Prognosis-related classifi cation and dynamic monitoring of immune status in patients with sepsis:A prospective observational study

BACKGROUND:The dynamic monitoring of immune status is crucial to the precise and individualized treatment of sepsis.In this study,we aim to introduce a model to describe and monitor the immune status of sepsis and to explore its prognostic value.METHODS:A prospective observational study was carried out in Zhongshan Hospital,Fudan University,enrolling septic patients admitted between July 2016 and December 2018.Blood samples were collected at days 1 and 3.Serum cytokine levels(e.g.,tumor necrosis factor-α[TNF-α],interleukin-10[IL-10])and CD14+monocyte human leukocyte antigen-D-related(HLA-DR)expression were measured to serve as immune markers.Classifi cation of each immune status,namely systemic inflammatory response syndrome(SIRS),compensatory anti-inflammatory response syndrome(CARS),and mixed antagonistic response syndrome(MARS),was defined based on levels of immune markers.Changes of immune status were classifi ed into four groups which were stabilization(SB),deterioration(DT),remission(RM),and non-remission(NR).RESULTS:A total of 174 septic patients were enrolled including 50 non-survivors.Multivariate analysis discovered that IL-10 and HLA-DR expression levels at day 3 were independent prognostic factors.Patients with MARS had the highest mortality rate.Immune status of 46.1%patients changed from day 1 to day 3.Among four groups of immune status changes,DT had the highest mortality rate,followed by NR,RM,and SB with mortality rates of 64.7%,42.9%,and 11.2%,respectively.CONCLUSIONS:Severe immune disorder defi ned as MARS or deterioration of immune status defi ned as DT lead to the worst outcomes.The preliminary model of the classifi cation and dynamic monitoring of immune status based on immune markers has prognostic values and is worthy of further investigation.

Growth performance,oxidative stress and immune status of newly weaned pigs fed peroxidized lipids with or without supplemental vitamin E or polyphenols

Background:This study evaluated the use of dietary vitamin E and polyphenols on growth,immune and oxidative status of weaned pigs fed peroxidized lipids.A total of 192 piglets(21 days of age and body weight of 6.62±1.04 kg)were assigned within sex and weight blocks to a 2×3 factorial arrangement using 48 pens with 4 pigs per pen.Dietary treatments consisted of lipid peroxidation(6%edible soybean oil or 6%peroxidized soybean oil),and antioxidant supplementation(control diet containing 33 IU/kg DL-α-tocopheryl-acetate;control with 200 IU/kg additional dl-α-tocopheryl-acetate;or control with 400 mg/kg polyphenols).Pigs were fed in 2 phases for 14 and 21 days,respectively.Results:Peroxidation of oil for 12 days at 80°C with exposure to 50 L/min of air substantially increased peroxide values,anisidine value,hexanal,and 2,4-decadienal concentrations.Feeding peroxidized lipids decreased(P<0.001)body weight(23.16 vs.18.74 kg),daily gain(473 vs.346 g/d),daily feed intake(658 vs.535 g/d)and gain:feed ratio(719 vs.647 g/kg).Lipid peroxidation decreased serum vitamin E(P<0.001)and this decrease was larger on day 35(1.82 vs.0.81 mg/kg)than day 14(1.95 vs.1.38 mg/kg).Supplemental vitamin E,but not polyphenols,increased(P≤0.002)serum vitamin E by 84%and 22%for control and peroxidized diets,respectively(interaction,P=0.001).Serum malondialdehyde decreased(P<0.001)with peroxidation on day 14,but not day 35 and protein carbonyl increased(P<0.001)with peroxidation on day 35,but not day 14.Serum 8-hydroxydeoxyguanosine was not affected(P>0.05).Total antioxidant capacity decreased with peroxidation(P<0.001)and increased with vitamin E(P=0.065)and polyphenols(P=0.046)for the control oil diet only.Serum cytokine concentrations increased with feeding peroxidized lipids on day 35,but were not affected by antioxidant supplementation(P>0.05).Conclusion:Feeding peroxidized lipids negatively impacted growth performance and antioxidant capacity of nursery pigs.Supplementation of vitamin E and polyphenols improved total antioxidant capacity,especially in pigs fed control diets,but did not restore growth performance.

