MW-9, a chalcones derivative bearing heterocyclic moieties, ameliorates ulcerative colitis via regulating MAPK signaling pathway / 中国药理学通报

Aim To investigate the therapeutic effect of the MW-9 on ulcerative colitis(UC)and reveal the underlying mechanism, so as to provide a scientific guidance for the MW-9 treatment of UC. Methods The model of lipopolysaccharide(LPS)-stimulated RAW264.7 macrophage cells was established. The effect of MW-9 on RAW264.7 cells viability was detected by MTT assay. The levels of nitric oxide(NO)in RAW264.7 macrophages were measured by Griess assay. Cell supernatants and serum levels of inflammatory cytokines containing IL-6, TNF-α and IL-1β were determined by ELISA kits. Dextran sulfate sodium(DSS)-induced UC model in mice was established and body weight of mice in each group was measured. The histopathological damage degree of colonic tissue was assessed by HE staining. The protein expression of p-p38, p-ERK1/2 and p-JNK was detected by Western blot. Results MW-9 intervention significantly inhibited NO release in RAW264.7 macrophages with IC50 of 20.47 mg·L-1 and decreased the overproduction of inflammatory factors IL-6, IL-1β and TNF-α(P<0.05). MW-9 had no cytotoxicity at the concentrations below 6 mg·L-1. After MW-9 treatment, mouse body weight was gradually reduced, and the serum IL-6, IL-1β and TNF-α levels were significantly down-regulated. Compared with the model group, MW-9 significantly decreased the expression of p-p38 and p-ERK1/2 protein. Conclusions MW-9 has significant anti-inflammatory activities both in vitro and in vivo, and its underlying mechanism for the treatment of UC may be associated with the inhibition of MAPK signaling pathway.

Effect of Scutellaria baicalensis Georgi on metabolism in RSV infection mice based on metabolomics / 药学学报

This study, aiming at finding biomarkers which can assist in the diagnosis of respiratory syncytial virus (RSV) pneumonia and analyzing the metabolic pathways of anti-RSV activity of Scutellaria baicalensis Georgi (SG)., explores the improvement effect of SG on mice models infected by RSV with the metabolomics technology based on UPLC-Q-Exactive HF X-MS. Mice models affected by RSV are established by nasal drip method and the changes of body weight, rectal temperature and pathological damage of lung tissue are evaluated. The lung tissue samples of mice in each group are collected and analyzed by UPLC-Q-Exactive HF X-MS. The differential metabolites of SG drug intervention are explored by metabolomics technology, and the metabolic pathways regulated by SG are analyzed. The results show that SG can significantly improve the pathological state of the lung tissue of the mice and make its body weight and rectal temperature tend to be normal. In the lung tissue samples, 46 biomarkers, such as guanine, L-asparagine, and arachidonic acid, are screened for disease development in RSV model mice. SG improved RSV infection by recalling 22 potential biomarkers, such as uric acid, arachidonic acid, and alanine. The 22 potential markers mainly involved 11 abnormal metabolic pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, and arachidonic acid metabolism, alanine, aspartic acid and glutamate metabolism are closely related to the five metabolic pathways. SG improves RSV-infected mice mainly by regulating amino acids, lipids, cofactors and vitamins and nucleotide metabolites. All animal experiments were conducted under the guidance and approval of the Animal Ethics Review Committee of Shandong University of Traditional Chinese Medicine. (approval number: SDUTCM20210311001).

Clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors / 中华内科杂志

Objective: Cancer immunotherapy can lead to various side effects, termed immune-related adverse events (irAE). This study summarized and analyzed the clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors (ILICI). Methods: This is a retrospective case series study involving 11 patients diagnosed with ILICI at the Peking Union Medical College Hospital from November 2019 to November 2021. Patient demographic information and clinical data, including gender, age, ILICI onset, clinical and radiological manifestations, pathological features, treatment, and resumption of ICI were retrospectively collected and analyzed. Results: The patients were primarily males (9/11) with a median age of 65 (range: 32-73) years. ICI mainly resulted in either partial remission (4/11) or stable disease (3/11). ILICI occurred after a median of two cycles of anti-programmed cell death-1 (PD-1) therapy, with a median time from the initial and last anti-PD-1 therapy to ILICI onset of 57 days and 17 days, respectively. ILICI was mostly severe (3/11) or very severe (6/11). While the clinical and radiological manifestations were non-specific, the pathological features were active lobular hepatitis and portal inflammation, with prominent CD8+T lymphocyte infiltration. The basic treatment was hepatoprotective drugs (10/11). Glucocorticoids were used as the primary therapy (9/11) but were ineffective in 4 of 9 cases. Of these, 3 of 9 cases received combined treatment with mycophenolate mofetil (MMF), only one of whom achieved remission. By the end of the study, 2 of 11 cases had resumed ICI and neither had experienced an ILICI relapse. Conclusion: The ILICI patients in this study had a corresponding history of ICI treatment and pathological features. The main treatment included hepatoprotective drugs and glucocorticoids. Immunosuppressive drugs were added for some cases but had poor efficacy.

