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OBJECTIVE To explore the effect and mechanism of the alcoholic extract from Scabiosa comosa against hepatic fibrosis （HF）. METHODS Intragastrical administration of carbon tetrachloride was given to induce HF model. By observing the pathological changes in liver tissue， mRNA and protein expressions of HF indexes [α-smooth muscle actin （α-SMA）， collagen type Ⅰ] and phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） pathway-related factors were detected， and the improvement effects and possible mechanism of low-dose， medium-dose and high-dose （50， 100， 200 mg/kg） of alcoholic extract from S. comosa on HF model rats were investigated. Drug-containing serum was prepared by intragastrical administration of alcoholic extract from S. comosa at a concentration of 1 800 mg/（kg·d） （calculated by the amount of raw material）. The effects of drug- containing serum of alcoholic extract from S. comosa on the expression of miRNA-21 were observed through the intervention of HSC-T6 cells with low， medium and high concentrations of drug-containing serum of alcoholic extract from S. comosa （diluted to 10%， 15%， 20%）. miRNA-21 mimics or inhibitors were used to transfect HSC-T6 cells， and the mRNA and protein expressions of factors related to the PI3K/Akt signaling pathway were detected. RESULTS The results of in vivo experiments showed that low， medium and high doses of alcoholic extract from S. comosa significantly ameliorated the histopathological changes in liver tissue of HF rats， and the percentage of collagen was significantly reduced （P＜0.01）； mRNA and protein expressions of the indicators related to HF as well as PI3K and Akt were significantly reduced （P＜0.01）， and mRNA and protein expressions of phosphatase and tensin homolog deleted on chromosome ten （PTEN） were increased in liver tissue of rats （P＜0.01）. The results of in vitro experiments showed that drug-containing serum of alcoholic extract from S. comosa significantly inhibited the expression of miRNA-21 at low， medium and high concentrations （P＜0.01）； whereas after transfection with miRNA-21 mimics， it was found that miRNA-21 mimics significantly increased mRNA and protein expressions of PI3K and Akt （P＜0.01）， while significantly decreased mRNA and protein expressions of PTEN （P＜0.01）； after transfection with miRNA-21 inhibitor， the changes of above indexes were opposite to the above results （P＜0.01）. CONCLUSIONS Alcoholic extracts of S. comosa may inhibit the PI3K/Akt signaling pathway by affecting the expression of miRNA-21， so as to achieve the effect of anti-hepatic fibrosis.
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Objective To investigate the role and mechanism of action of Scabiosa atropurea in inhibiting the proliferation of hepatic stellate cells using cell experiment. Methods A total of 20 Wistar rats were randomly divided into control group and administration group, with 10 rats in each group. The rats in the control group were given normal saline by gavage, and those in the administration group were given Scabiosa atropurea by gavage to prepare drug-containing serum. HSC-T6 cells were incubated with the serum from the control group (10%) or the low-, middle-, and high-dose serum containing Scabiosa atropurea (10%, 15%, and 20%, respectively). MTT assay was used to observe the effect of different drug concentrations on cells in different periods of time; flow cytometry was used to measure cell apoptosis; qRT-PCR and Western blot were used to measure the mRNA and protein expression levels of fibrosis markers (α-SMA, collagen Ⅰ) and PI3K/Akt signaling pathway-related factors in hepatic stellate cells (HSCs). A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t - test was used for further comparison between two groups. Results Compared with the control group, the low-, middle-, and high-dose serum containing Scabiosa atropurea groups had a significant reduction in the OD value of cells (all P < 0.05) and a significant increase in the overall apoptosis rate of cells (all P < 0.05). The results of qRT-PCR showed that compared with the control group, the low-, middle-, and high-dose serum containing Scabiosa atropurea groups had significant reductions in the mRNA expression levels of α-SMA, collagen Ⅰ, PI3K, and Akt and a significant increase in the mRNA expression level of PTEN (all P < 0.05); Western blot showed that compared with the control group, the low-, middle-, and high-dose serum containing Scabiosa atropurea groups had significant reductions in the protein expression levels of α-SMA, collagen Ⅰ, PI3K, Akt, and p-Akt and a significant increase in the protein expression level of PTEN (all P < 0.05). Conclusion The Mongolian medicine Scabiosa atropurea can inhibit the proliferation of HSC-T6 cells and promote their apoptosis, possibly by regulating fibrosis markers and the PI3K/Akt signaling pathway to exert an anti-liver fibrosis effect.
