[Clinical study of immune-targeting combined with attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma].

Objective: To evaluate the efficacy and safety of brentuximab vedotin (BV) combined with rituximab and attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma (cHL). Methods: A prospective, non-randomized, risk-assigned study. Clinical data (including age, gender, B symptoms, bulky disease, CD30 and Epstein-Barr virus-encoded RNA(EBER) expression, clinical stage, risk stratification, etc.) of 28 intermediate to high-risk cHL children diagnosed and treated at Beijing Children's Hospital Affiliated to Capital Medical University from October 2022 to May 2024 were collected. Immuno-targeted combined with attenuated chemotherapy was administered based on risk stratification and early treatment response. The patients were followed up until May 1st, 2024. The infusion reactions and adverse reactions after treatment were recorded. Results: In all 28 patients, there were 22 males and 6 females, the age was 12 (5,16) years, 16 cases (57%) presented with bulky disease and 10 cases (36%) with B symptoms. The most common pathological type was nodular sclerosis (14 cases, 50%). There were 7 cases of stage Ⅱ, 14 cases of stage Ⅲ and 7 cases of stage Ⅳ according to the Ann Arbor staging system. There were 5 cases in the intermediate-risk group and 23 cases in the high-risk group. EBER was positive in 20 cases (71%) and negative in 6 cases (21%), and CD30 antigen was expressed in tumor cells of all enrolled children. Treatment duration: 5 cases (18%) received 4 courses of treatment, 21 cases (75%) received 6 courses of treatment, and 2 cases (7%) received 8 courses of treatment, 25 cases (89%) achieved complete metabolism response (CMR) through early assessment after 2 courses of chemotherapy. The CMR rates were 100% in intermediate-risk group and 87% in high-risk group, respectively. Four patients (14%) finally received residual field radiotherapy. Toxicities included grade Ⅰ-Ⅱ myelosuppression, early infusion reaction and mild peripheral neuropathy, only one case of grade 3 adverse events was recorded and did not affect sequential treatment. At the end of treatment and 3 months of follow-up, the levels of IgA, IgG and IgM were all decreased compared with the baseline before chemotherapy, and the total B cell count began to be lower than the level before chemotherapy at the early stage of treatment (after 2 courses). The total B cell count monitored during treatment was 50 (0, 101)×106/L and was 12 (0, 25)×106/L at the end of treatment. The follow-up time was 6 (3, 13) months, all 28 children had event-free survival and all achieved complete remission. At 6 and 9 months of follow-up, IgA, IgG, IgM and total B cell counts returned to pre-chemotherapy baseline levels, respectively. Conclusion: BV combined with rituximab attenuated chemotherapy has demonstrated efficacy and a tolerable safety profile in the treatment of cHL in children, and significantly reduce radiation rate.

[Long-term efficacy and prognostic factors of Beijing Children's Hospital-2009-lymphoblastic lymphoma in the treatment of T-lymphoblastic lymphoma in children and adolescents].

Objective: To summarize the long-term efficacy of Beijing Children's Hospital-2009-lymphoblastic lymphoma (BCH-2009-LBL) in the treatment of T-lymphoblastic lymphoma (T-LBL) in children and adolescents and to explore the prognostic factors. Methods: T-LBL children admitted to Beijing Children's Hospital Affiliated to Capital Medical University from January 2009 to April 2017 were retrospectively included. According to clinical stage, prognostic genes and treatment response, the children were divided into low, intermediate and high risk groups, and stratified treatment was performed according to the BCH-2009-LBL protocol, with follow-up until December 31, 2023. The clinical characteristics and therapeutic effect of each group were compared. Survival curve was drawn by Kaplan-Meier method, and the difference in survival rate between groups was compared by log-rank test. Multivariate Cox regression model was used to analyze the prognostic factors. Results: A total of 146 patients were included, the age of disease onset [M(Q1, Q3)] was 8.0 (1.5, 14.0) years old. There were 107 (73.3%) males and 39 (26.7%) females. Clinical staging: 1 case in stage Ⅰ and 1 case in stage Ⅱ (0.7% each), 41 cases (28.1%) cases in stage Ⅲ and 103 cases(70.5%) in stage Ⅳ. There were 1 case (0.7%), 93 cases (63.7%), and 52 cases (35.6%) in the low, intermediate, and high-risk groups, respectively. The follow-up time was 121 (80, 180) months, and the 5-year and 10-year event-free survival (EFS) rates were 76.4% and 75.0%, respectively. The 5-year EFS rates of low, intermediate and high risk groups were 100.0%, 81.3% and 67.3%, respectively. There was significant difference in remission between the middle-risk group and the high-risk group on the 8th day of hormone pretreatment and at the end of induction (both P<0.05). Recurrence/progression occurred in 29 cases (recurrence rate 19.9%), and the recurrence time was 15 (3, 74) months, in which 26 cases died and only 3 cases survived. Infection-related death occurred in 6 cases (4.1%). The failure or progression of hormone pretreatment at d8 (HR=10.089, 95%CI: 1.266-80.387, P=0.029) and the failure to achieve complete remission at the end of induction (mid-term evaluation) (HR=7.638, 95%CI: 2.411-24.199, P=0.001) were the risk factors for EFS rate of intermediate risk group. The above indexes had no statistical significance on EFS rate in high-risk groups (all P>0.05). Conclusions: BCH-2009-LBL regimen shows good efficacy in the treatment of pediatric T-LBL. The failure or progression of hormone pretreatment at d8 and the failure to achieve complete remission at the end of induction (mid-term evaluation) were the risk factors for EFS rate.