Regulatory Effect of Quyu Huatan Tongmai Prescription on Intestinal Microflora in Golden Hamster with Hyperlipidemia / 中国实验方剂学杂志

ObjectiveTo explore the regulatory effect of Quyu Huatan Tongmai prescription on intestinal mircoflora of hyperlipidemia golden hamster and scientific evidence for the compatibility. MethodSyrian golden hamsters were randomized into normal， model， prescription， stasis-dispelling （Quyu）， phlegm-dissolving （Huatan）， and detoxification （Jiedu） groups， with 8 in each group. Hyperlipidemia in golden hamsters was induced by high-fat diet （4 weeks）. Then hamsters in the Quyu group （1.11 g·kg-1）， Huatan group （0.39 g·kg-1）， Jiedu group （0.07 g·kg-1）， and prescription group （1.42 g·kg-1） were given （ig） corresponding drugs and those in the normal group and the model group received （ig） distilled water of equivalent volume， once a day for 6 weeks. Serum lipids were determined， and hematoxylin-eosin （HE） staining was used to observe the pathological morphology of the liver. Feces were collected for 16S rRNA gene high-throughput sequencing of intestinal flora. ResultCompared with normal group， the model group demonstrated increase in body weight （P<0.05， P<0.01） and blood lipids （P<0.01）， decrease in intestinal flora diversity （P<0.05， P<0.01）， and variation of the relative abundance of intestinal flora at phylum， family， and genus levels （P<0.05， P<0.01）. Compared with the model group， Quyu Huatan Tongmai prescription controlled the body weight change， reduced the serum triglyceride （TG）， total cholesterol （TC）， and low density lipoprotein cholesterol/high density lipoprotein cholesterol ratio （LDL-C/HDL-C） （P<0.05， P<0.01）， improved the structure of intestinal flora， decreased the ratio of Firmicutes to Bacteroides （P<0.01）， raised the abundance of Bacteroidaceae， Porphyromonadaceae， Rikenellaceae， and Pasteurella （P<0.05， P<0.01）， and lowered the relative abundance of Coriobacterium （P<0.05） in hyperlipidemia golden hamsters. All the split prescriptions improved blood lipids and intestinal flora of the hamsters and particularly， the lipids-lowering effect of the Jiedu group and the regulation of flora in the Huatan group were closer to those of the prescription group. ConclusionQuyu Huatan Tongmai prescription and the split prescriptions all alleviated the hyperlipidemia of golden hamsters to different degrees possibly by regulating intestinal flora structure and improving intestinal microecology. The effect of the prescription group was most significant， and coming in second was the Huatan group. This study also provides scientific evidence for the effect of Quyu Huatan Tongmai prescription.

Qi-Tai-Suan, an oleanolic acid derivative, ameliorates ischemic heart failure via suppression of cardiac apoptosis, inflammation and fibrosis / 中国天然药物

Although anti-thrombotic therapy has been successful for prevention of deaths from acute myocardial infarction (MI), by far, there are few preventive and therapeutic options for ischemic heart failure (IHF) after MI. Qi-Tai-Suan (QTS) is an oleanolic acid (OA) derivative which once underwent a clinical trial for treating hepatitis. In this study, we investigated the potential cardioprotective effect of QTS on IHF. IHF mouse model was constructed by coronary artery ligation in male C57BL/6J mice, and the protective effects of QTS on IHF were examined by echocardiography measurement, histological and TUNEL analysis, etc. We found that QTS exhibited promising cardioprotective effect on IHF. QTS treatment significantly improved cardiac function of IHF mice and the symptoms of heart failure. Notably, QTS had much better oral bioavailability (F = 41.91%) in mice than its parent drug OA, and took effects mainly as its original form. Mechanistically, QTS ameliorated ischemic heart failure likely through suppression of cardiac apoptosis, inflammation and fibrosis. Taken together, QTS holds great promise as a preventive and therapeutic agent for ischemic heart failure and related diseases.

