[BCS1Neonatal growth retardation and lactic acidosis initiated by novel mutation sites in L gene].

This study aims to analyze the clinical characteristics and genetic variations of two cases with developmental delay and lactic acidosis in a family, and to explore the relationship between genetic variations and clinical features. A retrospective analysis was conducted on the clinical characteristics of two siblings with developmental delay and lactic acidosis who were treated at the Neonatal Department of Children's Hospital of Chongqing Medical University in May 2019 and December 2021, respectively. Whole-exome sequencing was used to detect genetic variations in the affected children. Homology modeling of the BCS1L protein was performed to analyze the structural and functional changes of the protein. The correlation between genetic variations and clinical phenotypes was analyzed. The results showed that the main clinical features of the two affected children in this family were manifestations of mitochondrial respiratory chain complex Ⅲ deficiency, including prematurity, developmental delay, respiratory failure, lactic acidosis, cholestasis, liver dysfunction, renal tubular lesions, coagulation dysfunction, anemia, hypoglycemia, hypotonia, and early death. Whole-exome sequencing revealed a novel deletion mutation c.486_488delGGA (p.E163del) and a novel missense mutation c.992C>T (p.T331I) in the BCS1L gene. Structural analysis of the homology modeling showed that the compound heterozygous mutation had a significant impact on protein function. In conclusion, the novel mutation site c.992C>T (p.T331I) in the BCS1L gene is a "likely pathogenic" mutation, and the compound heterozygous mutation is closely related to the phenotype of mitochondrial respiratory chain complex Ⅲ deficiency.

Hepatic necro-inflammation and elevated liver enzymes: evaluation with MRI perfusion imaging with gadoxetic acid in chronic hepatitis patients.

AIM: To evaluate liver necro-inflammation and function by using gadoxetic acid-enhanced dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), with histological analysis as the reference standard. MATERIALS AND METHODS: Seventy-nine subjects (21 healthy subjects; 58 chronic hepatitis patients) who received gadoxetic acid-enhanced DCE-MRI were divided into three subgroups: no (A0, n = 31), mild (A1, n = 27), and moderate-severe (A2-A3, n = 21) activities. Two DCE-MRI models were measured: (1) a dual-input single-compartment model to obtain absolute arterial, portal venous, and total blood flow, arterial fraction (ART), distribution volume, and mean transit time; (2) a curve analysis method to obtain peak, slope, and AUC (area under curve). The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels also obtained. Statistical testing included Kruskal-Wallis tests for continuous data, Pearson's correlation tests, and multiple linear regression analyses. RESULTS: Hepatic necro-inflammatory activity grades were significantly correlated with fibrotic stages, serum ALT level, ART and AUC. ART was helpful to predict the mild activity (≤ A1 versus >A1; Az = 0.728), whereas AUC could differentiate no activity from any activity (A0 versus >A0; Az = 0.703). Peak, slope and AUC were all associated with AST and ALT (p < 0.05). CONCLUSION: Gadoxetic acid-enhanced DCE-MRI parameters may be used to evaluate the severity of hepatic necro-inflammation and function.

[Clinical phenotypic and genotypic analysis of 5 pediatric patients with ß-ketothiolase deficiency].

