[Associations of blood pressure change with change in foods' intake among adults with mild to moderate hypertension].

Objective: To explore the association between the intake and changes in various types of food and the changes in blood pressure in patients with mild to moderate hypertension. Methods: Mild to moderate hypertension participants with complete baseline and outcome data were included from DECIDE-Diet study, a multicenter, randomized controlled trial. Dietary records and blood pressure measurements at both 7-day run-in (baseline) and 28-day intervention phases were collected for enrolled participants. Blood pressure change was defined as the difference between blood pressure at the end of trial and the baseline blood pressure. Baseline intake of food was the average daily intake during the run-in period, and the intake increment was defined as the difference between the average intake during the trial period and the average intake during the run-in period. After adjusting for age, sex, study center, intervention groups, baseline body mass index (kg/m2), antihypertension medication use, and baseline total calorie intake, a linear regression model was used to analyze the associations of the before-after-intervention change in blood pressure with baseline intake and intake increment of foods. Results: A total of 258 patients with mild to moderate hypertension were included, including 133 males, aged (56.5±9.9) years. (1) After adjusting for confounding factors, there was no significant association between baseline intake of food and baseline blood pressure (all P>0.05). The blood pressure change was negatively associated with baseline intakes of tubers, vegetables, and vegetable oils but positively with baseline intake of meats; and was negatively associated with intake increment of whole grains and fish (all P<0.05). (2) The multiple linear regression analysis showed that baseline intake of vegetables (ß=-0.021, P=0.004), vegetable oils (ß=-0.260, P=0.002), and increment in intake of fish (ß=-0.128, P=0.026) were all significantly associated with changes in systolic blood pressure; baseline intake of vegetables (ß=-0.017, P=0.002), vegetable oils (ß=-0.182, P=0.001), dairy products (ß=0.021, P=0.022), and increment in intake of fish (ß=-0.092, P=0.010) were all significantly associated with changes in diastolic blood pressure. Conclusion: Increasing the intake of whole grains, vegetables, vegetable oils, and fish and decreasing the intake of meat may be beneficial for blood pressure control in patients with mild to moderate hypertension.

[Protective effect of intervention with cannabinoid type-2 receptor agonist JWH133 on pulmonary fibrosis in mice].

Objective: JWH133, a cannabinoid type 2 receptor agonist, was tested for its ability to protect mice from bleomycin-induced pulmonary fibrosis. Methods: By using a random number generator, 24 C57BL/6J male mice were randomly divided into the control group, model group, JWH133 intervention group, and JWH133+a cannabinoid type-2 receptor antagonist (AM630) inhibitor group, with 6 mice in each group. A mouse pulmonary fibrosis model was established by tracheal instillation of bleomycin (5 mg/kg). Starting from the first day after modeling, the control group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution, and the model group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution. The JWH133 intervention group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg, dissolved in physiological saline), and the JWH133+AM630 antagonistic group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg) and AM630 (2.5 mg/kg). After 28 days, all mice were killed; the lung tissue was obtained, pathological changes were observed, and alveolar inflammation scores and Ashcroft scores were calculated. The content of type Ⅰ collagen in the lung tissue of the four groups of mice was measured using immunohistochemistry. The levels of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in the serum of the four groups of mice were measured using enzyme-linked immunosorbent assay (ELISA), and the content of hydroxyproline (HYP) in the lung tissue of the four groups of mice was measured. Western blotting was used to measure the protein expression levels of type Ⅲ collagen, α-smooth muscle actin (α-SMA), extracellular signal regulated kinase (ERK1/2), phosphorylated P-ERK1/2 (P-ERK1/2), and phosphorylated ribosome S6 kinase type 1 (P-p90RSK) in the lung tissue of mice in the four groups. Real-time quantitative polymerase chain reaction was used to measure the expression levels of collagen Ⅰ, collagen Ⅲ, and α-SMA mRNA in the lung tissue of the four groups of mice. Results: Compared with the control group, the pathological changes in the lung tissue of the model group mice worsened, with an increase in alveolar inflammation score (3.833±0.408 vs. 0.833±0.408, P<0.05), an increase in Ashcroft score (7.333±0.516 vs. 2.000±0.633, P<0.05), an increase in type Ⅰ collagen absorbance value (0.065±0.008 vs. 0.018±0.006, P<0.05), an increase in inflammatory cell infiltration, and an increase in hydroxyproline levels [(1.551±0.051) µg/mg vs. (0.974±0.060) µg/mg, P<0.05]. Compared with the model group, the JWH133 intervention group showed reduced pathological changes in lung tissue, decreased alveolar inflammation score (1.833±0.408, P<0.05), decreased Ashcroft score (4.167±0.753, P<0.05), decreased type Ⅰ collagen absorbance value (0.032±0.004, P<0.05), reduced inflammatory cell infiltration, and decreased hydroxyproline levels [(1.148±0.055) µg/mg, P<0.05]. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group showed more severe pathological changes in the lung tissue of mice, increased alveolar inflammation score and Ashcroft score, increased type Ⅰ collagen absorbance value, increased inflammatory cell infiltration, and increased hydroxyproline levels. Compared with the control group, the expression of α-SMA, type Ⅲ collagen, P-ERK1/2, and P-p90RSK proteins in the lung tissue of the model group mice increased, while the expression of type Ⅰ collagen, type Ⅲ collagen, and α-SMA mRNA increased. Compared with the model group, the protein expression of α-SMA (relative expression 0.60±0.17 vs. 1.34±0.19, P<0.05), type Ⅲ collagen (relative expression 0.52±0.09 vs. 1.35±0.14, P<0.05), P-ERK1/2 (relative expression 0.32±0.11 vs. 1.14±0.14, P<0.05), and P-p90RSK (relative expression 0.43±0.14 vs. 1.15±0.07, P<0.05) decreased in the JWH133 intervention group. The type Ⅰ collagen mRNA (2.190±0.362 vs. 5.078±0.792, P<0.05), type Ⅲ collagen mRNA (1.750±0.290 vs. 4.935±0.456, P<0.05), and α-SMA mRNA (1.588±0.060 vs. 5.192±0.506, P<0.05) decreased. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group increased the expression of α-SMA, type Ⅲ collagen, P-ERK1/2, and P-p90RSK protein in the lung tissue of mice, and increased the expression of type Ⅲ collagen and α-SMA mRNA. Conclusion: In mice with bleomycin-induced pulmonary fibrosis, the cannabinoid type-2 receptor agonist JWH133 inhibited inflammation and improved extracellular matrix deposition, which alleviated lung fibrosis. The underlying mechanism of action may be related to the activation of the ERK1/2-RSK1 signaling pathway.

