Identification of Prognostic Related Hub Genes in Clear-Cell Renal Cell Carcinoma / 中国医学科学杂志(英文版)

Objective To identify new genes that correlate with prognosis of clear-cell renal cell carcinoma (ccRCC)

Comparison and correlation analysis of sleep parameters between watch-type sleep monitor (Actiwatch) and polysomnography / 北京大学学报(医学版)

OBJECTIVE@#With the rapid development of sleep medicine, there are various methods for detecting sleep diseases. This study compared the correlation between the lightweight watch-type sleep monitor (Actiwatch) and the "gold standard" polysomnography (PSG) in the Chinese population, in order to provide a basis for clinical application.@*METHODS@#From August 2018 to December 2019, 121 subjects who simultaneously performed sleep breathing monitoring (PSG) and wearing a watch-type sleep monitor (Actiwatch) in the Sleep Center of Peking University People's Hospital were enrolled. All subjects received PSG and Actiwatch at the same time, and filled out the sleep diary next morning. Monitoring indicators were collected for linear correlation analysis and paired t test to compare the differences.@*RESULTS@#Under low sensitivity conditions, the correlation coefficient of total sleep time (TST) between PSG and Actiwatch was 0.53 (P < 0.05). Paired t test analysis showed that there was no significant difference between the TSTs of Actiwatch and PSG (t=-0.890, P=0.36). According to age stratification, the smaller the age, the stronger the correlation between the TSTs of Actiwatch and PSG, and the coefficient could be up to 0.92 (P < 0.05). Paired t test showed that there was no significant difference between them (t=-1.057, P=0.35). According to the stratification by diagnosis, the correlation coefficient between the TSTs of Actiwatch and PSG in normal PSG group could be as high as 0.79 (P < 0.05), the results of paired t test showed that there was no significant difference between the TSTs of Actiwatch and PSG in normal PSG group (t=-0.784, P=0.44).@*CONCLUSION@#As a wearable home recorder, when the analysis parameters of Actiwatch were set as low sensitivity, PSG and Actiwatch had the highest TST correlation. The younger the age, the stronger correlation between the TSTs of Actiwatch and PSG. The PSG and Actiwatch subjects with normal PSG presentation had a higher TST correlation.

Advances on the role of miRNAs in the formation of alcoholic fatty liver / 解放军医学杂志

Alcoholic fatty liver disease (AFLD) is a pathological change of liver steatosis caused by long-term heavy alcohol consumption. The mechanism of AFLD formation mainly includes abnormal lipid metabolism, immune-inflammatory reaction, intestinal flora imbalance, alcohol metabolism enzyme disorder and so on. In recent years, numerous studies have confirmed that microRNA (miRNA) plays an important role in diagnosis and treatment of many diseases, the molecular regulatory mechanism of miRNAs involved in AFLD formation has also become a research focus. The majority of studies have explored the role of miRNAs in AFLD formation by exploring the targeting role of miRNAs of key genes in the formation pathway of AFLD, and establishing an expression network with genes that promote or inhibit the expression of downstream genes of this signaling pathway. In present paper, the important miRNAs in the formation pathway of AFLD and their regulatory mechanisms in AFLD are reviewed, so as to provide theoretical basis for further understanding the function of miRNAs and its relevant mechanisms in AFLD.

Quality control of Dandeng Tongnao Ruanjiaonang based on UPLC fingerprint combined with chemical pattern recognition / 中国中药杂志

To establish the ultra performance liquid chromatography (UPLC) fingerprint of Dandeng Tongnao Ruanjiaonang and conduct a systemic, comprehensive quality evaluation of the drug by combining with a chemical pattern recognition method. In this study, Waters UPLC ultra-high performance liquid chromatography instrument and ACQUITY UPLCHSS T3 chromatographic colum n were employed to perform the separation with acetonitrile-0.1% formic acid aqueous solution as the mobile phase for gradient elution; and the detection wavelength was set at 256 nm to establish the UPLC fingerprint of 10 batches of Dandeng Tongnao Ruanjiaonang. Then, the further quality assessment of the drug was carried out by similarity evaluation, Cluster Analysis(CA), Principal Component Analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Finally, 77 peaks were recognised as common peaks in the fingerprint, and 15 peaks of them were identified using standard references. The similarity value of these 10 batches of drugs was all above 0.960, indicating a relatively stable quality. But minor differences were still discovered between the batches of the drug by CA and PCA. Finally, 6 common peaks were recognised as the quality makers using OPLS-DA method. The analysis method established in this study was scientific, accurate, reliable and simple; fingerprint combined with chemical pattern recognition technique can be used to systematically and comprehensively evaluate the drug quality of Dandeng Tongnao Ruanjiaonang; what's more, it could also provide a reference for the quality control of traditional Chinese medicine and its preparations at the same time.

