Objective:To optimize the extraction technology for Sanren Tongbian mixture. Methods:The water amount,decoction time and decoction frequency as the evaluation factors,and the content of amygdalin and the paste-forming rate as the evaluation indi-ces,the extraction process of Sanren Tongbian mixture was optimized by L9 (34 ) orthogonal design. Results: The optimal extraction conditions were as follows:adding 8-fold amount of water, decocting twice with 1. 5h for each time. Conclusion: The study provides scientific basis for the research of the extraction technology of Sanren Tongbian mixture, and the further experiments proved that the op-timized process is stable and feasible.

Objective:To explore the characteristics, diagnosis, and treatment of precursor B-cell acute lymphocytic leukemia with C- MYC rearrangement (preBLL) in children. Methods:The clinical data in 2 cases of childhood preBLL in Department of Hematology, Children′s Hospital Affiliated to Capital Institute of Pediatrics in June and August 2019 were summarized and analyzed.Results:Both cases were acute lymphoblastic leukemia with precursor B-cell immunophenotype.Hepatosplenomegaly and peripheral white blood cells were significantly increased, and the morphology of bone marrow was L3. C- MYC rearrangement was discovered by cytogenetic tests.Both children have received the treatment of the mature B-cell tumor protocol (FAB/LMB96), and early remission was developed in 1 case with TP53 gene mutation but relapsed thereafter and died finally.Another case had reached sustained complete remission after treatment. Conclusions:Children with preBLL is rare, and routine C- MYC rearrangement should be performed in children with Precursor B-cell lymphoblastic leukemia whose morphology of bone marrow was L3.Its treatment needs to be further studied, and multi-center clinical trials need to be actively conducted to analyze and summarize large numbers of cases to identify effective protocol and improve the prognosis.

BACKGROUND:Ideal osteochondral tissue-engineered scaffolds should be able to mimic the normal structure ofhuman articular cartilage. OBJECTIVE:To prepare a layered osteochondral composite scaffold based on the anatomical and physiological functions of osteochondral articular cartilage and to observe its repair effect on osteochondral defects in rabbits. METHODS:The poly (lactide-glycolide acid)/β-tricalcium phosphate organic solution was sprayed on the surface of cartilage scaffold using rapid prototyping technology. The layered osteochondral composite scaffold was formed by the“dissolving-adhesion”process. Sixty rabbits were enrol ed, modeled into left knee articular cartilage defects, and then randomly divided into three groups. The layered osteochondral composite scaffold and cartilage scaffold were implanted into experimental and control groups, respectively. Those without any treatment served as controls. Gross and histological observations of the defect region were performed at 12 and 24 weeks after implantation. RESULTS AND CONCLUSION:Gross observation:At 12 weeks after implantation, the defects in the control group were obvious and not repaired at al;the 24-week defect area was decreased, covered by newly formed tissues, but with rough surface. In the experimental group, the defect surface was flat after 12 weeks of implantation, the texture was soft, and the boundary with the surrounding tissues was unclear;at 24 weeks, the defect was covered with transparent cartilaginous tissues and the surface was smooth. Histological observation:At 12 weeks after implantation, the irregular cal us appeared in the control group, but the trabeculae were not formed;in the experimental group, the thickness of the new cartilage was similar with that of the normal cartilage and there was irregular trabecular bone under the cartilage. After 24 weeks of implantation, there were new tissues in the control group, but the thickness was irregular and uneven and the trabecular structure was irregular;while the cartilage surface was smooth and repaired wel in the experimental group. In contrast, repair effect in the control group was poor as assessed by gross and histological observations. These results show that the layered composite scaffold holds a similar structure with human articular cartilage and can promote the repair of articular cartilage defects.