Application and Prospect of Platelet Multi-Omics Technology in Study of Blood Stasis Syndrome / 中国结合医学杂志

The abnormality of platelet function plays an important role in the pathogenesis and evolution of blood stasis syndrome (BSS). The explanation of its mechanism is a key scientific issue in the study of cardiovascular and cerebrovascular diseases and treatment. System biology technology provides a good technical platform for further development of platelet multi-omics, which is conducive to the scientific interpretation of the biological mechanism of BSS. The article summarized the pathogenesis of platelets in BSS, the mechanism of action of blood activating and stasis resolving drugs, and the application of genomics, proteomics, and metabonomics in platelet research, and put forward the concept of "plateletomics in BSS". Through the combination and cross-validation of multi-omics technology, it mainly focuses on the clinical and basic research of cardiovascular and cerebrovascular diseases; through the interactive verification of multi-omics technology and system biology, it mainly focuses on the platelet function and secretion system. The article systematically explains the molecular biological mechanism of platelet activation, aggregation, release, and other stages in the formation and development of BSS, and provides a new research idea and method for clarifying the pathogenesis of BSS and the mechanism of action of blood activating and stasis resolving drugs.

Realgar (α-As4S4) Treats Myelodysplastic Syndromes through Reducing DNA Hypermethylation / 中国结合医学杂志

DNA hypermethylation is an epigenetic modification that plays a critical role in the oncogenesis of myelodysplastic syndromes (MDS). Aberrant DNA methylation represses the transcription of promotors of tumor suppressor genes, inducing gene silencing. Realgar (α-As4S4) is a traditional medicine used for the treatment of various diseases in the ancient time. Realgar was reported to have efficacy for acute promyelocytic leukemia (APL). It has been demonstrated that realgar could efficiently reduce DNA hypermethylation of MDS. This review discusses the mechanisms of realgar on inhibiting DNA hypermethylation of MDS, as well as the species and metabolisms of arsenic in vivo.

Relationship between thyroid function, iodine nutrition and autoantibodies in pregnant women / 中华地方病学杂志

Objective:To analyze the relationship between thyroid function, iodine nutrition level and thyroid autoantibodies in pregnant women.Methods:In 2016, pregnant women were selected from different water iodine areas in Tianjin. A disposable urine sample of 25 ml was collected to determine urine iodine, and 3 ml of intravenous non-anticoagulated blood was collected to determine serum thyroid hormones and thyroid autoantibodies. Chemiluminescence immunoassay was used to determine the thyroid function indexes [free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid-stimulating hormone (TSH)], thyroid peroxidase antibody(TPOAb) and thyroglobulin antibody (TgAb) levels in pregnant women. According to serum TSH and FT 4 levels, pregnant women were divided into the euthyroidism group and subclinical hypothyroidism group(referred to as hypothyroidism). Urine iodine arsenic-cerium catalytic spectrophotometry was used to detect the urine iodine level of pregnant women. The correlation between urinary iodine levels and thyroid function indexes of the two groups of pregnant women was analyzed, and single factor and multivariate logistic regression were used to analyze the influencing factors of hypothyroidism. Results:There were 798 pregnant women in the euthyroidism group and 28 pregnant women in the hypothyroidism group. The hypothyroidism detection rate was 3.39% (28/826). In the euthyroidism group and hypothyroidism group, 43.73% (349/798) and 46.43% (13/28) of pregnant women had urine iodine levels < 150 μg/L, respectively. There was no correlation between urine iodine level and serum TSH ( r = 0.038, P > 0.05), and a positive correlation with serum FT 4 ( r = 0.077, P < 0.05). The differences between the euthyroidism group and the hypothyroidism group in the median (interquartile range) of TPOAb and TgAb were statistically significant ( Z = - 3.986, - 3.411, P < 0.05). After logistic regression analysis, TPOAb was a risk factor for hypothyroidism ( OR = 3.428, 95% CI: 1.131 - 10.388). Conclusions:Urine iodine and thyroid autoantibodies should be screened as routine examination items before or during pregnancy. Correct iodine deficiency in time, avoid blindly excessive iodine supplement, and reduce the occurrence of subclinical hypothyroidism in pregnant women, so as to reduce the adverse effects on mothers and their offspring.

