Previous studies have demonstrated that plasminogen actiator (PA) activity is significantly high in semen of infertile men, which is also high in semen when azoospermia or oligozoospermia is induced by injection of testosterone enanthate (TE) into healthy adult men or rhesus monkeys. To further clarify the source and possible role of PA in semen, the present study was undertaken to examine: (1) whether the mRNAs for tissue type PA (tPA), urokinase type PA (uPA), and PA inhibitor-1 (PAI-1) are expressed in epididymis, seminal vesicle and prostate gland of rhesus monkeys; and (2) whether PA has some effect on in vitro sperm capacitation as judged by the potential of sperm motility, acrosome reaction (AR) and in vitro fertilization. Our results showed that (1) mRNAs for PA and PAI-1 were expressed in epididymis, seminal vesicle and prostate gland, and (2) uPA, but not tPA, improved sperm mobility, induced AR and enhanced sperm capacity to fertilize mature eggs. Thus, it is concluded that PA activity in semen comes not only from testis and epididymis, but also from seminal vesicle and prostate gland; and that uPA, but not tPA, may play a role in sperm capacitation.

Objective: To investigate the determinants affecting the heart rate deceleration capacity (DC) in patients with dilated cardiomyopathy (DCM). Methods: One hundred patients with DCM (DCM group) and 202 healthy subjects (control group) were respectively enrolled. Echocardiography and 24 hours electrocardiogram were performed in all subjects. DC value was compared between the two groups. Multiple regression analysis was made to evaluate the related determinants of DC ((age, sex, echocardiographic parameters including the left atrial diameter (LAD) and left ventricular ejection fraction (LVEF)). Results: (1) DC value was significantly lower in DCM group than in control group( (4.40±2.03) ms vs. (7.30±1.81) ms, P<0.01), prevalence of DC value≤4.5 ms was significantly higher in DCM group than in control group (62% vs. 6%, P<0.01). (2) DC value in the DCM group decreased in proportion to increasing LAD dimension, DC value was (5.60±2.04) ms, (4.50±2.07) ms and (3.60±1.62) ms (P<0.05) in DCM patients with LAD≤40 mm, 40 mm50 mm, respectively. (3) DC value in the DCM group was negatively related to the LAD (r=-0.366, P<0.01), positively related to the LVEF (r= 0.241, P<0.01), but not related with age and sex. Multiple factors regression analysis showed that increased LAD was related to the reduced DC values independtly. Conclusion DC value of the patients in the DCM group is decreased, which indicate the decrease of the vagus nerve tension, and increased LAD is related to the reduced DC value independtly in DCM patients.

Background:A ruptured hepatocellular carcinoma (HCC) is often fatal.In addition to surgery and transarterial embc lization,radiofrequency ablation (RFA) might be another option for treating a ruptured HCC.Unfortunately,conventional RFA has a limited ablation zone;as such,it is rarely used to treat ruptured tumors.Case presentation:This case was a 60-year-old man who had a large,ruptured HCC in which hydrochloric acid (HCI)-enhanced RFA successfully controlled the bleeding and made the tumor completely necrotic.Conclusion:Considering the effectiveness of HCI-enhanced RFA in achieving hemostasis and tumor ablation,it might be a new option for treating large,ruptured HCCs.

The oral administration of bioactive macromolecular drugs such as proteins, peptides and nucleic acids represents unprecedented challenges from the drug delivery point of view. One key consideration is how to overcome the gastrointestinal tract absorption barrier. Recent studies suggest that microfold cell (M cell), a kind of specialized antigen-sampling epithelial cell which is characterized by a high endocytic rate and low degradation ability, may play an important role in macromolecule oral absorption. The development of an in vitro M cell coculture system and its modified models greatly advanced the study of M cells and the development of oral delivery system for macromolecular drugs. The special structure, function and formation characteristics, and biomarkers of M cell are summarized in this review. The applications of in vitro M cell models in developing oral delivery system ofbioactive macromolecular drugs are discussed.
Administration, Oral ; Animals ; Drug Delivery Systems ; methods ; Humans ; Intestinal Mucosa ; cytology ; Macromolecular Substances ; administration & dosage ; pharmacokinetics ; Models, Biological ; Peptides ; administration & dosage ; pharmacokinetics ; Peyer's Patches ; cytology ; Proteins ; administration & dosage ; pharmacokinetics ; Vaccines ; pharmacokinetics

BACKGROUNDTakayasu arteritis (TA) is a rare inflammatory arteriopathy of unknown etiology. The aim of this study was to investigate the genetic susceptibility to TA in a Chinese population.

