Modified Xiao Xianxiongtang Inhibits Epithelial-Mesenchymal Transition of Human Gastric Cancer MGC803 Cells via Wnt/β-catenin Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the inhibitory effect of modified Xiao Xianxiongtang on epithelial-mesenchymal transition （EMT） of human gastric cancer MGC803 cells and its relationship with secretory glycoprotein Wnt/β-catenin pathway. MethodThe BALB/c nude mice were implanted with human gastric cancer MGC803 cell suspension in the heterotopic subcutaneous position for inducing tumor. After successful modeling， they were randomly divided into the model group， low-， medium-， and high-dose （16.0，32.0，and 64.0 g·kg-1） groups of modified Xiao Xianxiongtang， and capecitabine （400 mg·kg-1） group， with eight mice in each group， and gavaged with the corresponding drugs， once per day， for 28 consecutive days. Those in the capecitabine group received one-week discontinuation after every two weeks of treatment. The general state and body weight of the nude mice were observed， and the transplanted tumor volume was measured. After being killed， they were weighed and the tumor inhibition rate was calculated. Hematoxylin-eosin （HE） staining was carried out for observing the pathological changes in transplanted tumor tissues. The gene and protein expression levels of Wnt1 and β-catenin were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， followed by the determination of matrix metalloproteinase-9 （MMP-9）， vascular endothelial growth factor （VEGF）， N-cadherin， E-cadherin， Vimentin， and Snail protein expression by Western blot. The expression levels of cyclooxygenase 2 （COX2） and prostaglandin E2 （PGE2） were detected by enzyme-linked immunosorbent assay （ELISA）. ResultIt was found that the transplanted tumor in each group showed different growth trends with time， with the most obvious growth observed in the model group. Compared with the model group， the low-， medium-， and high-dose modified Xiao Xianxiongtang groups exhibited reduced tumor volume and slowed growth to varying degrees over time. After medication for days 7，14，21，and 28， the tumor volumes in the low- and high-dose modified Xiao Xianxiongtang groups and capecitabine group declined （P<0.05， P<0.01）， and that in the medium-dose Xiao Xianxiongtang group was also remarkably reduced after medication for days 14，21，and 28 （P<0.01）. Compared with the model group， the high-dose modified Xiao Xianxiongtang group and capecitabine group showed a significant reduction in the relative tumor volume after treatment for days 7，14，21，28 （P<0.01）， and the low- and medium-dose modified Xiao Xianxiongtang groups also presented with decreased relative tumor volume after treatment for days 14，21，28 （P<0.05， P<0.01）. Compared with the model group， the modified Xiao Xianxiongtang at low， medium， and high doses and capecitabine all increased the tumor inhibition rate to varying degrees （P<0.01）， down-regulated the mRNA and protein expression levels of Wnt1 and β-catenin in tumor tissue （P<0.05， P<0.01） and protein expression levels of MMP-9， VEGF， N-cadherin， Vimentin， and Snail （P<0.05， P<0.01）， up-regulated E-cadherin protein expression （P<0.05， P<0.01）， and reduced COX2 and PGE2 contents （P<0.05， P<0.01）. ConclusionModified Xiao Xianxiongtang inhibits the EMT of human gastric cancer MGC803 cell-transplanted tumor， which may be related to Wnt/β-catenin pathway.

Acetylation of Rehmannia glutinosa polysaccharides and antioxidant activity of acetylated derivatives / 中国中药杂志

This study aims to acetylate Rehmannia glutinosa polysaccharides by acetic anhydride method, optimize process parameters and evaluate their antioxidant activity. With the degree of substitution(D_s) as a criterion, the effects of reaction time, acetic anhydride-to-polysaccharides ratio and temperature were investigated. Process parameters were optimized by single-factor experiment and response surface methodology. The infrared spectroscopy(IR) and scanning electron microscopy(SEM) proved the successful acetylation and were employed to preliminarily analyze the structural characteristics of acetylated derivatives. The results showed that the D_s was 0.327 under the optimal technological conditions, including m(acetic anhydride):m(R. glutinosa polysaccharides)=2.70, reaction time 3.0 h and temperature 48 ℃. Further, the antioxidant properties of acetylated derivatives were investigated in vitro and acetylation was found effective to improve the antioxidant activity of R. glutinosa polysaccharides. This study provides a reference for the further development and application of R. glutinosa polysaccharides.

