 cases and review of the literature.

Patient Concerns: 3 young-adult patients with FL received ASCT as first-line treatment.

Diagnosis: All the 3 patients were no more than 30 years old and the diagnosis of FL was confirmed by histopathological and immunohistochemical evaluations. They all had multi-organ involvements, and two of them presented with a "leukemic-like" manifestation. Compared with those in the previous literatures, the 3 patients were relatively younger and had more invasive clinical features.

Interventions: The 3 patients received combined chemotherapy plus rituximab, followed by first-line ASCT.

Outcomes: All the 3 patients got complete remission and minimal residual disease negativity after ASCT, The median follow-up time was 109 (97-117) months, and all of them were in remission more than 8 years after transplant.

Lessons: Guidelines for FL are mainly based on elderly patients, but are not suitable enough for all, especially for the young FL patients. For young patients with certain high-risk FL, first-line ASCT does not go against the guidelines, and should be recommended individually.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000020395DOI Listing
May 2020

IgH translocation with undefined partners is associated with superior outcome in multiple myeloma patients.

Eur J Haematol 2020 Sep 9;105(3):326-334. Epub 2020 Jun 9.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.

Background: In multiple myeloma (MM), impact of specific chromosomal translocations involving IgH (14q21 locus, including t(4;14), t(11;14), and t(14;16)) has been explored extensively. However, over 15% MM patients harboring IgH translocation with undefined partners have long been ignored.

Methods: A prospective non-randomized cohort study with a total of 715 newly-diagnosed MM cases was conducted, 13.6% of whom were t(14;undefined) positive. The whole cohort was divided into four groups: no IgH split (47.7%); t(14;undefined) (13.6%); t(11;14) (17.6%); and t(4;14) or t(14;16) group (21.1%).

Results: Median OS for the four groups was 84.2, not reached (NR), 58.7, and 44.2 months, respectively, with P values for t(14;undefined) vs no IgH split, t(11;14), and t(4;14)/t(14;16) groups of 0.197, 0.022, and 0.001, respectively. In bortezomib-based group, the survival advantage gained by t(14;undefined) group was much more significant compared to t(11;14) and t(4;14)/t(14;16) groups. Importantly, t(14;undefined) turned out to be an independent predictive factor for longer OS of MM patients in multivariate analysis, especially in the context of bortezomib treatment. Similar results were also observed in the PUMCH external validation cohort.

Conclusion: Collectively, our data confirmed and externally validated the favorable prognosis of the t(14;undefined) groups, especially in the era of novel agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ejh.13440DOI Listing
September 2020

Polycomb-like Protein 3 Induces Proliferation and Drug Resistance in Multiple Myeloma and Is Regulated by miRNA-15a.

Mol Cancer Res 2020 07 20;18(7):1063-1073. Epub 2020 Apr 20.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.

Multiple myeloma remains incurable due to the persistence of a minor population of multiple myeloma cells that exhibit drug resistance, which leads to relapsed and/or refractory multiple myeloma. Elucidating the mechanism underlying drug resistance and developing an effective treatment are critical for clinical management of multiple myeloma. Here we showed that promoting expression of the gene for polycomb-like protein 3 (PHF19) induced multiple myeloma cell growth and multidrug resistance and . was overexpressed in high-risk and drug-resistant primary cells from patients. High levels of were correlated with inferior survival of patients with multiple myeloma, in the Total Therapy 2 cohort and in the Intergroup Francophone du Myeloma (IFM) cohort. Enhancing expression levels increased , and expression in multiple myeloma cells. PHF19 also bound directly with EZH2 promoted the phosphorylation of EZH2 through PDK1/AKT signaling. miR-15a is a small noncoding RNA that targeted the 3'UTR of . We found that downregulation of led to high levels of in multiple myeloma cells. These findings revealed that served a crucial role in multiple myeloma proliferation and drug resistance and suggested that the pathway made a pivotal contribution to multiple myeloma pathogenesis, offering a promising approach to multiple myeloma treatment. IMPLICATIONS: Our findings identify that mediates EZH2 phosphorylation as a mechanism of myeloma cell drug resistance, providing a rationale to explore therapeutic potential of targeting in relapsed or refractory patients with multiple myeloma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1541-7786.MCR-19-0852DOI Listing
July 2020

YWHAE/14-3-3ε expression impacts the protein load, contributing to proteasome inhibitor sensitivity in multiple myeloma.

Blood 2020 07;136(4):468-479

Jerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.

