Heterozygous CAPZA2 mutations cause global developmental delay, hypotonia with epilepsy: a case report and the literature review.

CAPZA2 encodes the α2 subunit of CAPZA, which is vital for actin polymerization and depolymerization in humans. However, understanding of diseases associated with CAPZA2 remains limited. To date, only three cases have been documented with neurodevelopmental abnormalities such as delayed motor development, speech delay, intellectual disability, hypotonia, and a history of seizures. In this study, we document a patient who exhibited seizures, mild intellectual disability, and impaired motor development yet did not demonstrate speech delay or hypotonia. The patient also suffered from recurrent instances of respiratory infections, gastrointestinal and allergic diseases. A novel de novo splicing variant c.219+1 G > A was detected in the CAPZA2 gene through whole-exome sequencing. This variant led to exon 4 skipping in mRNA splicing, confirmed by RT-PCR and Sanger sequencing. To our knowledge, this is the third study on human CAPZA2 defects, documenting the fourth unambiguously diagnosed case. Furthermore, this splicing mutation type is reported here for the first time. Our research offers additional support for the existence of a CAPZA2-related non-syndromic neurodevelopmental disorder. Our findings augment our understanding of the phenotypic range associated with CAPZA2 deficiency and enrich the knowledge of the mutational spectrum of the CAPZA2 gene.

Apolipoprotein A-1 protected hepatic ischaemia-reperfusion injury through suppressing macrophage pyroptosis via TLR4-NF-κB pathway.

BACKGROUND AND AIMS: Apolipoprotein A-1 (ApoA-1), the major apolipoprotein of high-density lipoprotein, plays anti-atherogenic role in cardiovascular diseases and exerts anti-inflammation effect in various inflammatory and infectious diseases. However, the role and mechanism of ApoA-1 in hepatic ischaemia-reperfusion (I/R) injury is unknown. METHODS: In this study, we measured ApoA-1 expression in human liver grafts after transplantation. Mice partial hepatic I/R injury model was made in ApoA-1 knockout mice, ApoA-1 mimetic peptide D-4F treatment mice and corresponding control mice to examine the effect of ApoA-1 on liver damage, inflammation response and cell death. Primary hepatocytes and macrophages were isolated for in vitro study. RESULTS: The results showed that ApoA-1 expression was down-regulated in human liver grafts after transplantation and mice livers subjected to hepatic I/R injury. ApoA-1 deficiency aggravated liver damage and inflammation response induced by hepatic I/R injury. Interestingly, we found that ApoA-1 deficiency increased pyroptosis instead of apoptosis during acute phase of hepatic I/R injury, which mainly occurred in macrophages rather than hepatocytes. The inhibition of pyroptosis compensated for the adverse impact of ApoA-1 deficiency. Furthermore, the up-regulated pyroptosis process was testified to be mediated by ApoA-1 through TLR4-NF-κB pathway and TLR4 inhibition significantly improved hepatic I/R injury. In addition, we confirmed that D-4F ameliorated hepatic I/R injury. CONCLUSIONS: Our study has identified the protective role of ApoA-1 in hepatic I/R injury through inhibiting pyroptosis in macrophages via TLR4-NF-κB pathway. The effect of ApoA-1 may provide a novel therapeutic approach for hepatic I/R injury.

[Intellectual status and factors influencing the intelligence in children with attention deficit and hyperactive disorder]. / æ³¨æ„ç¼ºé™·å¤šåŠ¨éšœç¢å„¿ç«¥çš„æ™ºåŠ›çŽ°çŠ¶åŠå ¶å½±å“å› ç´ .

OBJECTIVES: To study the intellectual level and the factors influencing the intelligence in children aged 6-16 years with attention deficit hyperactivity disorder (ADHD). METHODS: A retrospective study was conducted on 2 861 children who were diagnosed with ADHD according to the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition between October 2014 and September 2022 at Henan Children's Hospital. The Wechsler Intelligence Scale for Children-Fourth Edition was used to assess the intellectual levels of the ADHD children. Based on intelligence quotient (IQ) scores, the intellectual levels were classified into five categories: borderline (70-79), low average (80-89), average (90-109), high average (110-119), and superior (≥120). The intellectual levels among the children of different genders, grades, and parental education levels were compared. RESULTS: Among the 2 861 ADHD children, 569 (19.89%) were classified as borderline, 846 (29.57%) as low average, 1 304 (45.58%) as average, 111 (3.88%) as high average, and 31 (1.08%) as superior. The boys had lower scores in working memory, processing speed, and overall IQ than the girls (P<0.05). There were significant differences in perceptual reasoning, working memory, processing speed, and overall IQ scores among different grade groups (P<0.05). The scores in language comprehension, perceptual reasoning, working memory, processing speed, and overall IQ were found to be associated with parental education level in ADHD children (P<0.05). CONCLUSIONS: The proportion of ADHD children with low average and borderline intellectual levels is relatively high. The IQ level of ADHD children is influenced by gender, grade level and parental education level.