Objective: To summarize the clinical and genetic characteristics of children with ß-ketothiolase deficiency (BKTD). Methods: The clinical characteristics, biochemical, markers detected by tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS), as well as the variants in ACAT1 gene among 5 children with BKTD in Children's Hospital of Chongqing Medical University between October 2018 and December 2022 were retrospectively analyzed. Results: The onset age of the disease in 5 patients (4 males and 1 female) ranged from 9.7 to 28.0 months. During the acute phase, severe metabolic acidosis was observed with a pH of 6.9-7.1, as well as hypoglycaemia (2.3-3.4 mmol/L) and positive urinary ketone bodies (+-++++). Blood levels of methylcrotonyl carnitine, methylmalonyl carnitine and malonyl carnitine were 0.03-0.42, 0.34-1.43 and 0.83-3.53 µmol/L respectively and were significantly elevated. Urinary 2-methyl-3-hydroxybutyric acid was 22-202 and 3-hydroxybutyric acid was 4-6 066, both were higher than the normal levels. Methylcrotonylglycine was mild elevated (0-29). The metabolites detected by MS/MS and GC/MS were significantly reduced after treatment. Analysis of ACAT1 gene mutation was performed in 5 children. Most variants were missense (8/9). Four previously unreported variants were identified: c.678G>T (p.Trp226Cys), c.302A>G (p.Gln101Arg), c.627_629dupTGA (p.Asn209_Glu210insAsp) and c.316C>T (p.Gln106Ter), the first 2 variants were predicted to be damaging by SIFT, PolyPhen-2 and Mutation Taster software. c.316C>T (p.Gln106Ter) is a nonsense variant. Conclusions: ß-ketothiolase deficiency is relatively rare, lacks specific clinical manifestations, however severe metabolic acidosis, hypoglycemia, and ketosis during the acute onset were consistent findings. Missense mutations in the ACAT1 gene are common genetic causes of ß-ketothiolase deficiency.

Systematic review and meta-analysis of the diagnostic accuracy of procalcitonin, C-reactive protein and white blood cell count for suspected acute appendicitis.

BACKGROUND: The aim was to evaluate the diagnostic value of procalcitonin, C-reactive protein (CRP) and white blood cell count (WBC) in uncomplicated or complicated appendicitis by means of a systematic review and meta-analysis. METHODS: The Embase, MEDLINE and Cochrane databases were searched, along with reference lists of relevant articles, without language restriction, to September 2012. Original studies were selected that reported the performance of procalcitonin alone or in combination with CRP or WBC in diagnosing appendicitis. Test performance characteristics were summarized using hierarchical summary receiver operating characteristic (ROC) curves and bivariable random-effects models. RESULTS: Seven qualifying studies (1011 suspected cases, 636 confirmed) from seven countries were identified. Bivariable pooled sensitivity and specificity were 33 (95 per cent confidence interval (c.i.) 21 to 47) and 89 (78 to 95) per cent respectively for procalcitonin, 57 (39 to 73) and 87 (58 to 97) per cent for CRP, and 62 (47 to 74) and 75 (55 to 89) per cent for WBC. ROC curve analysis showed that CRP had the highest accuracy (area under ROC curve 0·75, 95 per cent c.i. 0·71 to 0·78), followed by WBC (0·72, 0·68 to 0·76) and procalcitonin (0·65, 0·61 to 0·69). Procalcitonin was found to be more accurate in diagnosing complicated appendicitis, with a pooled sensitivity of 62 (33 to 84) per cent and specificity of 94 (90 to 96) per cent. CONCLUSION: Procalcitonin has little value in diagnosing acute appendicitis, with lower diagnostic accuracy than CRP and WBC. However, procalcitonin has greater diagnostic value in identifying complicated appendicitis. Given the imperfect accuracy of these three variables, new markers for improving medical decision-making in patients with suspected appendicitis are highly desirable.

Effects of fumarate on ruminal ammonia accumulation and fiber digestion in vitro and nutrient utilization in dairy does.

The objective of this study was to evaluate effects of fumarate on ruminal ammonia accumulation and fiber digestion in vitro and on feed intake and nutrient utilization in dairy does. Batch cultures of mixed rumen microorganisms were used to study effects of different concentrations of fumarate on fermentation with various N sources (ammonia as ammonium bicarbonate, casein amino acids, casein peptides, gelatin peptides) and feeds (bermudagrass hay, mixed diet of 60% bermudagrass hay plus 40% concentrate) for 6 and 24h, respectively. Substrates were grouped into pairs for separate incubations. Monosodium fumarate was added to incubation tubes to achieve final concentrations of 0, 5, and 10mM fumarate. More ammonia accumulated at the end of incubation with added ammonium bicarbonate. Ammonia concentration was higher for peptide compared with amino acid incubation, and for casein peptide compared with gelatin peptide. Addition of fumarate linearly decreased ammonia for all N sources and for feed substrates. For all substrate types, fumarate treatment increased acetate, propionate, and total volatile fatty acids (VFA), decreased acetate to propionate ratio, and tended to reduce branched-chain VFA. Digestion of feed neutral detergent fiber (NDF) by rumen microorganisms was improved by fumarate along with elevated endoglucanase and xylanase activities. In an animal metabolism experiment, 8 dairy does (4 per treatment) were used in a completely randomized design for 21 d. Does were fed a hay plus concentrate diet without (control) or with fumarate (6 g/head per day) supplementation to determine feed intake, whole-tract nutrient digestibility, and N utilization. Fumarate treatment did not affect weight change or feed intake but increased whole-tract digestion of gross energy, crude protein, and cellulose. Digested N was increased by fumarate supplementation; however, N retention was unaffected. Plasma glucose concentration was elevated with fumarate but urea N concentration remained unchanged. Fumarate addition had significant effects on rumen microbial fermentation by decreasing ammonia and branched-chain VFA, and by increasing acetate and propionate, and NDF digestion. These effects were reflected in the improvement in whole-tract gross energy, crude protein, and cellulose digestion and elevated plasma glucose concentration when dairy does were supplemented with fumarate.