[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.

[Changes of HER2 low expression status in primary and recurrent/metastatic breast cancer].

Objective: To investigate the evolution and clinical significance of HER2 low expression status in HER2 negative patients in primary and recurrent/metastatic breast cancers. Methods: The data and archived sections of 259 breast cancer patients with recurrence/metastasis and HER2-negative primary foci were collected from January 2015 to January 2022 at the Fourth Hospital of Hebei Medical University, and the HER2 status of primary and recurrence/metastasis foci was determined by immunohistochemistry (IHC), among which IHC 2+patients were subject to fluorescence in situ hybridization (FISH). The HER2 status was classified as HER2-0 group; patients with IHC 1+, IHC 2+and no FISH amplification were classified as HER2 low expression group; and patients with IHC 3+, IHC 2+and FISH amplified were classified as HER2-positive group. The changes of HER2 status in patients with HER2 low expression in primary versus recurrent/metastatic breast cancer foci were compared, and their clinicopathologic characteristics and prognosis were analyzed. Results: The overall concordance rate between primary and recurrent/metastatic HER2 status in breast cancer was 60.6% (157/259, κ=0.178). A total of 102 patients (102/259, 39.4%) had inconsistent primary and recurrent/metastatic HER2 status; 37 patients (37/259, 14.3%) had HER2-0 at the primary foci and HER2-low expression at the recurrent/metastatic; and 56 patients (56/259, 21.6%) had HER2-low expression in the primary foci and HER2-0 in the recurrent/metastatic. The recurrent/metastatic foci became low-expressing compared with the recurrent/metastatic foci which remained HER2-0 patients, with longer overall survival time, higher ER and PR positivity, lower Ki-67 positivity index, and lower tumor histological grade; all with statistically significant differences (all P<0.05). In the primary HER2-low group, patients with recurrent/metastatic foci became HER2-0 while those with recurrent/metastatic foci remained low expression; there were no statistically significant differences in clinicopathological features and overall survival time (all P>0.05). Conclusions: Unstable HER2 status in patients with HER2-0 and low expression in primary versus recurrent/metastatic breast cancer foci, and HER2-0 in the primary foci but low HER2 expression status in recurrence/metastasis is associated with favourable prognosis, and testing HER2 status in recurrence/metastasis can provide more treatment options for such patients.

[Comparison of air filled anterior approach of sternocleidomastoid muscle and space of sternocleidomastoid muscle for treatment of thyroid papillary carcinoma under axillary endoscope].