Thirty-year follow-up observation of the impact of iodine fortification strategy on intellectual development of children / 中华地方病学杂志

Objective:To follow up and observe the intellectual development of school children aged 8 to 10 in Baicheng County, Xinjiang Uygur Autonomous Region, which was a severe iodine deficiency disorders region in history, before and after effective control of the disease, in order to evaluate the impact of iodine supplementation on protection of children's intellectual development and provide a theoretical basis for scientific supplements of iodine.Methods:From 1989 to 2018, Combined Raven's Test for Rural in China (CRT-RC) was used to observe the intellectual development status of 660 Uyghur school children aged 8 to 10 in Baicheng County in 1989, 2002, 2006, 2012 and 2018, respectively. Children's intelligence quotient (IQ) was calculated using CRT-RC's 1987 normal sample of rural children in the same age group; the data of average iodized salt coverage rate (C-IS) and childhood goiter rate (GR) from multiple local surveys and the median urinary iodine (MUIC) of children were collected, combined with the "Criteria for Elimination of Iodine Deficiency Disorders" (GB 16006-2008) and the United Nations International Children's Emergency Fund (UNICEF) recommended standards, the status of iodine deficiency during children's growth (IDG) was divided into complete exposure to iodine deficiency, no exposure, and semi-exposed. The Flynn effect (FE) gain was calculated using norm samples of children aged 8 to 10 in 1987, 1996 and 2006 of CRT-RC, and the differences in children's intellectual development after FE correction before and after IDG reached the standard were compared.Results:The IQ of children were (81.67 ± 14.13), (83.26 ± 14.05), (89.68 ± 13.58), (98.50 ± 14.33) and (103.23 ± 15.25) points in Baicheng County in 1989, 2002, 2006, 2012 and 2018, respectively, the difference between different years was statistically significant ( F = 58.357, P < 0.01). The three indicators of C-IS, GR, and MUIC didn't meet the standards during the IDG evaluation period in the 1989, 2002, and 2006 groups, which were the complete exposure to iodine deficiency; in the 2012 group, only the MUIC met the standard, which was semi-exposed; in the 2018 group, three indicators all met the standard, which was no exposure. The FE gains of 1987 with 1996, 1996 with 2006 were 0.96 points/year and 0.74 points/year, respectively; after FE correction, the actual gains of IQ of 2002 and 2006 compared with 1989, 2012 and 2018 compared with 2006 were - 9.57, - 6.11, 4.38, and 4.67 points, respectively. Conclusions:In iodine deficiency areas, intermittent iodine supplementation (1989 - 2009) for children exposed to iodine deficiency during growth still cannot effectively protect children's intellectual development; continuous and effective iodine supplementation (2010 - 2018) with iodized salt as the core and covering children's growth period has obvious positive effects on protection of children's normal intellectual development. In the future, we will continue to observe the influence of IDG full-cycle suitable iodine nutrition on children's intellectual development.

Development of an eco-friendly and fast HPLC method for quantitative analysis of four nucleosides in Cordyceps and related products / 中国天然药物

An eco-friendly and fast HPLC method was developed for the determination of adenosine, inosine, guanosine and uridine in Cordyceps and related products (fermented mycelia of Hirsutella sinensis andPaecilomyces hepiali). The sample was ultrasonically extracted using 0.5% phosphoric acid solutions for 2.5 min. Sample separation was performed on a Poroshell SB-Aq column (50 mm × 4.6 mm, 2.7 μm) using eco-friendly mobile phase consisting of formic acid and ammonium formate aqueous solution at a flow rate of 1.0 mL·min

Research progress of change of platelet in blood stasis syndrome and effect of traditional Chinese medicine / 中国中药杂志

