Objective To investigate the value of the senile degenerative aortic valve calcification (AVC) and to analyze the correlative risk factors by color Doppler echocardiograph.Methods Aortic valves of 110 cases with AVC (study group) and 110 cases without AVC (control group) were observed by color Doppler echocardiograph.All the patients with AVC have been excluded of congenital and other acquired valves' diseases.The aortic valve' s shape and the diameters of aortic root were measured.At the same time,the peak systolic and diastolic velocities of aorta were detected.The different features were compared between the two groups.Results Test results showed significant differences in study group:Anteroposterior diameter of aortic annulus and the area of aortic valve were decreased by calcification; The anteroposterior diameter of aortic sinus increased and aorta transvalvular pressure gradient augmented; Detection rate of atherosclerosis (AS) of aorta and the peripheral artery stenosis of the study group were higher than that of control group; The AS increased pulse pressure and aggravated AVC; Correlative risk factors,in addition to age,included hypertension,hypercholesterolemia,osteoporosis,and so on.The correct diagnosis of the correlated diseases were on the basis of clinical examines.The rate of AVC with multi-factor was higher than that with single-factor.In addition,gender difference and the diameters of ascending aortic showed no significant difference in two groups.Relationship between diabetes of correlative factors and the rate of AVC showed no significant difference in two groups.Conclusion Morphologic abnormality and malfunction of aortic valve and the large artery in elder patients were caused by senile degenerative AVC.The more correlative risk factors,the worse showed.

Objective To investigate the possible association of circulating components of GH-IGFs-IGFBPs system with the GHR-exon 3 genotype in idiopathic short stature (ISS) children. Methods Genomic DNA was extracted and isolat-ed from peripheral leukocytes in 108 ISS children. GHR-exon 3 polymorphism was analyzed with multiplex poly-merase chain reactions (PCR) assay. According to the results of genotype, ISS children were divided into GHRfl group and GHRd 3 group. The height and weight were recorded in two groups. The body mass index (BMI) and BMI standard deviation score (SDS) were measured. The serum levels of insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3, IGF-1 SDS and IGFBP3 SDS were calculated. GH stimulation test was used to measure the serum GH peak value. Fifty-five ISS chil-dren were treated with recombine human GH [0.15 IU/(kg·d)] for three months to analyse the association of IGF-1 response of GH treatment and genotypes. Results There were 63 GHRfl and 45 GHRd3 in 108 ISS children. There were no signifi-cant differences in BMI, IGF-1, IGFBP3, GH peak, IGF-1 SDS and IGFBP3 SDS between two groups (P>0.05). Multiple stepwise regression analysis showed that age, IGFBP3, lg (BMI) and lg (GH peak) were influencing factors of lgIGF-1 (P<0.05). In 55 ISS children treated with rhGH, there were 34 cases of GHRd3. The differences of △IGF-1 and △IGF-1 SDS were higher in GHRd3 group than those of GHRfl group (n=21). Conclusion The GH sensitivity may be a risk factor in ISS children, which may not be related with GHR polymorphism.

Objective To explore the curative effects of mesenchymal stem cells(MSC)that overexpress in murine type 1 diabetes nephropathy (DN).Methods Mice were randomly divided into normal control(NC) group,DN group,C3-treated group,C3-MIGR1-treated group and C3-MIGR1-ICAM-1-treated group.Mice were given streptozotocin until the DN model was set up.The murine DN model was treated with murine MSC(C3H10T1/2),transfection empty vector of murine MSCs(C3H10T1/2-MIGR1/MSC) and murine MSCs (C3H10T1/2-ICAM-1/MSC)that overexpressed ICAM-1.After transplantation, the pathological features of kidneys were observed by Masson staining and the number of homing MSC cells to the kidney was calculated on days 1,3,7 by frozen section, while qPCR was used to analyze the expression of signaling molecules for collagen1, TGF-β1 and SMAD2 after treatment with various MSCs.Results Compared with DN group, the renal fibrosis treated with MSCs overexpressing ICAM-1 was significantly decreased by Masson staining.Three and seven days after transplant, the homing cells of MSC in different groups displayed no difference using tissue freezing section method.Furthermore, TGF-β1/SMAD signaling was lowly activated after the treatment with MSCs that overexpressed ICAM-1 compared with model mice(P<0.01).Conclusion MSCs that overexpress ICAM-1 can protect kidneys in the DN model.