The mechanism and effects of remdesivir-induced developmental toxicity in zebrafish: Blood flow dysfunction and behavioral alterations.

The antiviral drug remdesivir has been used to treat the growing number of coronavirus disease 2019 (COVID-19) patients. However, the drug is mainly excreted through urine and feces and introduced into the environment to affect non-target organisms, including fish, which has raised concerns about potential ecotoxicological effects on aquatic organisms. Moreover, studies on the ecological impacts of remdesivir on aquatic environments have not been reported. Here, we aimed to explore the toxicological impacts of microinjection of remdesivir on zebrafish early embryonic development and larvae and the associated mechanism. We found that 100 µM remdesivir delayed epiboly and impaired convergent movement of embryos during gastrulation, and dose-dependent increases in mortality and malformation were observed in remdesivir-treated embryos. Moreover, 10-100 µM remdesivir decreased blood flow and swimming velocity and altered the behavior of larvae. In terms of molecular mechanisms, 80 differentially expressed genes (DEGs) were identified by transcriptome analysis in the remdesivir-treated group. Some of these DEGs, such as manf, kif3a, hnf1ba, rgn, prkcz, egr1, fosab, nr4a1, and ptgs2b, were mainly involved in early embryonic development, neuronal developmental disorders, vascular disease and the blood flow pathway. These data reveal that remdesivir can impair early embryonic development, blood flow and behavior of zebrafish embryos/larvae, probably due to alterations at the transcriptome level. This study suggests that it is important to avoid the discharge of remdesivir to aquatic ecosystems and provides a theoretical foundation to hinder remdesivir-induced ecotoxicity to aquatic environments.

Biliary Tract Cancer at CT: A Radiomics-based Model to Predict Lymph Node Metastasis and Survival Outcomes.

Purpose To evaluate a radiomics model for predicting lymph node (LN) metastasis in biliary tract cancers (BTCs) and to determine its prognostic value for disease-specific and recurrence-free survival. Materials and Methods For this retrospective study, a radiomics model was developed on the basis of a primary cohort of 177 patients with BTC who underwent resection and LN dissection between June 2010 and December 2016. Radiomic features were extracted from portal venous CT scans. A radiomics signature was built on the basis of reproducible features by using the least absolute shrinkage and selection operator method. Multivariable logistic regression model was adopted to establish a radiomics nomogram. Nomogram performance was determined by its discrimination, calibration, and clinical usefulness. The model was internally validated in 70 consecutive patients with BTC between January 2017 and February 2018. Results The radiomics signature, composed of three LN-status-related features, was associated with LN metastasis in primary and validation cohorts (P < .001). The radiomics nomogram that incorporated radiomics signature and CT-reported LN status showed good calibration and discrimination in primary cohort (area under the curve, 0.81) and validation cohort (area under the curve, 0.80). Patients at high risk of LN metastasis portended lower disease-specific and recurrence-free survival than did those at low risk after surgery (both P < .001). High-risk LN metastasis was an independent preoperative predictor of disease-specific survival (hazard ratio, 3.37; P < .001) and recurrence-free survival (hazard ratio, 1.98; P = .003). Conclusion A radiomics model derived from portal phase CT of the liver has good performance for predicting lymph node metastasis in biliary tract cancer and may help to improve clinical decision making. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Laghi and Voena in this issue.

A radiomics approach to predict lymph node metastasis and clinical outcome of intrahepatic cholangiocarcinoma.