Objective: To evaluate the application of the anterior sternocleidomastoid muscle approach in transaxillary endoscopic thyroidectomy. Methods: The clinical data of 180 patients undergoing transaxillary endoscopic thyroidectomy for thyroid cancer in the Department of General Surgery of the Affiliated Hospital of Nantong University from March 2021 to March 2023 were retrospectively analyzed. There were 27 males and 153 females, aged (37.5±8.0)years, range: 27 to 52 years. The anterior approach of sternocleidomastoid muscle was used in 100 cases, and the interspace approach of sternocleidomastoid muscle was used in 80 cases between the two groups. The postoperative efficacy, complications and satisfaction of the two groups were compared. Results: There was no difference between the two groups in the number of lymph node dissection (using nano carbon tracer), hospital stay, and postoperative complications (transient decrease in parathyroid function, laryngeal nerve injury) (P>0.05). The anterior approach of sternocleidomastoid muscle had shorter cavity building time[(17.8±2.9)vs(20.1±3.7) min], less drainage volume the second day after operation[(18.7±5.2)vs(23.5±6.3) ml], and less discomfort in the neck (P<0.05). Conclusion: The anterior approach of sternocleidomastoid muscle under complete transaxillary endoscopy has certain advantages in the time of cavity construction, the drainage volume the second day after the operation, and the reduction of cervical discomfort after the operation. The operation is safe and reliable.

[Efficacy of intravenous drug information management system on the improvement of anemia in maintenance hemodialysis patients].

Objective: To investigate the effect of information management of intravenous drugs on anemia in maintenance hemodialysis patients. Methods: The information management of intravenous drugs was a management system developed by the Hemodialysis Center of Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital in April 2020. The parameters six months before and after the use of the information management system were retrospectively collected and compared, including the rate of reaching the standard of hemoglobin, ferritin, transferrin saturation rate and the incidence of cardiovascular events. Specifically, the control stage was from October 2019 to March 2020, which was before the use of information management, and the study stage was from April to September 2020, which was after the use of information management. Results: There were 285 patients (190 males and 95 females) included in the control stage, with an average age of (62.4±13.2) years, while 278 patients (193 males and 85 females) were included in the study stage, with an average age of (62.8±13.2) years. Compared with the control stage, the rate of reaching the standard of hemoglobin [47.8% (797/1 668) vs 40.2% (687/1 710), P<0.001], ferritin [39.0% (217/556) vs 31.2% (178/570), P=0.006], and transferrin saturation [64.7% (360/556) vs 58.6% (334/570), P=0.034] increased in the study stage. The incidence of cardiovascular events in the study stage was 11.2% (31/278), which was significantly lower than that in the control stage [16.5% (47/285)] (P=0.043). Conclusion: The information management of intravenous drugs in the hemodialysis center may help improve the anemia status in maintenance hemodialysis patients.

[The 500th case: pain in both hip joints, headache, and diplopia].

A male child, aged 5 years and 3 months, was admitted to the Oncology Department with a history of pain in both hip joints, headache, and diplopia lasting for 40 days. Physical examination did not reveal definitive signs or obvious abnormalities in the nervous system. Imaging studies showed only abnormalities in the craniocerebrum and spinal cord. Routine cerebrospinal fluid (CSF) analysis revealed elevation in the total number of white blood cells, mainly mononuclear cells. Biochemical analysis of CSF showed normal glucose and chloride levels, and increased protein concentrations. The possibility of central nervous system (CNS) infection was initially considered. Subsequently, antibacterial and antiviral therapy was administered; however, this treatment was ineffective. Further examination of CSF through immunophenotyping revealed mature B-cell lymphoma with CNS involvement; there were no neoplastic lesions detected elsewhere in the body. Thus, the patient was diagnosed with primary central nervous system lymphoma (PCNSL). Complete remission was achieved after chemotherapy with the CNCL-2017-mature B-cell lymphoma regimen. Thus far, all chemotherapy cycles have been completed, the patient remains in complete remission, and the follow-up is ongoing. Clinicians should pay close attention to PCNSL in children.

[Analysis of serum immunoglobulin level in children with Burkitt lymphoma].