The relationship between the levels and function of endothelial progenitor cells and factor V Leiden and protein C deficiency in patients with primary Budd-Chiari syndrome.

OBJECTIVE: Budd-Chiari syndrome (BCS) is a life-threatening hepatic disease characterized by hepatic venous obstruction at the level of hepatic vein, hepatic venules, or inferior vena cava. No evidence reported the relationship between the endothelial progenitor cells and the deficiency of factor V Leiden and protein C in patients with primary Budd-Chiari syndrome. PATIENTS AND METHODS: We recruited participants between June 2014 and July 2015. For primary BCS group, 28 patients were collected. 20 patients were included in the NAFLD group. Another 73 healthy participants were recruited into the control group. None of the patients and participants had received interventional therapy or had undergone surgery prior to being recruited. Levels and functions of endothelial progenitor cells (EPCs) were examined. The factor V Leiden mutation, protein C deficiency and protein S deficiency were evaluated. Finally, the relationship between the levels and function of endothelial progenitor cells and factor V Leiden and protein C deficiency in patients with primary Budd-Chiari syndrome was analyzed. RESULTS: The results showed that no significant differences were found between the BCS (and NAFLD) and control group considering age, sex, BMI, smoking (p>0.05 for variables). However, significant differences were observed in TG, TC, HDL-C, white blood cells, hemoglobin, ALT, AST, ALP, γ-GT, total bilirubin, and albumin (p<0.05 for variables). Compared with the healthy participants, significant downregulation was found in BCS and NAFLD patients regarding CD34+/CD45-, late outgrowth endothelial cells (OECs) colonies, OECs proliferation, and OECs tubulogenesis (p<0.001 for variables). Among the 28 BCS patients, factor V Leiden mutation (n=10, 35.71%, OR 12.67, 95% CI 5.24-27.93) and hereditary protein C deficiency (n=4, 14.29%, OR 7.48, 95% CI 2.02-21.43) were more prevalent than those in the control group. These results suggested that factor V Leiden mutation and protein C deficiency were major risk factors for BCS. Finally, we demonstrated that factor V Leiden and protein C deficiency may negatively regulate the OECs levels and functions in BCS patients. CONCLUSIONS: It's important to improve the OECs levels and functions, and to prevent the deficiency of factor V Leiden and protein C in the treatment of BCS.

Vertebral osteonecrosis: MR imaging findings and related changes on adjacent levels.

