[Clinical study of 15 cases of primary non-immunodeficient central nervous system lymphoma in children].

Clinical data of 15 primary central nervous system lymphoma (PCNSL) children aged ≤18 years admitted to our hospital between May 2013 to May 2023 were retrospectively analyzed. Our goal was to summarize the clinical features of children and investigate the therapeutic effect of a high-dose methotrexate (HD-MTX) based chemotherapy regimen on this disease. The male-to-female ratio was 2.7∶1, and the median age was 7.2 (2.3-16.4) years at diagnosis. The initial clinical symptoms were primarily cranial hypertension, with imaging findings revealing multiple lesions. Pediatric PCNSL with normal immune function has a favorable prognosis with HD-MTX-based chemotherapy. Patients with a stable disease can be treated with minimal or no maintenance. HD-MTX-based chemotherapy remains effective when the disease progresses or recurs after an initial course of non-HD-MTX-based chemotherapy.

[Clinical study of mature B-cell lymphoma in 11 children with chromosome 11 long-arm abnormalities].

Objective: To explore the clinical, pathological, diagnostic, treatment, and prognostic features of children with mature B-cell lymphoma (MBCL) . Methods: This retrospective study included pediatric patients with MBCL with chromosome 11 long-arm abnormalities who were diagnosed and treated at our hospital from December 2018 to February 2023. Results: Among the 11 pediatric patients with MBCL, nine were male and two were female, with a median age of 9 (2-13) years and a median disease course of 1.8 (0.5-24) months. The clinical manifestations were cervical lymph node enlargement in four patients, nasal congestion and snoring in four patients, abdominal pain in two patients, and difficulty breathing in one patient. There were seven cases of Burkitt's lymphoma, two of follicular lymphoma, and two of advanced B-cell lymphoma according to the pathological morphology examination. No patients had central nervous system or bone marrow involvement, and no extensive metastasis was observed on B-ultrasound or positron emission tomography-computed tomography (PET/CT). One patient had a huge tumor lesion. The Revised International Pediatric Non-Hodgkin Lymphoma Staging System classified four patients as stage Ⅱ, five as stage Ⅲ, and two as stage Ⅳ. 11q probe detection showed five cases of 11q gain, three of 11q loss, and three of both gain and loss. FISH showed positive MYC expression in three patients, including eight with advanced B-cell lymphoma with 11q abnormalities and three with Burkitt's lymphoma with 11q abnormalities. According to the 2019 edition of the National Health Commission's diagnostic and treatment guidelines for invasive MBCL in children, one patient was classified as Group A, two as Group B, and eight as Group C. Early evaluation of the efficacy showed complete remission. After mid-term evaluation, the intensity of chemotherapy was reduced in Group B and Group C. Among two cases of chemotherapy, the remaining nine cases had a median follow-up of 32 (6-45) months, and none had event-related survival. Conclusion: The incidence of MBCL with 11q abnormalities in children is low, clinical symptoms are mild, and progression is slow. The absence of MYC, BCL2, BCL6 rearrangements, C-MYC negative and 11q abnormalities on FISH is an important diagnostic indicator, and reducing the intensity of chemotherapy can improve prognosis.

[Mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 regimen in the treatment of pediatric Burkitt lymphoma].

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ2=4.16, P=0.041) and group C2 (χ2=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ2=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.

[Effects of different surface treatments on the bonding strength between the lithium disilicate glass ceramic and resin cements].