The traditional Chinese medicine(TCM) syndrome of blood stasis refers to blood stagnation in meridians and viscera, with the main symptoms of pain, mass, bleeding, purple tongue, and unsmooth pulse. Cardiovascular and cerebrovascular diseases are among the major chronic diseases seriously harming the health of the Chinese. Among the coronary heart disease and stroke patients, most demonstrate the blood stasis syndrome. Platelet is considered to be one of the necessary factors in thrombosis, which closely relates to the TCM syndrome of blood stasis and the occurrence of cardiovascular and cerebrovascular diseases. The clinical and laboratory research on platelet activation and aggregation has been paid more and more attention. Its purpose is to treat and prevent blood stasis syndrome. In this study, the authors analyzed the research on the dysfunctions of platelets in blood stasis syndrome, biological basis of TCM blood stasis syndrome, and the effect of blood-activating stasis-resolving prescriptions on platelets, aiming at providing a reference for exploring the mechanism of platelet intervention in the treatment of TCM blood stasis syndrome and the pathways and targets of Chinese medicine in the prevention and treatment of the syndrome.

Metabonomics: A Useful Tool to Reveal Underlying Relationships between Altered Chinese Medicine Syndromes and Ultrafiltration in Treatment of Heart Failure / 中国结合医学杂志

OBJECTIVE@#To reveal the underlying relationships between Chinese medicine (CM) syndromes and ultrafiltration (UF) in the treatment of heart failure based on a metabonomic approach.@*METHODS@#Seventeen acute decompensated heart failure (ADHF) patients were enrolled, and their CM syndromes before and after UF were collected. In addition, their venous plasma collected before and after UF was used for liquid chromatographmass spectrometer-based metabonomic analysis. Both reversed phase liquid chromatography and hydrophilic interaction liquid chromatography were used to analyze the plasma samples. Partial least-squares to latent structure-discriminant analyses were used for data analysis.@*RESULTS@#An obvious difference was observed pre- and post-treatment. A total of 17 potential biomarkers associating with alterd syndromes with UF including hypoxanthine, 1-methylhistidine, phytosphingosine, O-decanoyl-R-carnitine, etc. were screened out, showing a significant change after UF. The major adjusted metabolic pathways were purine metabolism, histidine metabolism, leucine and isoleucine metabolism, arginine and proline metabolism, carnitine shuttle, sphingolipid metabolism and phospholipid metabolism.@*CONCLUSIONS@#Metabonomic approach is a useful tool to identify potential biomarkers of altered syndromes link to UF and could provide a theoretical basis for further research on the therapeutic mechanism of UF combined with CM.

Advances of the effects of iodine on brain development / 中华地方病学杂志

Iodine is an essential element in the synthesis of thyroid hormones. The normal brain development of children depends on thyroid hormone, and the critical period is in the first three years of life. Iodine deficiency is the most influential and preventable factor that is known to cause brain neurodevelopmental disorders in children. Therefore, research on the relationship between iodine nutrition and thyroid function of pregnant women and brain development of offspring has always been a hot spot in the research and prevention of iodine deficiency disorders. However, there has been no clear conclusion on the influence and extent of thyroid dysfunction such as hidden iodine deficiency in pregnant women (urinary iodine is 100-150 μg/L), subclinical hypothyroidism and hypothyroidism on the brain development of offspring. This article reviews the research in this field, the related research on the effects of iodine deficiency, iodine supplementation and iodine overdose on children's brain development, and introduces the preventive and therapeutic effects of iodine and thyroxine supplementation during pregnancy.

Re-examination of the safety of potassium iodate in edible salt——evidences and clarification of the use and toxicological studies of iodate as reinforcer / 中华地方病学杂志

In response to the recent interest in potassium iodate iodized (KIO 3) salt safety, we reviewed the background of KIO 3 in replacing of potassium iodine (KI) as salt fortificator and its effect in prevention and control of iodine deficiency disorders (IDD) or endemic goiter, the decision-making changes of fortificator of iodized salt in China, the research and progress of toxicology, and whether IO 3- exits in urine without decomposition or not. Our inclusions are: it is believed that the decision of the international organizations and agencies of national and local governments about the safety of KIO 3 in iodized salt is supported by adequate and scientific evidents. When it comes to the safety of KIO 3 added in iodized salt, it must be based on the trace amount of KIO 3 in salt which is limited while intaking. Reductive substances in food, cooking heating or reduction system of human body might quickly reduce trace IO 3- to I -, therefore, IO 3- might not be found in fresh urine.