BACKGROUND AND PURPOSE: No prior report has comprehensively discussed the intravertebral vacuum cleft sign and the fluid sign on MR images of vertebral osteonecrosis. The purpose of this study was to investigate MR images of osteonecrotic vertebral bodies and adjacent intervertebral disks and vertebral bodies. METHODS: We retrospectively reviewed MR images of patients with vertebral osteonecrosis. Affected vertebral bodies with osteonecrosis were defined as an avascular area (nonenhanced area on enhanced T1-weighted images) with collections of intravertebral fluid (hyperintense signal on T2-weighted images), air (signal void on all images), or both. The degree of vertebral collapse was classified as mild (>50%) or severe (<50%) preserved vertebral height. Changes in adjacent intervertebral disks or vertebral bodies 2 above and 2 below the affected vertebrae were compared. RESULTS: We enrolled 112 patients (30 men, 82 women; 121 vertebral bodies) in our study. Intravertebral air alone was observed in 48 involved levels (39.7%), intravertebral fluid alone was found in 47 (38.8%), and both coexisted in 26 (21.5%). Degree of vertebral collapse in affected vertebral bodies significantly differed with presence of air or fluid (P < .05). Vertebral compression fractures adjacent to the affected vertebral bodies were more common in those with intravertebral air alone than in those with intravertebral fluid alone (P < .05). CONCLUSION: Vertebral collapse was more advanced and adjacent vertebral compression fractures were more frequent in patients with intravertebral air than in those with intravertebral fluid.

Childhood obesity, gender, actual-ideal body image discrepancies, and physical self-concept in Hong Kong children: cultural differences in the value of moderation.

Childhood obesity is increasingly prevalent in Western and non-Western societies. The authors related multiple dimensions of physical self-concept to body composition for 763 Chinese children aged 8 to 15 and compared the results with Western research. Compared with Western research, gender differences favoring boys were generally much smaller for physical self-concept and body image. Objective and subjective indexes of body fat were negatively related to many components of physical self-concept, but--in contrast to Western research--were unrelated to global self-esteem and slightly positively related to health self-concept. In support of discrepancy theory, actual-ideal discrepancies in body image were related to physical self-concept. However, consistent with the Chinese cultural value of moderation, and in contrast to Western results, being too thin relative to personal ideals was almost as detrimental as being too fat. The results reflect stronger Chinese cultural values of moderation and acceptance of obesity than in Western culture and have implications for social and educational policy in China.

Histone Acetylation and Plant Development.

Reversible histone acetylation and deacetylation at the N-terminus of histone tails play a crucial role in regulation of gene activity. Hyperacetylation of histones relaxes chromatin structure and is associated with transcriptional activation, whereas hypoacetylation of histones induces chromatin compaction and gene repression. Histone acetylation and deacetylation are catalyzed by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. Emerging evidences revealed that plant HATs and HDACs play essential roles in regulation of gene expression in plant development and plant responses to environmental stresses. Furthermore, HATs and HDACs were shown to interact with various chromatin-remodeling factors and transcription factors involved in transcriptional regulation of multiple developmental processes.

Cloning and characterization of the 5'-flanking region of metallothionein-I gene from Chinese hamster ovary cells.

The 5'-flanking region of the Chinese hamster ovary metallothionein-I gene (MT-I) was isolated and sequenced. This region contains several cis-regulatory sequences, including metal-responsive element (MRE), AP1-binding site, Sp1-binding site and glucocorticoid-responsive element (GRE). These elements are located within 250 bases upstream of the transcription initiation site, as determined by primer extension. This region was fused with a reporter gene that could be activated by the challenge of cadmium only when the MREs were present. Thus, the isolated DNA is the promoter region of the CHO MT-I gene.

Molecular cloning of Chinese hamster metallothionein II gene and its 5' flanking region.

A genomic DNA clone containing Chinese hamster metallothionein II (MTII) gene and its 5' flanking region was isolated from Cd resistant Chinese hamster ovary (CHO) cells. DNA sequence analysis showed that there are three exons and two introns in the structure of the MTII gene. Further characterization of the 5' flanking region reveals the possible transcription initiation site, metal responsive element and basal-level enhancer sequence. Putatively, this is the promoter region of CHO MTII gene.

Self-perception of physical competences in preadolescent overweight Chinese children.