High protein load is a feature of multiple myeloma (MM), making the disease exquisitely sensitive to proteasome inhibitor (PIs). Despite the success of PIs in improving patient outcome, the majority of patients develop resistance leading to progressive disease; thus, the need to investigate the mechanisms driving the drug sensitivity vs resistance. With the well-recognized chaperone function of 14-3-3 proteins, we evaluated their role in affecting proteasome activity and sensitivity to PIs by correlating expression of individual 14-3-3 gene and their sensitivity to PIs (bortezomib and carfilzomib) across a large panel of MM cell lines. We observed a significant positive correlation between 14-3-3ε expression and PI response in addition to a role for 14-3-3ε in promoting translation initiation and protein synthesis in MM cells through binding and inhibition of the TSC1/TSC2 complex, as well as directly interacting with and promoting phosphorylation of mTORC1. 14-3-3ε depletion caused up to a 50% reduction in protein synthesis, including a decrease in the intracellular abundance and secretion of the light chains in MM cells, whereas 14-3-3ε overexpression or addback in knockout cells resulted in a marked upregulation of protein synthesis and protein load. Importantly, the correlation among 14-3-3ε expression, PI sensitivity, and protein load was observed in primary MM cells from 2 independent data sets, and its lower expression was associated with poor outcome in patients with MM receiving a bortezomib-based therapy. Altogether, these observations suggest that 14-3-3ε is a predictor of clinical outcome and may serve as a potential target to modulate PI sensitivity in MM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood.2019004147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378455PMC
July 2020

Cdc37 suppression induces plasma cell immaturation and bortezomib resistance in multiple myeloma via Xbp1s.

Oncogenesis 2020 Mar 5;9(3):31. Epub 2020 Mar 5.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China.

Multiple myeloma (MM) is the second most prevalent hematologic malignancy. Although the use of bortezomib (BTZ) significantly improves MM therapy, intrinsic and acquired drug resistance to BTZ remains a major clinical problem. In this study, we find that Cdc37, a key co-chaperone of Hsp90, is downregulated in relapsed MM patients, especially after BTZ treatment, suggesting a link between Cdc37 and BTZ resistance. Suppression of Cdc37 or inhibition of Cdc37/Hsp90 association induces plasma cell dedifferentiation, quiescence of MM cells, and BTZ resistance in MM. Furthermore, we discover that Cdc37 expression correlates positively with Xbp1s, a critical transcription factor for plasma cell differentiation in MM samples. Depletion/inhibition of Cdc37 downregulates Xbp1s, while overexpression of Xbp1s in MM cell lines partially rescues plasma immaturation and BTZ resistance. It is suggested that Xbp1s may act as a key downstream effector of Cdc37. Experiments with a mouse model also demonstrate that Cdc37 inhibition promotes plasma cell immaturation, confers BTZ resistance, and increases MM progression in vivo. Together, we identify a critical factor and a new signaling mechanism that regulate plasma cell immaturation and BTZ resistance in MM cells. Our findings may constitute a novel strategy that overcomes BTZ resistance in MM therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41389-020-0216-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058164PMC
March 2020

NEK2 induces autophagy-mediated bortezomib resistance by stabilizing Beclin-1 in multiple myeloma.

Mol Oncol 2020 04 29;14(4):763-778. Epub 2020 Jan 29.

Department of Hematology, Xiangya Hospital, Central South University, Changsha, China.

NEK2 is associated with drug resistance in multiple cancers. Our previous studies indicated that high NEK2 confers inferior survival in multiple myeloma (MM); thus, a better understanding of the mechanisms by which NEK2 induces drug resistance in MM is required. In this study, we discovered that NEK2 enhances MM cell autophagy, and a combination of autophagy inhibitor chloroquine (CQ) and chemotherapeutic bortezomib (BTZ) significantly prevents NEK2-induced drug resistance in MM cells. Interestingly, NEK2 was found to bind and stabilize Beclin-1 protein but did not affect its mRNA expression and phosphorylation. Moreover, autophagy enhanced by NEK2 was significantly prevented by knockdown of Beclin-1 in MM cells, suggesting that Beclin-1 mediates NEK2-induced autophagy. Further studies demonstrated that Beclin-1 ubiquitination is decreased through NEK2 interaction with USP7. Importantly, knockdown of Beclin-1 sensitized NEK2-overexpressing MM cells to BTZ in vitro and in vivo. In conclusion, we identify a novel mechanism whereby autophagy is activated by the complex of NEK2/USP7/Beclin-1 in MM cells. Targeting the autophagy signaling pathway may provide a promising therapeutic strategy to overcome NEK2-induced drug resistance in MM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/1878-0261.12641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138399PMC
April 2020

X-linked ichthyosis: Molecular findings in four pedigrees with inconspicuous clinical manifestations.

J Clin Lab Anal 2020 May 16;34(5):e23201. Epub 2020 Jan 16.

Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Background: X-linked ichthyosis (XLI) is the second most common type of ichthyosis, which is characterized by wide and symmetric distribution of adherent, dry, and polygonal scales on the skin. Steroid sulfatase (STS) gene, which is located at chromosome Xp22.31, has been identified as the pathogenic gene of XLI.

Methods: In this study, chromosome karyotype analysis, bacterial artificial chromosomes-on-Beads™ (BoBs) assay, fluorescence in situ hybridization (FISH), and single nucleotide polymorphism array (SNP-array) were employed for the prenatal diagnoses in three pregnant women with high-risk serological screening results and a pregnant woman with mental retardation.

Results: STS deletion was identified at chromosome Xp22.31 in all four fetuses. Postnatal follow-up confirmed the diagnosis of ichthyosis in two male fetuses and revealed normal dermatological manifestations in other two female fetuses carrying ichthyosis.

Conclusion: The results of the present study demonstrate that a combination of karyotypying, prenatal BoBs, FISH, and SNP-array may avoid the missed detection of common microdeletions and ensure the accuracy of the detection results, which provides a feasible tool for the reliable etiological diagnosis and better genetic counseling of XLI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcla.23201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246362PMC
May 2020

Fatigue Limit of Custom 465 with Surface Strengthening Treatment.