Additional risk factors associated with thrombosis and pregnancy morbidity in a unique cohort of antiphospholipid antibody-positive patients / 中华医学杂志(英文版)

BACKGROUND@#Antiphospholipid syndrome (APS) is an autoimmune prothrombotic condition with significant morbidity. The objective of this study was to identify additional clinical and epidemiological risks of arterial thrombosis, venous thrombosis, and pregnancy morbidities in a large cohort of persistent antiphospholipid antibodies (aPLs)-positive carriers.@*METHODS@#This was a cross-sectional cohort study of 453 consecutive patients with a documented positive aPL who attended Peking University People's Hospital. Among 453 patients screened, 297 patients had persistent positive aPL. We compared asymptomatic aPL carriers with thrombotic and obstetric APS patients. And the univariate analysis and multivariable logistic regression were used to evaluate the association between different risk factors and APS clinical manifestations. The levels of circulating markers of neutrophil extracellular traps (NETs) (cell-free DNA and citrullinated histone H3 [Cit-H3]) were assessed and compared among aPL-positive carriers with or without autoimmune disease and APS patients.@*RESULTS@#Additional risk factors associated with arterial thrombosis among aPL-positive carriers included: smoking (odds ratio [OR] = 6.137, 95% confidence interval [CI] = 2.408-15.637, P  = 0.0001), hypertension (OR = 2.368, 95% CI = 1.249-4.491, P  = 0.008), and the presence of underlying autoimmune disease (OR = 4.401, 95% CI = 2.387-8.113, P < 0.001). Additional risks associated with venous thrombosis among aPL carriers included: smoking (OR = 4.594, 95% CI = 1.681-12.553, P  = 0.029) and the presence of underlying autoimmune disease (OR = 6.330, 95% CI = 3.355-11.940, P < 0.001). The presence of underlying autoimmune disease (OR = 3.301, 95% CI = 1.407-7.744, P  = 0.006) is the additional risk, which demonstrated a significant association with APS pregnancy morbidity. Higher circulating levels of cell-free DNA and Cit-H3 were observed among APS patients and aPL patients with autoimmune diseases compared with those aPL carriers without underlying autoimmune diseases. Furthermore, control neutrophils that are conditioned with APS patients'sera have more pronounced NET release compared with those treated with aPL carriers'sera without underlying autoimmune diseases.@*CONCLUSIONS@#We identified several potential additional risk factors for APS clinical manifestations among a large cohort of Chinese aPL carriers. Our data may help physicians to risk stratify aPL-positive Asian patients.

Are the release characteristics of Erzhi pills in line with traditional Chinese medicine theory? A quantitative study / 中西医结合学报

OBJECTIVE@#Traditional Chinese medicine (TCM) has been widely used throughout China to prevent and cure diseases for thousands of years, and now it is a part of the integrative medicine field that is available in Western societies. To ensure the safety and quality of the herbal medicines that are a major part of the TCM tradition, they must be held to modern pharmaceutical standards. Erzhi pill (EZP) is a Chinese Pharmacopeia-listed herbal preparation that is used in the long-term clinical management of post-menopausal symptoms, osteoporosis and menstrual disorders. Until now, whether the drug release mechanism of EZP is in line with its intended TCM usage has not been studied.@*METHODS@#The release of specnuezhenide from three EZPs (self-made, Leiyunshang and Renhe) in simulated gastric fluid (SGF), acetate buffer (pH 4.5 buffer) and simulated intestinal fluid (SIF) was investigated in a dissolution test. The water uptake capacity and erosion extent of the three EZPs were investigated using swelling and erosion studies. The drug release mechanism was further assessed through statistical model fitting, using DDSolver software.@*RESULTS@#The release of specnuezhenide from all three EZPs in SGF was less than 50% within a 4 h period. However, over 70% of the specnuezhenide was released from each EZP in both pH 4.5 buffer and SIF in the same time. Analysis of the swelling and erosion behaviors and the drug release mechanism of the three EZPs confirmed that the release rate from EZP followed a sustained release profile, which was an interactive combination of swelling and erosion.@*CONCLUSION@#This study showed that the release pattern from the pills was in line with the intended TCM use of EZP. TCM had not only theoretically considered sustained release from the pills, but also formulated them to achieve this release pattern. When establishing quality control standards for pills, the theoretical TCM usage and the actual release patterns need to be considered.