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OBJECTIVE@#To explore the genetic basis for three fetuses with duodenal atresia or stenosis detected by ultrasonography.@*METHODS@#Clinical data of three fetuses identified at the Women's Hospital Affiliated to Zhejiang University School of Medicine between January 2021 and August 2022 were collected. Umbilical cord blood and amniotic fluid samples of the fetuses and peripheral blood samples of their parents were collected and subjected to G-banded chromosomal karyotyping and single nucleotide polymorphism array (SNP array) analysis.@*RESULTS@#Prenatal ultrasound of the three fetuses revealed duodenal atresia or stenosis. No karyotypic abnormality was detected, whilst SNP array has identified 1.4 ~ 1.9 Mb duplications at 17q12 in all of them, which were all predicted to be pathogenic copy number variations (CNVs).@*CONCLUSION@#The 17q12 duplications probably underlay the duodenal atresia and stenosis in these fetuses, and chromosomal CNVs should be considered in duodenal atresia and stenosis.
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Pregnancy , Humans , Female , DNA Copy Number Variations , Constriction, Pathologic , Prenatal Diagnosis , Fetus/diagnostic imaging , Chromosome AberrationsABSTRACT
OBJECTIVE：To study the improv ement effects of Mongolian medici ne eligen- 7 on hepatic fibrosis （HF）and its mechanism. METHODS ：Taking rat hepatic stellate cells HSC-T 6 as research object ，the cells were divided into model group （blank serum ）and low-dose ，medium-dose and high-dose groups of eligen- 7 containing serum （10％，15％ and 20％ eligen-7 containing serum ）. Transforming growth factor β solution（0.2 mg/mL）was added into the cells for 48 h to induce liver fibrosis model，and then added into the corresponding blank or drug-contained serum. The optical density （OD）of cells in each group was measured and inhibition rate of cell proliferation was calculated （after treated for 24，48 and 72 h）. The apoptotic rate and cycle distribution of cells were detected ；mRNA and protein expression of type Ⅰ collagen（Collagen Ⅰ），α-smooth muscle actin （α-SMA），phosphatidylinositol-3-kinase and protein-serine-threonine kinase （PI3K/Akt）signaling pathway related factors （PI3K， Akt，PTEN）were also detected （after treated for 24 h）. Wistar rats were further divided into blank group ，model group and low-dose，medium-dose and high-dose groups of eligen- 7（135，270，405 mg/kg），with 10 rats in each group. Blank group and model group were given 0.5％ sodium carboxymethyl cellulose solution intragastrically ；other groups were given relevant medicine intragastrically，once a day ，for consecutive 10 weeks. After last intragastric administration ，the pathomorphological changes of liver tissue were observed ；mRNA and protein expression of Collagen Ⅰ，α-SMA，PI3K，Akt and PTEN were detected in liver tissue. RESULTS ：Compared with model group ，OD value （except for medium-dose and high-dose groups of eligen- 7 containing serum）and the proportion of cells at S phase in administration groups were decreased significantly （P＜0.01）；late apoptotic rate ， early apoptotic rate （except for low-dose group ），total apoptotic rate and the proportion of cells at G 2/M phase increased significantly（P＜0.01）；mRNA and protein expression of Collagen Ⅰ，α-SMA，PI3K and Akt in cells and liver tissue were decreased significantly （P＜0.05 or P＜0.01），those of PTEN were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS ： Eligen-7 shows the effect of anti-hepatic fibrosis ， themechanism of which may be related to regulating the activity of PI 3K/Akt signaling pathway and promoting the apoptosis of hepatic stellate cells.
