Venous thromboembolism in children with acute lymphoblastic leukemia in China: a report from the Chinese Children's Cancer Group-ALL-2015 / 医学前沿

Venous thromboembolism (VTE) is a complication in children with acute lymphoblastic leukemia (ALL). The Chinese Children's Cancer Group-ALL-2015 protocol was carried out in China, and epidemiology, clinical characteristics, and risk factors associated with VTE were analyzed. We collected data on VTE in a multi-institutional clinical study of 7640 patients with ALL diagnosed in 20 hospitals from January 2015 to December 2019. First, VTE occurred in 159 (2.08%) patients, including 90 (56.6%) during induction therapy and 108 (67.92%) in the upper extremities. T-ALL had a 1.74-fold increased risk of VTE (95% CI 1.08-2.8, P = 0.022). Septicemia, as an adverse event of ALL treatment, can significantly promote the occurrence of VTE (P < 0.001). Catheter-related thrombosis (CRT) accounted for 75.47% (n = 120); and, symptomatic VTE, 58.49% (n = 93), which was more common in patients aged 12-18 years (P = 0.023), non-CRT patients (P < 0.001), or patients with cerebral thrombosis (P < 0.001). Of the patients with VTE treated with anticoagulation therapy (n = 147), 4.08% (n = 6) had bleeding. The VTE recurrence rate was 5.03% (n = 8). Patients with VTE treated by non-ultrasound-guided venous cannulation (P = 0.02), with residual thrombus (P = 0.006), or with short anticoagulation period (P = 0.026) had high recurrence rates. Thus, preventing repeated venous puncture and appropriately prolonged anticoagulation time can reduce the risk of VTE recurrence.

Epidemiological characteristics of leprosy in China from 2016 to 2020 / 中华皮肤科杂志

Objective:To analyze epidemiological characteristics of leprosy in China from 2016 to 2020, and to provide a scientific basis for further elimination of leprosy.Methods:Data collation and statistical analysis were conducted on annual reports on leprosy epidemic surveillance in China (excluding Hong Kong, Macao, and Taiwan regions) from 2016 to 2020.Results:From 2016 to 2020, a total of 2 697 new cases of leprosy were reported in China, including 46 (1.71%) children, 894 (33.15%) females, 374 (13.87%) floating people, 2 443 (90.58%) multibacillary cases, and 546 (20.24%) cases of grade 2 disabilities. A total of 203 relapsed cases were reported in the meantime. By the end of 2020, there had been 1 893 registered leprosy cases in China, and the number of cases was 68.62% fewer than that in 2010 (6 032 cases) ; there were 36 (1.2%) counties or cities with a prevalence rate above 1 per 100 000, and 72 (17.73%) new cases suffered from grade 2 disabilities.Conclusion:From 2016 to 2020, the reported incidence and prevalence of leprosy in China steadily decreased year by year, and overall, leprosy was still lowly prevalent.

A new 3D-printed ankle fusion prosthesis for the treatment of osteosarcoma in the distal tibia: a case report / 中华骨科杂志

To report the short-term clinical outcome of three cases of distal tibial osteosarcoma treated with a novel 3D-printed ankle fusion prosthesis for limb preservation. The patients were admitted to the Department of Bone Tumor, Shanghai General Hospital from January 2020 to June 2021, with one male and two female cases, aged 18, 12, and 14 years, respectively, all diagnosed with distal tibial osteosarcoma (Ennecking stage IIb). A new self-designed ankle fusion prosthesis was used to perform osteosarcoma resection and prosthetic reconstruction of the distal tibia. The operation time, blood loss, postoperative American Orthopedic Foot and Ankle Society Score (AOFAS) and ankle range of motion were recorded. All the 3 patients successfully completed the operation and were followed up for 22 months, 18 months and 12 months, respectively. The operation time was 140 min, 110 min and 200 min, and the blood loss was 200 ml, 200 ml and 350 ml, respectively. At the last follow-up, the AOFAS were 86, 90 and 95 points, and the range of motion of ankle flexion and extension were 30°, 15° and 30°. There was no local recurrence or lung metastasis at the last follow-up. The novel 3D-printed ankle fusion prosthesis in the distal tibia is safe and effective for the reconstruction of bone defects after resection of osteosarcoma in the distal tibia, and the early postoperative function is satisfactory.