Objective　To explore the characteristics of toxic heavy metal pollution in atmospheric PM2.5 (Particulate matter 2.5) during winter in Nanning City and to evaluate the health risks for the population. Methods　Atmospheric PM2.5 samples were continuously collected in the urban areas of Nanning from January to February 2019. The concentrations of seven toxic heavy metals, including cadmium (Cd), arsenic (As), chromium (Cr), lead (Pb), nickel (Ni), mercury (Hg), and manganese (Mn) in atmospheric PM2.5 were analyzed by X-ray fluorescence spectrometry. The pollution characteristics of toxic heavy metals were studied by geo-accumulation index and enrichment factor methods, and their health risks to children and adults were assessed using the health risk assessment model of the United States Environmental Protection Agency. Results　The mass concentration of atmospheric PM2.5 in Nanning in winter 2019 was (44±29) μg/m3, which was generally at a low level. Different degrees of pollution were found for Hg, Cd, As, Cr, and Pb in PM2.5, with Hg and Cd being more seriously polluted. Hg and Cd were highly enriched in PM2.5, followed by Pb with moderate enrichment. These three elements mainly originated from man-made pollution. As, Cr and Ni were mildly enriched and affected by both natural and anthropogenic sources. The non-carcinogenic risks were in the order of As>Pb>Hg>Cr>Cd>Mn>Ni. The total non-carcinogenic risks for the three populations were all less than 1, which is within acceptable limits. The carcinogenic risks were ranked as Cr>As>Cd>Ni, with Cr, As, and Cd posing carcinogenic risks to children and adults ranging from 1×10-6 to 1×10-4. Moreover, the total carcinogenic risks of heavy metals (Cr, As, Cd, and Ni) were higher than 1×10-4 for children, indicating a potential carcinogenic risk. Conclusions　The mass concentration of PM2.5 and heavy metal elements in Nanning City during the winter of 2019 was relatively low, but the pollution of heavy metals still exists. The non-carcinogenic risk of heavy metals is within an acceptable range, but the carcinogenic risk poses a potential danger to children.

Objective To compare the efficacy of contrast-enhanced ultrasound (CEUS) and enhanced CT (CECT) in differential diagnosis of benign and malignant space-occupying lesions of gallbladder.Methods The clinical data of 68 cases of space-occupying lesions of gallbladder confirmed by surgery and biopsy were retrospectively analyzed.The diagnostic accuracy,sensitivity and specificity of CEUS and CECT were analyzed and compared.Results In a total of 68 cases of space-occupying lesions of gallbladder,31 cases were benign lesions and 37 were malignant lesions (gallbladder cancer).For the benign lesions cases,CEUS and CECT were mainly hyper-enhanced in the early stage of enhancement,which were 90.3％ and 83.9％,respectively.In the late stage of enhancement,they were mostly low-enhanced,which were 93.5％ and 87.1％,respectively.For the gallbladder cancer cases,CEUS and CECT were predominantly hyper-enhanced in the early stage of enhancement,which were 94.6％ and 89.2％,respectively,and were all low-enhanced in the late stage of enhancement.In the differential diagnosis for benign and malignant space-occupying gallbladder lesions by CEUS,the differences in peak time,extinction time,peak intensity and average transit time were statistically significant (all P＜0.01).The inhomogeneous enhancement rates were 41.9％ and 48.4％ respectively for CEUS and CECT in the benign lesions cases,and 94.6％ and 91.9％ in the gallbladder cancer cases.Besides,the incomplete gallbladder wall rates are 89.2％ and 91.9％ in the gallbladder cancer cases.However,these differences were all not statistically significant (all P＞0.05).In the diagnosis of benign and malignant lesions cases,the diagnostic accuracy of CEUS and CECT were 92.6％ and 89.7％,the sensitivity was 93.5％ and 90.3％,and the specificity was 89.2％ and 83.8％,respectively,but the differences were not statistically significant (all P＞0.05).Conclusion CEUS and CECT have comparable efficacy in differential diagnosis of benign and malignant space-occupying lesions of gallbladder.CEUS has advantages over CECT and is worthy of extensive clinical application and promotion.