Materials (Basel) 2020 Jan 6;13(1). Epub 2020 Jan 6.

Qing'an Group Corporation Limited, Xi'an 710077, China.

In order to study the effect of nitriding or shot peening on the surface modification and fatigue properties of martensitic stainless-steel Custom 465, the residual stress and micro-hardness of the strengthened layer are determined by X-ray and micro-hardness tester, respectively. The up-and-down method is used to measure the rotational bending fatigue strength at 1 × 10 cycles, and the fatigue fracture characteristic is observed by scanning electron microscopy. The relationship between surface residual stress and internal fatigue limit of surface strengthening treatment is discussed. Results show that nitriding or shot peening surface strengthening layer forms a certain depth of compressive residual stress, where in the surface compressive residual stress of the nitrided specimens is greater than the shot peened specimens. The micro-hardness of the nitrided or shot peened surface strengthening layer is significantly improved, where in the surface micro-hardness of nitriding specimens are higher than shot peening specimens. The nitriding or shot peening surface strengthening can significantly improve the fatigue limit of Custom 465, wherein the fatigue limits of nitrided and shot peened surface strengthened specimens are 50.09% and 50.66% higher than that of the un-surface strengthened specimens, respectively. That is, the effect of the two strengthening methods on fatigue limit is not very different. The fracture characteristics show that the fatigue crack of the un-surface strengthened specimens originates from the surface, while the fatigue crack of surface strengthened specimens originates from the subsurface layer under the strengthened layer. The relationship between the internal fatigue limit and the surface residual stress of the surface strengthened specimen can be used as a method for predicting the fatigue limit of the surface strengthened specimens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ma13010238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981755PMC
January 2020

1q21 gain but not t(4;14) indicates inferior outcomes in multiple myeloma treated with bortezomib.

Leuk Lymphoma 2020 05 16;61(5):1201-1210. Epub 2019 Dec 16.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.

Chromosome 1q21 aberrations in multiple myeloma have attracted much attention for a long time, however, the prognostic value is still under investigation. We confirmed the independent prognostic impact of 1q21 aberrations in this non-randomized clinical study. Our study noted that additional copies and larger clonal size of 1q21 gain did not worsen the outcome. We discovered that 1q21 gain was associated with the acquisition of new chromosome abnormalities and genomic instability, evidenced by the strong correlation between 1q21 gain and complex karyotypes or the acquisition of more than two cytogenetic aberrations. Moreover, 1q21 gain and/or del(17p) were powerful enough to discriminate high-risk patients. Furthermore, 1q21 gain retained unfavorable even when stratified by concurrent presence of t(4;14), especially in the bortezomib arm. Finally, although bortezomib might benefit patients with 1q21 gain, it could not completely overcome its adverse effects, suggesting the necessity of more effective therapies for these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10428194.2019.1700503DOI Listing
May 2020

Percutaneous Endoscopic Interlaminar Lumbar Discectomy with Local Anesthesia for L5-S1 Disc Herniation: A Feasibility Study.

Pain Physician 2019 11;22(6):E649-E654

The First Affiliated Hospital of Harbin Medical University, Nangang, Harbin, P.R. China.

Background: General anesthesia (GA), which is routinely applied in patients who undergo percutaneous endoscopic interlaminar lumbar discectomy (PEILD) of L5-S1 disc herniation, is closely associated with postoperative cognitive dysfunction (POCD) in the elderly. Local anesthesia (LA) is an alternative pain control protocol that has not yet been fully evaluated.

Objectives: To evaluate the feasibility of LA in PEILD compared with GA.

Study Design: A retrospective study.

Setting: This study took place at the First Affiliated Hospital of Harbin Medical University.

Methods: A total of 120 patients (aged 60-85 years) diagnosed with L5-S1 disc herniation and with American Society of Anesthesiologists fitness grade I or II between March 2016 and August 2017 were enrolled in the current study. Patients were randomly divided into LA group and GA group. For LA, 0.25% lidocaine was injected layer-by-layer into skin, subcutaneous tissue, fasciae, lumbar facet joint, muscle, and ligamentum flavum followed by injection of 1.33% lidocaine into epidural space; for GA, propofol, sufentanil, and cisatracurium were infused intravenously at 1 to 2 mg/kg, 0.3 µg/kg, and 0.15 mg/kg, respectively. Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and MacNab Criteria (MNC) evaluated the feasibility of LA as pain control protocol in comparison to GA before and after operation. The development of POCD was assessed by the Mini-Mental State Examination 1 and 7 days postsurgery. Feasibility of LA as a pain control protocol was also evaluated by patient's willingness to receive the same surgical procedure immediately and 24 hours after the surgery, and intraoperative fluoroscopy use, blood loss, surgery duration, postoperative bed confinement, and duration and cost of hospital stay were also evaluated.

Results: Patients in both LA and GA groups had comparable VAS grade, ODI, and MNC pre- and post-PEILD, with significant pain reduction after operation. However, POCD developed only in GA group but not in LA group. In addition, compared with GA, LA group did not require postoperative bed confinement, had significantly shorter hospital stay, and lower hospital cost. Low intraoperative VAS grade and willingness to receive the same procedure reflected the acceptance of LA by patients.