Construction and application of a bone tumor database / 中华骨科杂志

Objective:To explore the construction and application methods of multicenter bone tumor-specific database.Methods:Experts from multiple centers including Shanghai General Hospital, Shanghai Changzheng Hospital, Zhongshan Hospital, Shanghai Sixth People's Hospital, Ruijin Hospital, Fudan University Shanghai Cancer Center and Shanghai Ninth People's Hospital established a standard dataset for bone tumors through research and discussion. Clinical data will be automatically collected and standardized according to standard fields. A database will be built and a users' interface will be developed to ensure secure data storage, while providing services such as exporting raw data, visualizing statistical analysis, establishing clinical queue research projects, et al. Finally, the bone tumor database will be shared by integrating with the Shenkang's Big Data Platform to achieve multi-center data integration.Results:A standard data set for bone tumors containing 603 fields has been established and published. An automated data collection system for bone tumors has been established, including complete data collection, data collation and visualization functions. The data categories include modules such as patients' electronic case information, laboratory information on blood routine, biochemistry and tumor markers, imaging information, surgery information, pathology information and radiotherapy records. Personal information such as patients' names and ID numbers are desensitized and encrypted and can be exported for further research. From 2015 to 2023, the total number of bone tumor cases collected in the database was 10,789. From 2015 to 2019, 112 cases of the osteosarcoma cohort were retrospectively analyzed for admission, with a statistical 5-year survival rate of 68%.Conclusion:A regional bone tumor specialty big data network and data sharing platform has been established, along with data sharing mechanisms and standards including data standards, security standards, and quality evaluation standards. This provides data and efficient new solutions for the construction of China's bone tumor database, as well as a research and development platform for standardized diagnosis and treatment of bone tumors and new technologies.

Progress in molecular diagnosis of Diamond-Blackfan anemia / 国际儿科学杂志

Diamond-Blackfan anemia(DBA)is a rare hereditary anemia.About 90% of them have symptoms in infancy, and about 50% are complicated with congenital malformations.Genetic abnormalities were found in 70% to 80% of DBA cases, mainly autosomal dominant inheritance, and a few were recessive or X-linked inheritance.The main gene mutations of DBA are ribosomal protein gene mutations and deletions.More than 20 mutation genes related to DBA have been found in the ribosomal protein(RP)gene encoding ribosome, of which RPS19 gene mutation is the most common.In addition, there are TSR2 genes related to ribosome function and non-RP genes related to DBA like phenotype, such as GATA1, EPO and ADA2 genes.These genes play a key role in the differentiation and proliferation of erythroid cells.Molecular diagnosis is an important criterion to diagnose and distinguish classical DBA from non-classical DBA.This review summarizes the latest research progress in the genetics, gene mutation and molecular diagnosis of DBA.

Comparison of the efficacy of middle meningeal artery embolization and conventional therapy for chronic subdural hematomas: a propensity score matching study / 中华放射学杂志

Objective:To compare the effect of middle meningeal artery embolization (MMAE) versus conventional therapy for chronic subdural hematoma (CSDH).Methods:Retrospective analysis of 38 patients with 48 CSDHs treated with MMAE from May 2019 to May 2021 was performed. Comparisons were made with a conventional treatment for 126 patients with 126 CSDHs from January 2016 to May 2021. The MMAE and conventional treatment patients were matched by the propensity score matching method, and a total of 25 pairs of patients (31 pairs of CSDHs) were successfully matched. The CSDH recurrence, rescue treatment, radiographic follow-up outcome, clinical improvement and complication between the two groups were compared by t test, χ 2 test or Fisher exact probability methods. Results:The rescue treatment rate in MMAE group was significantly lower than that in conventional treatment group [0 (0/31) vs 19.4% (6/31), P=0.024] and the complete resolution rate at 6 months follow-up in MMAE group was significantly higher than that in conventional treatment group [96.8 (30/31) vs 74.2% (23/31), P=0.026]. In terms of CSDH recurrence, there was a trend of lower recurrence in the MMAE group [3.2%(1/31) vs 22.6% (7/31), P=0.053]. The complete resolution rate at 3 months follow-up was 61.3% (19/31) in MMAE group and 45.2% (14/31) in conventional treatment, clinical improvement rate was 92.0% (23/25) in MMAE group and 88.0% (22/23) in conventional treatment, good outcome rate (mRS≤2) was 92.0% (23/25) in MMAE group and 84.0% (21/25) in conventional treatment, complication rate was 0(0/25) in MMAE group and 4.0% (1/25) in conventional treatment, and there were no significant differences in all above-mentioned parameters ( P>0.05). Conclusions:The MMAE may be considered as a safe and effective treatment for CSDH, and MMAE for CSDH is associated with lower trend of recurrence, lower rescue treatment rate and better radiographic follow-up outcome than conventional therapy.