Biologically important proteins related to membrane receptors, signal transduction, regulation, transcription, and translation are usually low in abundance and identified with low probability in mass spectroscopy (MS)-based analyses. Most valuable proteomics information on them were hitherto discarded due to the application of excessively strict data filtering for accurate identification. In this study, we present a staged-probability strategy for assessing proteomic data for potential functionally important protein clues. MS-based protein identifications from the second (L2) and third (L3) layers of the cascade affinity fractionation using the Trans-Proteomic Pipeline software were classified into three probability stages as 1.00-0.95, 0.95-0.50, and 0.50-0.20 according to their distinctive identification correctness rates (i.e. 100%-95%, 95%-50%, and 50%-20%, respectively). We found large data volumes and more functionally important proteins located at the previously unacceptable lower probability stages of 0.95-0.50 and 0.50-0.20 with acceptable correctness rate. More importantly, low probability proteins in L2 were verified to exist in L3. Together with some MS spectrogram examples, comparisons of protein identifications of L2 and L3 demonstrated that the staged-probability strategy could more adequately present both quantity and quality of proteomic information, especially for researches involving biomarker discovery and novel therapeutic target screening.
Databases, Protein ; Mass Spectrometry ; Probability ; Proteins ; chemistry ; metabolism ; Proteomics ; Software

Objective:To analyze the clinical features, genetic characteristics, treatment and follow-up results of patients with hydrocephalus caused by methylmalonic acidemia combined with homocysteinuria, and to discuss the optimal strategies for assessing and treating such patients.Methods:From January 1998 to December 2020, 76 patients with hydrocephalus due to methylmalonic acidemia combined with homocysteinuria in the Department of Pediatrics in 11 hospitals including Peking University First Hospital were diagnosed by biochemical, genetic analysis and brain imaging examination. The patients were divided into operation-group and non-operation-group according to whether they underwent ventriculoperitoneal shunt. The clinical features, laboratory examinations, genotype, and follow-up data were retrospectively analyzed. Data were compared between the two groups using rank sum test, and categorical data were compared using χ 2 test. Results:Among the 76 patients (51 male, 25 female), 5 were detected by newborn screening, while 71 were diagnosed after clinical onset, 68 cases (96%) had early-onset, 3 cases (4%) had late-onset. The most common clinical manifestations of 74 cases with complete data were psychomotor retardation in 74 cases (100%), visual impairment in 74 cases (100%), epilepsy in 44 cases (59%), anemia in 31 cases (42%), hypotonia or hypertonia in 21 cases (28%), feeding difficulties in 19 cases (26%) and disturbance of consciousness in 17 cases (23%). Genetic analysis was performed in 76 cases, all of whom had MMACHC gene variations, including 30 homozygous variations of MMACHC c.609G>A. The most common variations were c.609G>A (94, 62.7%), followed by c.658_660del (18, 12.0%), c.567dupT (9, 6.0%) and c.217C>T (8, 5.3%). Therapy including cobalamin intramuscular injection, L-carnitine and betaine were initiated immediately after diagnosis. A ventriculoperitoneal shunt operation was performed in 41 cases (operation group), and 31 patients improved after metabolic intervention (non-operation group). There was no significant difference in the age of onset, the age of diagnosis, the blood total homocysteine, methionine, and urinary methylmalonic acid concentration between the two groups (all P>0.05). The symptoms of psychomotor development, epilepsy, and visual impairments improved gradually after a long-term follow-up in the operation group. Conclusions:Hydrocephalus is a severe complication of methylmalonic acidemia combined with homocysteinuria. The most common clinical manifestations are psychomotor retardation, visual impairment, and epilepsy. It usually occurs in early-onset patients. Early diagnosis and etiological treatment are very important. Hydrocephalus may improve after metabolic intervention in some patients. For patients with severe ventricular dilatation, prompt surgical intervention can improve the prognosis.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective:To investigate the factors affecting phenotypes in the patients of methylmalonic acidemia combined with homocysteinemia cblC type with MMACHC c. 609G>A homologous variant. Methods:A retrospective study on the clinical manifestations, complications, treatment, and outcome in 164patients of cblC type with MMACHC c. 609G>A homologous variant was conducted.The patients were diagnosed by biochemical and genetic analysisfrom January 1998 to December 2020. Results:Among the 164 patients, 2 cases were prenatally diagnosed and began treatment after birth. They are 3 and 12 years old with normal physical and mental development. Twenty-one cases were diagnosed by newborn screening. Among them, 15 cases had with normal development. They were treated fromthe age of two weeks at the asymptomatic period. Six cases began treatment aged 1 to 3 months after onset. Their development was delayed. One hundred and forty-one cases were clinically diagnosed. Their onset age ranges from a few minutes after birth to 6 years old. 110 cases had early-onset (78.0%). 31 cases had late-onset (22.0%). Five of them died. 24 patients lost to follow-up. Of the 141 clinically diagnosed patients, 130 (92.2%) with psychomotor retardation, 69 (48.9%) with epilepsy, 39 (27.7%) with anemia, 30 (21.3%) had visual impairment, 27 (19.1%) had hydrocephalus, 26 (18.4%) had feeding difficulties, 7 (5.0%) with liver damage, and 5 (3.5%) with metabolic syndrome. The frequency of hydrocephalus and seizures was significantly higher in the early-onset group. The urinary methylmalonic acid increased significantly in the patients with epilepsy. During the long-term follow-up, the level of plasma total homocysteine in the seizure-uncontrolled group was significantly higher than that in the seizure-controlled group, the difference had a statistical significance ( P<0.05). Conclusion:Most of the patients with MMACHC c. 609G>A homozygous variant had early-onset disease, with a high mortality and disability rate. If not treated in time, it will lead to neurological damage, resulting in epilepsy, mental retardation, hydrocephalus, and multiple organ damage. Pre-symptomatic diagnosis and treatment are crucial to prevent irreversible neurological damage. Neonatal screening and prenatal diagnosis are important to improve the outcome of the patients.

