Genetic characteristics and survival analysis of 27 cases of juvenile myelomonocytic leukemia / 中华儿科杂志

Objective: To investigate the genetic and genomic profiling of juvenile myelomonocytic leukemia (JMML) and factors affecting its survival rate. Methods: Clinical characteristics, cytogenetics, molecular biology results and survival status of children with 27 JMML cases admitted to the Hematology Department of Children's Hospital, Capital Institute of Pediatrics from December 2012 to December 2021 were analyzed retrospectively, and the outcomes of the children were followed up. Kaplan-Meier method was used for survival analysis. Univariate analysis was used for analyzing factors affecting the overall survival (OS) rates of patients who received hematopoietic stem cell transplantation (HSCT). Log-Rank test was used for comparison of survival curves. Results: Among 27 JMML cases, there were 11 males and 16 females. The age of disease onset was 28 (11,52) months. There are 20 cases of normal karyotype, 4 cases of monosomy 7, 1 case of trisomy 8,1 case of 11q23 rearrangement and 1 case of complex karyotype. A total of 39 somatic mutations were detected.Those involved in RAS signal pathway were the highest (64%(25/39)), among which PTPN11 mutation was the most frequent (44% (11/25)). A total of 17 cases (63%) received HSCT, 8 cases (30%) did not receive HSCT, and 2 cases (7%) lost follow-up. For children receiving transplantation, the follow-up time after transplantation was 47 (11,57) months. The 1-year OS rate of high-risk transplantation group (17 cases) and high-risk non transplantation group (6 cases) was (88±8)% and (50±20)% respectively, with a statistically significant difference (χ2=5.01, P=0.025). The 5-year OS rate of the high-risk transplantation group was (75±11)%. The survival time of those who relapsed or progressed to acute myeloid leukemia after transplantation was significantly shorter than that of those who did not relapse (χ2=6.80, P=0.009). The OS rate of patients with or without PTPN11 mutation was (81±12) % and (67±19)% respectively (χ2=0.85, P=0.356). Conclusions: The main pathogenesis involved in JMML is gene mutation related to RAS signaling pathway, and the most common driver gene of mutation is PTPN11. Allogeneic HSCT can significantly improve the survival rate of high-risk JMML patients. The recurrence or progression after transplantation was related to poor prognosis.

Changes of Macular Microcirculation After Near Work in Myopic Patients / 中山大学学报(医学科学版)

ObjectiveTo compare the changes of retinal microcirculation indexes in the anterior and posterior macular areas of the eyes used at close range and to explore the possible causes of myopia affected by near work. MethodsWatching mobile phone video for 1 hour at close range was used as the method of defining near work. The OCTA technology was used to measure the superficial retinal microcirculation indexes within 6 by 6 mm macular area before and after near work， including the superficial retinal VLD from the nerve fiber layer to the inner boundary of the outer plexiform layer， the VPD， nonperfusion area of FAZ， FAZ-P and FAZ circulation，. The FAZ was divided int center， inner layer， outer layer and overall according to the region， and 11 microcirculation indexes were obtained to compare the differences between before and after near work. ResultsThe indexes of superficial retinal microcirculation in the macular area generally decreased after near work， except for FAZ-A and FAZ-P（P = 0.148， 0.975）. The largest differences among both VLD and VPD occurred between the central and inner layer（Difference = 1.00， 0.80， 0.02， 0.02，P = 0.001， 0.008， 0.001， 0.008）. No differences in microcirculation indexs were observed in the macular area after near work with different diopters and axial lengths. ConclusionNear work may affect the occurrence and development of myopia by affecting the changes of retinal microcirculation in the superficial layer of macula， leading to ischemia and hypoxia.