OBJECTIVE: To compare self-perceptions of physical competences in overweight and in normal weight preadolescent Chinese children. DESIGN: Cross-sectional study. SETTING: Three primary schools and a university hospital in Hong Kong. SUBJECTS: A total of 634 children, comprising 558 (462 normal weight, 96 overweight) aged 8-12 y randomly sampled from three primary schools, and 76 similar age overweight children recruited from the community for a diet and exercise intervention programme. MEASUREMENTS: Height, weight and percentage body fat were measured. Self-perceptions of physical competences were determined by Physical Self-Descriptive Questionnaire (PSDQ). Corresponding actual physical competences were measured by physical fitness tests. RESULTS: Overweight children perceived themselves to have significantly more body fat than normal weight children, with poorer appearance, sports competence, endurance, coordination, flexibility, overall physical self-concept and self-esteem, but to be no less healthy, no less physically active and no less strong. Overweight children performed less well than normal weight children in measures of endurance, coordination and flexibility but better in strength. Poor self-perception of physical competences appeared only partly related to deficiencies in actual physical competences. CONCLUSION: Overweight children have poorer self-perception of their physical competences but do not perceive themselves to be less strong, healthy or physically active than normal weight children. Exercise programmes for overweight children could be more effective if designed with the knowledge of these self-perceptions.

Chain of rings: a radiographic sign of papillary thyroid cancer.

Papillary thyroid cancer is the most common form of thyroid malignancy in children and adult with frequent metastases to the cervical lymph nodes. We present a case of metastatic papillary thyroid cancer with remarkable imaging findings of consecutive metastatic calcified lymph nodes resembling a chain of rings. While accompanying by a coarsely calcified thyroid mass, possible thyroid cancer should be considered and serve as a guide to warrant further thyroid cancer evaluation.

Metal-induced metallothionein gene expression can be inactivated by protein kinase C inhibitor.

The effects of protein kinase C (PKC) inhibitors on the metallothionein (MT) gene expression induced by metals were investigated. When PKC inhibitor (H7 or chelerythrine) was administered to Cd resistant, MT gene-amplified Chinese hamster ovary (CdR) cells, the induction of MT mRNA by Cd or Zn was blocked. Treating the CdR cells with a PKA-specific inhibitor, HA1004, did not cause an inhibition of metal-induced MT gene transcription. The inhibitory effect was effectuated by adding inhibitors within 40 min of exposing the cells to Cd. Apparently, AP1 was not involved in this down-regulatory effect of PKC inhibitor on MT gene expression since the inducibility of MT promoter was blocked by H7 even in the absence of the AP1-binding sequence. For Cd-treated cells, Cd accumulation in the cell was similar with or without H7 treatment. However, H7 markedly reduced cellular Zn accumulation when the cells were treated with Zn. Cycloheximide treatment increased the level of MT mRNA. This elevation can also be blocked by treating the cell with PKC inhibitor. Results in this study suggest that PKC participates in the process of metal-induced MT gene expression.

A study on beams passing through hip prosthesis for pelvic radiation treatment.

PURPOSE: To study the dose distributions at the interface due to the presence of a metal implant; to show the dose distributions in combined fields in the presence of hip prostheses; and to demonstrate the capabilities and limitations of a conventional system. METHODS AND MATERIALS: Perturbations in the dose distribution caused by a hip prosthesis can result in unacceptable dose inhomogeneities within the target volume and in regions where tissues interface with implant. The Monte Carlo technique and a conventional treatment planning system are used to calculate the dose distributions. RESULTS: Dose increases of 15% in tissue are seen at the interface between metal implant and tissue. Dose reductions of 5-25% or 10-45% are observed in the shadow of the hip prosthesis made of 0.5-3-cm-thick titanium or steel alloy respectively. We compared predicted dose distribution between the Monte Carlo simulation and a commercial treatment planning system (CADPLAN). We found that CADPLAN underestimated the attenuation of hip prostheses. This has led to overestimation of the target dose by 14% for a typical four-field box technique. CONCLUSIONS: An acceptable dose distribution can be achieved with a proper lateral beam weighting and compensation using an eight-field technique. The beam compensation may be applied to achieve an adequate target dose.

Specific terminal DNA replication sequence of X chromosomes in different tissues of a live-born triploid infant.