OBJECTIVES: This study was conducted in order to establish and validate a radiomics model for predicting lymph node (LN) metastasis of intrahepatic cholangiocarcinoma (IHC) and to determine its prognostic value. METHODS: For this retrospective study, a radiomics model was developed in a primary cohort of 103 IHC patients who underwent curative-intent resection and lymphadenectomy. Radiomics features were extracted from arterial phase computed tomography (CT) scans. A radiomics signature was built based on highly reproducible features using the least absolute shrinkage and selection operator (LASSO) method. Multivariate logistic regression analysis was adopted to establish a radiomics model incorporating radiomics signature and other independent predictors. Model performance was determined by its discrimination, calibration, and clinical usefulness. The model was internally validated in 52 consecutive patients. RESULTS: The radiomics signature comprised eight LN-status-related features and showed significant association with LN metastasis in both cohorts (p < 0.001). A radiomics nomogram that incorporates radiomics signature and CA 19-9 level showed good calibration and discrimination in the primary cohort (AUC 0.8462) and validation cohort (AUC 0.8921). Promisingly, the radiomics nomogram yielded an AUC of 0.9224 in the CT-reported LN-negative subgroup. Decision curve analysis confirmed the clinical utility of this nomogram. High risk for metastasis portended significantly lower overall and recurrence-free survival than low risk for metastasis (both p < 0.001). The radiomics nomogram was an independent preoperative predictor of overall and recurrence-free survival. CONCLUSIONS: Our radiomics model provided a robust diagnostic tool for prediction of LN metastasis, especially in CT-reported LN-negative IHC patients, that may facilitate clinical decision-making. KEY POINTS: • The radiomics nomogram showed good performance for prediction of LN metastasis in IHC patients, particularly in the CT-reported LN-negative subgroup. • Prognosis of high-risk patients remains dismal after curative-intent resection. • The radiomics model may facilitate clinical decision-making and define patient subsets benefiting most from surgery.

Preoperative Salivary Cortisol AM/PM Ratio Predicts Early Postoperative Cognitive Dysfunction After Noncardiac Surgery in Elderly Patients.

BACKGROUND: The diagnosis of postoperative cognitive dysfunction (POCD) requires complicated neuropsychological testing and is often delayed. Possible biomarkers for early detection or prediction are essential for the prevention and treatment of POCD. Preoperative screening of salivary cortisol levels may help to identify patients at elevated risk for POCD. METHODS: One hundred twenty patients >60 years of age and undergoing major noncardiac surgery underwent neuropsychological testing 1 day before and 1 week after surgery. Saliva samples were collected in the morning and the evening 1 day before surgery. POCD was defined as a Z-score of ≤-1.96 on at least 2 different tests. The primary outcome was the presence of POCD. The primary objective of this study was to assess the relationship between the ratio of AM (morning) to PM (evening) salivary cortisol levels and the presence of POCD. The secondary objective was to assess the relationship between POCD and salivary cortisol absolute values in the morning or in the evening. RESULTS: POCD was observed in 17.02% (16 of 94; 95% confidence interval [CI], 9.28%-24.76%) of patients 1 week after the operation. A higher preoperative AM/PM salivary cortisol ratio predicted early POCD onset (odds ratio [OR], 1.56; 95% CI, 1.20-2.02; P = .001), even after adjusting for the Mini-Mental Sate Examination score (odds ratio, 1.55; 95% CI, 1.19-2.02; P = .001). The area under the receiver operating characteristic curve for the salivary cortisol AM/PM ratio in individuals with POCD was 0.72 (95% CI, 0.56-0.88; P = .006). The optimal cutoff value was 5.69, with a sensitivity of 50% and specificity of 91%. CONCLUSIONS: The preoperative salivary cortisol AM/PM ratio was significantly associated with the presence of early POCD. This biomarker may have potential utility for screening patients for an increased risk and also for further elucidating the etiology of POCD.

[Correlation between serum microRNA-122 and insulin resistance in obese children].

OBJECTIVE: To study the relationship between serum microRNA-122 (miR-122) and insulin resistance in obese children. METHODS: Forty-seven children with severely obesity aged 7-14 years and 45 age- and gender matched healthy children with normal weight (control group) were enrolled. The levels of height, weight, waistline, hip circumference, fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG), total cholesterol (TC), free fatty acid (FFA), interleukin-6 (IL-6) and miR-122 in the two groups were measured. Body mass index (BMI), waist-hip ratio (WHR) and insulin resistance index (HOMA-IR) were calculated. RESULTS: Compared with the control group, the height, weight, BMI, WHR, FINS, HOMA-IR, TG, FFA, IL-6, and miR-122 levels in the obese group were significantly increased (P<0.05). MiR-122 levels in the obese group were positively correlated with FINS, HOMA-IR and IL-6 levels (r=0.408, 0.442, and 0.464 respectively, P<0.05). The changes of miR-122 have a linear regression relationship with IL-6 (b'=0.318, P<0.05). CONCLUSIONS: The elevated serum miR-122 levels may be correlated with insulin resistance in obese children. The mechanism needs to be further studied.