Study on chemical constituents of Tiandan Tongluo Capsule based on UPLC-Q-Orbitrap HRMS / 中草药

Objective: To clarify the chemical constituents of Tiandan Tongluo Capsule and establish a precise and effective identification method for the complex composition of TCM. Methods: This objective was achieved mainly depending on the information of the accurate mass and the multistage fragment ions obtained by ultra-high performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry (UPLC-Q-Orbitrap HRMS), comparing the relative retention time and the mass spectrometric data of the standard substance and consulting the reference literature. Results: Forty compounds were identified in this study, including the phenoliacids, anthraquinones, flavones, phthalides, fatty acids, and the others. Conclusion: This study can identify various chemical constituents of Tiandan Tongluo Capsule systematically, accurately, and rapidly. Moreover, the scientific theory basis will be provided for the pharmacodyamic material basis and the quality control of this drug at the same time.

Mechanism of Xuebijing Injection in anti-acute lung injury based on network pharmacology / 中草药

Objective: To predict the action targets of anti-acute lung injury active ingredients of Xuebijing Injection, and investigate the “multi-components, multi-targets, and multi-pathways” mechanism. Methods: Reverse molecular docking was used to forecast its targets of 38 main active components of Xuebijing Injection. The relevant targets of acute lung injury were searched through literature mining and multiple databases and compared with the predicted component targets. The protein interaction network was constructed by Cytoscape software, and topological analysis was performed to screen the key targets of anti-acute lung injury of Xuebijing Injection. And GO enrichment analysis and KEGG analysis were carried out on the key targets through DAVID database. Results: The network analysis indicated that 38 active ingredients affected 143 key target proteins directly or indirectly, involved in 71 biological processes, 29 cellular components, 40 molecular function, and 25 KEGG pathways. These active compounds might participate in regulating the processes of gene, protein, external stimulus, and interfering the mitogen-activated protein kinase (MAPK), phosphatidyl inositol 3-kinase (PI3K)-Akt, and other signaling pathways to play a role in resisting to acute lung injury. Conclusion: The anti-acute lung injury effect of Xuebijing Injection showed the characteristics of traditional Chinese medicine in multi-components, multi-targets, and multi-pathways. This research provides a scientific basis for elucidation of the anti-acute lung injury pharmacological mechanism of Xuebijing Injection.

Clinic study on 47 cases of Neer Ⅱ and Ⅲ proximal humeral fractures treated with proximal humeral internal locking system / 重庆医学

Objective To investigate the clinic efficacy of proximal humeral internal locking system(PHILOS) in the treatment of Neer Ⅱ and Ⅲ proximal humeral fractures.Methods From January 2013 to December 2015,a total of 47 patients with Neer Ⅱ and Ⅲ proximal humeral fractures was treated with PHILOS fixation in our hospital.The operative time,blood loss in operation,hospital stay,complications,Constant scores and radiography films were retrospectively analyzed.Results All 47 patients were followed up for an average of (19.2 ±9.6) month.The average operative time,the level of average intraoperative blood loss,the mean hospitalization time and the complication rate were(95.6 ±43.1) min,(108 ± 41.6) mL,(11.3 ±3.2) d and 14.7 ％ respectively.The Constant score was improved from(21.74 ± 8.24) preoperatively to(82.83 ± 7.21) at the last follow-up,and the difference was statistically significant(t=-36.57,P＜0.01).Conclusion Fixation with PHILOS is a safe and effective treatment for patients with Neer Ⅱ and Ⅲ proximal humeral fractures.