Clinical Efficacy of Haplo-HSCT of ATG Combined with PTCy for Children with Myelodysplastic Syndrome / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in combination of ATG and post-transplant cyclophosphamide (PTCy) -induced immune tolerance after transplantation in treatment of childhood myelodysplastic syndromes(MDS）.@*METHODS@#From July 2016 to November 2020, a total of 8 children with MDS receiving the haploidentical allo-HSCT combined with ATG and PTCy-induced immune tolerance after transplantation in our hospital were enrolled, whose clinical data were retrospected and analyzed.@*RESULTS@#Median age at diagnosis of the 8 children (1 male and 7 females) was 6.4 (range, 10 months to 15 years) years old. The median medical history of MDS was 2.7 years (range, 3 months to 8 years). Among the 8 patients, 7 cases were diagnosed with refractory cytopenia of childhood and one with refractory anemia with excess of blasts. The HSC donors were father, mother or brother of patients and HLA matching in 6-9/12 loci were identical. All the donors were healthy and didn't carry the same pathogenic genes as the recipients. The median age of donors was 36.4 (range, 25 to 49) years old. The median mononuclear cell (MNC) number of the graft was 19.8, ranging in (13.2-47.3)×108/kg, and the median CD34+ cell number was 11.8×106/kg, ranging in (5.0-18.3)×106/kg. Graft-versus-host disease prophylactic regimen was started on day 3 and 4 after transplantation, in which cyclophosphamide (50 mg/kg·d) was administered by intravenous infusion. From day 5 after transplantation, low-dose tacrolimus was administered by intravenous infusion and mycophenolate mofetil was administered orally. The median time of neutrophil and platelet engraftment was 12.6 (rang, 11 to 15) days and 13.3 (rang, 11 to 18) days, respectively. All the patients achieved full donor chimerism on neutrophil engraftment after transplantation. The median follow-up time was 1 032 (rang, 747 to 1 536) days. Both overall survival rate and disease-free survival rate were 100%.@*CONCLUSION@#Haplo-HSCT combined with ATG and PTCy-induced immune tolerance after transplantation is a safe and effective treatment for children with MDS.

Diagnosis of Fanconi anemia in children with atypical clinical features: a primary study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Fanconi anemia is a severe congenital disorder associated with mutations in a cluster of genes responsible for DNA repair. Arriving at an accurate and timely diagnosis can be difficult in cases of Fanconi anemia with atypical clinical features. It is very important to increase the rate of accurate diagnosis for such cases in a clinical setting. The purpose of this study is to explore the clinical diagnosis of Fanconi anemia in children with atypical clinical features.</p><p><b>METHODS</b>Six cases of Fanconi anemia with atypical clinical features were enrolled in the study, and their clinical features were recorded, their FANCA gene transcription was assessed by RT-PCR, and FANCA mutations and the ubiquitination of FANCD2 protein were analyzed using DNA sequencing and western blotting respectively.</p><p><b>RESULTS</b>All six cases showed atypical clinical features including no apparent deformities, lack of response to immune therapy, and progressively increasing bone marrow failure. They also have significantly increased fetal hemoglobin, negative mitomycin-induced fracture test results, and carry a FANCA gene missense mutation. Single protein ubiquitination of FANCD2 was not observed in those patients.</p><p><b>CONCLUSION</b>The combination of clinical features, FANCA pathogenic gene mutation genotype and the absence of FANCD2 protein ubiquitination are helpful in the accurate and timely diagnosis of Fanconi anemia in children.</p>

The application of pedicle orbital fat flap for the correction of lacrimal groove and palpebromalar groove deformity in the middle-aged and old people / 中华整形外科杂志

<p><b>OBJECTIVE</b>To explore the effective techniques for correction of lacrimal groove and palpebromalar groove deformity in the middle-aged and old people.</p><p><b>METHOD</b>The lacrimal groove and palpebromalar groove deformity was corrected by the techniques of transcutaneous orbital fat releasing and pedicle orbital fat flap filling. From 1996 to 2011, 426 patients, aged from 35 to 72 (average, 48), were treated by the techniques. Among them, 54 patients had underwent the surgical treatment before this operation. 362 patients were followed up for 3-24 months.</p><p><b>RESULTS</b>Completely correction was achieved in 283 patients, obvious improvement in 79 patients. The result was not satisfied in 2 patients with severe deformity who had surgical treatment before.</p><p><b>CONCLUSION</b>The lacrimal groove and palpebromalar groove deformity can be effectively corrected by transcutaneous orbital fat releasing and pedicle orbital fat flap in the middle-aged and old people.</p>

Anatomic study on the mechanism of tear trough deformity and palpbromalar groove deformity / 中华整形外科杂志

