A new class of potent liver injury protective compounds: Structural elucidation, total synthesis and bioactivity study

A new class of potent liver injury protective compounds, phychetins A-D ( 1- 4) featuring an unique 6/6/5/6/5 pentacyclic framework, were isolated and structurally characterized from a Chinese medicinal plant Phyllanthus franchetianus. Compounds 2- 4 are three pairs of enantiomers that were initially obtained in a racemic manner, and were further separated by chiral HPLC preparation. Compounds 1- 4 were proposed to be originated biosynthetically from a coexisting lignan via an intramolecular Friedel-Crafts reaction as the key step. A bioinspired total synthesis strategy was thus designated, and allowed the effective syntheses of compounds 2- 4 in high yields. Some of compounds exhibited significant anti-inflammatory activities in vitro via suppressing the production of pro-inflammatory cytokine IL-1β. Notably, compound 4, the most active enantiomeric pair in vitro, displayed prominent potent protecting activity against liver injury at a low dose of 3 mg/kg in mice, which could serve as a promising lead for the development of acute liver injury therapeutic agent.

Overexpression of NAT10 induced platinum drugs resistance in breast cancer cell / 中华肿瘤杂志

Objective: To observe the platinum drugs resistance effect of N-acetyltransferase 10 (NAT10) overexpression in breast cancer cell line and elucidate the underlining mechanisms. Methods: The experiment was divided into wild-type (MCF-7 wild-type cells without any treatment) group, NAT10 overexpression group (H-NAT10 plasmid transfected into MCF-7 cells) and NAT10 knockdown group (SH-NAT10 plasmid transfected into MCF-7 cells). The invasion was detected by Transwell array, the interaction between NAT10 and PARP1 was detected by co-immunoprecipitation. The impact of NAT10 overexpression or knockdown on the acetylation level of PARP1 and its half-life was also determined. Immunostaining and IP array were used to detect the recruitment of DNA damage repair protein by acetylated PARP1. Flow cytometry was used to detect the cell apoptosis. Results: Transwell invasion assay showed that the number of cell invasion was 483.00±46.90 in the NAT10 overexpression group, 469.00±40.50 in the NAT10 knockdown group, and 445.00±35.50 in the MCF-7 wild-type cells, and the differences were not statistically significant (P>0.05). In the presence of 10 μmol/L oxaliplatin, the number of cell invasion was 502.00±45.60 in the NAT10 overexpression group and 105.00±20.50 in the NAT10 knockdown group, both statistically significant (P<0.05) compared with 219.00±31.50 in wild-type cells. In the presence of 10 μmol/L oxaliplatin, NAT10 overexpression enhanced the binding of PARP1 to NAT10 compared with wild-type cells, whereas the use of the NAT10 inhibitor Remodelin inhibited the mutual binding of the two. Overexpression of NAT10 induced PARP1 acetylation followed by increased PARP1 binding to XRCC1, and knockdown of NAT10 expression reduced PARP1 binding to XRCC1. Overexpression of NAT10 enhanced PARP1 binding to LIG3, while knockdown of NAT10 expression decreased PARP1 binding to LIG3. In 10 μmol/L oxaliplatin-treated cells, the γH2AX expression level was 0.38±0.02 in NAT10 overexpressing cells and 1.36±0.15 in NAT10 knockdown cells, both statistically significant (P<0.05) compared with 1.00±0.00 in wild-type cells. In 10 μmol/L oxaliplatin treated cells, the apoptosis rate was (6.54±0.68)% in the NAT10 overexpression group and (12.98±2.54)% in the NAT10 knockdown group, both of which were statistically significant (P<0.05) compared with (9.67±0.37)% in wild-type cells. Conclusion: NAT10 overexpression enhances the binding of NAT10 to PARP1 and promotes the acetylation of PARP1, which in turn prolongs the half-life of PARP1, thus enhancing PARP1 recruitment of DNA damage repair related proteins to the damage sites, promoting DNA damage repair and ultimately the survival of breast cancer cells.