Total hip arthroplasty with double mobility acetabular prosthesis: a 1-year follow up / 中国组织工程研究

BACKGROUND: To solve the dislocation following hip arthroplasty, a double mobility acetabular prosthesis has been developed, and its effect still needs to be confirmed through follow-up observation.OBJECTIVE: To explore the early clinical effectiveness of total hip replacement with double mobility acetabular prosthesis.METHODS: Thirty patients admitted from January 2013 to November 2015, were given total hip replacement with double mobility acetabular prosthesis, and were then followed up for 1 year. The hip function and loosening were evaluated by Harris hip scores, Beijing program scaling and imaging examination.RESULTS AND CONCLUSION: (1) All patients were followed up for 1 year. (2) The mean Harris hip score was significantly increased from preoperatively (39.7±3.87) to postoperatively (93.6±3.82), and the mean score of the Beijing program scaling was also significantly increased from (10.5±2.46) to (17.3±1.87) (both P < 0.05). (3) All patients suffered from moderate to severe pain before replacement, and 28 patients complained mild or no pain and 2 patients with moderate pain after operation. X-ray showed a stable hip. (4) To conclude, the total hip arthroplasty with double mobility acetabular prosthesis achieves satisfactory short-term treatment outcomes, but its long-term effect needs to be observed further.

Structure elucidation of degradation products of Z-ligustilide by UPLC-QTOF-MS and NMR spectroscopy / 药学学报

Z-Ligustilide, a major phthalide isolated from a widely used traditional Chinese medicine Ligusticum chuanxiong, possesses various pharmacological activities including neuroprotective, anti-inflammatory, antiproliferative and vasorelaxing effects. However, it is unstable and inclined to degrade in natural conditions, which limits its study and application greatly. In this study, degradation behavior of Z-ligustilide and its degradation products stored at room temperature under direct sunlight were investigated and structure elucidated by HPLC-UV, UPLC-QTOF-MS and NMR. Z-ligustilide degradation and total five degradation products were generated and detected. Two degradation products were unequivocally identified as senkyunolide I and senkyunolide H by comparison with reference compounds. Another two degradation products were further isolated by semi-preparative HPLC and structure elucidated as (E)-6, 7-trans-dihydroxyligustilide and (Z)-6, 7-epoxyligustilide by 1H and 13C NMR, respectively. The degradation pathways of Z-ligustilide were finally proposed. Oxidation, hydrolysis and isomerization are the major degradation reactions.

Analysis of chemical constituents of chuanxiong rhizoma absorbed into rat brain tissues by UPLC-Q-TOF-MS / 中国中药杂志

<p><b>OBJECTIVE</b>To analyze and identify the chemical constituents in rat brain tissues after oral administration of Chuanxiong Rhizoma extracts.</p><p><b>METHOD</b>The dosed and blank rat brain tissues were analyzed by UPLC-Q-TOF-MS. Different peaks were observed in total ion chromatograms and then identified according to their retention time, accurate mass weight, MS and MS/MS data.</p><p><b>RESULT</b>After oral administration of Chuanxiong Rhizoma extracts, 3 compounds were absorbed into rat brain tissues through BBB. They were identified as senkyunolide I, senkyunolide A and ligustilide.</p><p><b>CONCLUSION</b>The study is helpful for interpreting effective substance of Ligusticum chuanxiong.</p>

Advance of studies on bioactivity of flavonoid-metal complexes / 中国中药杂志

The flavonoid-metal complexes showed obviously stronger bioactivities such as antibiosis, antivirus, anti-inflammatory, anti-tumor and anti-free-radical, possibly because of the stronger binding force caused by the change in complex structure and accessibility to target spots, or the synergy effect between flavonoids and metallic ions. This essay summarizes studies on bioactivity and mechanism of flavonoid-metal complexes, in order to provide reference for in-depth study and development on effective constituents contained in flavonoid traditional Chinese medicines.