<p><b>OBJECTIVE</b>To study the anatomic mechanism of tear trough deformity and palabromalar groove deformity.</p><p><b>METHODS</b>Six cadavers (12 sides, 3 male, 3 female, an average age of 67.2 years) with tear trough deformity and palpbromalar groove deformity underwent lower eyelid and periorbital area dissection.</p><p><b>RESULTS</b>Tear trough deformity and palabromalar groove deformity locate at the junction of thin eyelid skin and thick cheek skin. Skin is closely attached to the orbicularis oculi muscle. The superior horder of the malar fat pad covers the junction of the palpebral and orbital portions of the orbicularis muscle, and does not descend with malar fat pad, which is also corresponded to the location of tear trough and palphromalar groove. The gap between the orbicularis oculi muscle and the levator labii superioris alaeque nasi muscle is not correspond to tear trough. The orbicularis retaining ligament arises from the orbital rim and ends at the junction of the palpebral and orbital portions of the orbicularis muscle, and the ligament connects with the deep part of the orbicularis muscle which directly attaches to the infraorbital rim. Suborbicular oculi fat pads locate at the inferolateral of the orbital region, thin and flabby. Orbital septal arises from the infraorbital rim, and the orbital fat extrudes anteriorly and inferiorly.</p><p><b>CONCLUSIONS</b>Tear trough deformity and palabromalar groove deformity are resulted from combination of age-related relaxation, atrophy and ptosis of layers of tissues. The orbital septal and the orbicularis retaining ligament prevent tissues from descending, which makes tear trough deformity and palabromalar groove deformity more visible.</p>

The treatment of lower eyelid retraction at the different degree / 中华整形外科杂志

<p><b>OBJECTIVE</b>To explore the effective methods for the correction of lower eyelid retraction at different degree.</p><p><b>METHODS</b>258 patients with lower eyelid retraction were treated in our department since 1999. The lower eyelid retraction could be divided into mild, moderate and severe degree. The lateral canthal anchoring (n = 150), Hamra's lower eyelid blepharoplasty (n = 80) and translid cheek lifting (n = 28) were adopted according to the severity. The therapeutic effect for different degree of lower eyelid retraction was compared.</p><p><b>RESULTS</b>98 patients were followed up for 3-12 months, including 51 patients of mild degree, 29 patients of moderate degree, and 18 patients of severe degree. The retraction were corrected completely in 91 patients. The lower eyelid was repositioned to the level of inferior limbus without inferior scleral show when eyes opened. The palpebral fissure could close completely. The blunt lateral canthus turned to be acute and the scar was inconspicious. The retraction was improved, but not corrected completely in 3 patients of moderate degree and 4 patients of severe degree. The complications included petechiae, chemosis, and so on.</p><p><b>CONCLUSIONS</b>The lower eyelid retraction can be corrected effectively if the appropriate techniques are performed according to the degree of retraction.</p>

Immediate reconstruction of tissue defects on eyelid caused by tumor excision / 中华整形外科杂志

<p><b>OBJECTIVE</b>To introduce the methods for immediate reconstruction of tissue defects on eyelid caused by tumor excision.</p><p><b>METHODS</b>Single or combined local skin flaps were used to repair tissue defects on eyelids after tumor excision.</p><p><b>RESULTS</b>Since 1994, 216 patients (224 sides) were treated. All flaps survived with primary healing. 149 patients were followed up for 3 months to 10 years with satisfactory results. 2 patients with squamous cell carcinoma recurred and reoperated with local skin flap again.</p><p><b>CONCLUSIONS</b>It is a simple, safe, flexible and reliable method to immediately repair the tissue defects with local flaps on eyelid caused by tumor excision.</p>

Clinical and genetic characteristics of a patient with dyskeratosis congenita / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the clinical features and gene mutation of a patient with dyskeratosis congenita, who was admitted in our hospital for thrombocytopenia.</p><p><b>METHOD</b>The clinical and laboratory data of a 4 years and 10 months old boy were summarized. DKC1 gene was analyzed using PCR amplification and DNA sequencing.</p><p><b>RESULT</b>The age of onset of the boy was 1 year. He presented with abnormal cutaneous pigmentation, nail dystrophy and mucosal leukoplakia accompanied by multi-system abnormalities. DKC1 (1058C-T, A353V) was detected in the patient.</p><p><b>CONCLUSION</b>The patient presented with classical features of dyskeratosis congenita and DKC1 (1058C-T, A353V) did exist in this patient. X-linked recessive dyskeratosis congenita was confirmed.</p>