Objective: To investigate the effects of different surface treatments protocol on the bonding strength between lithium disilicate glass ceramic and resin cements. Methods: Ceramic specimens of 15 mm×13 mm×3 mm were used to evaluate the effects of different surface treatments of hydrofluoric acid etching and silane coupling in current research. Firstly, the standard lithium ceramic specimens were divided into 8 groups (n=16), and were etched by 4.5% hydrofluoric acid for 0, 10, 20, 30, 40, 60, 120 and180 s. Then specimens in each group was further divided into two sub-groups. In one sub-group specimens were coated with coupling agents and in the other were not. Shear bonding strength (SBS) and failure mode were tested and analyzed. The surface morphologies of hydrofluoric acid-etched ceramic specimens were observed by the scanning electron microscopy (SEM). Secondly, after being etched by 4.5% hydrofluoric acid for 30 s, the lithium ceramic specimens were coated with coupling agents at different temperatures: room temperature (12 ℃) for 60 s, 60 ℃ hot air for 60 s and 100 ℃ hot air for 60 s (n=8). SBS and fracture mode were tested and analyzed. The infrared spectrum analysis was used to characterize the coupled surfaces of the ceramic samples. Results: The maximum SBS values were obtained after the specimens were etched for 30 s. The silane coupled group showed a higher SBS value [(25.91±4.30) MPa, P<0.05] than the no-silane-coupled group [(20.27±4.92) MPa]. SBS decreased with extended etching time (>30 s) and the SEM photos showed over-etching morphologies. The 60 ℃ hot air treatment resulted in the maximum SBS value [(28.70±5.32) MPa] than that of the room temperature [(20.08±3.64) MPa] or 100 ℃ hot air [(25.64±4.86) MPa, P<0.05]. And the cohesive failure mode was found in 60 ℃ hot air treatment group. The infrared spectroscopy analysis showed the highest amount of silicon oxide bond in the 60 ℃ hot air treatment group. Conclusions: In this study, for this product, the optimum etching time of 4.5% hydrofluoric acid was 30 s. Furthermore, an ideal SBS value could be obtained when the silane coupling agents were applied additionally. SBS could be increased substantially when the 30 s-etched-ceramic product was coated with silane coupling agents at 60 ℃ hot air for 60 s.

[Analysis of four cases with congenital pulmonary airway malformation complicated by chronic pulmonary aspergillosis].

Objective: To investigate the clinical characteristics, treatment and prognosis of congenital pulmonary airway malformation (CPAM) complicated with chronic pulmonary aspergillosis (CPA) in children. Methods: The clinical manifestation, laboratory test, radiological feature, treatment and prognosis of 4 pediatric patients diagnosis of CPAM with CPA ascertained between March 2016 and April 2020 at the Department of No.2 Respiratory Medicine and Thoracic Surgery of Beijing Children's Hospital were retrospectively analyzed. Results: The 4 children included 2 males and 2 females, their age ranged from 9.9 to 13.6 years. Cough presented in 3 cases, hemoptysis in 2 cases, whereas in 1 case, pneumothorax was the first manifestation of the condition. Past history revealed multiple hospital admissions for pneumonia in 2 children and 1 with more than 2 episodes of wheezing. Aspergillus IgG was positive in 3 patients. Significantly elevated total IgE and fumigatus-specific IgE levels were noted in 2 children. CT demonstrated multiple cystic lesions, and fungal balls were seen in 2 children. They all underwent lobectomy and the lung tissue from the 4 children all demonstrated CPAM with Aspergillus infection. Aspergillus fumigatus was isolated from the abscess collected during operation in 1 patient. Postoperative, voriconazole was given in 3 children for 8 weeks, recurrence was observed in 2 children with characteristics of allergic bronchopulmonary aspergillosis. Voriconazole was given in one patient for 12 weeks with no recurrence. Conclusions: CPAM might be complicated with CPA,if there are hemoptysis, and fungal ball in chest CT, cautious preoperative examinations for microorganism are necessary. The necessity and duration of postoperative antifungal therapy need to be determined on individual basis.

[Application of endobronchial ultrasound in children: an analysis of 4 cases].