[Research progress on the correlation between cirrhosis and frailty].

Frailty, which predicts high dependency and mortality, is a major challenge for healthcare systems in nations that are rapidly aging and is receiving increasing attention. Cirrhosis is often combined with frailty, which has a significant impact on patient health outcomes. Understanding the risk factors for frailty, elucidating the mechanism of cirrhosis combined with frailty, and early recognition and slowing down the occurrence and development of frailty are of great significance for the prognosis of cirrhotic patients. This article reviews the current research status of cirrhosis combined with frailty, including the definition and risk factors, mechanism, correlation, and intervention measures, in order to improve understanding and provide assistance for strengthening early identification, management, and intervention.

Regulatory role of phosphoproteins in the development of bovine small intestine during early life.

The small intestine is the primary site of nutrient digestion and absorption, which plays a key role in the survival of neonatal calves. A comprehensive assessment of the phosphoproteomic changes in the small intestine of neonatal calves is unavailable; therefore, we used phosphopeptide enrichment coupled with liquid chromatography-tandem mass spectrometry to investigate the changes in the phosphoproteome profile in the bovine small intestine during the first 36 h of life. Twelve neonatal male calves were assigned to one of the following groups: (1) calves not fed colostrum and slaughtered approximately 2 h postpartum (n = 3), (2) calves fed colostrum at 1 to 2 h and slaughtered 8 h postpartum (n = 3), (3) calves fed 2 colostrum meals (at 1-2 and 10-12 h) and slaughtered 24 h postpartum (n = 3), (4) calves fed 3 colostrum meals (at 1-2, 10-12, and 22-24 h) and slaughtered 36 h postpartum (n = 3). Mid-duodenal, jejunal, and ileal samples of the calves were collected after slaughter. We identified 1,678 phosphoproteins with approximately 3,080 phosphosites, which were mainly Ser (89.9%), Thr (9.8%), and Tyr (0.3%) residues; they belonged to the prodirected (52.9%), basic (20.4%), acidic (16.6%), and Tyr-directed (1.7%) motif categories. The regional differentially expressed phosphoproteins included zonula occludens 2, sorting nexin 12, and protein kinase C, which are mainly associated with developmental processes, intracellular transport, vesicle-mediated transport, and immune system process. They are enriched in the endocytosis, tight junction, insulin signaling, and focal adhesion pathways. The temporal differentially expressed phosphoproteins included occludin, epsin 1, and bridging integrator 1, which were mainly associated with macromolecule metabolic process, cell adhesion, and growth. They were enriched in the spliceosomes, adherens junctions, and tight junctions. The observed changes in the phosphoproteins in the tissues of small intestine suggest the protein phosphorylation plays an important role in nutrient transport and immune response of calves during early life, which needs to be confirmed in a larger study.

[The IL-6/STAT3 signaling pathway mediated by radiotherapy regulates the expression of PD-L1 in esophageal cancer cells].