We studied the aggregation of a recombinant engineering antibody (chA21). Anti-ErbB2 antibody chA21 was produced by fusing single-chain Fv (scFv) with human IgG1 Fc fragment, and it was proved to be a drug candidate for cancer therapy. We characterized the aggregation of chA21 by high performance sized-exclusive chromatography (HPSEC), dynamic light scattering (DLS), SDS-PAGE, indirect ELISA assay, and compared the influence of temperature and additive on the level of aggregation and binding activity. Conformation changes of different levels of aggregation were also analyzed via circular dichroism (CD). Finally, we analyzed which part of chA21 was involved in aggregation by cleaving it into scFv and Fc fragments. The results showed that chA21 could form aggregates in the storage solution. The aggregates interacted through non-covalent bonds and remained binding activity. Temperature and additive could slightly affect the level of aggregation and binding activity, while the conformations of chA21 were stable. Aggregation propensity of scFv fragment was almost same as chA21, indicating that scFv may be the major part to form the aggregates. The research on aggregation may be helpful to develop a suitable formulation for chA21 clinical application as well as provide direction for future antibody design and reconstruction.
Antibodies ; chemistry ; metabolism ; Humans ; Immunoglobulin Fc Fragments ; chemistry ; metabolism ; Immunoglobulin Variable Region ; chemistry ; metabolism ; Protein Conformation ; Protein Engineering ; methods ; Receptor Aggregation ; immunology ; Receptor, ErbB-2 ; chemistry ; immunology ; Recombinant Proteins ; biosynthesis ; chemistry ; genetics ; immunology

Myelodysplastic syndromes(MDS)represent a heterogeneous group of myeloid neoplasms initiated from stem cells and/or progenitor cells,which is primarily a disease of elderly.In childhood,MDS is uncommon.As for its mechanism,there has been a considerable improvement,involving cytogenetics,molecular biology.Besides,the rela-tionship between hematological clonal evolution and initiation,development and prognosis of MDS,has also been repor-ted systemically.These mechanisms are summarized and some characteristics of pediatric cases are reviewed.

OBJECTIVE: To analyze the clinical characteristics and spectrum of SPTB gene variants among 16 Chinese children with Hereditary spherocytosis (HS) and explore their genotype-phenotype correlation. METHODS: Sixteen children who were diagnosed with HS at the Affiliated Hospital of Capital Institute of Pediatrics from November 2018 to July 2022 were selected as the research subjects. Genetic testing was carried out by whole exome sequencing. Candidate variants were verified by Sanger sequencing and subjected to bioinformatic analysis and prediction of 3D structure of the protein. Correlation between the SPTB genotypes and clinical phenotypes was analyzed using Chi-squared test. RESULTS: The male-to-female ratio of the HS patients was 6 : 10, with the median age being 7-year-and-10-month. Clinical features of the patients have included anemia, reticulocytosis and gradual onset of splenomegaly. Mild, moderate and severe anemia have respectively occurred in 56.25% (9/16), 31.25% (5/16) and 12.50% (2/16) of the patients. SPTB gene variants were detected in all patients, among which 10 were unreported previously and 7 were de novo in origin. Loss of function (LOF) variants accounted for 93.75% (15/16). Only one missense variant was detected. Eleven, 4 and 1 of the variants had occurred in the repeat domain, CH1 domain, and dimerization domain, respectively. There was no significant correlation between the type or domain of the SPTB gene variants with the clinical features such as severity of anemia (x² = 3.345, P > 0.05). All of the variants were predicted to be pathogenic or likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics. CONCLUSION Mild to moderate anemia are predominant clinical features of the HS children harboring a SPTB gene variant, for which LOF variants are the main mutational type. The clinical feature of HS is unaffected by the type of the variants.
Child ; Female ; Humans ; Male ; Computational Biology ; Genetic Testing ; Genomics ; Genotype ; Spherocytosis, Hereditary/genetics* ; East Asian People/genetics* ; Spectrin/genetics*