Objective:To investigate the status of height and weight of 3-18-year-old children and adolescents in urban China, and to provide a basis for establishing puberty phase specific curves for age-specific height and age-specific weight.Methods:A cross-sectional survey of 218 185 children and adolescents aged 3-18 years in urban China was conducted by using the method of stratified random cluster sampling from January 2017 to December 2019. The sampling areas included 12 provinces municipalities in China and autonomous regions in total. Data were collected on weight, height, waist circumference, hip circumference and secondary sexual characteristics. The generalized additive model for location, scale, and shape (GAMLSS) was employed to establish percentile reference values and growth curves of height and weight for boys and girls aged 3-18 years. Wilcoxon rank sum test was applied to compare the P 50 value of height and weight between children of each Tanner stage and children of the same age ignoring the different puberty phase. Results:The 3rd, 50th, and 97th percentile curves for height and weight for age were developed for boys and girls aged 3-18 years. The 3rd, 50th, and 97th percentile curves for age-specific height and age-specific weight for each puberty phase were developed for boys and girls. Compared with all children ignoring the different puberty phase, boys aged 9 and over and girls aged 7 and over who are at Tanner stage 1 showed shorter height and lighter weight than those of the same age group (all P<0.01), the difference ranges of height at P 50 are -4.0 to -0.6 cm for boys, and -4.4 to 0.5 cm for girls; the difference ranges of weight are -4.8 to 0.4 kg for boys, and -4.0 to -0.3 kg for girls; children at Tanner stage 2 & 3 initially were taller and heavier than those of the same age group; and later grew shorter and lighter than those of the same age group, the two sets of curves cross over; boys aged 16 and under and girl aged under 14 who are at Tanner stage 4 were taller and heavier than those of the same age group (all P<0.01), the difference ranges of height at P 50 are 0.2 to 10.0 cm for boys, and 0.2 to 9.4 cm for girls; the difference ranges of weight at P 50 are 0.7 to 10.9 kg for boys, and 1.0 to 11.2 kg for girls, and the differences showed narrowing trend with age. Conclusion:The puberty phase specific growth curves of age-specific height and age-specific weight for boys and girls aged 3-18 years are established, it is useful for clinical work to evaluate physical development of children at different puberty phases.