Objective: To investigate the feasibility, clinical efficacy and safety of endobronchial ultasound (EBUS) in children. Methods: The radiological features, EBUS images, pathological results and intraoperative and postoperative complications of 3 cases who underwent EBUS examination and 1 case who underwent EBUS guided transbronchial needle aspiration (EBUS-TBNA) were retrospectively analyzed. Results: Among the 4 cases, 2 were males and 2 were females, with the onset age of 7.4-9.2 years. The child who underwent successful EBUS-TBNA was presented with fever and diagnosed with mediastinal lymphadenopathy before the operation, and the postoperative pathology indicated histiocytic necrotic lymphadenitis (HNL). The other 3 children diagnosed with primary airway tumors, whose pre-operative CT imaging found no infiltration in extra-bronchial structures, had the masses resected through EBUS. According to postoperative pathological findings, two were diagnosed with mucoepidermoid carcinoma and one with bronchial leiomyoma. The lesions were located at the opening of the right main bronchus in 1 case and at the main airway in 2 cases. EBUS showed abnormal echogenicity of the tracheal wall in the 3 cases, including hyperechoic area in the water capsule and mucous layer, relatively hypoechoic area in the submucosal smooth muscle layer, hyperechoic area in the inner cartilage layer, hypoechoic in the cartilage layer and hyperechoic in the outer cartilage layer. In one case, structural disorder of the submucosal smooth muscle layer and partial disruption of the cartilage layer of the tracheal wall were found at the lesion site, while the other 2 cases had intact tracheal wall structure. There were no postoperative complications such as pneumothorax or hemoptysis in the 4 children. Conclusion: EBUS is a safe and feasible technique for evaluating mediastinal lymph node enlargement and the degree of airway wall infiltration in primary airway tumor.

Veno-venous extracorporeal membrane oxygenation successfully treated a case of severe pulmonary hemorrhage caused by leptospirosis.

BACKGROUND: Pulmonary hemorrhage is an important complication of leptospirosis. Once acute respiratory distress syndrome (ARDS) occurs as a secondary condition, treatment is extremely difficult and the mortality rate is very high. CASE PRESENTATION: The patient was a 49-year-old. He was admitted to the hospital because he had experienced a fever and cough for 4 days. Hemorrhage, respiratory failure, ARDS and other symptoms appeared soon after admission. Due to severe pulmonary hemorrhage secondary to ARDS, mechanical ventilation was performed through tracheal intubation. During intubation, the patient suffered cardiac arrest, and the patient's condition worsened. He was confirmed to have leptospirosis through second-generation sequencing of the alveolar lavage fluid. Finally, we successfully treated the patient with penicillin as an anti-infective medication and venous-venous extracorporeal membrane oxygenation (v-vECMO). To the best of our knowledge, this report is the first to describe the successful application of ECMO in mainland China. CONCLUSIONS: Leptospirosis can induce serious but transient ARDS with a better prognosis than other causes of ARDS. Our patient was successfully treated with V-vECMO.

[Comparison of long-term efficacy between watch and wait strategy and total mesorectal excision in locally advanced rectal cancer patients with clinical complete response after neoadjuvant therapy].