Objective:To analyze clinical characteristics of neurosyphilis patients with abnormal mental behaviors as the initial symptom, and to provide a reference for clinical classification of, as well as outcome prediction and efficacy monitoring in neurosyphilis.Methods:Clinical data were collected from 67 HIV-negative neurosyphilis patients with abnormal mental behaviors as the initial symptom in the Second Affiliated Hospital of Soochow University from November 2012 to November 2019, and retrospectively analyzed. Statistical analysis was carried out by using t test. Results:Among the 67 patients, 52 (77.6%) were males, and 15 (22.4%) were females; there were 63 (94.0%) middle-aged and elderly patients and 4 (6.0%) adolescent patients; 38 (56.7%) patients were diagnosed with progressive general paresis, 21 (31.3%) with meningovascular neurosyphilis, 1 (1.5%) with meningeal neurosyphilis, 3 (4.5%) with tabes dorsalis, and 4 (6.0%) with mixed-type neurosyphilis. As laboratory examination showed, 67 patients all presented with positive serum rapid plasma reagin (RPR) test, serum Treponema pallidum particle agglutination (TPPA) test, and cerebrospinal fluid TPPA test, 55 (82.1%) had positive cerebrospinal fluid RPR test, 47 (70.1%) had elevated cerebrospinal fluid protein levels of > 0.45 g/L, 50 (74.6%) had increased white blood cell counts of > 8 ×10 6/L in cerebrospinal fluids, and 28 (41.8%) had elevated IgG levels in cerebrospinal fluids. Magnetic resonance imaging of the brain revealed multiple ischemic foci in 21 (31.3%) cases, multiple leukodystrophy in 17 (25.4%) , cerebral atrophy in 15 (22.4%) , infarction in 8 (11.9%) , and encephalitis-like changes in 2 (3.0%) . Of the 67 patients, 48 were treated with penicillin in aqueous solutions, 15 with ceftriaxone, and 4 with doxycycline. Six months later, the follow-up showed that 46 (68.7%) patients responded to the treatment, and the early course of disease was significantly shorter in the highly responsive group than in the poorly responsive group ( P < 0.05) . Conclusion:The middle-aged and elderly males were predominant in the neurosyphilis patients with abnormal mental behaviors as the initial symptom, magnetic resonance imaging is helpful for clinical classification and prognosis prediction of neurosyphilis, and early and standardized antisyphilitic treatment can markedly improve the prognosis of patients.

Objective To investigate the application value of tenofovir alafenamide fumarate(TAF)in patients with first-time hepatitis B virus-related decompensated cirrhosis(HBV-DC)and its impact on renal function and lipid metabolism.Methods A total of 57 patients with first-time HBV-DC who were hospitalized and received TAF antiviral therapy in The Affiliated Hospital of Xuzhou Medical University from January 1,2020 to December 31,2022 were enrolled,and all of them received TAF antiviral therapy.Related data were collected at baseline and at weeks 12,24,and 48 of treatment,including virological and serological indicators,liver and renal function,serum phosphorus,and blood lipids.The paired t-test or single group repeated measures ANOVA were used for comparison of normally distributed continuous data,the Friedman test was used for comparison of non-normally distributed continuous data,and the chi-square test or the Fisher's exact test were used for categorical data.Results A total of 52 patients completed the 48 weeks of follow-up.After 12,24,and 48 weeks of treatment,the patients achieving HBV DNA seroconversion accounted for 38.5%,63.5%,and 84.6%,respectively;the alanine aminotransferase normalization rate were 71.2%,82.7%,and 82.7%,respectively;the proportion of the patients with Child-Pugh class A disease increased to 55.8%,73.1%,and 92.3%,respectively.Within the 48 weeks of treatment,there were significant increases in the levels of cystatin C(χ2=35.163,P＜0.001)and serum phosphorus(F=8.600,P＜0.001)and low-density lipoprotein cholesterol(χ2=10.064,P=0.018).The ratio of total cholesterol/high-density lipoprotein cholesterol decreased continuously from 3.61(2.61～5.84)to 3.27(2.70～4.36)(χ2=5.000,P=0.172).Conclusion TAF can rapidly inhibit HBV replication and significantly improve liver function in HBV-DC patients,with no significant impact on renal function.However,blood lipid should be closely monitored.