Antiphospholipid syndrome: a clinical perspective / 中华医学杂志(英文版)

Antiphospholipid syndrome (APS) is a thromboinflammatory disease with a variety of clinical phenotypes. Primary thrombosis prophylaxis should take an individualized risk stratification approach. Moderate-intensity vitamin K antagonist such as warfarin remains the primary strategy for secondary thrombosis prophylaxis among APS patients, especially for patients with predominantly venous disease. For now, direct oral anti-coagulants should be avoided in most APS patients, especially those with history of arterial manifestations. Obstetric APS management should be tailored based on an individual patient's antiphospholipid antibody profile, and obstetric and thrombotic history. Pharmacological agents beyond anticoagulants may be considered for the management of microthrombotic and nonthrombotic manifestations of APS, although more data are needed. A relatively recent discovery in the area of APS pathogenesis is the implication of neutrophil extracellular traps in thrombin generation and initiation of inflammatory cascades. APS is a complex thromboinflammatory disease with a broad clinical spectrum. Personalized therapy according to an individual's unique thrombosis and obstetric risk should be advocated.

Imapct of home environment on emotional and behavioral problems in preschool children / 中华疾病控制杂志

Objective To investigate the status of mental health in preschool children of Yangzhou city, and to explore the effect of home environment. Methods A total of 2 531 children from 7 kindergartens were selected by random cluster sampling. Questionnaire (including SDQ tests) was used to analyse the status and characteristics of mental health. Results The rate of children with mental disorder was 6.4%, the most prominent problem was peer relationship difficulty (17.8%), followed by hyperactivity/inattention (13.7%), prosocial behavior (9.4%), conduct problems (7.0%) and emotional problems (5.7%). Except for emotional symptoms, the detection rates of all other investigated problems among boys were higher than those among girls. Logistic regression analysis showed that the low level of mother's education (OR=1.85, 95%CI:1.04-3.29) and the joint family (OR=1.81, 95%CI:1.19-2.75) were risk factors, and gender of girl was protective factor (OR=0.71，95%CI：0.51-0.98). Conclusions The rate of mental disorder is low, but hyperactivity in boys and emotional problems in girls are quite popular, especially in children who have mother with low level of education or live in the joint family.

Efficacy of acupuncture as adjunctive treatment on infertility patients with polycystic ovary syndrome / 中国针灸

<p><b>OBJECTIVE</b>To observe the efficacy differences between acupuncture combined with medication and medication alone for infertility patients with polycystic ovary syndrome (PCOS).</p><p><b>METHODS</b>According to random number table, a total of 60 infertility patients with PCOS were randomly assigned into an observation group and a control group, 30 cases in each one. The patients in the control group were treated with diane-35 from the 3rd day into menstruation, and one menstrual cycle was taken as a session of treatment. At the same time of using diane-35, the patients in the observation group were treated with acupuncture at Guanyuan (CV 4), Qihai (CV 6), Sanyinjiao (SP 6), Zusanli (ST 36), Zigong (EX-CA 1), Shenshu (BL 23), Pishu (BL 20), Weishu (BL 21) and Ganshu (BL 18) during non-menstruation period; the acupuncture was given once every two days, three treatments per week. The patients in both groups were treated for two sessions. The basic sex hormone and body mass index (BMI) were compared between the two groups before and after treatment. After ovulation induction treatment, the endometrial thickness, amount of mature follicle, ovulation rate, clinical pregnancy rate, occurrence rate of ovarian hyperstimulation syndrome (OHSS) and the number of early spontaneous abortion were compared between the two groups during ovulation.</p><p><b>RESULTS</b>After treatment, the luteinizing hormone (LH), testosterone (T) and BMI reduced in the observation group (all <0.05), while only LH reduced in the control group (<0.05). The reducing of estradiol (E), T and BMI in the observation group was more significant than that in the control group (all <0.05). The ovulation rate was 93.3% (28/30) in the observation group, which was higher than 80.0% (24/30) in the control group (<0.05). The rate of clinical pregnancy was 43.3% (13/30) in the observation group, which was higher than 33.3% (10/30) in the control group (<0.05). The differences of endometrial thickness, amount of mature follicle, occurrence rate of OHSS and number of early spontaneous abortion were not significant between the two groups (all >0.05).</p><p><b>CONCLUSION</b>Acupuncture as adjunctive treatment could improve BMI, reduce the levels of LH, E and T, increase ovulation reaction and effectively shorten reproduction cycles in infertility patients with PCOS.</p>