Limitations: The development of POCD was examined only 7 days after operation. The follow-up should be extended to 3 months and 2 years postoperation.

Conclusions: LA has satisfactory pain control and low-risk of POCD in PEILD and is well accepted by patients. The benefits of LA are no postoperative bed confinement, faster recovery, shorter hospital stay, and lower hospital cost.

Key Words: L5-S1 disc herniation, older patients, percutaneous endoscopic interlaminar lumbar discectomy, local anesthesia, general anesthesia, postoperative cognitive dysfunction, American Society of Anesthesiologists grade, Oswestry Disability Index, MacNab Criteria, Mini-Mental State Examination.
View Article and Find Full Text PDF

Download full-text PDF

Source
November 2019

Chromosomal microarray analysis for pregnancies with or without ultrasound abnormalities in women of advanced maternal age.

J Clin Lab Anal 2020 Apr 24;34(4):e23117. Epub 2019 Nov 24.

Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Background: Chromosomal microarray analysis (CMA) has been suggested to be routinely conducted for fetuses with ultrasound abnormalities (UA), especially with ultrasound structural anomalies (USA). Whether to routinely offer CMA to women of advanced maternal age (AMA) without UA when undergoing invasive prenatal testing is inconclusive.

Objective: This study aimed to evaluate the efficiency of CMA in detecting clinically significant chromosomal abnormalities in fetuses, with or without UA, of women with AMA.

Methods: Data from singleton pregnancies referred for prenatal CMA due to AMA, with or without UA were obtained. The enrolled cases were divided into AMA group (group A) and AMA accompanied by UA group (group B). Single nucleotide polymorphism (SNP) array technology and conventional karyotyping were performed simultaneously.

Results: A total of 703 cases were enrolled and divided into group A (N = 437) and group B (N = 266). Clinically significant abnormalities were detected by CMA in 52 cases (7.4%, 52/703; the value in group A was significantly lower than that in group B (3.9% vs 13.2%, P < .05); no statistic difference was observed with respect to submicroscopic variants of clinical significance between the two groups (0.9% vs 2.6%, P > .05).

Conclusions: Chromosomal microarray analysis should be available to all women with AMA undergoing invasive prenatal testing, regardless of ultrasound findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcla.23117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171339PMC
April 2020

The impact of response kinetics for multiple myeloma in the era of novel agents.

Blood Adv 2019 10;3(19):2895-2904

State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.

Rapid remission by induction therapy has long been recognized as an important predictor for long-time survival in acute leukemia. However, the impact of response kinetics on multiple myeloma (MM) seems to be different and remains unexplored. The relationship between response kinetics and outcome were assessed in 626 patients with newly diagnosed MM who were included in a prospective, nonrandomized clinical trial (BDH 2008/02). Patients were assigned to either immunomodulatory drug- or proteasome inhibitor-based therapy. The response depth, time to best response (T) and duration of best response (D) were collected. Depth of response was associated with superior outcomes, consistent with findings from other studies. However, the early responders (defined as T ≤3 months) showed significantly worse survival compared with late responders. We found that patients with rapid complete remission experienced inferior survivals comparable to those attaining a gradual partial remission. Moreover, 4 distinct response kinetics patterns were identified. Patients with gradual and sustained remission ("U-valley" pattern) experienced superior outcomes, whereas poor outcomes were observed in rapid and transient responders ("roller coaster" pattern) (median overall survival, 126 vs 30 months). The effects of response patterns on survival were confirmed in patients at different stages of disease and cytogenetic risk, including transplant-eligible patients and those attaining different extents of response depth. Collectively, our data indicated that slow and gradual response is a favorable prognostic factor in MM. In addition to response depth, the kinetic pattern of response is a simple and powerful predictor for survival even in the era of novel agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2019000432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784522PMC
October 2019

Monitoring the cytogenetic architecture of minimal residual plasma cells indicates therapy-induced clonal selection in multiple myeloma.

Leukemia 2020 02 7;34(2):578-588. Epub 2019 Oct 7.

State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 300020, Tianjin, China.

Recent attempts have focused on identifying fewer magnitude of minimal residual disease (MRD) rather than exploring the biological and genetic features of the residual plasma cells (PCs). Here, a cohort of 193 patients with at least one cytogenetic abnormalities (CA) at diagnosis were analyzed, and interphase fluorescence in situ hybridization (iFISH) analyses were performed in patient-paired diagnostic and posttherapy samples. Persistent CA in residual PCs were observed for the majority of patients (63%), even detectable in 28/63 (44%) patients with MRD negativity (<10). The absence of CA in residual PCs was associated with prolonged survival regardless of MRD status. According to the change of the clonal size of specific CA, patients were clustered into five groups, reflecting different patterns of clone selection under therapy pressure. Therapy-induced clonal selection exerted a significant impact on survival (HR = 4.0; P < 0.001). According to the longitudinal cytogenetic studies at relapse, sequential cytogenetic dynamics were observed in most patients, and cytogenetic architecture of residual PCs could to some extent predict the evolutional pattern at relapse. Collectively, the repeat cytogenetic evaluation in residual PCs could not only serves as a good complementary tool for MRD detection, but also provides a better understanding of clinical response and clonal evolution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41375-019-0590-xDOI Listing
February 2020

Clinical application of chromosomal microarray analysis in fetuses with increased nuchal translucency and normal karyotype.