METHODSFour single nucleotide polymorphisms (SNPs) those locate in the IL12B region (rs56167332), the MLX region (rs665268), the FCGR2A/FCGR3A locus (rs10919543), and the HLA-B/MICA locus (rs12524487), associated with TA in different population, were genotyped in 123 Chinese TA patients and 147 healthy controls from January 2013 to August 2014. A Chi-square test was used to test for genotype/allele frequencies variants.

RESULTSAmong the four SNPs, rs10919543 was found to be significantly associated with TA in the studied population. The GG genotype of rs10919543 at the FCGR2A/FCGR3A locus is a high risk factor (odds ratio [OR] = 6.532, 95% confidence interval [CI] = 2.402 - 17.763, P < 0.001) for TA. Among TA patients, the level of eosinophil granulocytes (Eos) in the peripheral blood was observed to be higher in the GG group of rs10919543 (n = 23, Eos = 0.11 [0.08, 0.17] ×109/L) than the GA + AA group (n = 100, Eos = 0.08 [0.05, 0.13] ×109/L, P = 0.028). No correlation between the genotypes of the other three SNPs and TA patients was observed.

CONCLUSIONSOur findings revealed unique genetic pattern in Chinese TA patients that may be partly responsible for the higher risk of TA in this population. FCGR2A/FCGR3A-related immune disorder might contribute to the etiology of TA.

Adolescent ; Adult ; Child ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Receptors, IgG ; genetics ; Takayasu Arteritis ; etiology ; genetics

Objective To evaluate the clinical features in Chinese patients with apical hypertrophic cardiomyopathy (AHCM) and typical hypertrophic cardiomyopathy (HCM). Methods This retrospective analysis included 160 patients hospitalized in Fuwai hospital. Patients were divided into three groups: apical hypertrophic cardiomyopathy ( AHCM, n = 41 ) group, non-obstructive typical hypertrophic cardiomyopathy group[NOHCM, LVOT ＜30 mm Hg(1 mm Hg =0. 133 kPa) at rest, n =52] and obstructive typical hypertrophic cardiomyopathy (OHCM, LVOT ≥ 30 mm Hg at rest, n = 67). Clinical features, diagnosis,therapy, and plasma levels of biomarkers of these three groups were analyzed. Results ( 1 ) The age at disease onset was older in AHCM group than in OHCM group [(49. 9 + 13. 6) years vs. (41.4± 14. 6)years, P ＜ 0. 01]. Exertional dyspnea appered more often in HCM patients than in AHCM patients, NT-proBNP level was significantly lower in AHCM patients than in OHCM patients (P =0. 001 ). Plasma CK-MB, LDH, TnI and MYO levels were similar among the three groups. (2) Thirty-three AHCM patients were first hospitalized for suspected coronary heart disease (CHD) and CHD was excluded in 18 cases (43.9%).(3) The frequency of giant negative T waves (depth≥10 mm) on ECG was 43.9%, 13.5% and 4.4%(P ＜ 0. 01 ) in AHCM, NOHCM and OHCM respectively. Half of AHCM patients showed left ventricular high voltage on ECG. (4) Cardiac magnetic resonance imaging is superior to echocardiography on correctly diagnosing AHCM. Conclusion AHCM patients differ from typical OHCM patients in clinical characteristics. There were significant differences on echocardiography and electrocardiography features among three groups. Cardiac magnetic resonance imaging and giant negative T waves on ECG are helpful for the diagnosis of AHCM.

BACKGROUNDPreterm premature rupture of membrane (PPROM) can lead to serious consequences such as intrauterine infection, prolapse of the umbilical cord, and neonatal respiratory distress syndrome. Genital infection is a very important risk which closely related with PPROM. The preliminary study only made qualitative research on genital infection, but there was no deep and clear judgment about the effects of pathogenic bacteria. This study was to analyze the association of infections with PPROM in pregnant women in Shaanxi, China, and to establish Bayesian stepwise discriminant analysis to predict the incidence of PPROM.

METHODSIn training group, the 112 pregnant women with PPROM were enrolled in the case subgroup, and 108 normal pregnant women in the control subgroup using an unmatched case-control method. The sociodemographic characteristics of these participants were collected by face-to-face interviews. Vaginal excretions from each participant were sampled at 28-36+6 weeks of pregnancy using a sterile swab. DNA corresponding to Chlamydia trachomatis (CT), Ureaplasma urealyticum (UU), Candida albicans, group B streptococci (GBS), herpes simplex virus-1 (HSV-1), and HSV-2 were detected in each participant by real-time polymerase chain reaction. A model of Bayesian discriminant analysis was established and then verified by a multicenter validation group that included 500 participants in the case subgroup and 500 participants in the control subgroup from five different hospitals in the Shaanxi province, respectively.