Analyzing the occupational hazard of 258 construction projects of Shunde in 2010 and 2011 / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To understand the changing trend of occupational hazard of industries in Shunde area and to provide the scientific evidence for the prevention of occupational diseases.</p><p><b>METHODS</b>The pre-evaluation of occupational hazard was carried out for the construction projects. The data about employee number scale, industry species, occupational hazard factors, hazard levels and prevention measures for construction projects were collected and analyzed. The data of Shunde Occupational Health Survey in 2011 served as the control data.</p><p><b>RESULTS</b>There were 258 construction projects in 2010 and 2011, in which the proportions of medium and large scales increased to 8.1% and 2.4% respectively, the proportions of the furniture and chemical industries decreased from 25.6% or/and 5.1% to 2.7% or/and 1.8%, the proportions of the high-tech industries increased from 1.8% to 9.2%. The proportions of the projects with serious, medium and slight occupational hazard levels were 4.3%, 67.8% and 27.9%, respectively. The proportions of the projects with harmful chemicals, dusts and physical factors were 34.2%, 46.8%, 42.6%, respectively.</p><p><b>CONCLUSION</b>The feature of occupational hazard in Shunde industries has changed at upgrading stage. We should pay attention to the prevention of occupational diseases in high-tech industries.</p>

Research progress studies on pharmacology and pharmacokinetics of ligustilide / 中国中药杂志

Ligustilide is contained highly or around 1% in such umbelliferous plants as Angelica sinensis and Ligusticum chuanxiong, is one of main bioactive constituents. It shows many pharmacological activities related to their efficacy. At present, ligustilide has attracted extensive attention and more and more studies have been reported, indicating that it is a promising compound. This essay summarizes the progress of pharmacological effects of ligustilide on neuroprotection, vasodilatation, anti-caner and anti-tumor, analgesia and anti-inflammation, and pharmacokinetics including absorption, distribution, metabolism and excretion, providing basis for further studies and development of ligustilide.

Expression of programmed cell death 5 and apoptosis during atrophy of the parotid gland cells / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the expression and relationship of programmed cell death 5 (PDCD5) and cell apoptosis in the parotid gland after leading duct ligation in rat and elucidate the role of PDCD5 on the atophy of parotid gland.</p><p><b>METHODS</b>The Wistar rat model of leading duct ligation was established, and the samples of parotid gland were obtained from different time point (0, 1, 3, 5, 7, 14, 21, 30, 60, 90 and 120 d). The expression of PDCD5 protein was examined by immunohistochemistry. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL).</p><p><b>RESULTS</b>The distribution of PDCD5 protein in normal parotid was in cytoplasm with uniformity. The expression of PDCD5 protein was significantly increased and reached the peak at 3 d (1.261 ± 0.048) following main duct ligation. PDCD5 was located both in cytoplasm and nuclear of parotid gland cells. The PDCD5 density in acinar cells was higher than that in duct cells at day 1 and 3 after duct ligation (P < 0.01). The apoptotic cells were obviously upregulated at 3 d after duct ligation. The apoptosis index observed in acinar cells [(21.750 ± 0.119)%] was more than that in duct cells [(5.720 ± 0.205)%]. The difference of apoptosis index between acinar cells and duct cells was statistically significant (P < 0.01). The increased PDCD5 levels were positively correlated with cell apoptosis induced by duct ligation.</p><p><b>CONCLUSIONS</b>The expression of PDCD5 is associated with the atophy of the parotid gland after rat parotid duct ligation, indicating that PDCD5 might play an important role in apoptotic pathways after parotid duct ligation.</p>

Synthesis of baicalin-copper and baicalin-aluminium complex and its bioactivity / 中国中药杂志