Ileum terminal antibiotic infusion affects jejunal and colonic specific microbial population and immune status in growing pigs

Background: Compared with oral antibiotics(primarily disrupt foregut microbiota), the present study used antibiotics with ileum terminal infusion to disrupt the hindgut microbiota, and investigated the changes in specific bacterial composition and immune indexes in the jejunum and colon, and serum of growing pigs. Twelve barrows(45 d of age, 12.08 ± 0.28 kg) fitted with a T-cannula at the terminal ileum, were randomly assigned to two groups and infused either saline without antibiotics(Control) or with antibiotics(Antibiotic) at the terminal ileum. After 25 d experiment, all pigs were euthanized for analyzing bacterial composition and immune status.Results: Ileum terminal antibiotic infusion(ITAI) altered dominant bacteria counts, with a decrease in Bifidobacterium, Clostridium cluster IV and Clostridium cluster IV in the colon(P < 0.05), and an increase in Escherichia coli in the jejunum(P < 0.05). ITAI decreased(P < 0.05) short-chain fatty acids concentrations in the colon. ITAI decreased interleukin-8(IL-8), IL-10 and secretory immunoglobulin A(sIgA) concentrations, and down-regulated IL-10, Mucin-1(MUC1), Mucin-2(MUC2) and zonula occludens-1(ZO-1) mRNA expression in the colonic mucosa(P < 0.05). In the jejunal mucosa, ITAI decreased interferon-γ(IFN-γ), tumor necrosis factor-α(TNF-α), s IgA and IgG levels together with down-regulation of IFN-γ, TNF-α, MUC2 and ZO-1 mRNA expression(P < 0.05). Furthermore, ITAI decreased IL-10, INF-γ, TNF-α, IgA and IgG concentrations in serum(P < 0.05). Correlation analysis revealed that the change in intestinal microbiota was correlated with alterations of Ig and cytokines.Conclusions: ITAI affected jejunal and colonic specific bacteria counts, and altered some immune markers levels in the jejunal and colonic mucosa and serum. These findings implicate the potential contribution of hindgut bacteria to immune response in the intestinal mucosa and serum of growing pigs.

RESEARCH OF NUTRITIONAL AND IMMUNE STATUS IN PATIENTS WITH GALLBLADDER CARCINOMA RADICAL CHOLECYSTECTOMY

Objective To inquire the nutritional and immune status in patients with gallbladder carcinoma before and after radical cholecystectomy.Methods The nutritional and immune status in patients with gallbladder carcinoma were assessed in 1 week before surgery, and on 3rd day, 7th day, 14th day and 21st day after operation respectively.Results All of the nutritional parameters but the serum level of iron, TIBC and transfterrin recovered within 3 week after operation. Remarkable decrease of serum IgG, IgA, IgM and C 3, C 4 complement, IL 2, CD 4, CD 4/CD 8 ratio, and the remarkable increase of serum SIL 2R and CD 8( P <0.01) on 3rd day after operation.Conclusion Adequate iron should be supplemented after the radical cholecystectomy for gallbladder carcinoma in the third postoperative week. Radical cholecystectomy with complete resection of the tumor and removal of lymph nodes played the important roles in the recovery of immune function.