Gene Polymorphism Is not Associated with Rheumatoid Arthritis Susceptibility in the Northern Chinese Han Population: A Case-Control Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Interleukin (IL)-37, also called IL1F7, is a natural inhibitor of inflammatory and immune responses. It is involved in the pathogenesis of rheumatoid arthritis (RA). This study aimed to investigate the role of IL1F7 gene polymorphism in RA susceptibility in a large cohort of patients.</p><p><b>METHODS</b>Five selected single-nucleotide polymorphisms in IL1F7 genes (rs2723186, rs3811046, rs4241122, rs4364030, and rs4392270) were genotyped by TaqMan Allelic Discrimination in Northern Chinese Han population. The allele and the genotype were compared between patients with RA and healthy controls. Association analyses were performed on the entire data set and on different RA subsets based on the status of the anti-cyclic citrullinated peptide antibody and the rheumatoid factor by logistic regression, adjusting for age and gender.</p><p><b>RESULTS</b>Trend associations were detected between rs2723186, rs4241122, rs4392270, and RA in Stage I (160 patients with RA; 252 healthy controls). Further validation in Stage II comprised 730 unrelated patients with RA (mean age: 54.9 ± 12.6 years; 81.6% females) and 778 unrelated healthy individuals (mean age: 53.5 ± 15.7 years; 79.5% females). No significant differences in the distributions of alleles and genotypes were observed between the case and control groups in both the entire set and the different RA subsets. Disease activity and age of RA onset were also not associated with genotype distributions.</p><p><b>CONCLUSION</b>IL1F7 gene polymorphism does not significantly influence RA susceptibility in the Northern Chinese Han population.</p>

Gene Polymorphism Is not Associated with Rheumatoid Arthritis Susceptibility in the Northern Chinese Han Population: A Case-Control Study / 中华医学杂志(英文版)

BACKGROUND@#Interleukin (IL)-37, also called IL1F7, is a natural inhibitor of inflammatory and immune responses. It is involved in the pathogenesis of rheumatoid arthritis (RA). This study aimed to investigate the role of IL1F7 gene polymorphism in RA susceptibility in a large cohort of patients.@*METHODS@#Five selected single-nucleotide polymorphisms in IL1F7 genes (rs2723186, rs3811046, rs4241122, rs4364030, and rs4392270) were genotyped by TaqMan Allelic Discrimination in Northern Chinese Han population. The allele and the genotype were compared between patients with RA and healthy controls. Association analyses were performed on the entire data set and on different RA subsets based on the status of the anti-cyclic citrullinated peptide antibody and the rheumatoid factor by logistic regression, adjusting for age and gender.@*RESULTS@#Trend associations were detected between rs2723186, rs4241122, rs4392270, and RA in Stage I (160 patients with RA; 252 healthy controls). Further validation in Stage II comprised 730 unrelated patients with RA (mean age: 54.9 ± 12.6 years; 81.6% females) and 778 unrelated healthy individuals (mean age: 53.5 ± 15.7 years; 79.5% females). No significant differences in the distributions of alleles and genotypes were observed between the case and control groups in both the entire set and the different RA subsets. Disease activity and age of RA onset were also not associated with genotype distributions.@*CONCLUSION@#IL1F7 gene polymorphism does not significantly influence RA susceptibility in the Northern Chinese Han population.

Application progress of molecularly imprinted polymers in separation of active ingredients from Chinese materia medica / 中草药

Separation of active ingredients from Chinese materia medica (CMM) by molecularly imprinted polymers has such advantages as high speed, low cost, being reusable, low pollution, and so on. Because of this reason, the synthesis of molecularly imprinted polymers and its application in separation have drawn more and more attention of researchers in the field of CMM all over the world. Obviously, the core of this research is to explore the relationship between the polymer-structure and separation efficiency. Based on the types of active ingredients of CMM (flavone, alkaloids, phenylpropanoids, terpenoids, etc.), the design principle of molecularly imprinted polymer, its preparation methods and latest application in separation of active ingredients from CMM were introduced. Therefore, this paper can provide a reference for designing new materials with higher selectivity in separation of active ingredients from CMM.