Short- and long-term outcomes of middle hepatic vein-oriented hepatectomy for advanced perihilar cholangiocarcinoma.

BACKGROUND: This study aimed to compare clinical outcomes of the middle hepatic vein (MHV)-oriented versus conventional hemihepatectomy for perihilar cholangiocarcinoma (PHC). METHODS: From 2008 to 2017, medical records of patients undergoing hemihepatectomy with caudate lobectomy for advanced PHC were reviewed retrospectively. MHV-oriented hepatectomy was defined as full exposure of the MHV on the dissection plane. Predictors of morbidity and survival were identified. RESULTS: A total of 125 patients were enrolled. MHV-oriented and conventional hepatectomies were performed in 44 and 81 patients, respectively. The curative resection rate, blood loss, transfusion, and survival were comparable between two groups; however, severe morbidity rate was significantly lower in the MHV-oriented group (9.1% vs 38.3%, P < 0.001). MHV-oriented approach was an independent predictor of severe morbidity, as were the age, bilirubin level, and blood transfusion. Severe morbidity was associated with significantly decreased overall survival and recurrence-free survival (RFS) (median 29.0 vs 46.9 months, P = 0.011 and 20.3 vs 31.1 months, P = 0.003, respectively). Multivariate analysis revealed that severe morbidity independently predicted shorter RFS (P = 0.025). CONCLUSIONS: MHV-oriented approach for advanced PHC is safe and associated with a significant decrease in severe morbidity. Severe morbidity adversely affects survival after surgery; therefore, optimal preoperative preparation and MHV-oriented hepatectomy with meticulous dissection remain of critical importance.

Astroglial MicroRNA-219-5p in the Ventral Tegmental Area Regulates Nociception in Rats.

BACKGROUND: The authors previously reported that noncoding microRNA miR-219-5p is down-regulated in the spinal cord in a nociceptive state. The ventral tegmental area also plays critical roles in modulating nociception, although the underlying mechanism remains unknown. The authors hypothesized that miR-219-5p in the ventral tegmental area also may modulate nociception. METHODS: The authors studied the bidirectional regulatory role of ventral tegmental area miR-219-5p in a rat complete Freund's adjuvant model of inflammatory nociception by measuring paw withdrawal latencies. Using molecular biology technologies, the authors measured the effects of astroglial coiled-coil and C2 domain containing 1A/nuclear factor κB cascade and dopamine neuron activity on the down-regulation of ventral tegmental area miR-219-5p-induced nociceptive responses. RESULTS: MiR-219-5p expression in the ventral tegmental area was reduced in rats with thermal hyperalgesia. Viral overexpression of ventral tegmental area miR-219-5p attenuated complete Freund's adjuvant-induced nociception from 7 days after complete Freund's adjuvant injection (paw withdrawal latencies: 6.09 ± 0.83 s vs. 3.96 ± 0.76 s; n = 6/group). Down-regulation of ventral tegmental area miR-219-5p in naïve rats was sufficient to induce thermal hyperalgesia from 7 days after lentivirus injection (paw withdrawal latencies: 7.09 ± 1.54 s vs. 11.75 ± 2.15 s; n = 8/group), which was accompanied by increased glial fibrillary acidic protein (fold change: 2.81 ± 0.38; n = 3/group) and reversed by intraventral tegmental area injection of the astroglial inhibitor fluorocitrate. The nociceptive responses induced by astroglial miR-219-5p down-regulation were inhibited by interfering with astroglial coiled-coil and C2 domain containing 1A/nuclear factor-κB signaling. Finally, pharmacologic inhibition of ventral tegmental area dopamine neurons alleviated this hyperalgesia. CONCLUSIONS: Down-regulation of astroglial miR-219-5p in ventral tegmental area induced nociceptive responses are mediated by astroglial coiled-coil and C2 domain containing 1A/nuclear factor-κB signaling and elevated dopamine neuron activity.

Label-Free Fluorescent Detection of Trypsin Activity Based on DNA-Stabilized Silver Nanocluster-Peptide Conjugates.