Mol Genet Genomic Med 2019 08 17;7(8):e811. Epub 2019 Jun 17.

Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fujian Provincial Key Laboratory for Prenatal Diagnosis and Birth Defect, Fuzhou, China.

Background: Submicroscopic chromosomal imbalance is associated with an increased nuchal translucency (NT). Most previous research has recommended the use of chromosomal microarray analysis (CMA) for prenatal diagnosis if the NT ≥ 3.5 mm. However, there is no current global consensus on the cutoff value for CMA. In this study, we aimed to discuss the fetuses with smaller increased NT which was between cutoff value of NT for karyotype analysis (NT of 2.5 mm in China) and the recommended cutoff value for CMA (NT of 3.5 mm) whether should be excluded from CMA test.

Methods: Singleton pregnant women (N = 192) who had undergone invasive procedures owing to an increased NT (NT ≥ 2.5 mm) were enrolled. Fetal cells were collected and subjected to single nucleotide polymorphism array and karyotype analyses simultaneously. Cases were excluded if the karyotype analysis indicated aneuploidy and apparent structural aberrations.

Results: Fourteen cases of aneuploidy and four cases of structural abnormalities were excluded. Of the remaining 174 cases, 119 fetuses had NTs of 2.5-3.4 mm, and 55 fetuses with NT ≥ 3.5 mm. Eleven copy number variants (CNVs) were identified. In fetuses with smaller NTs, six (6/119, 5.9%) variations were detected, including two (2/119, 1.6%) clinically significant CNVs (pathogenic or likely pathogenic CNV), one  likely benign CNV, two variants unknown significance, and one incidental CNV. Five (5/55, 9.1%) variations were found in fetuses with NT ≥ 3.5 mm. Among these CNVs, three (3/55, 5.5%) cases had clinically significant CNVs, and two had likely benign CNV. There were no statistically significant differences in the incidence of all CNVs and clinically significant CNVs in the two groups (p > 0.05).

Conclusion: CMA improved the diagnostic yield of chromosomal aberrations for fetuses with NTs of 2.5-3.4 mm and apparently normal karyotype, regardless of whether other ultrasonic abnormalities were observed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mgg3.811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687862PMC
August 2019

[Clinical Analysis of B-CLPD with Cytopemia as the Predominant Characteristic].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2019 Jun;27(3):839-843

State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hpspital, Chinese Acadmy of Medical Sciences, Tianjin 30020, China.

Objective: To investigate the clinical characteristics and therapeutic responte of patients with B-CLPD mainly manifested as cytopenia, so as to deeply understand this disease.

Methods: The clinical data of 13 B-CLPD patients with hematocytopenia as main manifestation, and the absolute count of lymphocytes<5×10/L, absence of hepatosplenic lymph-nodes and extramedullary invasion tin our department fron 2003 to 2018 were analyzed retrospectively. The clinical characteristics, therapeutic efficacy and adverse reactions of 3 patients were summarized.

Results: The median age of patients was 59 (43-76) years old, the median of lymphocyte was 1.86 (0.69-4.8) ×10/L, the levels of LDH and β2-microglubulin were normal in most patients, the monolineage and multilencage hematopoietic failure of different degrees existed in most all patients. The lymphocyte ratio in patients was 18.5%-94.0%, CD20 was positive in all patients, and yet the CD5-positive and CD-negative existed in 7 and 6 cases respectively. There was no significant difference in ratio of lymphocyte invasion among different immunophemtype. The FISH detection showed that there were no high risk genetic types. 92.3% of patients received rituximab treatment, most of them received chemotherapy of rituximab combined with C0P/CHOP like regimen, only 2 patients received fludarabine for comparatively short course. The analysis indicated that 8 out of 13 patients showed a certain theropeutic efficacy, however the drug-related hematopoietic suppression occurred in both 2 patients treated with fludarabin.

Conclusions: The B-CLPD accompanied with hematocytopenia often displays bone marrow hypohematopoiesis of different degree and easily confuses with the congenital and acquired hemotopoietic faiture diseases. The rituximab treatment may be more appropreate for these patients, but for patients received chemotherapy containing fludarabin, the persistant hematopoietic failure must be especially watched out.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2019.03.032DOI Listing
June 2019

miR-328-3p mediates the anti-tumor effect in osteosarcoma via directly targeting MMP-16.

Cancer Cell Int 2019 23;19:104. Epub 2019 Apr 23.

1Department of Spine Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001 Heilongjiang Province China.

Background: Increasing reports demonstrated that dysregulated expression of microRNAs (miRNAs) leads to the progression of various tumors. Previous studies revealed that miR-328-3p exhibited dysregulated expression in various types of tumors. However, its function and underlying mechanism in osteosarcoma (OS) are still unexplored.