Objective: To compare long-term efficacy between watch and wait (W&W) strategy and total mesorectal excision (TME) in patients who were diagnosed with locally advanced rectal cancer (LARC) and attained clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT). Methods: A retrospective cohort study was carried out. A total of 238 patients with stage II-III LARC exhibiting cCR after nCRT in Sun Yat-sen University Cancer Center from September 16, 2010 to January 9, 2018 were enrolled. Patients who were diagnosed with other malignant tumor within 5 years, did not receive regular follow-up in our center for more than 1 year and had no complete examination items after nCRT were excluded. Of 238 patients, 151 were male and 87 were female with a median age of 57 (27-83) years old. According to TNM stage, 61 cases were cII, 177 cases were cIII. Concurrent chemoradiotherapy (CCRT) was performed in 20 patients. CCRT plus induction/consolidated chemotherapy was performed in 218 patients. Intensity-modulated radiotherapy (IMRT) was applied to radiotherapy. The median radiation dose was 50 Gy/25 Fr for both the primary tumor and clinical target volumes, and the total dose was 45.0 to 50.6 Gy for 227 patients. In 27 patients, single-agent fluorouracil or capecitabine was used as concurrent chemotherapy. But in the other 211 patients, a combined regimen of oxaliplatin and fluorouracil or capecitabine was used. After nCRT, 59 and 179 patients received W&W (W&W group) and TME 6-12 weeks later (TME group), respectively. After the ending of treatment, patient was interviewed one time every 3 months and after 3 years, one time every six months. Overall survival (OS) rate, distant-metastasis-free survival (DMFS) rate, and local-recurrence-free survival (LRFS) rate were compared between two groups. The salvage treatment and sphincter preservation rate were analyzed. The survival curve was drawn with Kaplan-Meier method and evaluated by log-rank method. Results: In the cases treated with TME, the median interval from nCRT to surgery was 59 days. The postoperative pCR rate was 63.1%(113/179). The median follow-up time of the whole cohort was 41.8 (12.0-99.0) months. The 3-year and 5-year OS rates were 98.4% and 96.5%; the 3-year and 5-year LRFS rates were 96.5% and 96.5%; the 3- and 5-year DMFS rates were 91.0% and 87.9%, respectively. The 3-year OS rates in the W&W group and the TME group were 100% and 97.9%; the 5-year OS rates in W&W group and the TME group were 90.6% and 97.9% (P=0.339); The 3-year local recurrence rate (LRR) in the W&W group was 12.9% (7 cases recurred within 2 years), which was significanthy higher then that in the TME group (0.6%, P=0.003). Salvage surgery was successful in 5/6 cases. After salvage surgery, LRFS rate was not significantly different between the two groups (P=0.137). The 3-year DMFS rate in the W&W group and the TME group were 88.4% and 81.1%, whose difference was not significant (P=0.593). Recurrence with simultaneous metastasis was seen in 3/7 cases of the W&W group. The sphincter was preserved in 89.8% (53/59) of patients in the W&W group, which was significantly higher than 73.7% (132/179) in the TME group (P<0.001). When distance of tumor from the anal verge was ≤ 5 cm, the sphincter preservation rate (SPR) in the W&W group was 88.0% (44/50), which was significantly higher than the 54.4% (56/103) in the TME group (P<0.001). Conclusions: W&W is safe and feasible for patients with LARC and cCR after nCRT. The results should be verified by further clinical trials.

[Effect of silencing FABP3 gene on LPS-induced apoptosis and endoplasmic reticulum stress in alveolar epithelial cells].