Trypsin is important during the regulation of pancreatic exocrine function. The detection of trypsin activity is currently limited because of the need for the substrate to be labeled with a fluorescent tag. A label-free fluorescent method has been developed to monitor trypsin activity. The designed peptide probe consists of six arginine molecules and a cysteine terminus and can be conjugated to DNA-stabilized silver nanoclusters (DNA-AgNCs) by Ag-S bonding to enhance fluorescence. The peptide probe can also be adsorbed to the surface of graphene oxide (GO), thus resulting in the fluorescence quenching of DNA-AgNCs-peptide conjugate because of Förster resonance energy transfer. Once trypsin had degraded the peptide probe into amino acid residues, the DNA-AgNCs were released from the surface of GO, and the enhanced fluorescence of DNA-AgNCs was restored. Trypsin can be determined with a linear range of 0.0-50.0 ng/mL with a concentration as low as 1 ng/mL. This label-free method is simple and sensitive and has been successfully used for the determination of trypsin in serum. The method can also be modified to detect other proteases.

[Efficacy of heated humidified high-flow nasal cannula in preterm infants aged less than 32 weeks after ventilator weaning].

OBJECTIVE: To investigate the efficacy of heated humidified high-flow nasal cannula (HHHFNC) and nasal continuous positive airway pressure (nCPAP) in preterm infants aged 26-31(+6) weeks with respiratory distress syndrome after ventilator weaning. METHODS: A total of 161 preterm infants were randomly divided into two groups after ventilator weaning: HHHFNC treatment (n=79) and nCPAP treatment (n=82). The two groups were subdivided into 26-28(+6) weeks and 29-31+6 weeks groups according to the gestational age. The treatment failure rate, reintubation rate within 7 days after extubation, incidence of complications, and mortality during hospitalization were compared between the two groups. RESULTS: The treatment failure rate and reintubation rate showed no significant differences between the HHHFNC and nCPAP groups. The preterm infants aged 26-28(+6) weeks in the HHHFNC group had a significantly higher treatment failure rate than those in the nCPAP group (P<0.05), while the reintubation rate showed no significant difference. As for the preterm infants aged 29-31(+6) weeks, the treatment failure rate and reintubation rate showed no significant differences between the two groups. The incidence of complications and mortality showed no significant differences between the HHHFNC and nCPAP groups. CONCLUSIONS: In preterm infants aged 29-31(+6) weeks, HHHFNC has a similar efficacy as nCPAP after ventilator weaning, while in those aged less than 29 weeks, HHHFNC should be used with great caution if selected as the first-line noninvasive respiratory support.

[Status of penis and testicular development and effects of overweight/obesity on them in boys in the Zhengzhou area].

OBJECTIVE: To evaluate the current status of penis and testicular development in boys and the effects of overweight/obesity on their development in the Zhengzhou area of Henan Province. METHODS: Height, weight, waist circumference, hip circumference, penis length and testicular volume were measured in 3 546 4 to 12-year-old boys. The penis length and testicular volume were compared between the overweight/obesity and normal weight groups. RESULTS: Before 9 years of age, the testicular volume was progressively smaller, and after 9 years old, it gradually increased. By the age of 11, it increased rapidly. The penis length increased gradually between 4 and 11 years of age, and after the age of 11 it increased rapidly. Phimosis was found in 144 cases (4.01%) and cryptorchidism was found in 18 cases (0.51%). A total of 639 (18.02%) boys were overweight or obese among 3 546 boys. At the ages of 6 and 7 years, the testicular volume in the overweight/obesity group was greater than in the normal control group (P<0.05). The penis length in the overweight/obesity group was significantly shorter than in the normal control group (P<0.05) by the age of 11 years. The correlation analysis showed that the testicular volume at the ages of 4 and 5 years was positively correlated with height, weight, BMI, waist circumference and hip circumference in overweight/obese boys. The penis length at the ages of 7 and 8 years was negatively correlated with weight, waist circumference and hip circumference. By the age of 12 years, the penis length was positively correlated with the height. CONCLUSIONS: The development of penis and testicles in boys in the Zhengzhou area is in line with the level of sex development of Chinese boys. Overweight/obesity adversely affects the development of penis and testicles.

Apolipoprotein A-1 Accelerated Liver Regeneration Through Regulating Autophagy Via AMPK-ULK1 Pathway.