Local flap for reconstruction of nasal tip defect: functional and aesthetic evaluations / 中华整形外科杂志

<p><b>OBJECTIVE</b>To introduce the experience of reconstruction of nasal tip defect, which could obtain good functional and aesthetic results.</p><p><b>METHODS</b>Based on the aesthetic subunit principle, according to the size, shape, depth of nasal tip defect, and the conditions of surrounding skin, homologous local flap (include: frontonasal flap, bilobed flap, nasolabial flap, reforming rhomboid flap and forehead flap, etc.) was designed to cover the defect wound. The secondary defect of donor area was directly sutured.</p><p><b>RESULTS</b>A total of 83 patients with nasal tip defect were treated by local flap transfers. The area of the defect ranged between 0.6 x 0.6 cm and 2.5 cm x 2.5 cm. The nasal tip defect was successfully closed in all patients, and all flaps survived well without obvious complications. 76 out of these 83 patients were available for follow-up from 1 to 36 months. The repaired tissue was in good match with surrounding tissue, with nice nasal contour, and cosmetic results were satisfactory. No tumor recurrence occurred.</p><p><b>CONCLUSIONS</b>Based on the nasal aesthetic subunit principle, local flap could be used to reconstruct the nasal tip defect below 2.5 cm x 2.5 cm, and obtain good color, contour and texture in match with the surrounding skin. Cosmetic results were satisfactory.</p>

Nasolabial island pedicle flap for cutaneous reconstruction in the face / 第二军医大学学报

Objective: To investigate the application and outcome of nasolabial island pedicle flap in reconstruction of medium-sized skin defects in the face. Methods: From August 1997 to January 2005, advancement or transposition island pedicle flaps harvested from nasolabial fold were utilized to repair 23 medium-sized skin defects due to surgical removal of skin tumors or scars in the face. The size of the lesions ranged from 2.0 cm × 1.9 cm to 5.0 cm × 4.5 cm. Results: All flaps survived with primary healing postoperatively. With a follow-up ranging from 1-40 months, scars were camouflaged into natural skin tension line. No visible dog-ear, distortion of surrounding skin, or displacement of the anatomical landmarks were observed. Conclusion: The nasolabial island flap with a subcutaneous pedicle may be a reliable and ideal method for the reconstruction of medium-sized skin defects in the face.

Comparative study on bone marrow megakaryocytes in children with thrombocytopenic purpura, aplastic anemia and myelodysplastic syndrome / 中华儿科杂志