Extraintestinal manifestations and intestinal complications in children with Crohn's disease: an analysis of 54 cases / 中国当代儿科杂志

OBJECTIVE@#To summarize the extraintestinal manifestations and intestinal complications in children with Crohn's disease (CD).@*METHODS@#The clinical data of 54 children who were diagnosed with CD in Peking Union Medical College Hospital from January 2008 to December 2018 were collected for retrospective analysis of extraintestinal manifestations and intestinal complications. According to the location of the lesion, the children were divided into ileocolonic group (30 cases), colonic group (6 cases), and ileal group (18 cases).@*RESULTS@#In the 54 children, the mean age at diagnosis was 14.5±2.7 years, and the median duration from disease onset to definite diagnosis was 20 months (range: 1-36 months). Twenty-four patients (44%) had extraintestinal manifestations, with the two most common manifestations being growth retardation (11 cases, 20%) and oral mucosal ulcer (10 cases, 19%), followed by arthritis (2 cases, 4%), erythema nodosum (2 cases, 4%), and cholecystitis (2 cases, 4%). There were no significant differences in the incidence of extraintestinal manifestations among the three groups (P=0.792). The most common intestinal complications were anal fistula/perianal abscess (13 cases, 24%), followed by intestinal fistula (5 cases, 9%) and intestinal obstruction (4 cases, 7%). There was a significant difference in the incidence of intestinal complications among the three groups (P=0.0406). No intestinal complications were reported in the colonic group.@*CONCLUSIONS@#Extraintestinal manifestations and intestinal complications are common in children with CD. Perianal examinations should be performed in children with suspected CD. Intestinal complications are less common in children with colonic CD, which may be associated with relatively mild disease condition.

Evaluation and Early Diagnosis of Gastrointestinal Failure in Acute Pancreatitis / 中国医学科学院学报

To investigate the application of Acute Gastrointestinal Injury(AGI) grading in evaluating gastrointestinal failure in patients with acute pancreatitis(AP). In this retrospective observational study,patients presented with moderate severe AP and severe AP in our hospital from October 2013 to October 2016 were consecutively enrolled.Logistic regression analysis and receiver operating characteristic curve were used to explore and evaluate potential predictors of gastrointestinal failure. A total of 202 patients were included in this study,with 90 cases(44.6%) identified as gastrointestinal failure.Survival curve showed significantly increased risk of death in patients with gastrointestinal failure( < 0.05).Logistic regression analysis showed age(=1.06,95%:1.03-1.09,<0.001),complaint of stopping flatus and defecation(=7.02,95%:2.08-23.66,=0.002),increased counts of white blood cells in peripheral blood(=1.09,95%:1.02-1.17,=0.015),decreased level of serum albumin(=0.93,95%:0.86-1.00,=0.048),and increased level of serum creatinine at admission(=1.02,95%:1.01-1.04,=0.001) were the independent risk factors of gastrointestinal failure.The area under curves of Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) and Beside Index for Severity in Acute Pancreatitis (BISAP) scores in diagnosing gastrointestinal failure were 0.999 and 0.782,respectively. Gastrointestinal failure can remarkably increase the risk of death in patients with AP.Both APACHE Ⅱ and BISAP scores at admission are useful in diagnosing gastrointestinal failure in patients with AP.

Correlation between Vitamin D Status and Gut Microbiota in Patients with Inflammatory Bowel Disease / 中国医学科学院学报

Objective To investigate the correlation between serum total 25-hydroxyvitamin D[T-25(OH)D]level and fecal microbiota in patients with inflammatory bowel disease(IBD). Methods Twenty-three patients with IBD completed the tests for serum T-25(OH)D,and the fecal microbiota was studied using V4 hypervariable region of 16S ribosomal RNA(rRNA)gene sequencing.According to serum T-25(OH)D level,the patients were divided into three groups including vitamin D normal group(

Effects of intrauterine exposure to thyroid dysfunction on the development of brain neurons in neonatal rats / 中华内分泌代谢杂志