Efficacy and safety of granulocyte and granulocyte-macrophage colony-stimulating factors for the prevention of post-chemotherapy infections in pediatric hematologic neoplasms: a prospective multi-center study / 白血病·淋巴瘤

Objective:To explore the efficacy and safety of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and human granulocyte colony-stimulating factor (G-CSF) for the prevention of post-chemotherapy infections in pediatric hematologic neoplasms.Methods:A total of 134 children hospitalized for chemotherapy in 6 tertiary hospitals from July 2016 to June 2018 were collected, including 60 cases in Children's Hospital of Fudan University, 38 cases in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 29 cases in Children's Hospital Affiliated to Soochow University, 4 cases in the Affiliated Hospital of Qingdao University, 2 cases in Northwestern Women and Children's Hospital, and 1 case in Shandong Provincial Qianfoshan Hospital. The children were divided into GM-CSF group (38 cases), G-CSF group (45 cases) and GM-CSF+G-CSF group (51 cases) by using random number table method. The incidence of infections, the recovery time of absolute neutrophil counting (ANC), the decrease of blood platelet count (Plt) and the incidence of adverse reactions were compared among the three groups.Results:In all children, a total of 64 cases (47.8%) had infections during the myelosuppression phase after chemotherapy, of which 18 cases (47.4%) in GM-CSF group, 20 cases (44.4%) in G-CSF group, and 26 cases (51.0%) in GM-CSF+G-CSF group. The incidence of respiratory infection in G-CSF group was higher than that in GM-CSF group and GM-CSF+ G-CSF group [22.2% (10/45) vs. 2.6% (1/38), 4.0% (2/51), χ2 = 12.00, P = 0.002]. The median time to recovery of ANC > 1.5×10 9/L was 10.5 d (8 d, 15 d) in all children, 12 d (10 d, 16 d) in GM-CSF group, 9 d (8 d, 12 d) in G-CSF group, and 10 d (8 d, 16 d) in GM-CSF+G-CSF group. In all children, a total of 101 cases (75.4%) had Plt<50×10 9/L during the myelosuppression phase, and 79 cases (59.0%) had Plt <20×10 9/L. The differences in the incidence of Plt <50×10 9/L and <20×10 9/L among the three groups were not statistically significant (both P > 0.05). In all children, the adverse reactions occurred in 24 cases (17.9%), including 20 cases (14.9%) of fever, 2 cases (1.5%) of sore throat, 1 case (0.7%) of nausea, and 1 case (0.7%) of diarrhea; no adverse reactions of grade 2 or above occurred. The difference in the incidence of adverse reactions among the three groups was not statistically significant ( P>0.05). Conclusions:The efficacy of GM-CSF and G-CSF for the prevention of infections in pediatric hematologic neoplasms during the myelosuppression phase after chemotherapy is roughly equivalent, and combination of both has a good tolerance. The incidence of respiratory infection using GM-CSF alone or GM-CSF+G-CSF is low, which might benefit from the effect of GM-CSF on lung infections.

A novel inhibitor of N 6-methyladenosine demethylase FTO induces mRNA methylation and shows anti-cancer activities

N 6-methyladenosine (m6A) modification is critical for mRNA splicing, nuclear export, stability and translation. Fat mass and obesity-associated protein (FTO), the first identified m6A demethylase, is critical for cancer progression. Herein, we developed small-molecule inhibitors of FTO by virtual screening, structural optimization, and bioassay. As a result, two FTO inhibitors namely 18077 and 18097 were identified, which can selectively inhibit demethylase activity of FTO. Specifically, 18097 bound to the active site of FTO and then inhibited cell cycle process and migration of cancer cells. In addition, 18097 reprogrammed the epi-transcriptome of breast cancer cells, particularly for genes related to P53 pathway. 18097 increased the abundance of m6A modification of suppressor of cytokine signaling 1 (SOCS1) mRNA, which recruited IGF2BP1 to increase mRNA stability of SOCS1 and subsequently activated the P53 signaling pathway. Further, 18097 suppressed cellular lipogenesis via downregulation of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and C/EBPβ. Animal studies confirmed that 18097 can significantly suppress in vivo growth and lung colonization of breast cancer cells. Collectively, we identified that FTO can work as a potential drug target and the small-molecule inhibitor 18097 can serve as a potential agent against breast cancer.