The clinical and immunological feat ures of idiopathic inflammatory myopathy patients with rapid progressive interstitial lung disease / 中华风湿病学杂志

Objective To investigate the clinical and immunological features of rapid progressive interstitial lung disease (ILD) in patients with idiopathic inflammatory myopathy (ⅡM).Methods The medical records of 146 adult ⅡM patients associated with ILD in Peking University People's Hospital from February 1996 to February 2015 were retrospectively analyzed.They were divided into three subgroups:the classic DM,PM and the clinical amyopathic dermatomyositis (CADM),and were further stratified based on with or without rapid progressive ILD (RP-ILD).Chi-squared test was used for group comparisons of categorical data and independent-sample t test for numerical data.Results ① Among 146 patients,62 (42.5％) developed RP-ILD.The prevalence of RP-ILD in CADM was signifcantly higher than dermatomyositis (DM) and polymyositis (PM).② ILD occurred after or at the same time with ⅡM in more than 90％ of patients.ILD arising before or simultaneously with DM (named early-onset ILD) tended to progress rapidly.③ For the DM group,mechanic's hands,fever,lymphopenia,hypoxemia,hypoalbuminemia,and the elevation of globulin α1 were associated with RP-ILD.CADM-ILD with weakness of swallow muscles,increasing C-reactive protein (CRP) and globulin α2,decreased vital capacity and the relatively high level of segmented granulocytes in bronchoalveolar lavage fluid tended to undergo a rapid progressive clinical course.Additionally,the decreased free triiodothyronine (FT3) and the elevation of tumor markers including carcino-embryonic antigen (CEA),neuron specific enolase (NSE),cytokerantin-19-fragment (CYFRA211) and ferritin were significantly more frequent both in DM and CADM with RP-ILD (P＜0.05) patients.④ According to multivariate analysis,mechanic's hands [HR =31.747,95％CI (2.367,425.817),P=0.009] and the elevation of CEA [HR =57.047,95％CI (1.140,2 854.885),P=0.043] and CRP [HR=31.568,95％CI (1.818,548.093),P=0.018] were potential predictive factors for RP-ILD in DM and CADM patients,respectively.Conclusion The prevalence of RP-ILD in CADM is higher than DM and PM.ILD usually occurs after or simultaneously with ⅡM,early-onset ILD in DM patients tends to progressive rapidly.Increased tumor markers and decreased FT3 indicate the deterioration of disease.Mechanic's hands and the elevation of CEA and CRP are potential predictive factors for RP-ILD in DM and CADM patients,respectively.

Analysis of the clinical and laboratory features of 67 cases of scleroderma overlap syndrome / 中华风湿病学杂志

Objective To investigate the clinical and serologic features of scleroderma overlap syndromes.Methods Scleroderma overlap syndrome was diagnosed in 67 patients referred to our department from January 2003 to August 2013.Clinical and laboratory date were retrospectively analyzed.Comparisons between groups were tested by t test and chi-square test and Fisher exact method.Results ① Sixty-seven patients satisfied the criteria for scleroderma overlap syndrome,and 66 were female.The incidence of additional connective tissue diseases in the overlap syndrome group was systemic lupus erythematosus (SLE) in 27％,Sj(o)gren's syndrome (SS) in 24％,rheumatoid arthritis in 16％,dermatomyositis or polymyositis in 10％,two or more connective tissue diseases in 22％ respectively.② Systemic sclerosis preceded the development of additional connective tissue diseases was frequent (58％).The median onset age of SSc in SSc-SLE was younger,in contrast,SSc-SS was older.③ Antinuclear antibody (ANA) was positive in 87％ of patients,rheumatoid factor (RF) was in 42％.Anticentromere antibody (ACA) was more common in SSc-SS,RF and anti-cyclic citrullinated peptide (CCP) antibody were more frequent in SSc-RA,anti ds-DNA antibody was more common in SSc-SLE.Conclusion SSc-SLE is more common in scleroderma overlap syndrome in particular,and the median onset age of SSc in SSc-SLE is younger than others.There are distinct clinical and serological features that may predict the possibility of SSc patients with overlap syndrome.