Progress in the role of endometrial glucose metabolism in embryo implantation / 生理学报

The synthesis and decomposition of glycogen adjust the blood glucose dynamically to maintain the energy supply required by the cells. As the only hormone that lowers blood sugar in the body, insulin can promote glycogen synthesis by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and increasing glucose transporter translocation, and inhibit gluconeogenesis to lower blood glucose. In the endometrium, glycogen metabolism is active, but gluconeogenesis does not occur. The glycogen metabolism in the endometrium is controlled not only by the classical glucose regulating hormones, but also by the ovarian hormones. The functional activities related to implantation of the endometrium during the implantation window require glucose as energy source. A large amount of glucose is used to synthesize glycogen in the endometrium before implantation, which could meet the increased energy demand for embryo implantation. In diabetes, glycogen metabolism in the endometrium is impaired, which frequently leads to implantation failure and early abortion. This article reviews the glycogen metabolism in the endometrium and discusses its role in embryo implantation, which provide new ideas for embryo implantation research and infertility treatment.

Research progress of laboratory diagnostic methods of dengue virus / 中华疾病控制杂志

Dengue virus(DENV) has been identified by World Health Organization as a major public health problem in tropical and subtropical regions. In recent years, dengue outbreaks have become more and more frequent in the world. In 2019, dengue outbreaks of varying degrees have occurred in the Philippines, Thailand, Bangladesh, Myanmar and Chongqing City in China. The laboratory diagnostic method of DENV is of great significance to the prevention and control of dengue epidemic. Therefore, the methods and strategies of DENV laboratory diagnosis are reviewed in this paper. By reviewing the traditional diagnostic methods and looking forward to the emerging diagnostic strategies, this paper aims to provide a reference to select the appropriate laboratory diagnostic scheme for the outbreak of dengue.

The association between the two more common genetic causes of spermatogenic failure: a 7-year retrospective study / 亚洲男科学杂志(英文版)

Chromosomal abnormalities and Y chromosome microdeletions are considered to be the two more common genetic causes of spermatogenic failure. However, the relationship between chromosomal aberrations and Y chromosome microdeletions is still unclear. This study was to investigate the incidence and characteristics of chromosomal aberrations and Y chromosome microdeletions in infertile men, and to explore whether there was a correlation between the two genetic defects of spermatogenic failure. A 7-year retrospective study was conducted on 5465 infertile men with nonobstructive azoospermia or oligozoospermia. Karyotype analysis of peripheral blood lymphocytes was performed by standard G-banding techniques. Y chromosome microdeletions were screened by multiplex PCR amplification with six specific sequence-tagged site (STS) markers. Among the 5465 infertile men analyzed, 371 (6.8%) had Y chromosome microdeletions and the prevalence of microdeletions in azoospermia was 10.5% (259/2474) and in severe oligozoospermia was 6.3% (107/1705). A total of 4003 (73.2%) infertile men underwent karyotyping; 370 (9.2%) had chromosomal abnormalities and 222 (5.5%) had chromosomal polymorphisms. Karyotype analysis was performed on 272 (73.3%) patients with Y chromosome microdeletions and 77 (28.3%) had chromosomal aberrations, all of which involved sex chromosomes but not autosomes. There was a significant difference in the frequency of chromosomal abnormalities between men with and without Y chromosome microdeletions (P< 0.05).

Comprehensive genetic diagnosis of patients with Duchenne/Becker muscular dystrophy (DMD/BMD) and pathogenicity analysis of splice site variants in the DMD gene / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are caused by mutations in the DMD gene. The aim of this study is to identify pathogenic DMD variants in probands and reduce the risk of recurrence of the disease in affected families. Variations in 100 unrelated DMD/BMD patients were detected by multiplex ligation-dependent probe amplification (MLPA) and next-generation sequencing (NGS). Pathogenic variants in DMD were successfully identified in all cases, and 11 of them were novel. The most common mutations were intragenic deletions (69%), with two hotspots located in the 5' end (exons 2-19) and the central of the DMD gene (exons 45-55), while point mutations were observed in 22% patients. Further, c.1149+1G>A and c.1150-2A>G were confirmed by hybrid minigene splicing assay (HMSA). This two splice site mutations would lead to two aberrant DMD isoforms which give rise to severely truncated protein. Therefore, the clinical use of MLPA, NGS, and HMSA is an effective strategy to identify variants. Importantly, eight embryos were terminated pregnancies according to prenatal diagnosis and a healthy boy was successfully delivered by preimplantation genetic diagnosis (PGD). Early and accurate genetic diagnosis is essential for prenatal diagnosis/PGD to reduce the risk of recurrence of DMD in affected families.