Objective: To summarize changes of serum immunoglobulin levels before and after chemotherapy in children with Burkitt lymphoma (BL), so as to investigate the effects of chemotherapy and rituximab on serum immunoglobulin levels in children with BL. Methods: Clinical data of 223 children with newly diagnosed Burkitt lymphoma at Beijing Children's Hospital from January 2009 to April 2017 were analyzed retrospectively. They were treated according to the modified LMB 89 regimen and some of them received combined rituximab therapy during the chemotherapy. The serum immunoglobulin (IgA, IgM, IgG) before chemotherapy, at the time of discontinuing chemotherapy, as well as 6, 12, 24, 36 months after chemotherapy were collected. Changes of serum IgA, IgM and IgG with time among different treatment groups were compared using repeated measures ANOVA. Results: According to risk group, 223 children were devided into group B（n=53）and group C（n=170）. Before chemotherapy, 109 cases (48.9%) were combined with hypogammaglobulinemia. The serum IgA, IgM, and IgG levels of all the patients were (0.9±0.7), 1.2 (0.5, 1.3) and (7.2±2.9) g/L before chemotherapy, (0.5±0.4), 0.2 (0.1, 0.3) and (6.3±2.3) g/L at the time of discontinuing chemotherapy (t=13.63, Z=-11.99, t=4.57, all P<0.05). There were statistical difference in IgA, IgM levels of group B and IgA, IgM, IgG levels of group C before chemotherapy and at the time of discontinuing chemotherapy (t=8.86, Z=-6.28, t=11.19, Z=-10.15, t=4.50, all P<0.05). The differences of serum IgA and IgG levels at the time after chemotherapy among patients treated with chemotherapy alone and those treated with chemotherapy combined rituximab in group B and C were significant (F=5.38, P=0.002 and F=4.22, P=0.007). Conclusions: Approximately half of children with BL have already existed hypogammaglobulinemia at initial diagnosis prior to the start of treatment. The modified LMB 89 regimen have significant effect on humoral immunity of children with BL. In the process of immune reconstruction after chemotherapy, rituximab has more significant effect on serum IgA and IgG levels in BL patients.

[Verification of clinical applicability of the non-special perioperative administration for enhanced recovery after surgery of gastric cancer patients: a Chinese single-center observational report].

Objective: To verify clinical applicability of the non-special perioperative administration for enhanced recovery after surgery (ERAS) proposed by Japanese scholars in Chinese gastric cancer patients. Methods: The main measures of the non-special perioperative administration for ERAS are as follows: (1) discussion of multiple disciplinary team before surgery; (2) rehabilitation education for patients; (3) no routine bowel preparation before surgery; (4) placement of nasogastric tube for decompression routinely before operation and removal as early as 24 hours after surgery; (5) appropriate rehydration; (6) antibiotic prophylaxis before surgery; (7) place abdominal drainage tubes when necessary; (8) epidural patient-controlled analgesia and oral medication for postoperative pain management; (9) start low-molecular-weight heparin injection 48h after surgery and ambulation every day to prevent deep vein thrombosis; (10) postoperative dietary management and supplement with parenteral nutrition intermittently; (11) remove Foley catheter about 24 hours after surgery. A retrospective cohort study was performed, including 203 patients undergoing radical gastrectomy at Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital from January 2017 to December 2018. Inclusion criteria were patients who were ≤75 years old without distant metastasis by preoperative examination, were diagnosed as gastric adenocarcinoma by postoperative histopathology and had complete clinicopathological and follow-up data. Patients with history of other malignancies and gastrectomy, extensive implantation of the abdominal cavity or malignant ascites by intraoperative exploration, death within 1 month after surgery, and residual gastric cancer were excluded. The perioperative management methods were chosen by patients. There were 123 patients who followed non-special perioperative administration for ERAS (non-special preparation group) and 80 patients who underwent traditional perioperative management (traditional method group). The primary outcomes (postoperative hospital stay, time to the first flatus, time to the first fluid diet, time to the first ambulatory activity, morbidity of postoperative complication, mortality, and readmission rate) and secondary outcomes (operative time, intraoperative blood loss and postoperative pain score) were compared between the two groups. Results: Compared to the traditional method group, the non-special preparation group had shorter time to the first flatus [(3.6±1.1) days vs. (4.8±1.4) days, t=3.134, P=0.003], shorter time to the first liquid diet [(2.6±0.9) days vs. (5.5±1.6) days, t=15.105, P<0.001], shorter time to the first ambulatory activity [(1.9±0.5) days vs. (4.1±1.1) days, t=8.543, P<0.001] and shorter postoperative hospital stay [(9.6±2.3) days vs. (12.9±2.3) days, t=5.020, P<0.001]. Besides, incidences of pancreatic leakage [6.5% (8/123) vs. 16.3% (13/80), χ(2)=4.964, P=0.026], lymphatic leakage [1.6% (2/123) vs. 13.8% (11/80), χ(2)=11.887, P=0.001], peritoneal effusion [2.4% (3/123) vs. 10.0% (8/80), χ(2)=4.032, P=0.045], and gastroparesis [0.8% (1/123) vs. 7.5% (6/80), χ(2)=4.657, P=0.031] in the non-special preparation group were significantly lower. The overall morbidity of postoperative complications and incidences of pulmonary infection and intestinal adhesion were not significantly different between the two groups (all P>0.05). As for the secondary outcomes, compared to the traditional method group, the non-special preparation group had less intraoperative blood loss [(80.4±24.4) ml vs. (100.5±19.4) ml, t=3.134, P=0.003] and lower postoperative pain score [postoperative day 1: (4.4±0.3) vs. (5.3±0.8), t=2.504, P=0.037],while the difference in operative time was not significant (P>0.05). Conclusion: The non-special perioperative administration for ERAS proposed by Japanese scholars is effective and safe, which has certain clinical applicability and value for Chinese patients with gastric cancer.