Reconstruction strategy with recycled bone for distal tibial osteosarcoma / 中华骨科杂志

Objective:Limb salvage treatment for osteosarcoma in the distal tibiais challenging and the incidence of postoperative complications is high. To prove that the use of autologous bone inactivation to replant the ankle joint has a satisfactory clinical effect.Methods:This study retrospectively studied 6 cases (4 males and 2 females) of the osteosarcoma of the distal tibia from June 2018 to April 2019 in our center. The average case age was 16.8 years. All cases were first diagnosed in the center, and classic osteosarcoma was confirmed by biopsy. Before the operation, he received 4 courses of neoadjuvant chemotherapy. The tumor was resected under general anesthesia, and the tumor bone was inactivated and replanted for internal fixation and reconstruction. During the operation, the tumor segment was completely removed, and after a series of treatments, it was immersed in hypertonic saline at 65 °C for 45 min. After removal, the bone defect was filled with bone cement, and internal fixation materials such as plate screws and anchors were placed. Finally, soft tissue was rebuilt after the inactivated bone internal fixation complex (autograft-fixation composite, AFC) was replanted. Patients were treated with plaster for 3 months after surgery. Chemotherapy continued 2 weeks after surgery. Follow-up X-ray of the lower tibia were taken at 3 months, 6 months, and 12 months after the operation to evaluate the MSTS score and ankle function score (AOFAS) to evaluate the ankle function.Results:The patients were followed up for an average of 20 months. At 12 months after operation, no complications such as deep infection, mechanical failure of internal fixation, or local tumor recurrence occurred. The MSTS score averaged 26.7±2.6 points. The AOFAS average was 82.3±8.5 points. The VAS average is 2.7 points. Boneunionwasobserved in 5 cases during follow-up. All cases were satisfied with the treatment results.Conclusion:Limb salvage treatment of distal tibia osteosarcoma is more difficult. This study proves that the use of tumor bone inactivation and internal fixation to reconstruct the ankle joint can not only cure the tumor, but also has satisfactory limb function. It is an ideal strategy for limb salvage reconstruction.

RPL5 gene mutation causes Diamond-Blackfan anemia: a case report and literature review / 中华实用儿科临床杂志

Objective:To explore the clinical characteristics of Diamond-Blackfan anemia (DBA) in children caused by RPL5 gene mutation, thus improving the understanding of the etiology of DBA.Methods:The clinical data and sequencing results of a child with DBA caused by RPL5 gene mutation treated in the Children′s Hospital of Fudan University were analyzed.In addition, through literature review of reported DBA cases at domestic and home, summarized the clinical features of DBA.Results:The patient was an 8-year-old male child.Bone marrow puncture examination of the child showed DBA, and a heterozygous mutation of RPL5 gene c. 657C>G, p.Y219X was identified for the first time in the DBA case.A total of 47 cases of DBA were retrieved from the online databases plus the one reported in this study (48 cases in total), and their clinical features were summarized as follows: the incidence of DBA was similar in men and women.The number of DBA patients in Asia was lower than that in Europe and the United States.DBA was mainly a sporadic disease.Among the exon mutations in European and American cases of DBA, 43.0% of them had mutations in Exon3.The malformation rate of DBA patients with RPL5 mutation was 81.3% (39/48 cases, excluding short stature cases), which was higher than that of patients with other mutation types.The response rate of glucocorticoid therapy for DBA was 46.0%, which was lower than that of the overall response rate.Conclusions:chr1: 93303142(c.657 C>G, p.Y219X) is a newly detected mutation of RPL5 gene in the DBA case, which expands the pathogenic gene spectrum of DBA.Patients with RPL5 mutation have higher rates of teratogenicity and multiple teratogenicity, and a lower response rate to hormone therapy.

Seroprevalence of serum measles antibody in children with tumor after chemotherapy / 中华传染病杂志

Objective:To investigate the serum measles antibody in children with tumor and to provide the clinical evidence for measles vaccination strategy for this special population.Methods:From January 2016 to December 2018, the blood samples of children who were diagnosed with hematological malignancy or solid tumors and received chemotherapy in the Department of Hematology or Oncology Surgery of Children′s Hospital of Fudan University were collected. Enzyme-linked immunosorbent assay was used to quantitatively detect the level of measles IgG antibody, and dynamically monitor the changes of measles antibody level during chemotherapy. Kruskal-Wallis test and chi-square test were used for statistical analysis.Results:A total of 441 children with tumors were enrolled, with the positive rate of measles antibody of 79.1%(349/441), and only 43.3%(191/441) of children had the protective level of IgG antibody. There was a statistically significant difference of the antibody protection rate in children aged<eight months old, eight months old to <two years old, two years old to <six years old, and ≥six years old ( χ2=15.647, P<0.01). There was no statistically significant difference of the protection rate of serum measles antibody between children aged two to <six years and≥six years (43.8%(95/217) vs 41.1%(58/141), P>0.05). The protection rate of serum measles antibody in children with hematological malignancy and solid tumor were 45.6%(78/171) and 41.9%(113/270), respectively, and there was no statistically significant ( P>0.05). There were 16.3%(16/98) of children who were observed to lose the pre-existing protective antibody during chemotherapy. There was no statistically significant difference of the protection rate of serum among children who had finished chemotherapy <six months, six months to <one year, one year to <two years, and ≥two years ( P>0.05). Conclusions:Serum measles antibody is below the protective level in more than 50% of children with malignancy after chemotherapy. Chemotherapy can compromise the protective antibody against measles. It is recommended for this special population to re-schedule measles vaccine after individualized evaluation to acquire the immuneprotection against measles.