Methods: The expression of miR-328-3p in the tissues and OS cell lines was detected by qRT-PCR analysis. The effects of miR-328-3p in the proliferation were analyzed by MTT assay. The proliferation and apoptosis of OS cells were examined by colony formation assay and TUNEL staining respectively. The migration and tumor formation ability of OS cells were measured by wound healing assay and xenograft in vivo mice assay. Furthermore, the regulatory roles of miR-328-3p/MMP16 were determined by western blot and luciferase reporter assay.

Results: The expression of miR-328-3p was significantly decreased in OS tissues and cell lines. Furthermore, overexpression of miR-328-3p inhibited the cell proliferation and migration, but promoted the apoptosis of OS cells in vitro. Moreover, the analysis in vivo showed that miR-328-3p effectively suppressed the formation of tumors. According to the results of western blot analysis and luciferase reporter assay, we identified matrix metalloproteinase-16 (MMP-16) acted as a direct target of miR-328-3p. Moreover, the expression level of MMP-16, which participates in the occurrence and development of many cancers, was negatively correlated with the miR-328-3p expression in OS cells.

Conclusion: miR-328-3p inhibited the proliferation, migration but accelerated the apoptosis of OS by directly inhibiting MMP-16. And miR-328-3p/MMP-16 axis may be one of the mechanisms of OS development and a novel potential method for the treatment of OS in clinic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12935-019-0829-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477748PMC
April 2019

[Prenatal diagnosis and clinical analysis of two fetuses with Cat-eye syndrome].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2019 May;36(5):498-501

Center of Prenatal Diagnosis,Fujian Provincial Maternity and Child Health Hospital, Fuzhou, Fujian 350001, China. Email:

Objective: To determine the origin of supernumerary small marker chromosomes (sSMCs) carried by two fetuses.

Methods: Single nucleotide polymorphism array (SNP-array) and fluorescence in situ hybridization (FISH) analysis were carried out on cells cultured from the amniotic fluid samples.

Results: SNP-array analysis showed both fetuses to be arr[hg19]22q11.1q11.21(16 888 899-18 649 190)×4, with a duplicated 1.7 Mb region (16 888 899-18 649 190) leading to partial tetrasomy of 22q11.1-22q11.21. FISH confirmed that both fetuses were 47,XN,+mar.ish idic(22)(q11.2) (RP11-958H20 ++),which suggested a diagnosis of Cat-eye syndrome (CES). The appearance of abortuses were consistent with the diagnosis of CES.

Conclusion: Two fetuses with CES were diagnosed by genetic testing. The latter has provided a basis for genetic counseling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2019.05.021DOI Listing
May 2019

The therapeutic effect of secretome from human umbilical cord-derived mesenchymal stem cells in age-related osteoporosis.

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):1357-1366

a Department of Spine Surgery , the First Affiliated Hospital of Harbin Medical University , Harbin , China.

Senile osteoporosis is closely related to the loss of function of stem cells. In this study, we tried to investigate the potential of secretome from human umbilical cord-derived mesenchymal stem cells (hUCMSCs) in recovering stem cell ability from senescence and then delaying bone loss. We first harvested bone marrow-derived mesenchymal stem cells (BMSCs) from young and old rats and then compared their cellular characteristics such as cell growth, anti-senescence and differentiation. The results showed that these abilities were negatively affected by animal aging. Subsequently, aged BMSCs were exposed to secretome from hUCMSCs, and we found that this loss of cell potential can be modified by secretome treatment. Thereafter, the secretome was loaded into silk fibroin-based hydrogels and used for an in vivo animal study. The results showed that compared to the old untreated group, the bone formation capacity of aged rats was improved by local treatment of secretome-loaded silk fibroin hydrogels. In conclusion, these findings demonstrated that secretome from hUCMSCs has the capacity to recover stem cell potential and delay local bone loss in age-related osteoporosis, which could potentially be applied in osteoporosis therapy in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21691401.2019.1596945DOI Listing
December 2019

Molecular cytogenetic identification of small supernumerary marker chromosomes using chromosome microarray analysis.

Mol Cytogenet 2019 11;12:13. Epub 2019 Mar 11.

Fujian Provincial Key Laboratory for Prenatal diagnosis and Birth Defect, Fujian Provincial Maternity and Children's Hospital, affiliated hospital of Fujian Medical University, Fuzhou, 350001 Fujian China.

Background: This study aimed to evaluate the feasibility of chromosomal microarray analysis (CMA) in detecting the origin and structure of small supernumerary marker chromosomes (sSMCs) in prenatal and postnatal cases and to clarify sSMC-related genotype-phenotype correlations.

Results: Thirty-three cases carrying sSMCs were identified by banding cytogenetics. Of these cases, twenty-nine were first characterized by CMA and only two by FISH. The remaining two cases were excluded for their refusal to accept further examination. The chromosomal origins of twenty-two cases were successfully identified, in which pathogenetic copy number variations (PCNVs) were found in sixteen cases, four cases showed variants of uncertain significance (VOUS), one case showed benign CNVs, and one case showed probable PCNVs. For the nine cases with negative CMA results, only one of them contained centromere heterochromatin likely due to its normal phenotype, whereas reasons for the remaining eight cases were uncertain. We also found that CMA results indicating pathogenic abnormalities further affect the rate of pregnancy termination.