[Heterogeneity in PD-L1 expression on infiltrating immune cells between the primary and metastatic breast cancers].

Objective: To investigate the expression difference in PD-L1 on mesenchymal infiltrating immune cells between the primary and metastatic breast cancers, and to explore its relationship with clinicopathological parameters. Methods: All cases of primary breast cancer and their matched metastases diagnosed at the Fourth Hospital of Hebei Medical University between January 2010 and December 2018 were included. Immunohistochemistry (IHC) was used to detect the expression of PD-L1 (SP142) in interstitial infiltrating immune cells, and the expression of ER, PR, HER2 and Ki-67 in primary and matched metastases was detected. Statistical software SPSS 24.00 was used for statistical analysis. Kappa test was used for concordance/agreement analysis and McNemar test for difference analysis. Results: Among the 140 identified primary breast cancers, there were 52 cases with matched lymph node metastasis, 88 cases with distant metastasis, including 35 cases with liver metastasis, 21 cases with lung metastasis, 13 cases with chest wall metastasis, 11 cases with bone metastasis, 6 cases with brain metastasis, 1 case with small intestine metastasis, and 1 case with eyeball metastasis. The overall concordance rate of the PD-L1 expression on mesenchymal immune cells between primary breast cancer and paired metastatic breast cancer was 72.9% (κ=0.441). The concordance rate of PD-L1 expression between primary breast cancers and paired lymph node metastases, and that between primary breast cancers and distant metastases were 75.0% (κ=0.472) and 71.6% (κ=0.472), respectively. The inconcordance rate of interstitial immune cell PD-L1 expression between primary breast cancer and matched lung metastasis was 28.6%(6/21), and the difference was statistically significant (P=0.031). The expression of PD-L1 in mesenchymal immune cells of primary breast cancer was significantly correlated with tumor size, histological grade, vascular invasion, lymph node metastasis, and Ki-67 index (P<0.05). The PD-L1 expression was independently associated with lymph node metastasis (P<0.05), while the expression of PD-L1 in metastatic breast cancer interstitial immune cells was significantly related to the expression of ER (P<0.05). Conclusions: The expression of PD-L1 in the primary breast cancer is moderately concordant with that in paired metastases, but different from that in paired lung metastases. Therefore, the expression of PD-L1 in distant metastasis needs to be re-evaluated to optimize the treatment outcomes of PD-L1 based therapy.

[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.

Genera Acremonium and Sarocladium Cause Brown Spot on Bagged Apple Fruit in China.

Apple fruit spot disease has caused serious economic losses for years in China since the widespread application of fruit bagging in production. Although the three genera Trichothecium, Alternaria, and Acremonium have been reported to be the causal agents, studies on the disease etiology and pathogen biology are still sparse. Here, we report characterization of eight fungal isolates from lesions on 126 symptomatic fruit samples collected in Shaanxi Province, China. Pathogenicity of the isolates was assessed. DNA sequences were obtained at four loci, including D1/D2 domains of the large-subunit nrRNA gene, internal transcribed spacer regions 1 and 2, 5.8S nrDAN gene, a fragment of the actin gene, and a fragment of the ß-tubulin. Based on phylogenetic analysis and morphological features, three new species were found: Acremonium mali, Sarocladium liquanensis, and Sarocladium mali. In addition, we made the first report of Sarocladium terricola as a plant pathogen. Temperature and moisture significantly affected in vitro conidial germination of five Acremonium-like species, and their impact on infection of apple fruit was tested using Acremonium sclerotigenum. Conidia of five species germinated from 15 to 35°C in free water; four of the species had optimum temperature around 25°C, whereas conidia of S. terricola had an optimum temperature of 30°C. Conidial germination rate increased as relative humidity (RH) increased. The five isolates had relatively high conidial germination rates at RH > 97%, with a significant decline at 95% RH. Incidence of infection also increased in proportion to RH. In free water, conidial germination was relatively unaffected by temperature.