Objective To investigate the expression of MCT8, DCX, SHH and ARC/ARG3. 1 in brain neurons of neonatal rats exposed to thyroid dysfunction in uterus. Methods Wistar pregnant rats were randomly divided into control group and experimental groups that rats were drunk water with 1, 3, or 5 ppm propylthiouracil ( PTU). The thyroid function and morphological changes of PND1 and PND7 were detected. The expression of MCT8, DCX, SHH, ARC/ARG3. 1 protein in cerebral cortex and hippocampus were detected by Western blot or immunohistochemistry. Results (1) The levels of TT4 decreased significantly in PND1 pups of PTU 3 ppm and 5 ppm groups (P＜0.05 or P＜0.01). The TSH levels significantly increased while FT4 levels significantly decreased in pups of PTU 5 ppm group on PND7 ( P＜0. 05). ( 2) The number NV, V, S, and cross-sectional area of thyroid follicles in offspring of PTU groups were significantly higher than those in the control group on postnatal day 1 and 7 (P＜0.05 or P＜0.01, respectively). (3) The expression of MCT8 in cortex and hippocampus gradually increased with the increase dose of PTU on two postnatal days, but there was significant change in PTU 5 ppm group on PND1 ( P＜0.05). The expression of SHH in pup cortex decreased with the increase of PTU exposure dose on PND7. DCX protein expression in the pup cortex on two postnatal days showed an uptrend with the increase of PTU exposure dose. ARC/ARG3.1 protein levels in hippocampal CA1 area of the pups increased significantly in PTU 1 ppm group on PND1 than that in the same-day control group ( P＜0. 05). Conclusion The damaged neurons of neonatal rats exposed to hypothyroidism in utero can be improved with the gradual recovery of thyroid function, but can not be completely restored to normal level.

Effect of Aging on Experimental Colitis in Mice and Its Associated Mechanism / 中国医学科学院学报

Objective To explore whether aging increases severity of colitis in mice and its mechanism.Methods Young (6-8 weeks)and aged (56 weeks) C57Bl/6 mice were divided into the control and experimental group (n=5,each). Dextran sodium sulfate(DSS) was used to induce acute colitis mouse model in the experimental group.The mRNA expressions of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in colon were measured by RT-PCR. Tight junctions (TJs) of intestinal epithelial cells was examined by transmission electron microscopy (TEM). Protein expressions of E-cadherin and occludin were detected by Western blotting and immunohistochemistry in colon.Results Compared with the young DSS-induced mice,the aged DSS-induced mice had more weight loss(t=3.679,P=0.006),higher disease indexes (t=2.496,P=0.037),higher histologic scores(U=0.000,P=0.008) and higher colonic IL-6 level (U=4.000,P=0.191). The TJs of intestinal epithelial cells were discontinuous in old healthy rats,and the TJs were destroyed significantly in both young and aged DSS-induced mice. Compared with the young DSS-induced mice,the aged DSS-induced mice had decreased protein expressions of E-cadherin (t=0.184,P=0.863)and occludin (t=0.399,P=0.710).Conclusions Aging leads to more severe disease following DSS challenge. Age-related deterioration in the functions of the gastrointestinal barrier and integrity may be one of the possible mechanisms.

Amoxicillin-Clarithromycin-Containing Bismuth Quadruple Therapy for Primary Eradication of Helicobacter pylori / 中国医学科学院学报

Objective To evaluate the efficacy and safety of amoxicillin-clarithromycin-containing bismuth quadruple regimen as a primary therapy for Helicobacter pylori (Hp) eradication.Methods A total of 102 Hp-infected outpatients diagnosed by C-or C-urea breath test from December 2015 to June 2017 were enrolled and received 14-day bismuth quadruple therapy (esomeprazole 20 mg bid,bismuth potassium citrate 220 mg bid,amoxicillin 1000 mg bid,and clarithromycin 500 mg bid for 14 days). Hp status was assessed by C-or C-urea breath test 4 weeks,8 weeks,6 months,and 12 months after the treatment. The primary outcome was Hp eradication rate,which was analyzed by intention-to-treat (ITT) and per-protocol (PP) analyses. The second outcomes were Hp infection recurrence,symptomatic benefit from Hp eradication,and safety. Results A total of 101 patients,of which 65 patients had dyspeptic symptoms before eradication,completed the study. Hp eradication rates by ITT analysis and by PP analysis were 88.2% and 89.1%,respectively. Only in two of 84 patients,who were followed for 8 weeks after eradication,Hp became positive. No Hp recurrence happened at the 6-month and 12-month follow-up and the annual recurrence rate was 2.4%. The symptomatic relief rates at the 4-week,8-week,6-month and 12-month follow-up were 81.5%,75.4%,71.2%,and 70.2% respectively. Eleven of 101 patients had mild and similar side-effects,which were well tolerated.Conclusion Amoxicillin-clarithromycin-containing bismuth quadruple regimen can be used as the standard therapy for Hp eradication.