Chemical constituents from Vernonia bockiana / 中国天然药物

A new sesquiterpenoid and two pregnane steroids, named vernobockolide C (1) and vernobockones A and B (2 and 3), respevtively, along with a known sesquiterpenoid, 7, 10-epoxy-11-hydroxy-bisabol-2-en-15-al, were isolated from the aerial part of Vernonia bockiana. Their structures were elucidated on the basis of extensive spectroscopic data analysis, especially 2D NMR (HSQC, HMBC, and ROESY). This study further expands the chemical space of this underexplored species.

Application of probe-based confocal laser endomicroscopy in diagnosis of gastric carcinoma and precancerous lesions / 浙江大学学报·医学版

OBJECTIVE@#To assess the application of probe-based confocal laser endomicroscopy (pCLE) in diagnosis of gastric carcinoma and precancerous lesions.@*METHODS@#Patients underwent pCLE in the First Affiliated Hospital of Zhejiang University School of Medicine during December 2013 and November 2014 and in the First Affiliated Hospital of Zhejiang Chinese Medical University during January 2014 and December 2017 were enrolled. The consistency between pCLE diagnosis and pathological diagnosis of gastric lesions, including atrophic gastritis, gastric intestinal metaplasia, low-grade intraepithelial neoplasia and high-grade intraepithelial neoplasia (including gastric carcinoma) was analyzed.@*RESULTS@#Totally 154 gastric lesions from 119 patients were detected by pCLE. Using pathological diagnosis as gold standard, the sensitivity, specificity, coincidence rate and κ value of pCLE diagnosis for atrophic gastritis were 94.34%, 91.09%, 92.21%and 0.83; those indicators for gastric intestinal metaplasia were 84.47%, 92.16%, 87.01% and 0.72. The coincidence rate and κ value of pCLE diagnosis of complete gastric intestinal metaplasia were 0.75 and 0.49; for incomplete gastric intestinal metaplasia were 0.79 and 0.48, respectively. The sensitivity, specificity, coincidence rate and κ value of pCLE diagnosis for low-grade intraepithelial neoplasia were 85.29%, 87.50%, 87.01%and 0.66; those for high-grade intraepithelial neoplasia (including gastric carcinoma) were 95.83%, 97.17%, 96.75%and 0.92.@*CONCLUSIONS@#pCLE can be used for diagnosis of gastric carcinoma and pericancerous lesions and also for typing of gastric intestinal metaplasia.

Evaluation of confocal laser endomicroscopy on pathological changes of intestinal mucosa repairing for patients with ulcerative colitis / 中华消化内镜杂志

Objective To evaluate the advantages of confocal laser endomicroscopy(CLE)for function repairing of ulcerative colitis(UC). Methods Thirty patients with UC who were diagnosed and treated in the First Affiliated Hospital of Zhejiang University Medical College between July 2014 and December 2016 were enrolled in the study group. The control group consisted of 10 patients who were diagnosed as having colonic polyps with colonoscopy and underwent polypectomy in the same period. Both groups were examined with white light endoscopy and CLE,then the fluorescein leakage score was compared. Results There were 10 out of 30 cases in the study group whose whole intestinal mucosa were judged as normal under white light endoscopy. In the other 20 cases,there were parts of intestinal mucosa being judged as abnormal. All of the 10 cases in the control group were with normal colon mucosa. There was a significant difference on fluorescein leakage score by CLE between the study group which showed normal by white light endoscopy and the control group(P<0.05). The fluorescein leakage score by CLE was significant difference between the abnormal intestinal segment and normal intestinal segment in 20 patients with active UC(P<0.05). Spearman correlation analysis showed that there was non-ranked correlation between the fluorescein leakage score of CLE and histopathological findings of biopsy in UC patients with normal mucosa of the left colon under white light endoscopy(rs=0.394,P>0.05). Conclusion In the process of mucosal healing of UC patients,structural repair can be found firstly through CLE. Mucosal healing under white light endoscopy cannot represent the functional recovery. CLE is more effective than the histopathology in the evaluation of mucosal barrier function.