[Analysis of the arthropathies on no-bleeding history joints in pre-school age severe hemophilia A children].

Objective: To detect the arthropathies on no bleeding history joints in pre-school hemophilia A children in order to provide evidence for further prevention and control of joint disease in children with hemophilia A. Methods: This study was a cross-sectional study based on China Hemophilia Individualized prophylaxis study (CHIPS). The basic data of outpatients with hemophilia in Beijing Children's Hospital and Chengdu Women's and Children's Central Hospital between August 2016 and June 2017 were collected and a three-month follow-up was conducted. The target joints (six joints of bilateral elbows, knees and ankles) of thirty-four children aged 1-7 years old with severe hemophilia A were examined by ultrasound, X-ray and joint function examination (4-7 years old, hemophilia joint health score (HJHS)). To find out whether there are arthropathies in patient's joints with no bleeding history and analyze the relevant factors by chi-square test, rank sum test and other statistical methods. Results: There were 32 analyzable cases with 112 no-bleeding history target joints, 42.9% (48/112) were elbow joints. Arthropathies were revealed in 34.8% (39/112) of them by joint structural and functional examination and 46.2% (18/39) were ankles (χ(2)=8.379, P=0.015) . Ultrasound showed abnormalities in 18.3% (20/109) joints, X-ray showed abnormalities in 3.8% (3/79) joints and HJHS showed abnormalities in 25.3% (20/79) joints. There was no correlation between ultrasound and HJHS (r=0.015, P=0.895), no correlation was found between X-ray and HJHS (r=-0.101, P=0.390) either, which suggested that joint structural and functional examination could not replace each other. The related risk factors of arthropathies in this group were >4.91 years old (OR=3.917, 95%CI:1.610-9.528) and combining with target joint (OR=3.530, 95%CI:1.316-9.465). Conclusions: Detecting the joint structure and function on no bleeding history joints in pre-school hemophilia A children could reveal the arthropathies and majority of them were ankle arthropathies. Joint structural and functional examinations could not replace each other. For patients more than 5 years old and those with target joints, the joints with no complaint of bleeding should be examined regularly to reveal the arthropathies in time.

Synthesis of a lignin-based phosphorus-containing flame retardant and its application in polyurethane.

In this work, new lignin-based flame retardant LHDs were successfully synthesized through the reaction between lignin, 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) and hexamethylene diisocyanate (HDI). The chemical structure of LHD was characterized by FTIR, 1H NMR, 31P NMR. The thermal stability of LHD was studied by TGA. The results showed that the residual carbon content of L15HD (15% of lignin in LHD) at 600 °C reached 16.55%, indicating that this prepared flame retardant can be a type of good char forming agent. LHDs were then applied to prepare flame-retardant lignin-based polyurethane (FLPU). Lignin-based polyurethane (LPU) was synthesized by the reaction between lignin, polyethylene glycol 200 (PEG 200) and hexamethylene diisocyanate (HDI). The limiting oxygen index (LOI) value of the FLPU reached 30.2% when the addition content of L15HD (15% lignin in LHD) in L20PU (20% lignin in LPU) was 25%, exhibiting excellent flame-retardant properties. Scanning electron microscopy (SEM) analysis of the FLPU char residual showed that there was a continuous dense outer carbon layer on the residue surface, and the inner carbon layer had many expansion bubbles, indicating the LHDs have an excellent flame retardant effect for PU. In addition, FLPU presented better hardness and adhesion than PU. The hardness of FL15-25L20PU (lignin content in LPU was 20%, and added content of L15HD in LPU was 25%) reached 4H, and its adhesion was 0. These excellent properties illustrated that the LHDs are ideal flame retardants and reinforcing agents for LPU because of the co-curing and strong interface between LHD and LPU.

Effects of dietary Mn-methionine supplementation on the egg quality of laying hens.