Objective: To investigate the effect of silencing fatty acid binding protein 3 (FABP3) gene on lipopolysaccharide (LPS)-induced apoptosis and endoplasmic reticulum stress in alveolar epithelial cells A549. Methods: According to the processing method, A549 cells were divided into control group(A549 cells cultured for 24 h), LPS group (10 mg/L LPS treated A549 cells for 24 h), LPS+si-con group (10 mg/L LPS was used to treat A549 cells transfected with si-con for 24 h) and LPS+si-FABP3 group (10 mg/L LPS was used to treat A549 cells transfected with si-FABP3 for 24 h). Then quantitative real-time PCR was used to detect the level of FABP3, methylthiazoletrazolium was used to detect the cell proliferation, flow cytometry was used to detect the apoptosis, and Western Blot was used to detect the levels of FABP3, CyclinD1, cleaved-caspase-3, GRP78, ATF4, CHOP, cleaved-caspase-12 and p-Akt and PI3Kp110α protein expression. Enzyme-linked immunosorbent assay was used to detect the levels of IL-6, IL-8 and TNF-αlevels. Results: In the LPS group, FABP3 protein level (1.00±0.09) and mRNA (2.15±0.22), apoptosis rate [(26.1±2.6)%], inflammatory factor IL-6 [(554.4±55.4) ng/L], IL-8 [(389.3±38.5) ng/L] and TNF-α [(601.3±60.0) ng/L], cleaved-caspase-3 (1.00±0.11), GRP78 (1.05±0.11), ATF4 (1.20±0.12)), CHOP (1.05±0.10), cleaved-caspase-12 (1.10±0.11), p-Akt (0.88±0.08) and PI3Kp110α (0.75±0.08) protein levels were significantly higher than the control group [(0.53±0.05), (1.00±0.10), (4.5±0.5)%, (75.4±7.5) ng/L, (25.2±2.5) ng/L, (66.5±6.7) ng/L, (0.34±0.05), (0.35±0.05), (0.43±0.05), (0.37±0.04), (0.45±0.05), (0.16±0.04), (0.35±0.05)] (all P<0.05). Cell viability [(50.1±5.4)%] and CyclinD1 protein level (0.40±0.05) in LPS group were significantly lower than those in the control group [(100.1±12.4)%, (1.25±0.12)] (both P<0.05). Cell viability [(89.1±8.5)%] and CyclinD1 protein level (1.15±0.11) in LPS+si-FABP3 group were significantly higher than those in LPS+si-con group [(53.1±5.4)%, (0.42±0.05)] (both P<0.05). Apoptosis rate [(10.5±1.1)%], IL-6[(301.3±30.0) ng/L], IL-8[(189.4±19.0) ng/L], TNF-α [(400.1±40.1) ng/L], cleaved-caspase-3 (0.45±0.05), GRP78 (0.48±0.05), ATF4 (0.60±0.06), CHOP (0.55±0.05), cleaved-caspase-12 (0.60±0.06), p-Akt (0.50±0.05) and PI3Kp110α(0.45±0.05) in LPS+si-FABP3 group were significantly lower than those in LPS+si-con group [(28.1±2.8)%, (536.3±53.6) ng/L, (400.2±40.2) ng/L, (623.1±62.3) ng/L, (0.96±0.10), (1.02±0.10), (1.15±0.12), (1.10±0.11), (1.15±0.12), (0.90±0.09), (0.72±0.07)] (all P<0.05). Conclusion: Silencing FABP3 gene can inhibit LPS-induced alveolar epithelial cell apoptosis and endoplasmic reticulum stress, which may act by inhibiting the PI3K/Akt signaling pathway.

[Clinical characteristics of 46 pediatric diffuse large B-cell lymphoma and treatment outcome].

Objective: To summarize the clinical data of diffuse large B-cell lymphoma (DLBCL) in children and to evaluate the efficacy of Beijing Children's Hospital B cell lymphoma protocol in the treatment of pediatric DLBCL. Methods: The data (clinical, pathology, lab and image data) of 46 pediatric DLBCL admitted to the treatment group of Beijing Children's Hospital from January 2005 to June 2017 were collected and analyzed retrospectively. According to the risk factors of staging, existence of poor prognosis genes and giant tumors, stratified treatment was carried out according to the international standard modified LMB89 regimen with high dose and short course. The Kaplan-Meier method was used to calculate the event free survival (EFS) and the overall survival (OS). Results: (1) Among the 46 cases, there were 33 males and 13 females. The median age was 8.0 years. The time from the initial symptom onset to the diagnosis was more than 15 days in 45 children. Fourteen cases had B group symptoms (fever, night sweat, and weight lost), 25 cases had extranodal disease, 39 cases were stage Ⅲ and Ⅳ, 12 cases had bone marrow involvement, 3 cases had jawbone involvement. Thirty cases were group B and 16 cases were group C in the treatment group. (2) Initial symptoms: 6 cases had cervical mass, 20 cases had abdominal mass, 10 had abdominal pain with acute abdomen, 8 cases had fever, 2 cases had snore or upper respiratory tract obstruction. (3) Pathology result: 40 cases were germinal center B cell DLBCL, 6 cases were non germinal center B cell DLBCL, no case had the MYC gene rupture, double hit lymphoma and triple hit lymphoma. (4) Complication and evaluation: the tumor lysis syndrome was seen in 3 cases initially, severe infection and delayed treatment was seen in 1 case, no treatment related death. The first evaluation showed all cases were sensitive to chemotherapy (shrink>25%), the second evaluation showed 1 case had residual disease, the others were complete remission. (5) Treatment and outcome: the 5 year-EFS was the same with 5 year-OS, both were (97.8±2.2) %. Two cases relapsed after treatment off, early relapse was seen in 1 case, and died because of abandoning treatment. Late relapse was seen in 1 case and got a complete remission after Rituximab+group C protocol treatment. Conclusions: Pediatric DLBCL was common in school aged boys, most cases were at middle and late stage at the time of diagnosis. DLBCL had a good prognosis after the treatment with Beijing Children's Hospital's B cell lymphoma protocol, but late relapse could be seen.