The role of immunoglobulin G isotype rheumatoid factors on the diagnosis and prognosis of rheumatoid arthritis / 中华风湿病学杂志

Objective To investigate the diagnostic and prognostic value of immunoglobulin (Ig)G isotype rheumatoid factors (IgG-RF) in rheumatoid arthritis (RA).Methods Five hundred patients with RA were enrolled randomly.IgG-RF antibody was detected by enzyme-linked immunosorbent assay (ELISA).The correlations between serum IgG-RF antibody and clinical features,disease activities,laboratory of RA patients were evaluated.The comparison of continuous variables was performed by using the Student t-test or Mann-Whitney U test in accordance with normality testing.Chi-square test was performed for categorical variables.A value of P less than 0.05 was considered statistically significant.Results ① IgG-RF was positive in 41.0％ (205/500) of RA patients.In patients with anti-citrullinated protein/peptide autoanti-bodies (ACPA) negative,RF negative or the seronegative patients (both ACPA and RF were negative),the positive rate of IgG-RF was 22.4％(24/107),13.2％(17/129) and 9.1％(5/55),respectively.② Compared with patients with negative IgG-RF,patients with positive IgG-RF had higher rates of joint deformity [(58.5％(120/205) vs 39.3％(116/295),x2=17.918] and bone erosion [(75.6％(118/156) vs 60.3％(140/232),x2=9.796] (P＜0.01,respectively).③ The patients with positive IgG-RF had higher rates of elevated ESR(86.3％ vs 67.8％,x2=22.426),IgG(29.9％ vs 20.0％,x2=6.310),compared to patients with negative IgG-RF (P＜0.05,respectively),and levels of ESR [(59±35) mm/1 h vs (47±32) mm/1 h,t=3.989] and CRP [(390±450) mg/L vs (290±340) mg/L,t=3.004] was higher in IgG-RF positive group than the negative (P＜0.01,respectivelys).④ Compared with the IgG-RF negative patients,the positive group had higher smoking rates (22.9％ vs 12.5％,x2=9.227),higher current smoking rates (16.6％ vs 7.1％,x2=11.119) and higher smoking index [(107±238) vs (49±161),t=3.199](P＜0.05,respectively).Conclusion IgG-RF had its clinical values in RA diagnosis.IgG-RF is significantly associated with joint deformity,bone erosions and smoking.

Inhibitory effect and mechanism of paeoniflorin on proliferation of hypertrophic scar fibroblasts / 中国比较医学杂志

Objective To explore the inhibitory effect and related mechanism of paeoniflorin on proliferation of hypertrophic scar(HS)fibroblasts. Methods HS fibroblasts were cultured with 0(control),200,400,800 μmol/L of paeoniflorin for 24,48,and 72 h. Cell viability was detected by MTT assay. Cell apoptosis was detected using Hoechst staining. Cell cycle was measured by flow cytometry. The levels of type I collagen(COL I)and type III collagen(COL III)were detected by enzyme linked immunosorbent assay(ELISA). The expressions of transforming growth factor-β (TGF-β)/Smad signaling pathway related proteins, as well as matrix metalloproteinase 1(MMP1)and MMP13 were detected by Western blot. Results 200, 400, 800 μmol/L of paeoniflorin reduced the cell viability of HS fibroblasts significantly(P < 0.01), with the nuclei turning pale and shrunken, and caused cell cycle arrest at G1 phase(P <0.01). Moreover, the levels of COL I and COL III in the cells were decreased significantly(P < 0.01), and the expressions of MMP1, MMP13, TGF-β1, p-Smad2 and p-Smad3 were down-regulated significantly(P < 0.01). Conclusions Paeoniflorin can obviously inhibit the proliferation and collagen synthesis of hypertrophic scar fibroblasts,probably through inhibition of the TGF-β1/Smad signaling pathway.