Objective: To explore the possible mechanism of radiotherapy regulating the expression of PD-L1 in esophageal carcinoma. Methods: Three esophageal cancer cell lines (Eca109, Kyse150, TE1) were irradiated with different doses of X-rays, and 6 Gy+ AG490 group was set. The mRNA expression of PD-L1 was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The protein expressions of PD-L1, STAT3, p-STAT3 were detected by western blotting and the protein level of IL-6 was detected by ELISA. Results: The mRNA expressions of PD-L1 in Eca109, Kyse150 and TE1 were 2.86±0.30, 960.01±21.27 and 106.78±6.67, higher than 1.07±0.15 in normal esophageal cell line HET-1A (P<0.01). The protein expressions of PD-L1 in Eca109, Kyse150 and TE1 were 0.091±0.036, 1.533±0.079 and 0.914±0.035, higher than 0.063±0.01 in normal esophageal cell line HET-1A (P<0.01). After 48 hours of 6 Gy irradiation, the protein expression levels of PD-L1 in Eca109, Kyse150 and TE1 were 0.135±0.007, 1.66±0.06 and 1.32±0.06, higher than 0.09±0.01, 1.21±0.05 and 0.93±0.03 of the 0 Gy group (P<0.01), while the protein expression levels of p-STAT3 in Eca109, Kyse150 and TE1 were 1.44±0.26, 0.75±0.04 and 1.92±0.17, higher than 0.18±0.05, 0.48±0.02 and 0.36±0.06 of the 0 Gy group (P<0.01). IL-6 protein expression increased significantly after different doses of irradiation (P<0.01). After the IL-6/STAT3 signaling pathway was blocked by the specific inhibitor AG490, the expressions of PD-L1 of Eca109, Kyse150 and TE1 in the 6 Gy+ AG490 groups were 0.11±0.03, 1.07±0.08 and 0.96±0.11, without significant differences of 0.09±0.01, 0.96±0.05 and 0.85±0.09 of the 0 Gy group (P>0.05), while the protein expressions of p-STAT3 were 0.76±0.11, 0.59±0.06 and 0.96±0.12, without significant differences of 0.67±0.08, 0.54±0.06 and 0.84±0.11 of the 0 Gy group (P>0.05). Conclusion: Radiotherapy may regulate the expression of PD-L1 in esophageal cancer cells through IL-6 / STAT3 signaling pathway.

[Progress in immunologic and genetic research of chronic obstructive pulmonary disease with lung cancer].

Chronic obstructive pulmonary disease (COPD) and lung cancer are two of the respiratory diseases with the highest mortality, which have posed huge threat to human health and brought great burden to society and family. The mechanism of COPD with lung cancer is very complicated. In order to clarify the linkage between these two diseases, this review summarized the present researches of COPD and lung cancer from the aspects of immunology and genetics. The immunologic aspect focused on innate immune of neutrophil and macrophage, adaptive immune of B cell, T cell and oxidative stress. The genetic aspect focused on susceptibility gene and microRNA. Through the thorough elaboration of these researches, we hope to provide useful insights into the further research of mechanism, diagnosis and targeted therapy of COPD with lung cancer.

Evaluation of colostrum bioactive protein transfer and blood metabolic traits in neonatal lambs in the first 24 hours of life.

Colostrum is a unique resource that contributes to the passive transfer of immunity and plays a central role in the health status of neonatal ruminants. However, digestion and absorption of colostral proteins in the gut remain incompletely understood. Therefore, this study aimed to investigate the effect of bovine colostrum feeding on blood metabolic traits and to quantify colostral bioactive proteins in the gastrointestinal digesta and blood to evaluate intestinal transfer in neonatal lambs in the first 24 h of life. Fifty-four newborn lambs were used in this study, including 27 lambs fed pooled bovine colostrum and slaughtered at 6 (C6h), 12 (C12h), or 24 h (C24h) after birth; 18 lambs not fed any colostrum or milk and slaughtered at birth (N0h) or 24 h (N24h) after birth; and 9 milk-fed lambs slaughtered at 24 h (M24h) after birth. Lambs receiving colostrum or milk were bottle-fed within the first 2 h to obtain intakes of 8% of body weight at birth. Samples of blood and digesta from the abomasum, jejunum, and ileum were collected after slaughter. Serum concentrations of glucose, insulin, total protein, and aspartate aminotransferase were higher in colostrum-fed lambs than in N0h lambs. Serum concentrations of insulin, total protein, insulin-like growth factor 1, and γ-glutamyl transpeptidase were higher in C24h lambs than in N24h or M24h lambs. Apparent efficiencies of IgG absorption in C6h, C12h, and C24h lambs were 14.4, 26.8, and 17.2%, respectively, whereas apparent efficiencies of lactoferrin (LF), α-lactalbumin (α-LA), and ß-lactoglobulin (ß-LG) absorption were very low in colostrum-fed lambs, with mean values of 0.06, 0.002, and 0.003%, respectively. Concentrations of IgG, LF, α-LA, and ß-LG in the digesta of the abomasum, jejunum, and ileum rapidly decreased from C6h to C24h lambs, and the disappearance rates of IgG, LF, α-LA, and ß-LG were higher in lambs from C6h to C12h (62.1, 75.7, 91.3, and 95.0% for IgG, LF, α-LA, and ß-LG, respectively) than from C12h to C24h (34.6, 22.5, 7.5, and 2.2% for IgG, LF, α-LA, and ß-LG, respectively). These results indicated that bovine colostrum feeding improved the metabolic and immunological status of lambs, and that ingested colostral IgG was prone to intact uptake into the blood, whereas almost all ingested LF, α-LA, and ß-LG disappeared in the lumen of the gastrointestinal tract in a time-dependent manner. The findings provide novel information for exploring selective absorption of colostral compounds in the small intestine of lambs.