This study was conducted to investigate the effects of dietary manganese-methionine (Mn-Met) supplementation on the egg quality of laying hens. A total of 480 Jinghong-1 strain layers aged 53 wk were divided into 5 groups with 6 replicates of 16 layers. Birds in the control group were fed a diet supplemented with 60 mg Mn/kg in the form of MnSO4; the birds in other 4 experimental groups were fed a diet supplemented with 20, 40, 60, and 80 mg Mn/kg as Mn-Met, respectively. Dietary Mn-Met treatments significantly affected (P < 0.05) the albumen height, yolk color, and Haugh unit compared to those of the control diet. The Mn contents in the eggshell increased (P < 0.01) significantly by increasing the Mn-Met supplementation, whereas Mn content in eggshell was triple that in the yolk or albumen. Compared with the 60 mg/kg Mn-Met group, the transverse surface in the control group had (P < 0.01) a greater width of mammillary cones, and there were obvious cracks on the outer surface in the control. There was no difference (P > 0.05) in the eggshell gland (ESG) in the expression of calbindin-D28k (CaBP-D28k) mRNA in response to any diet treatment. In conclusion, dietary Mn-Met supplementation increased internal egg quality and the ultrastructure of the eggshell. Compared to the control, 60 mg/kg Mn-Met treatment resulted in improving egg quality, and 20 mg/kg Mn-Met treatment had similar effects the control treatment had on the egg quality. This indicates that the inorganic Mn can be replaced by the lower concentration of Mn-Met.

Effects of in ovo feeding of cationic amino acids on hatchability, hatch weights, and organ developments in domestic pigeon squabs (Columba livia).

This study was conducted to evaluate the effect of in ovo feeding of cationic amino acids on hatchability, hatch weights, and organ developments in pigeon squabs. Two experiments were conducted in this study. Eggs in Exp. 1 were subjected to modification of in ovo feeding in pigeons. Optimal time was determined by checking amniotic fluid volume, and suitable length was confirmed through ink injection. Results showed that the optimum time of in ovo feeding was on d 13 of embryonic development, and the suitable injected length was 20 mm to reach the amniotic cavity of the embryo. Eggs in Exp. 2 were transferred to access in ovo feeding of cationic amino acids. A total of 75 fertile pigeon eggs was randomly distributed into 5 treatments of 15 replicate eggs. Treatments in Exp. 2 consisted of non-injected controls (Control), a sterile buffered solution (0.75% saline), or a cationic amino acid mixture (> 98.5% purity crystalline L-arginine, > 98% purity crystalline L-lysine, and > 98.5% purity L-histidine) containing 0.1, 1, or 10% concentration (Conc.), which were relative to their total content in the eggs, respectively. The crystalline amino acids were dissolved in 200 µL buffered solution prior to in ovo feeding. After hatching, hatch weight (HW) and organ weight (OW) of the squabs were measured immediately. In ovo feeding of cationic amino acids increased the proportions of yolk-free hatch weight to hatch weight (YFHW/HW) (quadratic P = 0.01), and those of OW to YFHW including the heart (quadratic P = 0.01), kidney (quadratic P < 0.01), and liver (quadratic P = 0.02) compared to the control group, and the levels of those ratios were maximized in the 1% Conc group. Also, a proportion of small intestine weight to YFHW improved (linear P = 0.02, quadratic P = 0.05) after in ovo feeding. The organ weight of the head, leg, heart, lung, kidney, proventriculus, pancreas, liver, and small intestine correlated with YFHW positively (0.4 < correlation coefficient < 0.8, P < 0.05). In conclusion, cationic amino acids injection into amnion can improve the embryonic development, which may be mediated by the increment of relative organ weight.

[Construction and improvement of animal models with different positional osseous metastasis of prostate cancer in vivo].