Effect of inflammatory stress on hepatic cholesterol accumulation and hepatic fibrosis in C57BL/6J mice / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate whether inflammatory stress exacerbates hepatic cholesterol accumulation and liver fibrosis using a C57BL/6J mouse model of chronic inflammation.</p><p><b>METHODS</b>Twelve male C57BL/6J mice were given a high-fat diet (15.0% fat, 1.25% cholesterol, 0.5% cholic acid) and randomly assigned to the normal control group (n=6; subcutaneously injected with 0.5 mL of isotonic saline, every other day for 14 weeks) or the chronic inflammation model group (n=6; subcutaneously injected with of 0.5 mL of 10% casein, every other day for 14 weeks). At the end of week 14, the animals were sacrificed and blood was collected from the left ventricle for serological analysis of inflammatory markers and lipid profile, including serum amyloid A (SAA), interleukin-6 (IL-6), total cholesterol (TC) and free cholesterol (FC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL)). Extracted liver tissues were divided for use in histological analysis (lipid accumulation and fibrosis evaluated by Oil Red O, Sirius red and Masson's trichrome staining) and quantitative fluorescence real-time PCR (to measure b-actin normalized expression of TNF-a MCP1, SREBP-2, LDLr, HMGCoA-r, ATF-6, GRP78, BMP-7, TGF-b, and collagens type I and type IV). Comparisons between groups were made by the two-samples t-test or Satterthwaite t-approximation test, collagen type I and type IV.</p><p><b>RESULTS</b>Compared to the normal control group, the inflammation model group showed elevated serum IL-6 (12.55+/-4.75 vs. 32.41+/-7.42 pg/mL, P less than 0.01), reduced serum TC (14.82+/-1.56 vs. 10.62+/-0.48 mmol/L, P less than 0.01), up-regulated hepatic TNF-a mRNA expression (1.05+/-0.35 vs. 2.12+/-0.72, P less than 0.01), and elevated hepatic TC (12.10+/-2.57 vs. 23.21+/-8.75 mmol/L, P less than 0.05). In addition, the inflammation group showed abnormal lipid deposition, and increased and thickened reticular fibers. The livers of the inflammation group also showed up-regulated mRNA expression of SREBP-2 (normal control: 1.01+/-0.19 vs. 2.63+/-0.13, P less than 0.05), GRP78 (1.07+/-0.47 vs. 2.21+/-0.99, P less than 0.05), TGF-b (1.01+/-0.14 vs. 1.38+/-0.28, P less than 0.05), and collagen type I (1.02+/-0.27 vs. 1.71+/-0.51, P less than 0.05) and down-regulation of BMP-7 (1.01+/-0.15 vs. 0.55+/-0.25, P less than 0.01).</p><p><b>CONCLUSION</b>Activation of the inflammatory system exacerbates hepatic cholesterol accumulation and hepatic fibrosis in C57BL/6J mice.</p>

Expression of Wnt5a in the terminal rectum of children with anorectal malformation / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the expression of Wnt5a protein in the terminal rectum of children with anorectal malformation (ARM) and the possible association between Wnt5a and ARM.</p><p><b>METHODS</b>Specimens were obtained from 20 children with ARM, 7 children with acquired rectovestibular fistula and 6 children with non-gastrointestinal tract disease (control group). The expression of Wnt5a protein in the terminal rectum was determined by immunohistochemistry and Western blot.</p><p><b>RESULTS</b>Wnt5a was mainly expressed in the rectum of the myenteric nerve plexus, mucosal layer and submucosa in the control group. Compared with the control group, Wnt5a expression in the terminal rectum decreased significantly in the ARM group, and decreased more significantly in children with high ARM. The results of Western blot showed the expression of Wnt5a protein in the high, intermediate and low ARM groups were significantly lower than that in the acquired rectovestibular fistula and the control groups (P<0.01). The expression of Wnt5a protein in the high and the intermediate ARM groups were also lower than that in the low ARM group (P<0.01). There was no significant difference in the Wnt5a protein expression between the acquired rectovestibular fistula and the control groups.</p><p><b>CONCLUSIONS</b>The expression of Wnt5a in the termina1 rectum decreases in children with ARM, suggesting Wnt5a may play an important role in the development of ARM.</p>

Clinical significance of detection of internal anal sphincter in children with functional constipation / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the structural and functional changes of internal anal sphincter (IAS) in children with functional constipation (FC), and to evaluate the association between the thickness of IAS and the severity of clinical symptoms.</p><p><b>METHODS</b>A total of 35 children with FC(constipation group,17 with incontinence) between June 2008 and December 2008 at the Shengjing Hospital of China Medical University were evaluated using anal manometry and endosonography. These patients were compared to 23 hospitalized children who were excluded for digestive and endocrinal diseases(control group). A validated symptom score(SS) was used to assess the severity of symptoms. The sum of SS ranged between 0 and 65.</p><p><b>RESULTS</b>Anorectal manometry showed reflex relaxation of IAS in response to distension of rectal balloon in all patients. Rectal perceptional threshold in FC group was significantly higher than that in the controls[(42.4 ± 19.5) ml vs.(29.1 ± 15.6) ml, P<0.05]. The lowest volume for inducing reflex relaxation of IAS was significantly higher than that in the controls [(55.6 ± 31.6) ml vs.(30.5 ±13.8) ml, P<0.05]. The thickening of IAS was noted in all the patients[(3.8 ± 1.7) mm vs.(2.5 ± 1.0) mm, P<0.05]. However, there was no significant difference between FC and control in median resting anal sphincter pressure[(170.8 ± 62.3) mm Hg vs. (161.3 ± 51.1) mm Hg, P>0.05]. The median symptom score was 9.3 ± 4.3 in the FC group. The thickness of IAS correlated significantly with total symptom severity score(r=0.407, P<0.05). There was no correlation between thickness of IAS and age, sex, or duration of disease(P>0.05).</p><p><b>CONCLUSIONS</b>Structural and functional changes of internal anal sphincter exist in children with functional constipation. The thickness of internal anal sphincter correlates significantly with symptom severity.</p>