INFLUENCE OF IMMUNE STATUS OF THE IMMUNE DEFICIENT MICE ON THE METASTATIC PHENOTYPES OF THE HETEROGENEOUS CLONAL SUBLINES OF HUMAN LUNG GIANT CELL CARCINOMA

By using cell cloning technique, 4 sublines (A,C,D,E) were isolated from a cell line of human lung giant cell carcinoma (PLA-801). After subcutaneous inoculation in T-cell deficient BALB/c nude mice, the incidence of tumor growth and spontaneous metastasis were the highest in subline D, moderate in sublines A and E, and lowest in subline C. Tumor cells of subline C also showed similar low tumorigenicity in another T-cell deficient 615/ PB1 nude mice.However, in 615/PB1 beige nude mice with con-genitally combined immune-deficiency in both T and NK cell activity, tumor cells of the rarely metastatic subline C do produce significantly high frequency of tumor growth and spontaneous metastasis.Morphological studies (light microscope, electron microscope and immunohistochemistry) showed rich microfilaments and Vimentin positive in the cytoplasm of metastatic tumor cells. This may imply a possibility that tumor cells differentiate towards the direction favourable to spreading and metastasis.

Serum Zinc Levels and Immune Status of Children with Persistent Diarrhea Following Oral Zinc Supplementation

Background: Persistent diarrhea (PD) is a common disease in childhood worldwide. Clinical studies suggested that zinc supplementation is useful in most PD children. However, the relationship between the zinc and immune status of the PD children has not been reported. Objective: To examine serum zinc levels and immune status in 6 to 24 months old children with PD before and after 120 days of oral zinc supplementation and to evaluate the effects of zinc supplementation on serum zinc levels and immune status in PD children. Methods: A case control study was carried. Fifty-eight children aged 6 to 24 months with PD were enrolled. 58 patients were divided into two groups, zinc group (28 cases) and control group (30 cases). Laboratory investigation of serum zinc levels, Lymphocyte subsets (CD3+%, CD4+%, CD8+% and CD4+/CD8+ ratio) and immunoglobulins (IgG, IgA and IgM) levels was carried out in all these patients once at enrollment and again after 120 days of treatment. Results: Before treatment, the serum zinc concentration was 4.37 ± 1.23 μmol/L in zinc group and 4.42 ± 1.45 μmol/L in control group (P > 0.05). However, after treatment, the serum zinc concentrations in the zinc group were significantly higher (8.81 ± 2.56 μmol/L), as compared to the control group (4.12 ± 1.02 μmol/L) (P < 0.05). Regarding immune status, Lymphocyte subsets CD3+%, CD4+%, CD8+% and CD4+/CD8+ ratio and IgG, IgA and IgM levels of all the children with PD were measured once at enrollment and again after 120 days of treatment. There were no significant differences between the zinc and the control groups in CD3+%, CD4+%, CD8+% and CD4+/CD8+ ratios (P > 0.05) before giving treatment. However, after 120 days of treatment, in the zinc group there was a significant rise in CD4+% (53.60 ± 5.78). The CD4 was significantly higher in the zinc group as compared to the control group (44.73 ± 4.39) (P < 0.05). Besides CD4+%, the CD4+/CD8+ ratio was also found to be higher among zinc group (1.49 ± 0.29) as compared to the control group (1.26 ± 0.18) after treatment (P < 0.05). But there were no statistically significant differences in CD3+% and CD8+% between zinc and control group after treatment (P > 0.05). Regarding immunoglobulins, there were no significant differences between zinc and control group in IgG, IgA and IgM levels (P > 0.05) at the time of enrollment (before treatment). However, after treatment, the mean IgG levels in zinc group and control group were 6.36 ± 0.95 g/l and 5.67 ± 0.74 g/l, respectively, P < 0.05. Similarly, after treatment, IgM levels in the zinc group were found significantly higher (1.58 ± 0.13 g/l), as compared to the control group (1.43 ± 0.20 g/l) (P < 0.05) but no significant differences in IgA levels were evident between the two groups after treatment. Conclusion: Administration of oral zinc supplement improved both serum zinc levels and immune status in children with PD. Zinc supplementation should be administered as adjunctive therapy for PD children.