Analysis of clinical efficacy and prognosis of childhood T-cell acute lymphoblastic leukemia / 白血病·淋巴瘤

Objective:To evaluate the treatment efficacy of children with T-cell acute lymphoblastic leukemia (T-ALL) and to explore the prognostic risk factors.Methods:The clinical and laboratory data of children with newly diagnosed T-ALL in Children's Hospital of Fudan University and Children's Hospital of Shanghai from January 2002 to December 2014 were retrospectively analyzed and compared with children with newly diagnosed B-cell acute lymphoblastic leukemia (B-ALL) in the same period. The treatment protocols were based on the combination of the Berlin-Frankfurt-Münster (BFM)-ALL regimen with chemotherapy. The treatment response and infection of the children were observed. Cox proportional hazard regression model single-factor and multifactor analysis were used to evaluate the prognostic factors.Results:Seventy-one children with T-ALL and 333 children with B-ALL were enrolled. The clinical features including gender, age, central nervous system leukemia as well as the white blood cell count at first diagnosis were significantly different between the two groups (all P < 0.05). The prednisone good response rates of children with T-ALL were lower than that of B-ALL [78.9% (56/71) vs. 93.4% (311/333), P < 0.01], and the complete remission rates were lower than that of [94.4% (67/71) vs. 99.1% (330/333), P= 0.023]. By the end of follow-up, the relapse rates of children with T-ALL and B-ALL were 20.9% (14/67) and 16.4% (54/330) ( P= 0.369). The children with T-ALL had a shorter time to relapse compared with children with B-ALL [64.3% (9/14) vs. 35.2% (19/54), P= 0.049]. The 5-year overall survival (OS) rates of children with T-ALL and B-ALL were (62.1±6.4)% and (81.3±2.4)% (P < 0.05), and the 5-year event free survival (EFS) rates were (61.0±6.3)% and (71.0±2.7)% (P < 0.05). There was no significant difference in OS and EFS among pro/pre T-ALL, cortical T-ALL and mature T-ALL (both P > 0.05). The difference of EFS curves between children with early T-precursor (ETP)-ALL and non-ETP ALL was statistically significant ( P= 0.044). The most common infection site was respiratory tract [63.9% (186/291)], and the gram-negative bacteria accounted for 43.5% (20/46). Cox univariate analysis showed that prednisone poor response, bone marrow non-remission on day 33 of induction-therapy, relapse and sepsis were prognostic risk factors for children with T-ALL (all P < 0.05), and Cox multivariate analysis showed that the latter three were independent prognostic risk factors (all P < 0.05). Conclusions:The prognosis of children with T-ALL is worse than children with B-ALL, and T-ALL patients are prone to early relapse. The EFS of children with ETP-ALL is poor. Non-remission at the end of induction-therapy, relapse and sepsis are independent risk factors for prognosis.

Identification of a novel CHS1/LYST variant in a Chinese pedigree affected with Chediak-Higashi syndrome / 中华医学遗传学杂志

OBJECTIVE@#To detect pathological variant in two patients with Chediak-Higashi syndrome (CHS) from a consanguineous family and to explore its genotype-phenotype correlation.@*METHODS@#Clinical data was collected for this pedigree. Genomic DNA was prepared from probands' peripheral leukocytes and their relatives' fingernail. Whole exome sequencing and Sanger sequencing were carried out to detect potential variant of the LYST gene.@*RESULTS@#The proband presented with partial oculocutaneous albinism, immunodeficiency and acidophilic inclusion body in bone marrow and blood smears. A novel homozygous nonsense variant c.8782C>T (p.Gln2928*) was identified in exon 34 of the LYST gene in the sib pair. The same variant was found to be in heterozygous status in 6 unaffected individuals from the pedigree.@*CONCLUSION@#Above result enriched the mutational spectrum of CHS and provided a basis for genetic counseling and prenatal diagnosis for this pedigree.