Conclusions: This study showed that CMA combined with cytogenetic analysis is particularly effective in identifying sSMCs. However, in order to establish sSMC-related genotype-phenotype correlations, the inclusion of more sSMC cases will be necessary in future studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13039-019-0425-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416931PMC
March 2019

Secretory status of monoclonal immunoglobulin is related to the outcome of patients with myeloma: a retrospective study.

Blood Adv 2019 03;3(5):751-760

State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China; and.

The treatment of multiple myeloma (MM) with proteasome inhibitor (PI) bortezomib has significantly improved the survival of patients with MM. The 26S proteasome inhibitor targets the unfolded protein response (UPR) by inhibiting proteasome degradation of ubiquitinated paraprotein, subsequently leading to the lethal accumulation of paraprotein within the endoplasmic reticulum. According to secretory status of monoclonal immunoglobulin, newly diagnosed MM (NDMM) is divided into measurable and unmeasurable disease, which includes oligosecretory, nonsecretory, and nonproducer myeloma. The present study analyzed the clinical characteristics of 822 patients with NDMM who had either measurable or unmeasurable diseases and received bortezomib- or thalidomide-based therapies. Our results showed that the median progression-free survival (PFS) and overall survival (OS) of patients with MM was significantly longer in patients with measurable disease than those in oligosecretory, nonsecretory, and nonproducer MM (PFS: 27, 18, 19, and 2.0 months, respectively [ < .001]; OS: 51, 30, 22, and 2.0 months, respectively [ < .001]). Within the unmeasurable group, patients with nonproducer myeloma showed the shortest PFS and OS. Importantly, compared with thalidomide treatment, bortezomib significantly improved the PFS and OS of patients with MM with measurable disease (PFS: 25 and 33 months [ = .022], respectively; OS: 41 and 58 months [ < .001], respectively), but not those with unmeasurable disease (PFS: 18 and 16 months [ = .617], respectively; OS: 22 and 27 months [ = .743], respectively). Our results indicate that bortezomib-based therapy performed no better than thalidomide-based treatment in patients with unmeasurable MM. The results need to be confirmed in other patient cohorts, preferably in the context of a prospective trial.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2018019851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418498PMC
March 2019

Fetal congenital heart disease: Associated anomalies, identification of genetic anomalies by single-nucleotide polymorphism array analysis, and postnatal outcome.

Medicine (Baltimore) 2018 Dec;97(50):e13617

Department of the Prenatal Diagnosis Center, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fuzhou, China.

Background: Congenital heart disease (CHD) is one of the most common birth defects; however, the mechanisms underlying its development are poorly understood. Recently, heritable genetic factors, including copy number variations (CNVs) and single nucleotide polymorphisms (SNPs), have been implicated in its etiology. The aim of this study was to investigate the utility of a SNP array for the prenatal diagnosis of CHD and the improvement of prenatal genetic counseling and to compare this approach to traditional chromosome analysis.

Methods: One hundred and fortysix cases of CHD detected by prenatal echocardiography were analyzed. Of these, 110 were isolated CHD and 36 were of CHD with extracardiac defects. SNP analysis was performed using the Affymetrix CytoScan HD platform, which was followed by karyotype analysis. All annotated CNVs were validated by fluorescence in situ hybridization.

Results: Karyotype analysis identified chromosomal abnormalities in 19 of 146 cases. In addition to the 15 chromosomal abnormalities that were consistent with the results of karyotype analysis, the SNP array identified abnormal CNVs in an additional 15.2% (22/145) cases; of these, 15 were pathogenic CNVs, three were variations of uncertain clinical significance, and four were benign CNVs. The rates at which the SNP array detected pathogenic CNVs differed significantly between cases of isolated CHD and CHD with extracardiac defects (13.6% vs. 72.2%, P = .001). The results of the SNP array also affected the rate of pregnancy termination.

Conclusion: Combining SNP array with cytogenetic analyses is particularly effective for identifying chromosomal abnormalities in CNVs in fetuses with CHD, which also affects obstetrical outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000013617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320040PMC
December 2018

Chromosomal abnormalities and copy number variations in fetal ventricular septal defects.

Mol Cytogenet 2018 28;11:58. Epub 2018 Nov 28.

Department of the Prenatal Diagnosis Center, Fujian Provincial Maternity and Children's Hospital, affiliated hospital of Fujian Medical University, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fuzhou, China.

Background: This study aimed to evaluate the applicability of chromosomal microarray analysis (CMA), rather than traditional chromosome analysis, in prenatal diagnosis of ventricular septal defects (VSDs) for superior prenatal genetic counseling and to reveal a potential correlation between submicroscopic chromosomal aberrations and VSDs.

Results: Among the 151 VSD cases, 79 (52.3%) had isolated defects and 72 (47.7%) had additional ultrasound anomalies. Karyotype analysis identified 16 chromosomal abnormalities. Besides the 14 cases of chromosome abnormalities consistent with karyotype analysis, CMA identified an additional 20 cases (13.2%) of abnormal copy number variations (CNVs), of which 13 were pathogenetic CNVs, 5 were variations of uncertain clinical significance (VOUS) and 2 were benign CNVs. The detection rate of pathogenic CNVs in non-isolated-VSDs was significantly higher than that in isolated-VSDs (36.1% (26/72) vs. 1.3% (1/79),  = 0.001). We also found that CMA results indicating pathogenic abnormalities affected the rate of pregnancy termination.