Expression and significance of Notch-1 and Jagged-2 in patients with Hirschsprung disease / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the expression of Notch-1 and Jagged-2 in the normal and spastic segments of colon in patients with Hirschsprung disease(HD), and to explore the correlation of Notch-1 and Jagged-2 with pathogenesis of HD.</p><p><b>METHODS</b>From 2005 to 2010, resected colon specimens of 30 cases with HD were selected for this study. Normal colonic segments were served as control group, while the transitional and spastic segments as experimental group. Immunohistochemical staining, Western blotting, and RT-PCR were applied to detect the expression of Notch-1 and Jagged-2.</p><p><b>RESULTS</b>A large number of Notch-1 and Jagged-2 positive gangliocytes were observed in the control group, while none was observed in spastic segments. Significantly less Notch-1 and Jagged-2 positive gangliocytes were found in the transitional segments. Western blotting revealed that Notch-1 and Jagged-2 protein levels in spastic segments (0.19±0.02 and 0.13±0.04) were less than that in transitional segments and normal segments (0.58±0.05 and 0.52±0.04, 0.72±0.04 and 0.69±0.04, respectively)(P<0.05). RT-PCR revealed that Notch-1 and Jagged-2 mRNA levels were consistent with protein expression.</p><p><b>CONCLUSION</b>Notch-1 and Jagged-2 are not expressed in spastic colon segments, which may be associated with the pathogenesis of HD.</p>

Cell apoptosis during the cloacal embryonic development in rats with anorectal malformations / 中国当代儿科杂志

<p><b>OBJECTIVE</b>In the normal embryonic development of anorectum, apoptosis plays an important role. To explore the role of apoptosis in anorectal malformations (ARM), this study investigated cell apoptosis during the cloacal embryonic development in ARM embryos.</p><p><b>METHODS</b>ARM embryos were induced by intragastric administration of ethylenethiourea (125 mg/kg) for pregnant rats on embryonic day 10 (E10). The distribution of apoptotic cells in the cloaca was ascertained by hematoxylin and eosin and TUNEL staining in the normal control embryos (n=102) and ARM embryos (n=147) on E13, E13.5, E14, E15 and E16.</p><p><b>RESULTS</b>On E13, apoptotic cells were detected in the urorectal septum of rat embryos in the control group. With the development of embryos, the number of apoptotic cells in the mesenchyme of urorectal septum gradually increased and a large number of apoptotic cells were seen in the dorsal rectal mesenchyme. On E14, apoptotic cells appeared at the terminal rectum and the dorsal cloacal membrane. On E15, the urorectal septum fused with the cloacal membrane and apoptotic cells in the urorectal septum mesenchyme continuously extended down to the fusion region. Compared with the control group, apoptotic cells in the urorectal septum, the dorsal rectal mesenchyme and the cloacal membrane of the ARM rat embryos were significantly reduced during the embryonic development. The development of the urorectal septum was delayed and it did not fuse with the cloacal membrane in ARM embryos.</p><p><b>CONCLUSIONS</b>During the embryonic development of cloaca, abnormal apoptosis in the urorectal septum, the dorsal rectal mesenchyme and the cloacal membrane may be one of the reasons for anorectal malformations. The proper regulation of cell apoptosis may be one of the key mechanisms for normal development of anorectum in the embryonic stage.</p>

Evaluation of anorectal function after transanal one-stage endorectal pull through operation in children with Hirschsprung's disease / 中国当代儿科杂志