OBJECTIVETo investigate the status of exclusive breastfeeding(EBF) and possible influencing factors during 0-7 days postpartum in China.

METHODSDuring 2011 to 2013, healthy mothers and neonates who were in the period of 0- 7 days postpartum from 8 provinces across different regions of China were recruited to take the questionnaire investigations and physical examinations. Information about socio-economic, pregnant, and delivery status, infant healthy situation and feeding indicators was collected to calculate the rate of exclusive breastfeeding during 0- 7 days postpartum and analyze the influencing factors.

RESULTSA total of 1 882 pairs of mothers and neonates were covered by this study. The rate of EBF was 13.3% (250 cases) during 0- 7 days postpartum. Bottle feeding (OR=0.08, 95% CI: 0.05- 0.12), the mothers themselves mixed fed at their 0-4 months old (OR=0.22, 95%CI: 0.08-0.58), the mothers who had used methods to stimulate milk secretion (OR=0.58, 95% CI: 0.35- 0.94) might decrease the EBF rate. Compared with the mothers who believed that their breast milk was not enough for their infants, the mothers who believed breastmilk was enough may increase the EBF rate (OR=6.04, 95%CI: 3.34-10.94). Comparing to the EBF rate of Beijing, Yunnan (OR=0.10, 95%CI: 0.04-0.24), and Gansu(OR=0.03,95%CI: 0.01-0.08) had lower EBF rate during 0-7 days postpartum. What's more, the EBF rate increased with the increasing neonates' age (OR=1.33, 95% CI: 1.16- 1.53).

CONCLUSIONThe EBF rate during 0- 7 days postpartum is still low in China and had significant differences in different regions. Suboptimal feeding knowledge and practices affected the EBF rate significantly.

Bottle Feeding ; Breast Feeding ; statistics & numerical data ; China ; Female ; Humans ; Infant, Newborn ; Milk, Human ; Mothers ; Postpartum Period ; Pregnancy ; Surveys and Questionnaires

OBJECTIVETo observe the efficacy and adverse reaction of the improvement program of cladribine combined with cytarabine (2-CdA+Ara-C) in treatment of children with refractory high-risk Langerhans cell histiocytosis (LCH).

METHODS13 patients with refractory high-risk LCH or recurrent LCH were treated by combined 2-CdA+Ara-C chemotherapy. The treatment efficacy and the disease state in the process were evaluated according to the Histiocyte Society Evaluation and Treatment Guidelines (2009). The drug toxicity was evaluated according to the Common Terminology Criteria Adverse Events Version 4.0 (CTCAE v4.0, 2009).

RESULTSOf 13 patients, 10 cases achieved non active disease (NAD); 2 patients with liver cirrhosis before the improvement program with CIP-LCH-2012 gave up the treatment after 1 course of therapy; 1 patient died of infectious shock after chemotherapy with severe pulmonary infection and intestinal infection. All 13 patients had grade 3 of blood and lymphatic system toxicity; 10 patients had grade 1 of hepatobiliary and gastrointestinal side effects; 3 patients with liver cirrhosis before the improvement program had grade 2 or grade 3 of hepatobiliary system and gastrointestinal system side effects, including 1 patient of death.

CONCLUSIONThe improvement program of CIP-LCH-2012 had significant efficacy for children with refractory high-risk and relapsed LCH. The cladribine-associated toxicity was of significant myelosuppression, which may be tolerated in the most children patients. The program could be considered as a recommended salvage therapy for multi-system LCH (MS-LCH) after failure of first-line therapy, and as a first-line therapy for MS-LCH with risk organ injury. The program should be used with caution or dose-adjustment consideration for pre-treatment of severe organ damage exist, especially cirrhosis.

Child ; Cladribine ; therapeutic use ; Histiocytosis, Langerhans-Cell ; drug therapy ; Humans ; Immunosuppressive Agents ; therapeutic use ; Risk Factors ; Salvage Therapy