OBJECTIVE: To provide an important tool for the study of diagnose and treatment of prostate cancer (PCa) osseous metastasis and change of bone stress force on prostate cancer (PCa) osseous metastasis and a platform, which is more congruous to clinical process, for prevention and cure of neoplastic bone metastases, and to carry out the construction and improvement of animal models of PCa with different positional osseous metastasis in vivo. METHODS: Different gradient concentrations of RM-1 cells were inoculated into the cavity of left femoral bone or lumbar vertebra of mice (C57BL/6) respectively. The change of mouse activity, tumor formation, tumor size and survival time were observed respectively. And the femur tissue and spinal tissue were obtained from the mice after death. The gray value of iconography were measured by imageological examination of femur tissue, and the final histopathological examination were taken to determine the tumor type in both femur and spinal tissue. RESULTS: The tumor growth could be touched at the puncture site in all the mice after inoculated for 7 days. There were no obvious differences in the time of tumorigenesis, the rate of tumor growth and tumor size among the mice in the same group (P>0.05). As the result, the construction femoral bone and lumbar vertebra metastatic models of PCa had been confirmed by iconography and pathology detection. At the same time, the survival time of the mice inoculated with low concentrations of PCa cells was obviously longer than that of high concentrations of PCa cells ( at least 2 weeks longer). CONCLUSION: The animal models with different positional osseous metastasis (limbs and axial skeleton) of PCa using the same PCa cells (RM-1) had been first constructed successfully in our study. At the same time, a high success rate of construction of PCa animal model with bone metastasis was obtained by femoral bone marrow cavity injection of PCa cells. The rate of tumor growth was rapid, animal survival time was appropriate, and the PCa animal model with bone metastasis can be stably reproduced by our method. These animal models can be used to explore the pathogenesis of different positional PCa bone metastasis and provide a new platform, which were more congruous to clinical process, for prevention and cure of neoplastic bone metastases.

Gene expression of amino acid transporter in pigeon (Columbia livia) intestine during post-hatch development and its correlation with amino acid in pigeon milk.

This study was conducted to evaluate gene expression of the amino acid transporter in post-hatch pigeon small intestine and the association of pigeon milk amino acid with the above transporter's gene expression. A total of 48 pigeon breeding families were randomly allocated to 8 groups of 6 replicates of one parental pigeon pair and 2 squabs. Samples of pigeon milk and duodenum, jejunum, and ileum were collected on d 1, 2, 3, 4, 6, 8, 10, and 14 post hatch. The results showed that levels of crude protein (8.93 to 15.56%) were highest in pigeon milk on an air-dry basis. Amino acid content in pigeon milk remained constant in the first 4 d, declined abruptly at d 6, then increased dramatically from d 8 to 14. There was a significant effect of interaction between age and intestinal segments on those amino acid transporters gene expression. mRNA abundance of ATB0'+, SNAT-2, LAT-4, rBAT, b0'+AT, EAAT-3 and PAT-1 was highest in the ileum; B0AT1, asc-1, and IMINO were predominate in the jejunum; and CAT-1 and y+LAT2 were greatest in the duodenum. Age-related changes of amino acid transporter mRNA was inconsistent. mRNA levels of SNAT-2, rBAT, y+LAT2, b0'+AT, and EAAT-3 ascended with age, whereas that of asc-1, CAT-1, and IMINO diminished significantly. Levels of B0AT1 and PAT-1 mRNA abundance were minimized at d 6. However, few correlations were found between pigeon milk amino acid and the amino acid transporter gene expressions in squab small intestine. Our findings provide a comprehensive elaboration on ontogeny of the amino acid transporter in post-hatch pigeon intestine.

[Clinical analysis of chronic rhinosinusitis in the different age group patients].

Objective:To investigate the clinical materials of chronic rhinosinusitis (CRS) in the different age group patients and explore its clinical characteristics and prognosis.Method:A retrospective analysis was carried out in 395 CRS patients with surgical treatment in our hospital in the past three years. They were divided into the young group (18 to 39 years old ), the middle-aged group (40 to 59 years old ), and the old group (over 60 years old). The clinical symptoms, accompanying diseases and prognosis in CRS patients were analyzed.Result:Among the presenting symptoms,facial pain and rhinorrhea were most common in the young group (P< 0.05), while dysosmia was most common in the old group (P< 0.05). Allergy was more prevalent in the young group and the middle-aged group than the old group (P< 0.05). CRS without polyposis was the most common diagnosis in the young group and CRS with polyposis was the more common diagnosis in the middle-aged group and the old group (P< 0.05). Patients in the young group got higher rate of improvement in olfactory function while patients in the old group got higher rate of improvement in rhinorrhea following FESS (P< 0.05).Conclusion:CRS in different age groups had different clinical features and prognosis. We can improve the personalized treatment program to this disease through the classification and grading treatment.