[Clinical analysis of a modified LMB89 Group C regimen in the treatment of pediatric high-risk Burkitt lymphoma].

Objective: To analyze the therapeutic effect of a modified LMB89 Group C regimen in the treatment of pediatric high-risk Burkitt lymphoma. Methods: The clinical data of 172 children with newly diagnosed high-risk Burkitt lymphoma from January 2007 to April 2017 were retrospectively analyzed. All the cases were treated with the modified LMB89 Group C regimen. Results: The median age of the patients was 6 (1-14) years. The sex ratio was 5.1∶1, 144 boys (83.7%) and 28 girls (16.3%) . According to St. Jude staging classification, 2 patients (1.2%) were in stage Ⅱ, 54 (31.4%) in stage Ⅲ and 116 (67.4%) in stage Ⅳ. Of them, 46 patients (26.7%) had mature B cell acute lymphoblastic leukemia (B-ALL) , and 52 patients had central nervous system (CNS) involvement. According to risk group, the patients can be divided into group C1 (CNS1, without testicles/ovaries involvement, n=65) , group C2 (CNS2, testicles/ovaries involvement, n=55) and group C3 (CNS3, n=52) . A total of 145 patients received rituximab combined with chemotherapy during the treatment, 10 patients suffered from progressive disease and died, and 5 patients relapsed. Treatment-related mortality was 2.9%. With a median follow-up of 36.0 (0.5-119.0) months, 3-year overall survival (OS) rate was (88.9±2.4) % and event free survival (EFS) rate was (87.9±2.6) % for all patients. 3-year EFS rates were (96.9±2.1) %, (90.9±3.9) % and (73.4±6.5) % for Group C1, C2 and C3 respectively, and that of Group C3 was significantly lower than that of Group C1 (χ(2)=12.939, P=0.001) and Group C2 (χ(2)=6.302, P=0.036) . The 3-year EFS rates were (79.3±6.8) % and (44.4±16.6) % for patients in group C3 treated with chemotherapy combined with rituximab and chemotherapy alone (χ(2)=5.972, P=0.015) . Multivariable Cox regression analysis showed that Stage Ⅳ (including B-ALL) , residual diseases in mid-term evaluation were independent unfavorable prognostic factors[HR=4.241 (95%CI 1.163-27.332) , P=0.026; HR=32.184 (95%CI 11.441-99.996) , P<0.001]. Conclusions: The modified LMB89 Group C regimen has ideal effect for the children with high-risk Burkitt lymphoma.

[Clinical analysis of methylmalonic acidemia and hyperhomocysteinemia with diffuse lung disease as an initial or main presentation].