Retrospective Study Immune function status of postoperative patients with colon cancer for predicting liver metastasis

BACKGROUND Colon cancer(CC)has a high incidence rate.Radical resection is the main treatment method for CC;however,liver metastasis(LM)often occurs post-surgery.The liver contains both innate and adaptive immune cells that monitor and remove abnormal cells and pathogens.Before LM,tumor cells secrete cytokines and exosomes to adjust the immune microenvironment of the liver,thus forming an inhibitory immune microenvironment for colonization by circulating tumor cells.This indicates that the immune state of patients with CC plays a crucial role in the occurrence and progression of LM.AIM To observe and analyze the relationship between immune status and expression of tumor factors in patients with LM of CC,and to provide a scientific interven-tion method for promoting the patient prognosis.METHODS A retrospective analysis was performed.The baseline data of 100 patients with CC and 100 patients with CC who suffered from postoperative LM and were admitted to our hospital from May 2021 to May 2023 were included in the non-occurrence and occurrence groups,respectively.The immune status of the pa-tients and the expression of tumor factor-related indicators in the two groups were compared,and the predictive value of the indicators for postoperative LM in patients with CC was analyzed.RESULTS Compared with the non-occurrence group,the expression of serum carcinoem-bryonic antigen(CEA),CA19-9,CA242,CA72-4 and CA50 in patients in the occurrence group were significantly higher,while the expression of CD3+,CD4+,CD8+,natural killer(NK)and CD4+/CD25 in patients in the occurrence group were significantly lower(P<0.05).No significant difference was observed in other baseline data between groups(P>0.05).Multivariate logistic regression model analysis revealed that the expressions of CEA,CA19-9,CA242,CA72-4,CA50,CD3+,CD4+,CD8+,NK,and CD4+/CD25 were associated with the LM in patients with CC.High expressions of serum CEA,CA19-9,CA242,CA72-4 and CA50,and low expressions of CD3+,CD4+,CD8+,NK,and CD4+/CD25 in patients with CC were risk factors for LM(OR>1,P<0.05).The receiver operating characteristic curve showed that the area under curve for CEA,CA19-9,CA242,CA72-4,CA50,CD3+,CD4+,CD8+,NK,and CD4+/CD25 in the prediction of LM in patients with CC were all>0.80,with a high predictive value.CONCLUSION The expression of tumor factors and immune state-related indices in patients with CC is closely associated with the occurrence of LM.

Bacillus amyloliquefaciens 40 regulates piglet performance,antioxidant capacity,immune status and gut microbiota

Probiotics can improve animal growth performance and intestinal health.Bacillus species,Lactobacillus species,Bifidobacterium species,yeast etc.are the common types of probiotics.However,understanding the effects of probiotics on the immune status and gut microbiota of weaning piglets and how the probiotics exert their impact are still limited.This study aimed to investigate the effects of Bacillus amyloliquefaciens 40(BA40)on the performance,immune status and gut microbiota of piglets.A total of 12 litters of newborn piglets were randomly divided into 3 groups.Piglets in control group were orally dosed with phosphate buffered saline;BA40 group and probiotics group were orally gavaged with resuspension BA40 and a probiotics product,respectively.The results showed that BA40 treatment significantly decreased(P<0.05)the diarrhea incidence(from d 5 to 40),diamine oxidase,D-lactate,interleukin(IL)-1βand interferon-γconcentrations compared with control group and probiotics group.Meanwhile BA40 dramatically increased the total antioxidant capacity,IL-10 and secretory immunoglobulin-A concentrations in contrast to control group.For the microbial composition,BA40 modulated the microbiota by improving the abundance of Bacteroides,Phascolarctobacterium(producing short-chain fatty acids)and Desulfovibrio and reducing the proliferation of pathogens(Streptococcus,Tyzzerella,Vellionella and paraeggerthella).Meanwhile,a metabolic function prediction explained that carbohydrate metabolism and amino acid metabolism enriched in BA40 group in contrast to control group and probiotics group.For correlation analysis,the results demonstrated that BA40-enriched Phascolarctobacterium and Desulfovibrio provide insights into strategies for elevating the health status and performance of weaned piglets.Altogether,BA40 exerted stronger ability in decreasing diarrhea incidence and improved antioxidant activity,gut barrier function and immune status of piglets than the other treatments.Our study provided the experimental and theoretical basis for the application of BA40 in pig production.