<p><b>OBJECTIVE</b>Thrombocytopenic hemorrhage is one of the major appearance in pediatric hemorrhagic diseases, in which, idiopathic thrombocytopenic purpura (ITP) is the most common disease. Thrombocytopenia is the earliest phenomenon or the only one in certain phases of hemorrhagic diseases, such as ITP, aplastic anemia (AA) and myelodysplastic syndrome (MDS). By now, the pathogenesis of thrombocytopenia in different diseases has not been clearly determined. At present, it is very difficult to diagnose these diseases and estimate their prognosis with current clinical data. In this study, morphological characteristics and hematopoiesis function of bone marrow megakaryocyte in pediatric patients with ITP, AA and MDS were observed and the cause and mechanism of different thrombocytopenias were analyzed.</p><p><b>METHODS</b>There were 16 children with ITP, 17 with AA and 16 with MDS in this study. CD41 McAb immunohistochemical technique was used to detect micromegakaryocyte on bone marrow smears. Plasma clot culture and CD41 McAb immunohistochemical technique were used for the MK-colony forming assay. The colony formation rate of colony formation unit-megakaryocyte (CFU-MK) and burst formation unit-megakaryocyte (BFU-MK) were counted.</p><p><b>RESULTS</b>There was no statistical difference on the positive rates of micromegakaryocyte and type I lymphoid small micromegakaryocyte between groups of ITP and control. The number of micromegakaryocyte and the formation rates of CFU-MK in ITP group were significantly higher than those in control group. Among AA patients, the numbers of MK, micromegakaryocyte and the formation rates of CFU-MK, BFU-MK in vitro significantly decreased. There was no significant difference in the positive rate of micromegakaryocyte between groups of MDS and control, but the number of micromegakaryocyte and the positive rate of type I lymphoid micromegakaryocyte were significantly higher than those of control group. There was no statistical difference of the formation rate of CFU-MK between groups of MDS and control. But in 63% childhood patients, the formation rate of CFU-MK decreased, 25% increased,and 13% was normal; BFU-MK formation rate decreased significantly in MDS group.</p><p><b>CONCLUSION</b>Overproliferation of bone MKs may exist in most ITP patients. For obviating the nosogenetic factors, the normal MK releasing platelet could be easily found in the culture system. But the colony formation rate of MK decreased in a few patients with CITP. The abnormality of MK might be one of the reasons for thrombocytopenia in partial patients with ITP. Underproliferation of MKs may exist in AA, but no pathosishemogenesis was found. The dysfunction of early phase MK progenitor and stem cell might be the major reason for AA, but not the abnormality of hematopoietic microenvironment. There may be two kinds of megakaryocyte clones in bone marrow of children with MDS. One may be pathologic and potentially malignant micromegakaryocytes, the other may be the normal megakaryocytic precursors. The increase of pathologic MK resulted in abnormal development and maturation of MK in bone marrow. The change of megakaryopoiesis showed different in ITP, AA or MDS. Using bone marrow smear megakaryocyte counting, small micromegakaryocyte immunohistochemical detecting and the formation rate of bone marrow MK colony assay, the different thrombocytopenia can be diagnosed during the early stage of ITP, AA or MDS.</p>

Study on bone marrow megakaryocytes in children patients with idiopathic thrombocytopenic purpura / 中国实验血液学杂志

To observe the morphological characteristics and hematopoietic function of bone marrow megakaryocyte (MK) in children patients with idiopathic thrombocytopenic purpura (ITP), and to preliminary analyse the cause and mechanism of thrombocytopenia. CD41 McAb immunohistochemical technique was used to detect micromegakaryocyte in bone marrow smear. Plasma clot culture and CD41 McAb immunohistochemical technique were used for the MK-colony forming assay. The results showed that there was no statistical difference of the positive rate of micromegakaryocyte between groups of ITP and control, but type I lymphocyte-like micromegakaryocyte was infrequent. The number of micromegakaryocyte and the formation rates of CFU-MK and BFU-MK in ITP group were significantly higher than those in control group. The normal MK releasing platelet could be easily found in the culture system. The MK colony formation rate was decreased in a patient with chronic ITP. In conclusion, the increment of type II, III, IV micromegakaryocytes is one of pathologic phenomenon of ITP. These small megakaryocytes can develop and mature to normal megakaryocytes in the condition of ex vivo culture. The developmental abnormity of MK is a possible reason for thrombocytopenia among partial patients with ITP, especially the chronic cases.

A study on micromegakaryocyte in children with idiopathic thrombocytopenic purpura / 中华儿科杂志

<p><b>OBJECTIVE</b>Bone marrow megakaryocytes overly proliferate and abnormally develop among patients with idiopathic thrombocytopenic purpura (ITP). Previous studies showed that it resulted from the abnormal immune function of the body. But the changes in megakaryocytes, especially in micromegakaryocytes in this disease are unclear. The present study was designed to explore the growth and development status of megakaryocytes and the significance of changes in micromegakaryocytes in pediatric cases.</p><p><b>METHODS</b>Routine bone marrow smears assay and enzyme labeling for micromegakaryocytes with CD41 monoclonal antibody (McAb) were performed in 46 children with ITP. The level of platelet-associated immunoglobulin (PA-Ig) was measured with ELISA.</p><p><b>RESULTS</b>Among 46 children, 36 had acute ITP (AITP)and 10 chronic ITP (CITP). The number of megakaryocytes increased or was normal in 45 patients, but decreased only in 1 case of CITP. The positive rate of micromegakaryocytes and type I micromegakaryocytes was 98% (45/46) and 35% (16/46), respectively. The positive rate of type I micromegakaryocytes was higher in CITP (50%) cases than that in AITP (31%) cases, but the median of the other three types of micromegakaryocytes in CITP cases (159) was lower than that in the AITP cases (336). There was no relationship between the numbre of all types of megakaryocytes and the level of PA-Ig.</p><p><b>CONCLUSION</b>Majority of patients with ITP showed an increase in micromegakaryocytes, especially in type II, III and IV. The immune disturbance might not be the only reason for ITP. The abnormality of quality of megakaryocytes might be one of the potential causes for thrombocytopenia in some cases of ITP, especially in those of CITP. The appearance and the number of type I micromegakaryocytes might reflect the prognosis of cases of ITP.</p>