Objective: To improve the awareness of methylmalonic acidemia and hyperhomocysteinemia with diffuse lung disease as an initial or main presentation. Methods: A retrospective analysis of the clinical manifestations, radiological features, laboratory tests, genetic variations, treatments and prognoses was conducted in six children presented with diffuse lung disease and finally diagnosed with methylmalonic acidemia and hyperhomocysteinemia in Ward 2 of Department of Respiratory Diseases, Beijing Children's Hospital, from August 2017 to November 2018. Results: Six children were included in this study. Two children were male and four were female. The average age of onset was 28 months. The mean age at diagnosis was 34 months. The average interval from onset to diagnosis was 6 months. Four children who underwent genetic tests were found to have variants of gene MMACHC and diagnosed with CblC type. All children had respiratory symptoms and signs as initial or main presentation, which were tachypnea (5 cases), exercise intolerance (5 cases), cough (4 cases), cyanosis (4 cases), clubbing (4 cases), dyspnea (3 cases) and retractions (3 cases). Pulmonary arterial hypertension was found in all six children. Pericardial effusion (4 cases), kidney involvement (3 cases), nervous system involvement (3 cases), gastrointestinal system involvement (3 cases) and anemia (2 cases) also coexisted. The high resolution computed tomography (HRCT) features included dilated pulmonary artery (6 cases), ground-glass opacities (4 cases), diffuse poorly defined ground-glass centrilobular nodules (3 cases), pleural effusion (3 cases), thickening of interlobular septum (2 cases), etc. All children had an elevated concentration of methylmalonic acid in urine and homocysteine in plasma. Genetic tests were performed in four patients, and MMACHC genetic mutations were found in all of them. Clinical manifestations, HRCT features and pulmonary arterial hypertension turned better in five children after treatment. One patient who was not regularly followed-up died. Conclusions: Pulmonary involvement including diffuse lung disease and pulmonary arterial hypertension could coexist with methylmalonic acidemia and hyperhomocysteinemia, which may have respiratory symptoms and signs as the initial or main presentation. Characteristic HRCT features were found in some patients. Plasma homocysteine test is a quick method for screening the disease in children with diffuse lung disease and (or) pulmonary arterial hypertension. Both diffuse lung disease and pulmonary arterial hypertension may turn better after treatment.

[Clinical and prognostic analysis of 186 children with Burkitt's lymphoma].

Objective: To analyze the clinical features and prognostic factors of childhood Burkitt's lymphoma and to summarize the therapeutic effect of the mature B-cell lymphoma regimen of Beijing Children's Hospital. Methods: It was a retrospective study. From January 2007 to December 2015, 186 patients below 18 years of age with newly diagnosed, untreated Burkitt's lymphoma were enrolled. Three cases were eliminated because of the abandonment of the treatment and 183 cases were stratified and treated according to the mature B-cell lymphoma regimen of Beijing Children's Hospital, groups were as follows: A, n=1; B, n=59; C, n=123 and 97 patients in group C received combined rituximab therapy during the treatment. The clinical features and therapeutic effects of patients were analyzed, overall survival (OS) and event-free survival (EFS) were estimated by the Kaplan-Meier method. COX regression was used to identify the prognostic factors. Results: The median age at diagnosis was 5 (1-14) years. There were 159 males (85.5%) and 27 females (14.5%) , the male-to-female ratio was 5.9∶1. A total of 174 cases (93.5%) evolved to stage Ⅲ and Ⅳ. Eight cases did not achieve remission and progressed to death, 9 cases relapsed. Only 5 patients (2.7%) died of treatment-related complications. With a median follow-up time of 48.0 (0.5-128.0) months, the 5-year OS rate and EFS rate were (89.1±2.3) % and (87.8±2.5) %. There was significant difference in the 5-year EFS rate between group B and C ( (94.9±2.9) % vs. (84.0±3.4) %, χ(2)=4.258, P=0.039). The 5-year EFS rate was (73.1±8.7) % and (86.7±3.7) % for patients in the group C treated with chemotherapy only and those treated with chemotherapy combined rituximab, but no statistical difference was found between them (χ(2)=3.360, P=0.067) . Central nervous system (CNS) involvement, insensitivity to early phase chemotherapy, residual diseases in mid-term evaluation were independent unfavorable prognostic factors (HR=6.167, 9.102, 3.104, 95%CI: 2.293-16.592, 1.837-45.107, 1.182-8.153) . Conclusions: The large dose, short course treatment of mature B-cell lymphoma regimen of Beijing Children's Hospital is effective for pediatric Burkitt's Lymphoma. Combined treatment with rituximab can improve the efficacy. CNS involvement, insensitivity to early phase chemotherapy, residual diseases in mid-term evaluation are associated with increased risk of poor prognosis.