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Objective To evaluate the sensitivity and specificity of Rome Ⅲ criteria in diagnosis of functional dyspepsia (FD) and assess its value in differentiate FD from other organic diseases in upper gastrointestinal tract. Methods Four thousand nine hundred and sixty-two patients, who underwent gastroscopy from July to August 2006 and March to April 2007, were consecutively enrolled and interviewed face to face with a standard questionnaire. The patients who were diagnosed as FD were according to Rome Ⅲ criteria, and those who were diagnosed as upper gastrointestinal diseases, such as chronic erosive gastritis (CEG), gastric ulcer (GU), duodenal ulcer (DU) and gastric carcinoma (GC), were done by gastroscopy and pathology. The differences of clinical characteristics among these diseases were analyzed. Results The FD patients accounted for 7.58% (376/4962) with female in predominant (P = 0.000). The patient with CEG, GU, DU or GC accounted for 29.99% (1488/4962), 1.89% (94/4962),4.25% (211/4962) or 4.57% (227/4962), respectively, all with male in predominant (P<0.05). Further analysis indicated that the age of onset between patients with FD and DU was no difference, but was younger than those with other three diseases (P<0.05). The incidence of early satiation and postprandial in FD patients were higher than those in other patients (P<0.05). The incidence of belching, nausea and vomiting showed no difference among these patients(P>0.05). According to Rome Ⅲ criteria, the symptoms of epigastric pain, early satiation, postprandial fullness and epigastric burning had higher sensitivity and specificity (except epigastric burning)in diagnosing FD (P<0.05), with highest Youden index in epigastric pain (0.42) and postprandial fullness (0.46). Conclusion Rome Ⅲ criteria has high specificity and sensitivity in diagnosing FD, and also has an important value in differentiate FD from other organic diseases.
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Objective To investigate the clinical characteristics of primary gastrointestinal lymphoma (PGIL) on different origin site in order to improve its diagnosis.Methods The clinical data from 202 patients with PGIL diagnosed by histology from January 1999 to June 2007 were identified from the clinical databases of 8 hospitals in Wuhan area and retrospectively analyzed.The patients were divided into gastric,small intestinal and large intestinal lymphoma groups according to the site of origin and there clinical characteristics were compared.Results The PGIL localization was gastric in 113 (56.0%) cases, small intestine in 37(18.3%) cases and large intestine in 52 (25.7%) cases.One hundred and thirty (64.4%) were males and 72 (35.6%) were females.The male patients were predominant.The median duration of symptoms in gastric lymphoma group was longer than small intestinal lymphoma group (3.0 months vs.1.0 month,P=0.013).The most common symptoms were abdominal pain and anemia. The clinical stage was Ⅰ E and Ⅱ E in 71.3% of cases.The large intestinal lymphoma group presented more advanced-stage disease compared with gastric lymphoma group (P = 0.014).The frequent histological type was mucosa-associated lymphoid tissue lymphoma (MALT),diffuse large B-cell lymphoma and T-cell lymphoma.Gastric,small intestinal and large intestinal lymphomas presented more frequently as low-grade MALT lymphoma (56.9%),T-cell lymphoma (34.4%) and high-grade B-cell lymphoma (51.1%),respectively (all P value ＜0.05).The common macroscopic type of PGIL were nodular protruding and ulcerative type.Compared with gastric lymphoma,nodular protruding type was more common and ulcerative type was less common in large intestinal lymphoma (P = 0.000).The diagnosis confirmed by endoscopic biopsy were 58.7% (61/104),25.0% (4/16),48.2% (13/27) in gastric,small intestinal and large intestinal lymphoma groups,respectively.Conclusions The clinical characteristics are different in patients with different localization of PGIL including patient characters, initial symptoms,histological classification,clinical stage,macroscopic feature,endoscopic findings. Analysis of these clinical characteristics is helpful to improve its diagnosis.