BACKGROUND & AIMS: Apolipoprotein A-1 (ApoA-1), the main apolipoprotein of high-density lipoprotein, has been well studied in the area of lipid metabolism and cardiovascular diseases. In this project, we clarify the function and mechanism of ApoA-1 in liver regeneration. METHODS: Seventy percent of partial hepatectomy was applied in male ApoA-1 knockout mice and wild-type mice to investigate the effects of ApoA-1 on liver regeneration. D-4F (ApoA-1 mimetic peptide), autophagy activator, and AMPK activator were used to explore the mechanism of ApoA-1 on liver regeneration. RESULTS: We demonstrated that ApoA-1 levels were highly expressed during the early stage of liver regeneration. ApoA-1 deficiency greatly impaired liver regeneration after hepatectomy. Meanwhile, we found that ApoA-1 deficiency inhibited autophagy during liver regeneration. The activation of autophagy protected against ApoA-1 deficiency in inhibiting liver regeneration. Furthermore, ApoA-1 deficiency impaired autophagy through AMPK-ULK1 pathway, and AMPK activation significantly improved liver regeneration. The administration of D-4F could accelerated liver regeneration after hepatectomy. CONCLUSIONS: These findings suggested that ApoA-1 played an essential role in liver regeneration through promoting autophagy in hepatocytes via AMPK-ULK1 pathway. Our findings enrich the understanding of the underlying mechanism of liver regeneration and provide a potential therapeutic strategy for liver injury.

Prevention of malignant digestive system tumors should focus on the control of chronic inflammation.

Chronic inflammation, through a variety of mechanisms, plays a key role in the occurrence and development of digestive system malignant tumors (DSMTs). In this study, we feature and provide a comprehensive understanding of DSMT prevention strategies based on preventing or controlling chronic inflammation. The development and evaluation of cancer prevention strategies is a longstanding process. Cancer prevention, especially in the early stage of life, should be emphasized throughout the whole life course. Issues such as the time interval for colon cancer screening, the development of direct-acting antiviral drugs for liver cancer, and the Helicobacter pylori vaccine all need to be explored in long-term, large-scale experiments in the future.

[Inhibitory effect of icariin on acetylcholinesterase].

Acetylcholinesterase (AChE) inhibitors are mainly used in the treatment of Alzheimer's disease (AD). The inhibitory effect of icariin on the activity of AChE was investigated by inhibition kinetics. The binding interaction and binding sites between icariin and AChE were also studied by using fluorimetry and molecular docking, respectively. The results showed that icariin could potently inhibit the activity of AChE, the IC50 value was determined to be 3.50 x 10(-8) mol x L(-1), and the determined IC50 value to tacrine was 0.75 x 10(-8) mol x L(-1). Kinetic analyses showed that icariin is a reversible and mixed type AChE inhibitor. The inhibition constants K1 and K(IS) were determined to be 2.67 x 10(-8) and 4.43 x 10(-8) mol x L(-1), respectively. Icariin binds selectively to the AChE peripheral anionic site via hydrogen bonds and Van der Waals forces.

[Immunophenotyping and its clinical significance in childhood acute lymphoblastic leukemia].

OBJECTIVE: To study the immunophenotype and its relationship with clinical characteristics in children with acute lymphoblastic leukemia (ALL). METHODS: Bone marrow or blood samples (2-3 mL) with heparin anticoagulation from 139 children with ALL were obtained, and immunophenotypes were identified by flow cytometry. RESULTS: In 139 ALL children, there were 103 cases (74.1%) of B-ALL, 24 cases (17.3%) of T-ALL, 12 cases of T/B biphenotypic (8.6% of T/BALL). In the 103 children with B-ALL, CD19 (90.3%), CD10 (83.5%) and CD20 (27.2%) were expressed as major antigens. In the 24 children with T-ALL, the major antigens were CD3 (79.2%), CD7 (66.7%) and CD5 (33.3%). In the 12 children with B/T-ALL, T-lymphoid antigens included CD7 (50.0%) and CD5 (41.7%), while the B-lymphoid antigens included CD19 (50.0%) and CD10 (33.3%). Of the 139 children with ALL, 32 cases (23.0%) showed myeloid antigen expression (My+ ALL) and the main expression antigens were CD13, CD33, CD14 and MPO. CD34 was expressed in 31 cases. CD34-positive expression (15.6%) in My+ ALL children was significantly lower than in My-ALL children (24.3%). HLA-DR was expressed in 82 of the 139 ALL children. The expression of CD10, CD34 and HLA-DR in the standard-risk, medium risk, high-risk ALL children was significantly different. There were significant differences in gender and incidence of bleeding between the My+ ALL and My-ALL groups (P<0.05). CONCLUSIONS: Immunetyping can differentiate the sources of leukemic cells. The expression of CD10, CD34 and HLA-DR antigen is related to the clinical classification of ALL.