Quantitative comparative phosphoproteomic analysis of the effects of colostrum and milk feeding on liver tissue of neonatal calves.

Posttranslational modifications, mostly phosphorylation, are critical for protein structure and function. However, the association between liver phosphoproteins in neonatal calves and colostrum intake is not well understood. In this study, we examined the liver phosphoproteome profile in neonatal calves after receiving colostrum or milk. Liver tissue samples were collected from control calves (CON, n = 3) 2 h after birth and from calves that received colostrum (CG, n = 3) or milk (MG, n = 3) 24 h after birth. Hepatic phosphoprotein expression profiles were analyzed using quantitative proteomics based on the liquid chromatography-tandem mass spectrometry method. In total, 1,587 phosphorylated sites were identified in 1,011 liver proteins. The most abundant phosphorylation site AA was serine (87.5%), followed by threonine (11.9%) and tyrosine (0.5%). Among the 1,011 phosphoproteins, 219, 453, and 26 displayed differential expression in the CG versus MG, CG versus CON, and MG versus CON comparisons, respectively. Differentially expressed phosphoproteins in the CG-MG comparison included 3-phosphoinositide-dependent protein kinase 1, glucose transporter member 4, protein kinase N2, and vinculin, which were mainly involved in the glycogen metabolic process, transport, growth and development, and cell adhesion process, according to Gene Ontology analysis. Pathway analysis indicated their enrichment in the insulin signaling pathway, spliceosome, and adherens junction. The CG-CON comparison identified differentially expressed phosphoproteins and their target genes that were largely involved in the cellular process, macromolecule metabolic process, developmental process, and transport. Pathway analysis indicated their association with endocytosis, mechanistic target of rapamycin, AMP-activated protein kinase, and insulin signaling pathways. These data demonstrate that changes in the phosphoproteins of liver tissues may play an important role in energy metabolism and immune response in the calves that received colostrum. These results provide novel insights into the crucial roles of protein phosphorylation during the early life of newborn calves.

Changes in bacterial community and expression of genes involved in intestinal innate immunity in the jejunum of newborn lambs during the first 24 hours of life.

The newborn gut undergoes rapid colonization by commensal microorganisms and possible exposure to pathogens. The contribution of colostrum intake to host protection is well known; however, limited research exists on the intestinal innate immunity corresponding to colostrum intake during the passive immune transfer period in newborn ruminants. The aim of this study was to investigate the changes in bacterial community and expression of genes encoding toll-like receptors (TLR), mucins (MUC), antimicrobial peptides, and tight junctions in the jejunum of lambs that were fed colostrum during the first 24 h of life. Twenty-seven newborn lambs were used in this study, of which 18 lambs were bottle-fed pooled bovine colostrum within the first 2 h after birth to obtain an intake of approximately 8% of body weight. Lambs were slaughtered at 12 (n = 9) and 24 h (n = 9) after birth. The remaining 9 lambs without any feeding were slaughtered at 30 min after birth (0 h). Tissue and ligated segment samples from the jejunum were collected immediately after the lambs were slaughtered. The bacterial profile in the ligated jejunum segment was assessed using amplicon sequencing. The gene expression in the jejunum tissue was determined using quantitative real-time PCR. The relative abundances of Escherichia-Shigella, Lactobacillus, Lactococcus, and Streptococcus increased, whereas those of Sphingomonas, Phyllobacterium, Bradyrhizobium, and Rudaea decreased during the first 24 h of life. Expression of TLR2 and ß-defensin 109-like was upregulated at 12 h after birth, but a recovery was detected at 24 h; TLR3, TLR5, LYZ, MUC1, MUC13, MUC20, and CLDN7 showed a higher expression level in samples taken at 24 h than in those taken at 0 h. In addition, expression level of CLDN1, CLDN4, and the junctional adhesion molecule-1 tended to be higher at 24 h than at 0 h after birth. Correlation analysis indicated that TLR2 expression was negatively correlated with the relative abundance of Lactobacillus and Bradyrhizobium, whereas TLR5 expression was positively correlated with the relative abundance of Escherichia-Shigella and Pelagibacterium. These results suggest that TLR, MUC, antimicrobial peptides, and CLDN act together and play an important role in intestinal defense during the passive immune transfer period. They are potentially associated with microbial colonization. The findings from this study provide novel information to elucidate the role of colostrum components in regulating the development of the intestinal mucosal immune barrier in newborn lambs during the passive immune transfer period.