RESULTSThe sociological characteristics were not significantly different between the case and control subgroups in both training and validation groups (all P > 0.05). In training group, the infection rates of UU (11.6% vs. 3.7%), CT (17.0% vs. 5.6%), and GBS (22.3% vs. 6.5%) showed statistically different between the case and control subgroups (all P < 0.05), log-transformed quantification of UU, CT, GBS, and HSV-2 showed statistically different between the case and control subgroups (P < 0.05). All etiological agents were introduced into the Bayesian stepwise discriminant model showed that UU, CT, and GBS infections were the main contributors to PPROM, with coefficients of 0.441, 3.347, and 4.126, respectively. The accuracy rates of the Bayesian stepwise discriminant analysis between the case and control subgroup were 84.1% and 86.8% in the training and validation groups, respectively.

CONCLUSIONSThis study established a Bayesian stepwise discriminant model to predict the incidence of PPROM. The UU, CT, and GBS infections were discriminant factors for PPROM according to a Bayesian stepwise discriminant analysis. This model could provide a new method for the early predicting of PPROM in pregnant women.

OBJECTIVE: To observe the effects of moxibustion on the stem cell factor (SCF)/tyrosine kinase receptor (c-kit) signaling pathway and immune function in rats with diarrhea irritable bowel syndrome (IBS-D), and to explore the mechanism of moxibustion for IBS-D. METHODS: Among 52 young rats born from 6 healthy pregnant SPF rats, 12 rats were randomly selected into the normal group, and the remaining 40 rats were treated with the three-factor combination method of maternal separation, acetic acid enema and chronic restraint stress to establish the IBS-D rat model. Thirty-six rats with successful IBS-D model were randomly divided into a model group, a moxibustion group, and a medication group, 12 rats in each group. The rats in the moxibustion group were treated with suspension moxibustion at "Tianshu" (ST 25) and "Shangjuxu" (ST 37); the rats in the medication group were treated with intragastric administration of rifaximin suspension (150 mg/kg). All the treatments were given once a day for 7 consecutive days. The body mass, loose stool rate (LSR), the minimum volume threshold when abdominal withdrawal reflex (AWR) scored 3 were measured before acetic acid enema (35 days old), after modeling (45 days old), and after intervention (53 days old). After intervention (53 days old), HE staining was used to observe the morphology of colon tissue, and spleen and thymus coefficients were measured; ELISA method was used to detect serum inflammatory factors (tumor necrosis factor a [TNF-a], interleukin [IL]-10, IL-8), T-lymphocyte subsets (CD⁺₄, CD⁺₈, CD⁺₄₅), value of CD⁺₄/CD⁺₈ and immune globulin (IgA, IgG, IgM); real-time PCR method and Western blot method was used to detect the expression of SCF, c-kit mRNA and protein in colon tissue; immunofluorescence staining method were used to detect positive expression of SCF and c-kit. RESULTS: After intervention, compared with the normal group, in the model group, the body mass and the minimum volume threshold when AWR scored 3 were decreased (P<0.01), LSR, spleen and thymus coefficients, serum levels of TNF-α, IL-8, CD⁺₄, CD⁺₄₅, CD⁺₄/CD⁺₈, IgA, IgG, IgM were increased (P<0.01), serum IL-10 level and protein and mRNA expression of SCF and c-kit in colon tissue were decreased (P<0.01), and the positive expression of SCF and c-kit was decreased (P<0.01). Compared with the model group, in the moxibustion group and the medication group, the body mass and the minimum volume threshold when AWR scored 3 were increased (P<0.01, P<0.05), LSR, spleen and thymus coefficients, serum levels of TNF-α, IL-8, CD⁺₄, CD⁺₈, CD⁺₄₅, CD⁺₄/CD⁺₈, IgA, IgG, IgM were decreased (P<0.01, P<0.05), serum IL-10 level and protein and mRNA expression of SCF and c-kit in colon tissue were increased (P<0.01), and the positive expression of SCF and c-kit was increased (P<0.01). Compared with the medication group, in the moxibustion group, the level of serum CD⁺₄ was decreased (P<0.05), the value of CD⁺₄/CD⁺₈ was increased (P<0.01), and there was no significant difference in other indexes (P>0.05). The expression of SCF and c-kit mRNA was positively correlated with the minimum volume threshold when AWR scored 3 and IL-10 (P<0.01), and negatively correlated with remaining indexes (P<0.01, P<0.05). CONCLUSION Moxibustion could reduce visceral hypersensitivity, improve symptoms of abdominal pain and diarrhea in IBS-D rats, and its mechanism may be related to up-regulation of the expression of SCF/c-kit signaling pathway and improvement of IBS-D immune function.
Rats ; Animals ; Irritable Bowel Syndrome/therapy* ; Moxibustion/methods* ; Rats, Sprague-Dawley ; Interleukin-10 ; Interleukin-8 ; Maternal Deprivation ; Tumor Necrosis Factor-alpha ; Diarrhea ; Signal Transduction ; Homeostasis ; Receptor Protein-Tyrosine Kinases ; Immunity ; Immunoglobulin A ; Immunoglobulin M