Genetic variants in C1GALT1 are associated with gastric cancer risk by influencing immune infiltration

Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1(C1GALT1)is known to play a critical role in the development of gastric cancer,but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer risk.By using the genome-wide association study data from the database of Genotype and Phenotype(dbGAP),we evaluated such associations with a multivariable logistic regression model and identified that the rs35999583 G>C in C1GALT1 was associated with gastric cancer risk(odds ratio,0.83;95% confidence interval[CI],0.75-0.92;P=3.95×10^(-4)).C1GALT1 mRNA expression levels were significantly higher in gastric tumor tissues than in normal tissues,and gastric cancer patients with higher C1GALT1 mRNA levels had worse overall survival rates(hazards ratio,1.33;95%CI,1.05-1.68;P_(log-rank)=1.90×10^(-2)).Furthermore,we found that C1GALT1 copy number differed in various immune cells and that C1GALT1 mRNA expression levels were positively correlated with the infiltrating levels of CD4^(+)T cells and macrophages.These results suggest that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 into a promising predictor of gastric cancer susceptibility and immune status.

Effects of benzoic acid,Bacillus coagulans and oregano oil combined supplementation on growth performance,immune status and intestinal barrier integrity of weaned piglets

This experiment was conducted to investigate the effects of benzoic acid,Bacillus coagulans and oregano oil combined supplementation on growth performance,immune status and intestinal barrier integrity of piglets.In a 26-d experiment,25 piglets were randomly assigned to 5 treatments:1)a basal diet,negative control(NC),2)NC added with antibiotics,positive control(PC);3)NC added with benzoic acid at 3,000 g/t and Bacillus coagulans at 400 g/t(AB);4)NC added with benzoic acid at 3,000 g/t and o regano oil at 400 g/t(AO);5)NC added with 3,000 g/t benzoic acid and Bacillus coagulans at 400 g/t and oregano oil at 400 g/t(ABO);On d 27,all piglets were euthanized to obtain jejunal mucosa to measure immune status and intestinal barrier integrity.Results showed that pigs fed AB diet increased the final body weight and average daily body weight gain and decreased the ratio of feed to gain co mpared with NC group(P<0.05).Co mpared with NC group,AB,AO and ABO decreased serum tumor necrosis factor-a concentration and ABO decreased interleukin-1βconcentration in serum and jejunal mucosa(P<0.05).Compared with NC group,AB upregulated mRNA expressions of sodium-glucose cotransportel,claudin-1,occludin and mucin2 in jejunal mucosa and the populations of Bifidobacterium and Bacillus in cecal digesta(P<0.05).Compared with NC group,ABO increased jejunal mucosal occludin mRNA abundance and Bifidobacterium population in cecal digesta,and decreased Escherichia coli population in cecal digesta(P<0.05).Furthermore,AB and ABO increased Bacillus population in cecal digesta compared with PC group(P<0.05).These results indicated that dietary AB supplementation could improve growth performance and intestinal barrier integrity of piglets when fed antibiotic-free diets,which was possibly associated with the improvement of immune status and intestinal microflora.Dietary ABO supplementation is also beneficial to improve immune status and intestinal barrier integrity and micro flora of piglets.