Conclusions: This study showed that CMA combined with cytogenetic analysis is particularly effective in identifying CNVs in fetuses with VSDs and can have an effect on obstetrical outcomes. The elucidation of the etiology of VSDs suggested that gene mutations or other factors may be implicated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13039-018-0408-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264052PMC
November 2018

Genotyping polymorphic microhaplotype markers through the Illumina MiSeq platform for forensics.

Forensic Sci Int Genet 2019 03 16;39:1-7. Epub 2018 Nov 16.

Department of Forensic Genetics, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu 610041, Sichuan, China. Electronic address:

Microhaplotype markers are emerging forensic genetic markers that have received broad attention in forensics and may supplement existing genetic marker panels. Short tandem repeat polymorphisms (STRPs) and single nucleotide polymorphisms (SNPs) are the general genetic markers at present. Stutter and the high mutation rate of STR markers and the low polymorphism of SNP markers obstruct the solving of certain cases. Kidd proposed microhaplotype markers that encompass 2-4 SNPs. In this study, we screened microhaplotype loci through three criteria, and chose the Illumina MiSeq platform to sequence the new markers. A new nomenclature was proposed and Perl-based tool FLfinder was designed to genotype the microhaplotype marker. After counting the number of haplotypes in samples that were sequenced and calculating common forensic parameters, 13 loci with high polymorphism were reported. Twelve of the 13 loci had an average allele coverage ratio (ACR) of 0.72 to 0.92. Structure analysis showed that 2504 samples (1000 genome project) could be divided into 5 groupings of populations, and each one representing a continental origin. The finding indicates that microhaplotype markers could be used for individual identification and ancestry inference, and a new choice is provided for forensic practice in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fsigen.2018.11.005DOI Listing
March 2019

The association of HLA-C alleles with multiple myeloma in Chinese patients.

Exp Hematol Oncol 2018 23;7:19. Epub 2018 Aug 23.

1Department of Pathology and Lab Medicine, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020 China.

Background: The positive association of multiple myeloma (MM) risk with HLA-C loci C*07:02 g and C*02:02 g, and the negative association of that with C*05:01 g were statistically significant in Whites have recently been reported. However, no association between HLA-C alleles and MM risk was found in Asians/Pacific Islanders. Here we identified 316 Chinese patients with MM, and reported the results of our investigation of HLA-C in MM in Chinese population.

Methods: We identified 316 Chinese patients with MM diagnosed in our hospital, and typed for HLA-C by using Sanger sequence-based typing. The control was from laboratories of China Marrow Donor Program (CMDP), where HLA high resolution was provided in 564,856 volunteer adult donors.

Results: In contrast to the association of MM risk in Whites, we did not find the similar association in Chinese population. Nevertheless, four new associations between the MM risk were identified in Chinese patients. Our data demonstrated that Chinese patients with MM carry significantly increased frequencies of HLA-C*03:03 (FDR = 0.0269), HLA-C*07:63 (FDR = 0.0278) and HLA-C*08:22 (FDR = 0.0442) comparing with controls, while significantly decreased frequency of HLA-C*01:02 (FDR = 0.0414) comparing with controls.

Conclusion: Therefore, HLA-C region is a key risk locus for MM in Chinese population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40164-018-0112-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108132PMC
August 2018

Rapidly mutating Y-STRs study in Chinese Yi population.

Int J Legal Med 2019 Jan 30;133(1):45-50. Epub 2018 Jul 30.

Department of Forensic Genetics, West China School of Basic Sciences and Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, China.

Y-chromosomal short tandem repeats (Y-STRs) have been widely used in forensic analysis and population genetics. With low to moderate mutation rates, conventional Y-STR panels, including commercially available Y-STR kits, enable the identification of male pedigrees but typically fail to differentiate related male individuals. The introduction of rapidly mutating Y-chromosomal short tandem repeats (RM Y-STRs) with higher mutation rates (μ > 10) has been demonstrated to increase the discrimination capacity of unrelated men and the differentiation rate of related men compared with standard Y-STRs. To date, several studies have been performed worldwide. Here, 260 father-son pairs from Chinese Yi population were investigated, and 18.8% of them were differentiated with the 13 RM Y-STR markers, which was close to the theoretical estimate of 19.5% based on the mutation rates of these markers. Among the 57 mutations observed, repeat gains were more common than repeat losses (1.48:1), and one-step mutations were more common than two-step mutations (27.5:1). Locus-specific mutation rates ranged from < 3.85 × 10 (95% CI 0.00-1.41 × 10) to 3.85 × 10 (95% CI 1.86 × 10-6.96 × 10), with an average mutation rate of 1.46 × 10 (95% CI 1.11 × 10-1.89 × 10). Furthermore, we combined the father-son pair data from the present study with the data from the previous studies, generating an overall mutation rate of 1.70 × 10. The high differentiation rate obtained in the present study indicates the suitability of RM Y-STRs to distinguish paternal lineages in Chinese Yi population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00414-018-1894-5DOI Listing
January 2019