Expression of p-AKT and p-mTOR in pediatric Burkitt lymphoma and their correlation with prognosis / 中华病理学杂志

Objective@#To evaluate the expression of p-AKT and p-mTOR, the key proteins in PI3K/AKT/mTOR pathway in pediatric Burkitt lymphoma (BL), and to investigate the clinical and prognostic significance.@*Methods@#Fifty-eight cases of pediatric BL and thirty cases of reactive hyperplastic lymphadenitis (RH) were collected at Children′s Hospital of Fudan University from September 2011 to July 2018. Paraffin sections of tissues were immune stained for p-AKT and p-mTOR, and the expression was assessed and correlated with the clinical features and prognosis.@*Results@#A total of 58 cases were diagnosed and 6 cases lost the follow-up. Of the remaining 52 BL patients including 43 males and 9 females, the median age was 5 years (range: 2 to 14 years). Regarding to the correlation between the two biomarkers, Spearman test showed that p-mTOR was positively associated with the expression of p-AKT (r=0.759, P<0.001). Of all BL patients, the positive rates of p-AKT and p-mTOR were 62.1% (36/58) and 60.3%(35/58) respectively, both significantly higher than control group (P=0.011, P=0.035 respectively). The presence of p-AKT was significantly associated with higher lactate dehydrogenase (LDH≥573 IU/L) level in patients of the disease (P=0.006), while p-mTOR was increased both in the higher LDH and lower ratio of albumin to globulin (A/G) group (P=0.006, P=0.034 respectively). Expression of p-AKT and p-mTOR did not show any statistical correlation with sex, age, St.jude stage, tumor size, B-symptom present or not, number of extra-nodal sites or international prognostic index (IPI) (P>0.05). Fifty-two patients had a median follow-up of 40 months (range: 5-87 months). Univariate analysis showed that p-AKT expression was significant in predicting both inferior OS (5-year estimate, 72.7% vs. 94.7%, χ2=4.123, P=0.042) and PFS (5-year estimate, 66.7% vs. 94.7%, χ2=5.822, P=0.016). The 5-year OS rate was 71.0% (22/31) for the p-mTOR positive cohort of patients compared to 95.2% (17/21) for p-mTOR negative group (χ2=4.881, P=0.027); however, there was no statistical significance in 5-year PFS rate (P>0.05). Especially, the 5-year OS and PFS rate of p-AKT/p-mTOR double-positive group were significantly lower than negative control group (including absence of single p-AKT or p-mTOR expression, and absence of both) (OS: 69.0% vs. 95.7%, χ2=6.285, P=0.012; PFS: 65.5% vs. 91.3%, χ2=5.405, P=0.020). The results of multivariate COX proportional risk regression analysis indicated that p-AKT/p-mTOR double-positive, higher LDH and IPI score 3-5 were independent prognostic factors for both OS and PFS, and the bulky tumor (>10 cm) for PFS of pediatric BL.@*Conclusion@#The expression of p-AKT and p-mTOR may be a potential reference for diagnosis and the independent prognostic indicators of pediatric BL.

Expression of p-AKT and p-mTOR in pediatric Burkitt lymphoma and their correlation with prognosis / 中华病理学杂志