Co-fermented defatted rice bran alters gut microbiota and improves growth performance,antioxidant capacity,immune status and intestinal permeability of finishing pigs

Based on preparation of co-fermented defatted rice bran(DFRB)using Bacillus subtilis,Saccharomyces cerevisiae,Lactobacillus plantarum and phytase,the present study aimed to evaluate the effects of cofermented DFRB on growth performance,antioxidant capacity,immune status,gut microbiota and permeability in finishing pigs.Ninety finishing pigs(85.30±0.97 kg)were randomly assigned to 3treatments(3 replicates/treatment)with a basal diet(Ctrl),a basal diet supplemented with 10% unfermented DFRB(UFR),and a basal diet supplemented with 10% fermented DFRB(FR)for 30 d.Results revealed that the diet supplemented with FR notably(P<0.05)improved the average daily gain(ADG),gain to feed ratio(G:F)and the digestibility of crude protein,amino acids and dietary fiber of finishing pigs compared with UFR.Additionally,FR supplementation significantly(P<0.05)increased total antioxidant capacity,the activities of superoxide dismutase and catalase,and decreased the content of malonaldehyde in serum.Furthermore,FR remarkably(P<0.05)increased serum levels of Ig G,antiinflammatory cytokines(IL-22 and IL-23)and reduced pro-inflammatory cytokines(TNF-α,IL-1β and INF-γ).The decrease of serum diamine oxidase activity and serum D-lactate content in the FR group(P<0.05)suggested an improvement in intestinal permeability.Supplementation of FR also elevated the content of acetate and butyrate in feces(P<0.05).Moreover,FR enhanced gut microbial richness and the abundance of fiber-degrading bacteria such as Clostridium butyricum and Lactobacillus amylovorus.Correlation analyses indicated dietary fiber in FR was associated with improvements in immune status,intestinal permeability and the level of butyrate-producing microbe C.butyricum,which was also verified by the in vitro fermentation analysis.These findings provided an experimental and theoretical basis for the application of fermented DFRB in finishing pigs.

The expressions and clinical significance of CD107a and CD107b in chronic hepatitis B patients with different immune status

Objective To investigate the expressions of CD107a and CD107b on CD8+T lymphocytes in chronic hepatitis B(CHB)patients with different immune status.Methods Forty-three CHB patients were collected and classified according to the immune status(23 cases of atypical status,10 cases of immune tolerance and 10 cases of immune clearance).Another 10 cases were selected

Supplementation of vitamin E or a botanical extract as antioxidants to improve growth performance and health of growing pigs housed under thermoneutral or heat-stressed conditions

Background Heat stress has severe negative consequences on performance and health of pigs,leading to significant economic losses.The objective of this study was to investigate the effects of supplemental vitamin E and a botanical extract in feed or drinking water on growth performance,intestinal health,and oxidative and immune status in grow-ing pigs housed under heat stress conditions.Methods Duplicate experiments were conducted,each using 64 crossbred pigs with an initial body weight of 50.7±3.8 and 43.9±3.6 kg and age of 13-week and 12-week,respectively.Pigs(n=128)were housed individually and assigned within weight blocks and sex to a 2×4 factorial arrangement consisting of 2 environments(thermo-neutral(21.2℃)or heat-stressed(30.9℃))and 4 supplementation treatments(control diet;control+100 IU/L of D-α-tocopherol in water;control+200 IU/kg of DL-α-tocopheryl-acetate in feed;or control+400 mg/kg of a botanical extract in feed).Results Heat stress for 28 d reduced(P≤0.001)final body weight,average daily gain,and average daily feed intake(-7.4 kg,-26.7%,and-25.4%,respectively)but no effects of supplementation were detected(P>0.05).Serum vitamin E increased(P<0.001)with vitamin E supplementation in water and in feed(1.64 vs.3.59 and 1.64 vs.3.24),but not for the botanical extract(1.64 vs.1.67 mg/kg)and was greater when supplemented in water vs.feed(P=0.002).Liver vitamin E increased(P<0.001)with vitamin E supplementations in water(3.9 vs.31.8)and feed(3.9 vs.18.0),but not with the botanical extract(3.9 vs.4.9 mg/kg).Serum malondialdehyde was reduced with heat stress on d 2,but increased on d 28(interaction,P<0.001),and was greater(P<0.05)for antioxidant supplementation compared to control.Cellular proliferation was reduced(P=0.037)in the jejunum under heat stress,but increased in the ileum when vitamin E was supplemented in feed and water under heat stress(interaction,P=0.04).Tumor necrosis factor-αin jejunum and ileum mucosa decreased by heat stress(P<0.05)and was reduced by vitamin E sup-plementations under heat stress(interaction,P<0.001).Conclusions The addition of the antioxidants in feed or in drinking water did not alleviate the negative impact of heat stress on feed intake and growth rate of growing pigs.