Trends of soil-transmitted nematode infections in Jiangxi Province / 中国血吸虫病防治杂志

Objective To analyze the status and trends of soil-transmitted nematode infections in Jiangxi Province from 1989 to 2014,so as to provide the evidence for generating the strategy of soil-transmitted nematode prevention and control. Methods The data of three epidemiological surveys on human parasitic diseases(in 1989,2002 and 2014)were classified and analyzed. The stool examination by Kato-Katz's thick smear method was adopted for the investigation of soil-transmitted nematode infec-tions. Results The total infection rate of soil-transmitted nematodes decreased by 91.89％from 77.67％in 1989 to 6.30％in 2014,in which the infection rate of Ascaris lumbricoides decreased by 98.78％from 71.11％to 0.87％,the infection rate of Trich-uris trichiura decreased by 96.80％from 29.67％to 0.95％,and the infection rate of hookworm declined by 73.57％from 17.63％to 4.66％. The infection rates of soil-transmitted nematodes in the female were higher than those in the male in three surveys. In different ecological districts,the infection rates of soil-transmitted nematodes in the female were also higher than those in the male,except in Zhe-Min Ecological District in 2002 and 2014. A declined trend of the infection was showed in all age-groups in the three surveys,but it slowed down by the growth of age,i.e.,the reduction rate was 97.03％in the age group of<10 years while 80.62％in the age group of>70 years. In 2014,the number of persons infected with soil-transmitted nematodes occupied 65.4％of the whole number of persons infected with intestinal parasites. Conclusions The mean infection rates of soil-transmit-ted nematodes decrease obviously in human population in different ecological districts,but the soil-transmitted nematodes are still the main species in intestinal parasite infections. The sequence of dominant species changes from A. lumbricoides,hook-worm and T. trichiura in 1989 to hookworm,T. trichiura and A. lumbricoides in 2014. The rural female and elder people are the key population,while hookworm is the key species for the prevention and control of soil-transmitted nematodes.

Progress of non-genomic action of estrogen and its impact on female reproduction / 生理学报

Estrogen is one of the steroid hormones. Besides the genomic action mediated by its intracellular receptor on target cells, there is now increasing body of evidence indicating that estrogen also has non-genomic action. For the non-genomic action, estrogen binds to its receptor on cell membrane, subsequently rapidly activates various intracellular signaling pathways, such as PLC/Ca(2+), ERK/MAPK, cAMP-PKA, PI3K-AKT-NOS, and finally induces biological effects. The non-genomic effects of estrogen on physiologic and pathologic processes have been found in many tissues within the reproductive, nervous and cardiovascular systems and bone etc. In reproductive system, it has been demonstrated that estrogen plays important roles in follicle development, fertilization and embryo implantation, and it is involved in the genesis and development of genital tract tumors and breast cancer. In this review, we focus on the general characteristics of non-genomic action of estrogen, its main nonnuclear signaling pathways and physiological and pathological significance, especially its influences in female reproductive functions.

Progesterone-induced microRNA-1a inhibits the proliferation of endometrial epithelial cells / 生理学报

The aim of the present study was to investigate the effects of progesterone (P4)-induced microRNA-1a (miR-1a) on the proliferation of endometrial epithelial cells (EECs) and the underlying mechanism. In vivo, following subcutaneous injection of estradiol (E2) alone (E2 group) or combined injections of E2 and P4 (E2P4 group) in ovariectomized mice, quantitative real-time PCR (qPCR) was used to check the expression of miR-1a-3p in the directly isolated mouse EECs. The agomir or antagomir specific for miR-1a-3p was injected into one side of the uterine horns of ovariectomized mice pretreated with E2 alone or in combination with P4, and the non-specific control agomir or antagomir was injected into their contralateral horns. Flow cytometry was used to analyze the cell cycle of EECs. Immunohistochemistry (IHC) was used to examine the location and expression of cyclin D2, cyclin E1, and cyclin E2 in the uterine tissue sections. In vitro, primary cultured mouse EECs were pretreated with E2 alone (E2 group) or in combination with P4 (E2P4 group). qPCR was used to detect the expression of miR-1a-3p. Exogenous mimic of miR-1a-3p was transfected into E2-pretreated EECs, and EdU incorporation analysis was used to test the proliferation activity of the EECs. The result of in vivo experiment showed that the expression of miR-1a-3p in E2P4 group was significantly higher than that in E2 group (P < 0.05). The miR-1a-3p agomir arrested cell cycle at G1 to S transition in the mice injected subcutaneously with E2 alone (P < 0.05). Conversely, silencing of miR-1a-3p with transfection of miR-1a-3p antagomir promoted the entry of cells into S phase in the mice injected subcutaneously with both E2 and P4 (P < 0.05). The expressions of cyclin E1 and cyclin E2, except for cyclin D2, in uterine sections were also dramatically reduced by miR-1a-3p overexpression in the uterine epithelium (P < 0.05). In vitro, miR-1a-3p was not expressed in the cells of both E2 and E2P4 groups. The mimic of miR-1a-3p decreased EECs proliferation activity (P < 0.05). These results indicate that P4-induced miR-1a can inhibit the expression of cyclin E1 and cyclin E2, consequently suppressing the proliferation of mouse EECs by arresting cells at G1/S phase.