[Clinical features and diagnosis of childhood leukoencephalopathy with cerebral calcifications and cysts in four cases].

Objective: To investigate the clinical features and diagnostic bases of childhood leukoencephalopathy with cerebral calcifications and cysts (LCC). Methods: The clinical data involving manifestations and laboratory examinations of 4 children with LCC admitted to Beijing Children's Hospital Affiliated to Capital Medical University from 2012 to 2017 were retrospectively summarized. Each patient had a follow-up visit ranging from 4 months to 5 years and 9 months after initial examination. Results: Patients consisted of 2 males and 2 females, whose age of onset was respectively 2 years and 9 months, 6 years and 2 months, 7 years and 10 months, and 5 years and 1 month. The main clinical symptoms of these cases included headache, dizziness, partial seizure and claudication, and two of these cases had insidious onset. Cerebral calcifications and cysts with leukoencephalopathy were detected by neuroimaging in all patients. In addition, multifocal microhemorrhages and calcifications were observed by magnetic susceptibility-weighted imaging (SWI) series in 3 patients. Brain biopsy performed on 1 case disclosed a neuronal reduction in the cerebral cortex, loosening of focal white matter, multifocal lymphocyte infiltration, fresh hemorrhages, and gliosis, as well as angiomatous changes of blood vessels with hyalinized thicken-wall, stenotic or occlusive lumina and calcification deposits. The compound heterozygous mutations of n.*10G>A and n.82A>G in SNORD118 were identified in 1 case by target-capture next-generation sequencing. Sanger sequencing verified that the variant n.*10G>A was a novel mutation and it was of paternal-origin, while the variant n.82A>G was of maternal-origin, which had already been reported to be pathogenic to LCC. Follow-up study had shown continued partial seizure in 1 case and remissive claudication in another, while the remaining 2 cases had a relatively favorable outcome without obvious neurological symptoms at present time. Conclusions: The clinical manifestations of LCC are nonspecific, and the onset of the disease tends to be insidious. The triad neuroimaging findings of cerebral calcifications, cysts and leukoencephalopathy are essential to the diagnosis of the disease, and the signals of microhemorrhages revealed by SWI series provide another eloquent reference for the diagnosis. As biopsy is invasive and usually unavailable in the early stage, gene assessment, instead of pathological data, should be the gold standard in the diagnosis of LCC.

Supplementation with CTGF, SDF1, NGF, and HGF promotes ovine in vitro oocyte maturation and early embryo development.

The strategies for improving the in vitro maturation (IVM) of domestic animal oocytes focus on promoting nuclear and cytoplasmic maturation. The identification of paracrine factors and their supplementation in the culture medium represent effective approaches for oocyte maturation and embryo development. This study investigated the effects of paracrine factor supplementation including connective tissue growth factor (CTGF), nerve growth factor (NGF), hepatocyte growth factor (HGF), and stromal derived factor 1 (SDF1) on ovine oocytes and early parthenogenetic embryos using an in vitro culture system. First, we identified the optimal concentrations of CTGF (30 ng/mL), SDF1 (10 ng/mL), NGF (3 ng/mL), and HGF (100 ng/mL) for promoting oocyte maturation, which combined, induced nuclear maturation in 94.19% of oocytes. This combination also promoted cumulus cell expansion and inhibited oocyte/cumulus apoptosis, while enabling a larger proportion (33.04%) of embryos to develop into blastocysts than in the controls and prevented embryo apoptosis. These novel findings demonstrate that the paracrine factors CTGF, SDF1, NGF, and HGF facilitate ovine oocyte and early parthenogenetic embryo development in vitro. Thus, supplementation with these factors may help optimize the IVM of ovine oocytes and early parthenogenetic embryo development strategies.