<p><b>OBJECTIVE</b>To study synthesis of baicalin-copper and baicalin-aluminium complex and its antimicrobial, anti-tumor activity and anti-tumor effect against macrophages.</p><p><b>METHOD</b>Baicalin was reacted with metallic salt under a weak base condition to produce baicalin-copper and baicalin-aluminium complex. Baicalin and its synthesized complex were detected for antimicrobial activity against Staphylococcus aureus, Hay bacillus, Escherichia coli, Salmonella and Candida albicans by twofold broth dilution technique. Their anti-tumor activity against A549 and IC50 of HepG2 cells and anti-tumor effect against macrophages were detected by the MTT. And their phagocytic effect on macrophages was determined by the neutral red assay.</p><p><b>RESULT</b>The yields of baicalin-copper and baicalin-aluminium complex were 73.93% and 91.08%, respectively. The minimum inhibitory concentration (MIC) value against Staphylococcus aureus, Hay bacillus, Escherichia coli, Salmonella and Candida albicans was 0.0004, 0.0009, 0.0004, 0.0009, 0.000 4 mol x L(-1) for baicalin-copper complex and 0.0011, 0.0011, 0.0011, 0.0011, 0.0005 mol x L(-1) for baicalin-aluminium complex. The IC50 values against A549 and HepG2 cells were 89.6, 22.6 micromol x L(-1) for baicalin-copper complex, and 138.8, 97.2 micromol x L(-1) for baicalin-aluminium complex. The inhibitory ratio of macrophage on A549 cell was 43.52%, 80.89%, 52.66%, respectively, after the macrophages were stimulated by baicalin, baicalin-copper and baicalin-aluminium complex at a concentration of 160 micromol x L(-1).</p><p><b>CONCLUSION</b>The acute toxicity test in mice showed that the complex was nontoxic to mice. Baicalin-copper complex showed the highest antimicrobial, anti-tumor activity, and the strongest effect on the anti-tumor activity of macrophage, while baicalin showed the lowest activities compared with baicalin-copper and baicalin-aluminium complex.</p>

Preliminary survey on the distribution of Leptotrombidium deliense in some areas of Yunnan province / 中华流行病学杂志

Objective To investigate the distribution of Leptotrombidium deliense among different small mammal hosts in some areas of Yunnan province. Methods A field survey was carried out in some counties of Yunnan province and the small mammal hosts were captured, using mouse cages and traps with baits. Chigger mites on the surface of two auricles were scraped off by a bistoury, and then preserved in 70% ethanol. Every specimen of the chigger mites on the slides was finally identified into species under a microscope. Some conventional statistical methods were adopted to calculate all the collected chigger mite species and the constituent ratios of Leptotrombidium deliense in different areas and on different hosts, together with its prevalence and mean abundance on different hosts. Results A total of 10 222 small mammal hosts were captured from 19 counties and identified as 11 families, 34 genera and 62 species in 5 orders, and 92 990 individuals of chigger mites were collected from the body surface of these small mammal hosts. All the collected chigger mites were identified as 3 subfamilies, 22 genera, and 225 species. Meanwhile, Leptotrombidium deliensee only accounted for 1.659% of the total. The host specificity of Leptotrombidium deliense was very low and 1544 individuals of Leptotrombidium deliense collected from 8518 small mammal hosts belonged to 6 families, 13 genera and 19 species in 3 orders. Our results showed that Leptotrombidium delienses were mainly collected from Insectivora and Rodentia. Leptotrombidium deliense had long been considered as the dominant species of chigger mites and the main vector of tsutsugamushi disease in Yunnan province of China, but our results seemed not thoroughly supporting this point of view. Conclusion Traditionally, Leptotrombidium deliense was the dominant species and the main vectors of scrub typhus in Yunnan province. However, based on our results, the above view might be true in some local places and the composition of chigger mites and the main vector of tautsugamushi disease might be different in regions and habitats in Yunnan province.

Effect of ceftiofur hydrochloride on pharmacokinetics of matrine in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of ceftiofur hydrochloride on the pharmacokinetics of matrine in rats.</p><p><b>METHOD</b>The rats were divided into two groups: one group was administrated with matrine only (control group) and the other was administrated with matrine in combination with ceftiofur hydrochloride. HPLC-UV method was used for determining the plasma concentration of matrine in both groups. The pharmacokinetic parameters were calculated from the plasma concentration-time data using the DAS 2. 1. 1 software program.</p><p><b>RESULT</b>The main pharmacokinetic parameters for the control group were C(max) = 21.113 9 mg x L(-1), T(max) = 0.75 h, t1/2alpha = 1.34 h, t1/2beta = 3.509 h, AUC(0-t) = 90.984 mg x h(-1) x L(-1) and AUC(0-inifinity) = 100.346 mg x h(-1) x L(-1), and the data for the combination group were C(max) = 11.707 mg x L(-1), T(max) = 0.917 h, t1/2alpha = 1.598 h, t1/2beta = 3.247 h, AUC(0-t) = 53.28 mg x h(-1) x L(-1) and AUC(0-inifinity) = 60.035 mg x h(-1) x L(-1).</p><p><b>CONCLUSION</b>The plasma concentration of matrine and bioavailability in combination group were significantly lower than those of the control group. In combination group, matrine had a higher clearance and volume of distribution in the central compartments, as well as a lower volume of distribution in the peripheral compartments.</p>