[Association of cytotoxic T lymphocyte-associated antigen-4+49A/G polymorphism with childhood type 1 diabetes mellitus: a meta-analysis].

OBJECTIVE: To evaluate the association of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) + 49A/G polymorphism with type 1 diabetes mellitus (T1DM) in children. METHODS: Papers about the association of CTLA4+49A/G polymorphism with T1DM in children were collected by searching PubMed, EBSCO, CBM, CNKI, and Wanfang Data. A meta-analysis was performed to examine differences in the genotypes (AG, GG, and GG+AG) and G allele at position 49 of the CTLA-4 gene between a childhood T1DM group and a control group. RESULTS: A total of 10 papers involving 1084 T1DM children and 1338 healthy children were included. The Meta-analysis was performed to evaluate the association of the genotypes (AG, GG, and GG+AG) and the G allele at position 49 of the CTLA-4 gene with T1DM using a fixed effect model according to the heterogeneity test results of all studies. The pooled OR values (95% CI) were 1.13 (0.97-1.33), 1.42 (1.16-1.75), 1.20 (1.03-1.40), and 1.21 (1.09-1.33), suggesting a significant difference in genotypes (AG, GG, and GG+AG) and the G allele at position 49 of the CTLA-4 gene between the two groups. CONCLUSIONS: CTLA-4 +49A/G polymorphism is associated with T1DM in children.

Meta-analysis of cytochrome P4501A1 MspI gene polymorphism and childhood acute leukemia.

OBJECTIVE: To investigate the relationship between cytochrome P4501A1 (CYP1A1) Msp I gene polymorphism and childhood acute leukemia (AL). METHODS: Relevant literature was extensively searched and screened by Pubmed and Wanfang Database, Chinese Science Journal Database and Chinese Journal Net. Various data consolidation, combined OR values and their 95% CI were tested by RevMan 4.2; Funnel plots were used for the bias analysis. RESULTS: Six related literatures were found to meet the requirements. According to heterogeneity results, there was no significant difference in homozygous types(P>0.05), while there was significant difference in two others types (P all<0.05). For wild CYP1A1MspI homozygous for the reference group, Combined OR of heterozygous mutation, homozygous, heterozygous + homozygous mutation in AL and control groups were 1.18, 0.96, and 1.10 respectively. Subgroup analysis: Z values of CYP1A1MspI homozygous, heterozygous + homozygous in the acute lymphoblastic leukemia (ALL) and the control group were 0.10 and 0.76 respectively, Z values in non-acute lymphoblastic leukemia and control group were 0.74 and 0.75. CONCLUSION: There is no correlation between CYP1A1MspI gene polymorphism and the susceptibility of childhood AL.

[The interaction between genistein and beta-glucosidase].

The interaction between genistein and beta-glucosidase was studied using fluorescence quenching method and synchronous fluorimetry. The binding reaction was simultaneously studied by the AutoDock 4.2 molecular docking model. Data from fluorescence spectroscopy indicated that these interactions resulted in the endogenous fluorescence quenching of beta-glucosidase, which belongs to a static quenching mechanism. The calculated binding constants were 3.69 x 10(4), 3.06 x 10(4) and 2.36 x 10(4) L x mol(-1) at 17, 27 and 37 degrees C, respectively. The evidences from synchronous fluorescence showed the effect of genistein on the microenvironment around beta-glucosidase in aqueous solution. The inhibition test showed that the activity of beta-glucosidase could be inhibited by genistein. The determined bimolecular rate constant (k(i)) was 1.2 x 10(3) (mol x L(-1)(-1) x min(-1). Molecular docking was performed to reveal the possible binding mode or mechanism and suggested that genistein could bind strongly to beta-glucosidase. The results revealed that genistein tended to bind with beta-glucosidase mainly by hydrogen bond and hydrophobic interaction as well as electrostatic forces.