[Clinical and prognostic features of ovarian endometrioid carcinoma with synchronous endometrial lesions].

Objective: To compare the clinical and prognostic characteristics of ovarian endometrioid carcinoma (OEC) patients with synchronous endometrial lesions and patients with pure OEC. Methods: A retrospective review of the medical records of patients received initial treatment and a postoperative pathological diagnosis of OEC at Peking University People's Hospital between August 1998 and December 2017 were performed. According to the inclusion criteria, a total of 56 patients with OEC were included in the study, including 13 patients concurrent with simultaneous endometrial lesions (Group A) and 43 patients with pure OEC (Group B). Results: Patients with synchronous endometrial lesions accounted for 23% (13/56). Mean age of Group A at diagnosis was (44.9±8.3) years old, 2/13 of patients were postmenopausal, and no one had a history of hypertension, the first symptom of 5/13 people was irregular vaginal bleeding. Mean age of Group B patients at diagnosis was (52.7±10.2) years old, 53% (23/43) of patients were postmenopausal, and 28% (12/43) patients had the history of hypertension, the first symptom of 4 (9%, 4/43) people was irregular vaginal bleeding. The differences of age, menopause status, history of hypertension and initial symptoms between the two groups were statistically significant (all P<0.05). There were no significant differences in fertility history, dysmenorrhea history, age of menarche, history of endometriosis, preoperative and postoperative CA125 level, International Federation of Gynecology and Obstetrics (FIGO) stage, tumor grade, metastatic site and platinum-based chemotherapy drug resistance between the two groups (all P>0.05). The overall 5-year survival rate of OEC patients was 91.6%, and the overall 5-year progression-free survival rate was 76.6%. Among them, the 5-year survival rate of the OEC concurrent with simultaneous endometrial lesions group was 80.2%, and the pure OEC group was 93.4%; the 5-year progression-free survival rate of the OEC concurrent with simultaneous endometrial lesions group was 74.1%, and the 5-year progression-free survival rate of the pure OEC group was 77.3%. There were no significant differences between the two groups (all P>0.05). Multivariate analysis showed that the independent factors for the prognosis of OEC patients were FIGO stage (P=0.006) and residual lesion size (P=0.020). Conclusions: OEC patients have a high proportion of simultaneous endometrial lesions. OEC with simultaneous endometrial lesions are younger than patients with pure OEC. Synchronous endometrial lesions do not affect the prognosis of patients with OEC.

Label-free quantitative proteomics analysis reveals the fate of colostrum proteins in the intestine of neonatal calves.

The contribution of intestinally absorbed colostral immunoglobulins to the transmission of passive immunity is widely reported in neonatal calves. However, changes in the colostral proteome in the gastrointestinal digesta remain unclear. Therefore, this study aimed to investigate changes in colostral proteome affected by gastrointestinal proteases in neonatal calves. Twenty-one neonatal Holstein calves were used in this study, including 18 colostrum-fed calves slaughtered at 8 (CI, n = 6), 24 (CII, n = 6), and 36 h (CIII, n = 6) postpartum and 3 milk-fed calves slaughtered 24 h postpartum (MI, n = 3). The ingested colostrum and milk samples were collected from the mid-jejunum segment, following the sacrifice. The undigested colostrum or milk along with their ingested colostrum or milk samples were investigated using a label-free proteomics approach. Hierarchical clustering and principal component analysis of the quantified proteins revealed that the ingested colostrum from the CII and CIII groups and the ingested mature milk from the MI group appeared to share similar patterns. Analysis of the intestinal digesta revealed a time-dependent decrease in caseins, lactoferrin, and osteopontin protein levels, and an increase in cationic trypsin, chymotrypsin, and carboxypeptidase. Several protease inhibitors, such as α-1-antiproteinase, α-2-antiplasmin, and early lactation protein, were identified in the colostrum and intestinal digesta. In addition, we detected identical levels in the intestinal digesta and colostrum for albumin, α-1-acid glycoprotein, and plasminogen. Pathway analysis indicated that proteins increased in the intestinal digesta belonged to the following categories: biosynthesis of antibiotics, carbon metabolism, and biosynthesis of amino acids. These results indicated that selected colostral proteins were digested by gastrointestinal proteases, contributing to their intestinal absorption in calves. These findings provide new insights into the fate of the colostral proteome in the gastrointestinal tract and may aid in the identification of factors contributing to health management in neonatal calves.

Changes in expression of antimicrobial peptides and Fc receptors in the small intestines of neonatal calves during the passive immunity period.