Objective@#To evaluate the expression of p-AKT and p-mTOR, the key proteins in PI3K/AKT/mTOR pathway in pediatric Burkitt lymphoma (BL), and to investigate the clinical and prognostic significance.@*Methods@#Fifty-eight cases of pediatric BL and thirty cases of reactive hyperplastic lymphadenitis (RH) were collected at Children′s Hospital of Fudan University from September 2011 to July 2018. Paraffin sections of tissues were immune stained for p-AKT and p-mTOR, and the expression was assessed and correlated with the clinical features and prognosis.@*Results@#A total of 58 cases were diagnosed and 6 cases lost the follow-up. Of the remaining 52 BL patients including 43 males and 9 females, the median age was 5 years (range: 2 to 14 years). Regarding to the correlation between the two biomarkers, Spearman test showed that p-mTOR was positively associated with the expression of p-AKT (r=0.759, P<0.001). Of all BL patients, the positive rates of p-AKT and p-mTOR were 62.1% (36/58) and 60.3%(35/58) respectively, both significantly higher than control group (P=0.011, P=0.035 respectively). The presence of p-AKT was significantly associated with higher lactate dehydrogenase (LDH≥573 IU/L) level in patients of the disease (P=0.006), while p-mTOR was increased both in the higher LDH and lower ratio of albumin to globulin (A/G) group (P=0.006, P=0.034 respectively). Expression of p-AKT and p-mTOR did not show any statistical correlation with sex, age, St.jude stage, tumor size, B-symptom present or not, number of extra-nodal sites or international prognostic index (IPI) (P>0.05). Fifty-two patients had a median follow-up of 40 months (range: 5-87 months). Univariate analysis showed that p-AKT expression was significant in predicting both inferior OS (5-year estimate, 72.7% vs. 94.7%, χ2=4.123, P=0.042) and PFS (5-year estimate, 66.7% vs. 94.7%, χ2=5.822, P=0.016). The 5-year OS rate was 71.0% (22/31) for the p-mTOR positive cohort of patients compared to 95.2% (17/21) for p-mTOR negative group (χ2=4.881, P=0.027); however, there was no statistical significance in 5-year PFS rate (P>0.05). Especially, the 5-year OS and PFS rate of p-AKT/p-mTOR double-positive group were significantly lower than negative control group (including absence of single p-AKT or p-mTOR expression, and absence of both) (OS: 69.0% vs. 95.7%, χ2=6.285, P=0.012; PFS: 65.5% vs. 91.3%, χ2=5.405, P=0.020). The results of multivariate COX proportional risk regression analysis indicated that p-AKT/p-mTOR double-positive, higher LDH and IPI score 3-5 were independent prognostic factors for both OS and PFS, and the bulky tumor (>10 cm) for PFS of pediatric BL.@*Conclusion@#The expression of p-AKT and p-mTOR may be a potential reference for diagnosis and the independent prognostic indicators of pediatric BL.

Cutaneous tuberculosis / 中华皮肤科杂志

Cutaneous tuberculosis is an infectious disease caused by Mycobacterium tuberculosis complex.Its clinical manifestations vary with infection route,host immunity,etc.Traditional laboratory examinations,including acid-fast staining followed by direct microscopy,cultivation,histopathological examination and so on,still play important roles in the diagnosis and treatment of cutaneous tuberculosis.Development of a series of laboratory techniques represented by nucleic acid amplification tests provides significant support for accurate clinical diagnosis and treatment in recent years.This review summarizes advances in the etiology,pathogenesis,clinical manifestations,laboratory examinations and treatment of cutaneous tuberculosis.

Application of twist drill craniostomy with urokinase in chronic subdual hematoma / 国际外科学杂志

Objective To evaluate the clinical effect of chronic subdual hematoma between surgical procedure twist drill craniostomy with injecting urokinase into hematoma space and only with twist drill craniostomy.Methods Two hundred and twenty-five patients with chronic subdual hematoma patients who were admitted in the Affiliated Hospital of Yangzhou University from January 2011 to April 2017 were retrospectively analyzed.They were divided into two groups according to the different surgical methods,group A for twist drill craniostomy with injecting urokinase into hematoma space (n =116),group B only for twist drill craniostomy (n =109).Then the postoperative drainage volume and residual hematoma was analyzed by repeated measures,while radiographic grading system and recurrence rates after operation were compared between groups with statistical analysis which was done by ANOVA analysis or non-parametric rank sum test.Results The drainage volume 48 hours after surgery was(52.41 ± 7.86) ml in group A,(28.42 ± 4.46) ml in group B as well.The residual volumes which were calculated at 1 month,3 months after surgery was (23.35 ±4.18) ml and (15.31 ±6.15) ml in group A,comparing the volumes of (46.07 ± 5.96) ml and (25.60 ± 5.03) ml in group B.The radiographic grading system was evaluated by grade 1-4.There were 75(64.7％) cases in grade 1,32(27.6％) cases in grade 2,8(6.9％) cases in grade 3,1 (0.9％) cases in grade 4 of group A,as well as 42(38.5％) cases in grade 1,55(50.5％) cases in grade 2,11 (10.1％) cases in grade 3,1 (0.9％) cases in grade 4 of group B.The rate of recurrence for chronic subdural hematoma was 6.0％ in group A,while it was 15.6％ in group B.These data all had significant statistical difference between the two groups (P ＜ 0.05).Conclusion Twist drill craniostomy might be a safe,effective and mini-massive method for treating chronic subdual hematoma,while injecting urokinase into the hematoma space could significantly reduce the rate of recurrence and decrease the volume of hematoma.