Orthogonal factor analysis on metabolic syndrome / 中华流行病学杂志

To elucidate the principal of orthogonal factor analysis, using an example of factor analysis of metabolic syndrome. The basic structures and the fundamental concepts of orthogonal factor analysis were introduced and data involving 1877 women aged of 35-65 years, selected from a cross-sectional study, which was conducted in 1998 - 2001 in Shanghai, were included in this study. Factor analysis was carried out using principle components analysis with Varimax orthogonal rotation of the components of the metabolic syndrome. The different components of the metabolic syndrome were not linked closely with the other components and loaded on the six different factors,which mainly reflected by the variables of obesity, blood pressure, plasma glucose, plasma insulin, triglycerides and HDL-cholesterol respectively. Six major factors of the metabolic syndrome were uncorrelated with each other and explained 86% of the variance in the original data. The factor score and total factor score for the individual could be obtained according to the component score coefficient matrix. Although the components of the metabolic syndrome were related statistically, the finding of six factors suggested that the components of the metabolic syndrome did not show high degrees of intercorrelation. As a linear method of data reduction, the mode reduced a large set of measured intercorrelation variables into a smaller set of uncorrelated factors, which explained the majority of the variance in the original variables. Factor analysis was well suited for revealing underlying patterns or structure among variables showing high degrees of intercorrelation.

Different courses of esomeprazole-based triple therapy for Helicobactor pylori infection in children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the efficacy of esomeprazole-based 1 week or 2 weeks triple therapy for Helicobactor pylori (H. pylori) infection in children.</p><p><b>METHODS</b>One hundred and five children with H. pylori infection identified by 13C-UBT were randomly assigned into Group A (n=60) and Group B (n=45). The patients of the two groups were administered with 1 week or 2 weeks triple therapy consisting of esomeprazole, clarithromycin and amoxillin, respectively. They were followed up four weeks after drug withdrawal.</p><p><b>RESULTS</b>Recurrent abdominal pain was relieved in all of patients. Fifty-five patients (91.7%) showed 13C-UBT negative in Group A and 42 (93.3%) presented negative in Group B. There was no significant difference in the eradication rate of H. pylori.</p><p><b>CONCLUSIONS</b>Esomeprazole-based triple therapy for H. pylori infection is effective in children. The efficacy of esomeprazole-based 1 week or 2 weeks triple therapy for this disorder does not appear to be different.</p>

Relationship between Helicobacter pylori infection and Henoch-Schonlein purpura with gastrointestinal involvement in children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the relationship of Helicobacter pylori (H. pylori) infection with the development and relapse of Henoch-Schonlein purpura (HSP) with gastrointestinal involvement in children.</p><p><b>METHODS</b>Thirty-six HSP children with gastrointestinal manifestations and 16 of 32 HSP children without gastrointestinal involvement underwent gastroscopy and rapid urease test for H. pylori detection. Thirty healthy children served as the control group. All of the patients received 14C urea breath test and serum H. pylori antibody detections. H. pylori infection was definited when two of detection approaches demonstrated positive.</p><p><b>RESULTS</b>Twenty-one of 36 HSP patients with gastrointestinal manifestations were confirmed with H. pylori infection (58.3%). Of them, the relapsed patients had an H. pylori positive rate of 81.3% (13/16), which was significantly higher than that of the newly diagnosed patients (45.0%, 9/20) (chi(2)=4.49, P < 0.05). Nine of 32 HSP patients without gastrointestinal manifestations were confirmed with H. pylori infection (28.1%); 2 of 30 healthy children showed H. pylori positive (6.7%, 2/30). There was a significant difference in the H. pylori positive rate among the three groups (chi(2)=14.7, P < 0.01).</p><p><b>CONCLUSIONS</b>H.pylori infection may be associated with the development and relapse of HSP with gastrointestinal involvement in children.</p>