The contribution of colostrum to passive immunity transfer and intestinal protection is well known; however, the effects of colostrum intake on the expression of antimicrobial peptides (AP) and Fc receptors in the intestine of neonatal calves are unclear. Our aim was to investigate changes in the expression of AP and Fc receptor in the small intestine of calves in the first 36 h postpartum. Twenty-four Holstein bull calves were used in this study, of which 18 calves were administered 3.2 L of pooled colostrum for each calf per meal via an esophageal tube. Calves were slaughtered at 8 h (1 meal at 1-2 h), 24 h (2 meals at 1-2 h and 10-12 h), and 36 h (3 meals at 1-2 h, 10-12 h, and 22-24 h) postpartum. The remaining 6 calves without any milk administration were slaughtered at 2 h postpartum. Samples of blood and jejunum digesta were collected to determine immunoglobulin concentration using ELISA. Samples of the duodenum, jejunum, and ileum tissues after slaughter were collected to determine AP and Fc receptor expression using quantitative real-time PCR. In calves administered colostrum, IgG concentration in jejunum digesta rapidly decreased in an age-dependent manner (33.41, 9.47, and 0.34 mg/mL at 8, 24, and 36 h, respectively), whereas serum IgG concentration increased significantly, from 0.25 µg/mL at 2 h to 21.72 mg/mL at 24 h. Cathelicidin-4, ß-defensin (DEFB)-7, and enteric ß-defensin expression was upregulated at 8 h postpartum in the duodenum and jejunum compared with that at 2 h, but progressive recovery was detected from 24 h onward. Higher expression of cathelicidin-4, regenerating family member 3γ, lysozyme (LYZ), LYZ1, and LYZ2 and lower expression of DEFB, DEFB1, DEFB7, DEFB10, and enteric ß-defensin were observed in the duodenum and jejunum compared with the ileum. Differences in AP expression between intestinal regions suggested that the innate immune defense mechanism varied significantly among the duodenum, jejunum, and ileum. No difference in the expression of Fc fragment of the IgG receptor was observed either among ages or small intestinal regions. The Fcγ receptor (FcγR)Ia and FcγRIIb expression was the highest at 8 h compared with that at 2, 24, and 36 h, and expression of FcγRIa, FcγRIIb, and FcγRIIIa was higher in the duodenum and jejunum than in the ileum. These results indicated that AP and Fcγ receptors might play important roles in intestinal defense during the passive immunity period.

Alterations of the circular RNA profile in the jejunum of neonatal calves in response to colostrum and milk feeding.

Circular RNA (circRNA) have been suggested to contribute to regulating gene expression in various tissues and cells of eukaryotes. However, little is known regarding the expression pattern of circRNA and their potential function in the small intestine of neonatal calves that receive colostrum. In the current study, jejunum tissue samples were collected from control calves (2 h after birth; CT; n = 3) and neonatal calves that ingested colostrum (24 h after birth; CO; n = 3) or milk (24 h after birth; MK; n = 3) to compare the circRNA expression patterns using a high-throughput RNA sequencing approach. A total of 21,213, 17,861, and 21,737 circRNA were identified in the CT, CO, and MK groups, respectively. Only 13,254 of these circRNA were common to the 3 groups, suggesting high specificity of circRNA expression depending on nutrient type. In total, 243, 249, and 283 circRNA were differentially expressed in the CO versus CT, CO versus MK, and MK versus CT comparisons, respectively. Gene ontology analysis showed that the differentially expressed circRNA and their predicted or known target genes from the CO and MK groups were mainly involved in macromolecule metabolic process, response to stress, and vesicle-mediated transport. Moreover, pathway analysis showed that the Rap1 signaling pathway, focal adhesion, ubiquitin-mediated proteolysis, and extracellular matrix-receptor interaction were the most significantly enriched pathways. These data collectively indicate that circRNA are abundant and dynamically expressed when calves receive colostrum and act as microRNA sponges to regulate their target genes for jejunum function during the early development of newborn calves.

[Advances in epigenetic markers of dermatomyositis/polymyositis].

Idiopathic inflammatory myopathy (IIM) is a rare group of autoimmune diseases, characterized by chronic muscle weakness, muscle fatigue and infiltration of single nuclear cells in skeletal muscle. Its subtypes include dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) and immune-mediated necrotizing myositis (IMNM), and the most common subtypes are DM and PM. PM is an autoimmune disease mainly manifested by muscle damage. When the skin is involved, it is called DM. The incidence of IIM was relatively low, which was 1.16-19 per million people/year, but the mortality was high and the prognosis was poor. The pathogenesis of IIM is still unclear. Previous studies suggest that both immune and non-immune mechanisms are involved in its pathogenesis, especially cellular and humoral immunity. In recent years, researchers have conducted a number of studies on the pathogenesis of IIM, especially in the study of DM/PM with the application of high-throughput biometrics. Epigenetics is a discipline that refers to the genetic phenomena of DNA methylation spectrum, chromatin structure state and gene expression spectrum transferred between cells without any changes in DNA sequence, including DNA methylation, chromatin modification and non-coding RNA changes. A large number of studies have shown that epigenetic modification plays an important role in many diseases, especially in cancer. Recent studies have also found a series of epigenetic markers related to the occurrence and development of DM/PM, mainly in the aspect of non-coding RNA changes, such as miR-10a, miR-206, etc. And there has also been some research on DNA methylation. However, no studies have been reported on whether chromatin modification is involved in the pathogenesis of DM/PM. The pathogenesis of DM/PM is complex and diverse. With the development of research, certain microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) may become biological markers for the early diagnosis of DM/PM. Therefore, this paper mainly expounds the research progress of the biomarkers of DM/PM from the aspect of epigenetics.