Antibiotic Use in 1107 Acute Suppurative Tonsillitis Cases in Pediatric Outpatient Department / 现代医院

Objective To reduce unreasonable use of antibiotics in acute suppurative tonsillitis cases. Methods Retrospective analyses of 1107 acute suppurative tonsillitis cases from the pediatric outpatient department were conducted.According to course of antibiotic treatment, these cases were divided into the group of full course of treatment and the group of insufficient course of treatment.According to the types of antibiotic, the subjects were di-vided into azithromycin group and non-azithromycin group.Three months after the onset of illness, the occurrence of complications and illness relapse between full course of treatment group and insufficient course group, azithromycin group and non-azithromycin group were analyzed.Meanwhile, the cases were divided into Chinese mainland group, Macao and Taiwan group, and foreign group according to their native places and nationalities.We compared the num-ber of cases used insufficient course in these three groups and analyzed their reasons.Results The relapse rate was significantly lower in the full course treatment group compared with insufficient course treatment group ( P<0.05 ) , and significantly higher in non-azithromycin group compared with azithromycin group ( P<0.05 ) .The occurrence rate of insufficient course treatment in the Chinese mainland group was obviously higher than the Macao group, Tai-wan group and foreign group (P<0.05).The main reasons for insufficient course of treatment were the insufficient patients′obedience and some doctors′poor understanding of the disease course.Conclusion A full course treatment with antibiotics on acute suppurative tonsillitis are strongly suggested.It may be of great significant to strengthen the awareness of reasonable use of antibiotics among the inland citizens.

Efficacy and prognostic risk factors of childhood relapsed acute lymphoblastic leukemia：analysis from a single center / 白血病·淋巴瘤

Objective To investigate the efficacy and prognostic risk factors of ALL-R-2003 protocol in the treatment of relapsed childhood relapsed acute lymphoblastic leukemia (ALL) in single center. Methods A retrospective study of clinical data of 51 children with relapsed ALL from January 2004 to December 2014 was performed by using SPSS version 19.0 statistical software for statistical analysis. Results The median age at initial diagnosis of 51 patients was 5.5 years (range, 0.8-13.4 years). The median time from initial diagnosis to relapse was 25 months (range, 3-68 months) and follow-up time was 39 months (range, 3-116 months). The relapse rate in the standard-risk, intermediate-risk and the high-risk groups were 27.5 % (14/51), 29.4 %(15/51) and 43.1 % (22/51), respectively. The probability of 3-year overall survival (pOS) after relapse was (18.8±5.9)%and the probability of event free survival (pEFS) was (16.2±5.8)%. The 3-year pOS in very early relapse, early relapse and late relapse were 0, (11.7 ±7.7) % and (51.7 ±14.8) %, respectively (P= 0.000). There was no statistical difference in survival rate of different immunophenotype groups and sites of relapse (P> 0.05). The 3-year pOS of group S1, S2, S3, S4 were (50.0±35.4) %, (39.9±1.3) %, (10.0±9.5) % and 0, respectively (P=0.000). The 3-year pOS of bcr-abl and MLL gene positive groups were (25.0±21.7) %and 0, respectively, with no statistically significance compared with the negtive group [(24.1±12.0)%] (P>0.05). The 3-year pOS rates of children with bone marrow transplantation and without transplantation were (40.0 ±15.5) %and (13.0 ±5.9) % respectively (P= 0.038). Conclusions The children who in high risk group at initial diagnose are easily to meet earlier relapse and poorer prognosis. The survival period after relapse of bcr-abl or MLL gene positive cases is very short. Bone marrow transplantation can improve survival rate. Risk group at initial diagnose, relapse time and transplantation are the main factors influencing prognosis, and the relapse time and transplantation are the independent prognostic factors for relapsed childhood ALL.

A case of skin infection caused by Mycobacterium szulgai / 中华皮肤科杂志

A 7?year?old girl presented with a plaque on the left side of the face for 4 years. Skin examination revealed a well?marginated circular firm plaque measuring 6 cm × 5 cm in size on the left side of the face with purulent crusts on the surface, which was nontender to palpation. Histopathologic study showed ulceration and necrosis in some areas in the epidermis, diffuse dermal infiltration of lymphocytes, histiocytes and epithelioid cells with the presence of many neutrophilic granulocytes in some regions. Both periodic acid?Schiff(PAS)staining and acid?fast staining were negative. After 25 days of tissue culture, scotochromogenic Mycobacterium colonies grew, and colony smears showed positive acid?fast staining. The sequences of 16S rRNA and hsp65 genes of the fungal isolate showed 100%and 99%homology with those of Mycobacterium szulgai, respectively. After the treatment with rifampicin, isoniazid and ethambutol, the patient′s condition was improved.