Study on bone marrow megakaryocytes in children patients with myelodysplastic syndrome / 中国实验血液学杂志

The study was aimed to observe morphological characteristics and hematopoiesis function of bone marrow megakaryocyte in children patients with myelodysplastic syndrome (MDS), and analyse the cause and mechanism of thrombocytopenia. CD41 McAb immunohistochemical technique was used to detect micromegakaryocytes of bone marrow smear. Plasma clot culture and CD41 McAb immunohistochemical technique were used for the MK-colony forming assay. The colony formations of CFU-MK and BFU-MK were measured. The results showed that there was no significant difference of CFU-MK colony formation rate between groups of MDS and control. But, in 62.5% of children patients the colony formation rate of CFU-MK decreased, in 25% increased, and in 12.5% was normal while BFU-MK formation rate decreased in MDS group significantly. The number of micromegakaryocyte and the positive rate of type I lymphoid micromegakaryocyte were significantly higher than those of the control group. In conclusion, there may be two kinds of megakaryocyte clones in bone marrow of children patients with MDS. One is supposed to be pathologic and potentially malignant micromegakaryocytes, the another may be the normal megakaryocytic precursors. The thrombocytopenia in MDS patients induced by increase of pathologic MK leads to abnormal development and maturation of MK in bone marrow.

Detection of Borna disease virus-p24 specific antibody in the sera of schizophrenic patients of China by means of Western-blot / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To investigate whether Borna disease virus (BDV) infection is related to the schizophrenic patients from China.</p><p><b>METHODS</b>A reliable Western-blot method for detection of BDV-p24 antibody was established by adjusting the reaction conditions of BDV-p24 recombinant protein and specific antibodies. The sera of schizophrenic patients and normal controls from Heilongjiang Province were screened for specific BDV-p24 antibody by this method, and the BDV-p24 antibody positive sera were confirmed by the Western-blot method with sera-GST protein absorption.</p><p><b>RESULTS</b>Ten of 116 (8.6%) schizophrenic patients were found to be positive for BDV-p24 specific antibody, while no BDV-p24 specific antibody was found in sera of normal controls.</p><p><b>CONCLUSIONS</b>The results demonstrate that the Borna disease virus infection also exists in China, and the infection is possibly associated with schizophrenia in some way.</p>

The role of releasing the fibrous bundles across levator muscle in correcting congenital blepharoptosis / 中华整形外科杂志

<p><b>OBJECTIVE</b>To investigate the role of releasing the fibrous bundles across the levator muscle between the medial canthus and lateral canthsus near the top of tarsus in the correction of the congenital blepharoptosis.</p><p><b>METHODS</b>Twenty-seven patients with 40 eyes of blepharoptosis were undergoing the treatment. It was performed by releasing the fibrous bundles across the levator muscle between the medial canthus and lateral canthsus near the top of tarsus to correct the mild and moderate blepharoptosis. A further procedure can also be added to by folding the levator aponeurosis if necessary. In the severe blepharoptosis, the frontalis aponeurose flap may be applied for the suspension as well during the operation.</p><p><b>RESULTS</b>Of the 40 eyes in 27 cases with mild, moderate and severe blepharoptosis were treated by using this method, with 38 eyes corrected satisfactorily and 2 eyes corrected mostly in the following-ups from 3 months to 1 year.</p><p><b>CONCLUSION</b>The above mentioned technique may be a good, simple and effect method to corret congenital blepharoptosis.</p>