[Altered serum cytokine expression profile in systemic sclerosis and its regulatory mechanisms].

OBJECTIVE: To analyze the expression profile of serum cytokines in patients with systemic sclerosis (SSc) and explore its possible regulatory mechanisms. METHODS: Serum and DNA of peripheral blood mononuclear cells were collected from 30 SSc patients and 80 normal controls (NCs). According to the presence or absence of interstitial lung disease (ILD) in SSc, the patients were divided into SSc with ILD group and SSc without ILD group. According to the degree of skin involvement, the patients were divided into diffuse systemic scleroderma (dcSSc) group and limited systemic scleroderma (lcSSc) group. According to the presence of anti-topoisomerase-1 antibody (anti-Scl-70 antibody) in the serum of patients with SSc, they were divided into SSc Scl-70 (+) group and SSc Scl-70 (-) group. 27 cytokines in serum were detected by Luminex MAGPIX detection system and Bio-Plex Pro Human Cytokine 27-plex Assay kit: interleukin-1ß (IL-1ß), interleukin-1 receptor antagonist (IL-1ra), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12P70, IL-13, IL-15, IL-17, basic fiber growth factor (BASIC FGF), eotaxin, granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), interferon-γ (IFN-γ), interferon-gamma induced protein 10(IP-10), monocyte chemotactic protein 1(MCP-1), macrophage inflammatory protein-1α (MIP-1α), macrophage inflammatory protein 1ß(MIP-1ß), platelet-derived growth factor BB (PDGF-BB), regulated on activation in normal T-cell expressed and secreted (RANTES), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor(VEGF). Methylation sites were detected by Illumina 450K methylation chip. RESULTS: Compared with NCs group, the expression of 12 cytokines (BASIC FGF, eotaxin, G-CSF, GM-CSF, IFN-γ, IL-1ß, IL-1ra, IL-6, IP-10, MCP-1, TNF-α and RANTES) in the SSc group significantly increased (P<0.05), IL-5 was decreased expression in the SSc group (P<0.05), there was no significant difference in the expressions of the other 14 cytokines. Compared with lcSSc group, 9 cytokines (eotaxin, IL-5, MCP-1, IL-2, RANTES, IL17A, IL-8, MIP-1ß and PDGF-BB) increased in dcSSc group, but there was no significant difference. Compared with SSc without ILD group, IL-15 increased in SSC with ILD group [18.2 (172.97) ng/L vs. 2.03(0.05) ng/L, P<0.05]. Compared with SSc Scl-70 (-) group, the expression of IP-10 decreased in SSc Scl-70 (+) group [1 030 (2 196.6) ng/L vs. 1 878 (2 964) ng/L, P<0.05]. The correlation analysis of serum cytokines with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) showed that IL-6 was positively correlated with ESR (r =0.04, P= 0.017), MCP-1 (r=0.49, P=0.043) and MIP-1ß (r=0.41, P=0.007) positively correlated with CRP. By analyzing the changes of methylation sites of cytokines, it was found that cg17744604 in IL-10 TSS1500 region, cg06111286 in IL-12P70 TSS200 region, cg07935264 in IL-1ß TSS200 region, cg01467417 in IL-1ra TSS1500 region, cg03989987 in IL-1ra 5'UTR region and cg21099624 in VEGF TSS200 region were all hypomethylated. CONCLUSION: There were different cytokines expression profiles in the serum of SSc patients, and the altered cytokines were correlected with the degree of skin damage and pulmonary fibrosis. Many cytokines were regulated by methylation.

Analysis of Late Positive Component of Event-related Potentials by Face Expression Images in Traumatic Brain Injury Patients with Mood Disorders.

OBJECTIVES: To explore the application of event-related potentials （ERP） by positive, negative, and neutral face expression images in the evaluation of mood disorders in brain traumatic patients. METHODS: ERP was tested by face expression images in 24 patients mainly with anxiety and depression symptoms （depression group） and 19 patients mainly with hostile and suspicion symptoms （hostile group）, respectively. The findings were compared with those of the control group. RESULTS: There were no significant differences, between the depression group and the hostile group, on latencies and amplitudes of late positive potential （LPP） induced by the three types of face expression images, except the amplitude induced by negative face expression image. Compared with the control group, the latencies were extended and the amplitudes were lower in both depression and hostile groups. Within each group, the difference of latencies induced by the three images was not significant. The amplitudes induced by negative face expression image was higher than those induced by positive and neutral face expression images, with significant differences in the hostile group and the control group （P<0.05） but not in the depression group. CONCLUSIONS: Changes in latencies and amplitudes of LPP could be an objective indicator in the evaluation of mood disorders of brain traumatic patients. The LPP induced by negative face expression images could be more meaningful for patients mainly with anxiety and depression symptoms.