Single nucleotide polymorphism analysis of growth hormone gene in Tibet minipigs / 中国比较医学杂志

Objective To screen genotypes of small body in Tibet minipigs by single nucleotide polymorphism analysis (SNP) of growth hormone (GH) gene.Methods The PCR products are sequenced.According to the results, SNP analysis are applied in GH gene 5′fragment of 108 Tibet minipigs .Results Five mutation points were found by comparison.The polymorphism information content of the T45C locus is highest.The results of growth traits of different genotypes showed that the abdomen of 6~8 month old Tibet minipigs of TC genotype at T 45C mutation site is small; the weight and height of 3~5 month old Tibet minipigs of AA genotype at G 84A mutation site is small; the body length and height of 6~8month old Tibet minipigs of GG genotype at G 93A mutation site is small.Conclusion The AA TC, GG genotypes of T45C, G84A, G93A mutation sites in GH gene may be associated with small body .We also found that genetic mutations always occur in the above sites with high heterozygosity and genetic diversity , which can provide rich material for breeding research .

Cloning and sequence analysis of Tibet mini-pig’ s MSTN gene / 中国比较医学杂志

Objective To amplify the encoding full-length sequence of Tibet mini-pigs myostatin ( MSTN) gene and analysis the sequence by bioinformatics software.Method The RNA of liver tissues from Tibet mini-pig was extracted, and reversely transcribed into cDNA.The gene coding region sequence of myostatin gene was amplified through RT-PCR, and then the purified product of PCR was ligated with a pMD19-T and transferred into the bacterium DH5αfor replication.The positive clones were screened and sequenced. The sequence characters were analyzed by using bioinformatics method and phylogeny evolution tree was constructed with other twelve species.Results The coding redion of MSTN gene was 1128bp, and coded 375 amino acids.The amino acid homology analysis showed that the homology rate of amino acid sequence was 99%.Conclusions Molecular phylogeny evolution indicated that it had a close relation with human, dog, banna minipig, sheep, goat, cattle, horse, chimpanzee, rat, mouse except chick and zebrafish, and the most closely related with banna minipig.

An efficient method which can be used to transfect Tibetan minipig embryonic fibroblasts / 中国比较医学杂志

Objective To transfect EGFP gene to porcine embryonic fibroblasts ( PEFs) of Tibetan miniature pigs by Lonza Nucleofector II machine and compare the tansfection efficiency between this method and the lipofection method. Method A plasmid carrying green fluorescent protein ( GFP) was transfected into PEFs of Tibetan miniature pigs via the Lonza Nucleofector II machine ( program U020) and by Lipofectamine 2000.Results 5 hours after nucleofection, green fluorescence was observed, indicating 80%transfecting efficiency in the nucleofection group, which is significantly higher than the lipofection group. Conclusion Nucleofector II machine can efficiently transfect PEFs, provides a reliable method for efficiently generate transgenic Tibetan minipigs.

Progress on genetic basis of primary aldosteronism / 浙江大学学报·医学版

It has been proven that familial aldosteronism type I is related to 11-beta hydroxylase (CYP11B1)/aldosterone synthase (CYP11B2) chimeric genes. In recent years, accumulated evidences indicate that the genetic basis of primary aldosteronism may involve chromosome 7p22 candidate genes, polymorphisms of CYP11B1 and CYP11B2 genes, mutations of ion channel- related KCNJ5, ATP1A1, CACNA1D genes. The article reviews the progress on genetic basis of primary aldosteronism.