OBJECTIVE: To observe the effect of moxibustion on the regulation of nuclear factor-kappa B (NF-κB) and inflammatory factors by multiple microRNAs (miRNAs) in rats with diarrhea-predominant irritable bowel syndrome (IBS-D), and to explore the anti-inflammatory mechanism of moxibustion on IBS-D. METHODS: Twelve of 52 newborn rats were randomly selected into a normal group. The remaining rats were made into IBS-D model. A total of 36 rats with successful model were randomly divided into a model group, a medication group and a moxibustion group, 12 rats in each group. The rats in the medication group were intraperitoneally injected with pyrrolidine dithiocarbamate (PDTC). The rats in the moxibustion group were treated with moxibustion at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) for 20 min each time. All the intervention was given once a day for 7 days. Before and after modeling as well as after intervention, the body mass, loose stool rate and the minimum volume threshold of abdominal withdrawal reflex (AWR) were measured. After intervention, the contents of serum tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-8 were detected by ELISA method; the morphology of colon tissues was observed by HE staining, and the expressions of miR-155, miR-125b, miR-29b, miR-31, miR-18a and NF-κB p65 mRNA in colon tissues were detected by real-time PCR. The expressions of NF-κB p65, TNF-α, IL-1β and IL-8 protein in colon tissues were detected by immunofluorescence. RESULTS: After modeling, the body mass and the minimum volume threshold of AWR in the model group were lower than those in the normal group (P<0.01); the rates of loose stool in the model group were higher than those in the normal group (P<0.01); after intervention, in the model group, the inflammatory infiltration of colon tissues was obvious, and the serum levels of TNF-α, IL-1 β, IL-8 were higher than those in the normal group (P<0.05); the expression of miR-155, miR-125b, miR-29b, miR-31, miR-18a and NF-κB p65 mRNA in colon tissues was higher than that in the normal group (P<0.05); the protein expression of NF-κB p65, TNF-α, IL-1β, IL-8 was also higher than that in the normal group (P<0.01). After intervention, the body mass and the minimum volume threshold of AWR in the medication group and the moxibustion group were both higher than those in the model group (P<0.05); the loose stool rate in the medication group and the moxibustion group were lower than those in model group (P<0.05); the inflammatory cells infiltration in the colon tissues was less, the serum levels of TNF-α, IL-1β and IL-8 as well as the protein expression of NF-κB p65, TNF-α, IL-1β and IL-8 in the colon tissues in the medication group and the moxibustion group were lower than those in the model group (P<0.05, P<0.01). The expression of miR-125b, miR-31, miR-18a and NF-κB p65 mRNA in the medication group were lower than those in the model group (P<0.05). The expression of miR-155, miR-125b, miR-29b, miR-31, miR-18a and NF-κB p65 mRNA in the moxibustion group were lower than those in the model group (P<0.05). The miR-155, miR-125b, miR-29b, miR-31, miR-18a were positively correlated with NF-κB p65 mRNA (0<r<1, P<0.01). CONCLUSION The anti-inflammatory mechanism of moxibustion at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) for IBS-D rats may be related to regulating multiple miRNAs to inhibit NF-κB signal pathway and reduce the expression of inflammatory factors.
Animals ; Diarrhea/therapy* ; Interleukin-8/genetics* ; Irritable Bowel Syndrome/therapy* ; MicroRNAs/genetics* ; Moxibustion ; NF-kappa B/metabolism* ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Tumor Necrosis Factor-alpha/genetics*