[Atypical polypoid adenomyoma of the uterus: a clinicopathological review of 27 cases].

Objective: To investigate the clinical and pathological characteristics of atypical polypoid adenomyoma (APA) for improvement of the diagnosis, different diagnosis and treatment of the disease. Methods: The clinical data, pathological characteristics, and the follow-up information were retrospectively analyzed in 27 cases of APA admitted in Peking Univeristy People's Hospital from 2007 to 2016. Results: The median age was 42.6 years old (range 25-60 years old). Fifteen patients were nullipara, 2 patients were postmenopausal. The most common presenting symptom was abnormal uterine bleeding (81%, 22/27) . Leisions were obtained by using hysteroscopy in 23 cases, hysterectomy 3 cases and dilatation and curettage 1 case. Fertility preserving treatments were performed in 10 patients who had strong desire for fertility, among which 1 case progressed into endometrial carcinoma. Among 15 patients underwent hysterectomy and (or) bilateral salpingo-oophorectomy, 9 cases of them had endometrial atypical hyperplasia. Endometrial carcinoma along with APA were found in three patients, 2 cases of them underwent hysterectomy and bilateral salpingo-oophorectomy and pelvic lymphadenectomy, the other one received medication for fertility preservation. Follow up information were available in 24 cases (89%, 24/27) with a median follow up of 46 months (range 4-108 months), 1 case recurred and 1 case progressed into endometrial carcinoma. One case died of other malignancy, while the other patients were alive. Conclusions: APA is a rare uterine neoplasm mixed with epithelial and mesenchymal component. It occurs mostly in childbearing-age women and its diagnosis is dependent on pathology. Although it's clinical course is benign, there is risk of co-existance of endometrial carcinoma and endometrial atypical hyperplasia. For those who has desire of fertility, the treatment strategy is completely removed the lesion and closely followed up. For those who do not desire to preserve fertility, hysterectomy may be an option.

[Therapeutic effect of IGF-1R-targeting inhibitor (TAE226) on malignant pleural effusion in nude mice].

OBJECTIVE: To study the therapeutic effect of IGF-1R inhibitor TAE226 on malignant pleural effusion (MPE) in nude mice. METHODS: Human lung carcinoma A549 cells were injected into the pleural cavity of nude mice to establish MPE model. The mice were randomly divided into model group and treatment group, and were orally administered with distilled water and TAE226 (20 mg/kg) in the same volume, respectively. The volume of pleural effusion and tumor weight of the two groups were observed. HE staining was used to reveal the histological changes and enzyme-linked immunosorbent assay (ELISA) was used to detect the IGF-1R protein expression. IGF-1R mRNA level in the tumor tissue was determined by RT-PCR. Microvessel density (MVD) and cell proliferation index (PI) were assessed by immunohistochemical analysis. The protein expression levels of IGF-1R, p-IGF-1R, PI3K and p-PI3K in the tumor tissue were determined by Western blotting. RESULTS: The volumes of pleural effusion were (241.4±89.7) µl and (121.7±78.8) µl in the model and treatment groups, respectively (P<0.05). The tumor weight of treatment group was (316.7±186.3) mg, significantly lower than that of the model group (671.4±281.4) mg (P<0.05). RT-PCR analysis showed that IGF-1R mRNA level was 0.914±0.029 in the treatment group, significantly lower than that of the model group (1.152±0.037, P<0.01). The ELISA data revealed that IGF-1R protein expression level of the model group was significantly higher than that of the treatment group [(41.0±4.7) µg/L vs. (24.0±3.1) µg/L, P<0.01]. Immunohistochemical analysis showed that there were significant differences between MVD and PI in the model and treatment groups [MVD, 34.75±3.49 vs. 22.25±3.63; PI, (75.25±7.15)% vs. (45.75±5.12)%; P<0.01 for both). Western blot data showed that IGF-1R and PI3K protein expression levels were not significantly different between the model and treatment groups (1.03±0.33 vs. 0.98±0.37 and 1.05±0.28 vs. 0.98±0.19), respectively (P>0.05), but p-IGF-1R and p-PI3K protein expression levels had significant differences between the two groups (1.08±0.10 vs. 0.51±0.08 and 1.12±0.09 vs. 0.86±0.09), respectively (P<0.01 for both). CONCLUSIONS: The IGF-1R inhibitor can effectively inhibit the formation of malignant pleural effusion. Its mechanism may be related to the suppression of tumor cell proliferation, invasion and angiogenesis through inhibition of PI3K signaling. TAE226 treatment may be a potential therapeutic regimen of treating malignant pleural effusion.