Using the thymidine pulse method, DNA replication kinetics were studied on cells derived from cartilage, gonad, lymphocytes, and skin of a live-born triploid (69,XXY) infant with typical clinical findings. Replication studies showed that 3% of the lymphocytes had one early and one late replicating X, and 97% of the lymphocytes, and cartilage, gonad, and skin cells had two early replicating X's. Asynchronous DNA replication between the two early replicating X's was observed in all tissues (range 25-40%). The predominant terminal replication sequence of X chromosomes from chondrocytes, gonad, and skin fibroblast differed from that of the lymphocytes. Thus, a tissue-specific DNA replication pattern of the early-replicating X chromosome may be present. In every tissue, the last band to complete DNA replication was Xq21. Polymorphisms of metaphase chromosomes of parents and the patient were studied by Q-banding. The possible origin of the extra haploid set of chromosomes is discussed.

DNA replication sequence in a dicentric (functionally monocentric) X chromosome formed by the joining of two X chromosomes at region p22.

In this study we used densitometry to evaluate DNA replication kinetics in a rearranged chromosome formed by the joining of two X chromosomes at region p22. No 45X mosaicism is present in peripheral blood or fibroblast cultures. The patient has primary amenorrhea, short stature, and gonadal dysgenesis. The sequence of replication in the majority of cells is p11, q11, q13, q22-24, q12, p22, q26, q28, q27, q25, and p21, q21. Thus p11 is the earliest region to replicate, and q21 is the last. In 66% of 127 cells analyzed, the replication pattern is asymmetric, and bands q12, q26, and q28 are most likely to be out of phase on the two sides of the breakpoint. We find that band p22 has a delay of replication compared to an abnormal X derived from two X chromosomes joined at the q23 region previously reported by us. Structural rearrangement may therefore delay replication in the region of the break.

Determination of percentage depth-dose curves for electron beams using different types of detectors.

According to the new AAPM TG-51 dosimetry protocol, reference dosimetry for electron beams is performed at depth of d(ref)=0.6R50-0.1 (cm) instead of d(max) recommended in TG-21. In clinical practice most electron beams are normalized at d(max). Therefore it becomes more important to get an accurate percentage-depth-dose (%dd) curve particularly for higher-energy electron beams in which the depth d(ref) is away from d(max). When ionization chambers are used in determining %dd curves the water-to-air stopping-power ratios and the fluence correction factors are required. The TG-51 recommends that the stopping-power ratios for realistic electron beams be used instead of the monoenergetic stopping-power ratios used in TG-21. This investigation aims to study the effects of those correction factors on the determination of %dd curves. We observed 1% deviations in the value of %dd at d(ref) for 15 and 18 MeV beams between a plane-parallel NACP and a cylindrical IC-10 chamber without considering the fluence correction factors P(fl). We explored a method to derive the fluence correction factors at any depth by using the existing fluence correction data at d(max) and tested its feasibility. We compared %dd curves measured by a diode detector and a NACP chamber with stopping-power ratios recommended by TG-51 and those recommended by TG-21. We found that for 15 and 18 MeV beams the difference in the values of %dd at d(ref) between using those two different stopping-power ratios is about 0.5%. Excellent agreement is found between %dd curves measured by the diode and by the NACP chamber when the stopping-power ratios recommended by TG-51 are used.

Head-up tilt test without intravascular cannulation in children and adolescents.

Previous studies of head-up tilt test have shown that testing at high degrees lacks specificity in children. We suspected that the high false positive rate might be related to the intravascular catheter and other maneuvers incorporated in the test and therefore studied the sensitivity and specificity of standing and HUT at 80 degrees without any invasive procedure and other maneuvers in children and adolescents. Twenty three patients (11.8+/-2.7 years) with recurrent typical neurally mediated syncope and 35 normal control children (11.6+/-3.0 years) underwent motionless standing for 15 min and tilting to 80 degrees for 30 min. Continuous finger arterial pressure monitoring and ECG were performed during the test. Eight (35%) of the 23 patients developed symptoms of near syncope during motionless standing. Thirteen (57%) of them had positive results at 80 degrees tilting for 30 min. The symptoms of syncope were not always corresponding to excessive haemodynamic changes. None of the controls developed any symptoms or excessive hemodynamic changes. Without intravascular instrumentation and other autonomic maneuvers, active motionless standing or HUT at 80 degrees for 30 min is highly specific but of limited sensitivity for the investigation of vasovagal syncope.