<p><b>OBJECTIVE</b>The short-term efficacy of the transanal one-stage endorectal pull through operation for Hirschsprung's disease is satisfactory. However the long-term outcome of anorectal function has not been fully understood. The aim of this study was to evaluate the stooling pattern, colonic motility and anal sphincter performance after transanal one-stage pull through operation in children with Hirschsprung's disease.</p><p><b>METHODS</b>Fifty-eight children who underwent transanal one-stage pull through operation for Hirschsprung's disease were followed up. The mean follow-up duration was 15.8 months (range, 6-24 months). The stooling patterns of the patients were investigated by the informed questionnaire. Barium enema, defecography, total and segmental colonic transit time and the anorectal vector manometry were performed. Thirty- three healthy children were used as controls.</p><p><b>RESULTS</b>Most of patients had normal stool consistency and frequency. Postoperative enterocolitis occurred in 3 patients, and constipation was found in five patients. Postoperative soiling was observed in 9 patients. None of the 58 patients had incontinence, cuff infection, anastomotic leak and mortality. The barium enema showed that the configuration of the colon recovered well in most of patients. Postopertive defecography showed the anorectal angle of all the patients was open, fixed and bigger than that of preoperation and the healthy controls (P < 0.01). Postoperatively, the mean total gastrointestinal transit time (TGITT), the left colonic transit time (LCTT) and rectosigmoid colonic transit time (RSTT) in the 58 patients were significantly shorter than preoperatively (P < 0.01) and were similar to those of the control group. The rectoanal inhibitory reflex was regained in 5 patients. The anal maximal pressure of the patients with constipation in resting and squeezing condition were significantly higher than those of the asymptomatic patients and controls (P < 0.05). The vector volume (VV) and vector symmetric index (VSI) in patients with soiling were significantly lower than those in preoperation and the controls (P < 0.05). The VSI in the patients with constipation was significantly higher compared with the controls (P < 0.05).</p><p><b>CONCLUSIONS</b>The stooling function, colonic motility and anal sphincter performance manifest well in most of the patients after the transanal endorectal pull through operation for Hirschsprung's disease. Stooling disorders in few cases are probably related to decrease or disappearance of the sigmoid loops, dysfunction of the "neorectosigmoid", an open and fixed anorectal angle and achalasia of the internal anal sphincter.</p>

Determination of total and segmental colonic transit time in constipated children / 中华儿科杂志

<p><b>OBJECTIVE</b>To determine the total and segmental colonic transit time of normal Chinese children and to explore its value in constipation in children.</p><p><b>METHODS</b>The subjects involved in this study were divided into 2 groups. One group was control, which had 33 healthy children (21 males and 12 females) aged 2 - 13 years (mean 5 years). The other was constipation group, which had 25 patients (15 males and 10 females) aged 3 - 14 years (mean 7 years) with constipation according to Benninga's criteria. Written informed consent was obtained from the parents of each subject. In this study the simplified method of radio opaque markers was used to determine the total gastrointestinal transit time and segmental colonic transit time of the normal and constipated children, and in part of these patients X-ray defecography was also used.</p><p><b>RESULTS</b>The total gastrointestinal transit time (TGITT), right colonic transit time (RCTT), left colonic transit time (LCTT) and rectosigmoid colonic transit time (RSTT) of the normal children were 28.7 +/- 7.7 h, 7.5 +/- 3.2 h, 6.5 +/- 3.8 h and 13.4 +/- 5.6 h, respectively. In the constipated children, the TGITT, LCTT and RSTT were significantly longer than those in controls (92.2 +/- 55.5 h vs 28.7 +/- 7.7 h, P < 0.001; 16.9 +/- 12.6 h vs 6.5 +/- 3.8 h, P < 0.01; 61.5 +/- 29.0 h vs 13.4 +/- 5.6 h, P < 0.001), while the RCTT had no significant difference. X-ray defecography demonstrated one rectocele, one perineal descent syndrome and one puborectal muscle syndrome, respectively.</p><p><b>CONCLUSION</b>The TGITT, RCTT, LCTT and RSTT of the normal children were 28.7 +/- 7.7 h, 7.5 +/- 3.2 h, 6.5 +/- 3.8 h and 13.4 +/- 5.6 h, respectively. With the segmental colonic transit time, constipation can be divided into four types: slow-transit constipation, outlet obstruction, mixed type and normal transit constipation. X-ray defecography can demonstrate the anatomical or dynamic abnormalities within the anorectal area, with which constipation can be further divided into different subtypes, and combined use of the gastrointestinal transit time and X-ray defecography is of clinical importance in exploration of etiology of constipation.</p>