Changes of CD8⁺ T cells in dextran sulfate sodium-induced colitis mice pretreated with oral immune regulation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It has been reported that CD8(+) regulatory cells could be induced upon oral tolerance. The purpose of this study was to investigate the changes of CD8α(+) T cells in dextran sulfate sodium (DSS)-induced colitis mice pretreated by oral immune regulation.</p><p><b>METHODS</b>The effects of five low oral doses of colitis-extracted proteins (CEP) on colitis were evaluated by clinical manifestation and histological lesions. The percentages of CD8α(+) T cells gating on CD3(+) T cells were evaluated in the gut-associated lymphoid tissues (GALT) and the spleens by flow cytometry. Differences between the two groups were compared by Student's t test or Mann-Whitney U test.</p><p><b>RESULTS</b>Compared to bovine serum albumin (BSA)-fed control mice, administration of CEP resulted in marked alleviation of colitis. The proportion of CD8α(+) T cells, not only in intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs) of the large intestine (LI) but also in spleen from CEP-fed colitis mice, was significantly higher than that from BSA-fed colitis mice (LI-IELs: (71.5 ± 5.4)% vs. (60.1 ± 4.3)%, P < 0.01; LI-LPLs: (60.7 ± 5.2)% vs. (51.9 ± 4.7)%, P < 0.01; spleen: (24.1 ± 3.6)% vs. (20.3 ± 4.1)%, P < 0.05; n = 8). Mucosal repair in repair-period mice five days after termination of DSS treatment was also accompanied by an increase of CD8α(+) T cells in large intestinal mucosal lymphocytes (LI-IELs: (72.1 ± 3.7)% vs. (61.5 ± 4.5)%, P < 0.01; LI-LPLs: (62.1 ± 5.7)% vs. (52.7 ± 3.6)%, P < 0.01; n = 8). The proportion of CD3(+) T cells increased in Peyer's patches (PPs) and decreased in mesenteric lymph nodes (MLNs) from colitis mice compared to untreated mice, whereas the change pattern of CD3(+) T cells in PPs and MLNs from CEP-fed colitis mice was just on the contrary.</p><p><b>CONCLUSION</b>Improvement of DSS-induced colitis resulted from oral immune regulation is associated with an increase in CD8α(+) T cells in spleen and large intestinal mucosa.</p>

Protective effect of breviscapine on cardiac function in children after cardiopulmonary bypass undergoing open heart surgery / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To assess the condition of myocardial injury after cardiopulmonary bypass (CPB) and the effects of breviscapine (BVC) on cardiac function in children undergoing open heart surgery.</p><p><b>METHODS</b>Thirty-six children (ASA II or III, aged 2-65 months) scheduled to receive ventricular septal defect repairing were randomly assigned to three groups, the control group treated with saline, and the BVC treated groups treated respectively with low dose (0.5 mg/kg) and high dose (1.0 mg/kg) BVC, 12 patients in each group. Saline or BVC (in volume of 15 mL) was administered intravenously after induction of anesthesia with micro-pump within 30 min. Blood levels of troponin I (cTn-I ) and malondialdehyde (MDA) were measured at different time points: pre-operation (T0), during aortic unclamping (T1), and 30 min, 1 h, 6 h, 24 h after aortic unclamping (T2, T3, T4, T5). And the time of operation, CPB, aortic unclamping, and the condition of drainage in 24 h after operation as well as the dosages of narcotics (midazolam, propofol and fentanyl) used were recorded.</p><p><b>RESULTS</b>No significant difference among groups was found in terms of sex ratio, age, body weight, time of aortic unclamping, CPB and operation, as well as the dosages of narcotics used and the volume of post-operation drainage. Compared with baseline (T0), levels of cTn-I at T1, T4 and T5 increased significantly in all three groups (P<0.01), with the peak revealed at T4; cTn-I in the control group were higher than those in the low dose BVC treated group at T1 and T4 (P<0.01), and those in the high dose BVC group at T1, T4, and T5, while it was insignificantly different between the two BVC treated groups. Level of plasmal MDA began to rise in all groups at T1 with the peak revealed at T2, it lowered after then, and reached the baseline at T5; comparison between groups showed that it was lower in the BVC treated groups than in the control group at T1-T4.</p><p><b>CONCLUSIONS</b>Different degree of cardiac injury always happens after open heart surgery and CPB, showing high level of cTn- I within 24 h with the peak revealed at 6 h after aortic unclamping. Intravenous perfusion BVC before CPB at the dose of 0.5 or 1 mg/kg could protect the cardiac function to some extent.</p>