Supplementation with alpha-glycerol monolaurate during late gestation and lactation enhances sow performance,ameliorates milk composition,and improves growth of suckling piglets

Background Physiological changes during lactation cause oxidative stress in sows,reduce immunity,and hamper the growth capacity of piglets.Alpha-glycerol monolaurate(α-GML)has potential for enhancing the antimicrobial activity of sows and the growth of suckling piglets.Methods Eighty sows were allocated randomly to four groups:basal diet and basal diets supplemented with 500,1000,or 2000 mg/kgα-GML.The experiment started on d 85 of gestation and lasted until piglets were weaned on d 21 of lactation.The number of live-born piglets was standardized to 12 tion,body weight of piglets was measured and milk samples±1 per sow on day of parturition.On d 0 and21 of lactawere obtained from sows,and serum samples and feces from piglets were obtained on d 21.Results Feed intake,backfat loss,and weaning estrus interval did not differ among the four groups of sows.Maternalα-GML supplementation increased(P<0.05)the body weight of piglets at weaning and the apparent total tract digestibility of crude fat of sows.The immunoglobulin A and immunoglobulin G levels were greater(P<0.05)in a quadratic manner in the milk of sows as dietaryα-GML increased.Concerning fatty acid profile,C12:0,C15:0,C17:0,C18:2n6c,C18:3n3,C24:0,and C22:6n3 were higher(P<0.05)in linear and quadratic manners in colostrum of sowsfedα-GML diets compared with the control sows.There was lower(P<0.05)n-6:n-3 polyunsaturated fatty acid ratio in milk than in the control sows.Maternalα-GML increased the abundance of Firmicutes(P<0.05)and decreased the abundance of Proteobacteria(P<0.05)of piglet fecal microbiota.Conclusions Dietary supplementation withα-GML improved milk immunoglobulins and altered fatty acids of sows,thereby improving the health of piglets.

Dietary oregano essential oil supplementation improves intestinal functions and alters gut microbiota in latephase laying hens

Background:Dietary essential oil(EO)supplementation can exert favorable effects on gut health in broilers.However,it is unknown whether EO could improve intestinal functions,consequently beneficial for egg performance and quality in late-phase laying hens.This study was aimed to investigate the potential effects of EO on production performance,egg quality,intestinal health and ileal microbiota of hens in the late phase of production.A total of 28860-week-old Hy-line Brown laying hens were randomly divided into 4 groups and fed a basal diet(control)or basal diets supplemented with oregano EO at 100,200 and 400 mg/kg(EO100,EO200 and EO400).Results:Dietary EO supplementation resulted in a quadratic decrease(P<0.05)in feed conversion ratio with lower(P<0.05)feed conversion ratio in EO200 group than the control during weeks 9–12 and 1–12 of the trial.Compared to the control,EO addition resulted in higher(P<0.05)eggshell thickness at the end of week.4,8 and 12 and higher(P<0.05)chymotrypsin activity.There was a quadratic elevation(P<0.05)in ileal chymotrypsin and lipase activity,along with a linear increase in villus height to crypt depth ratio.Quadratic declines(P<0.05)in mRNA expression of IL-1β,TNF-α,IFN-γ and TLR-4,concurrent with a linear and quadratic increase(P<0.05)in ZO-1 expression were identified in the ileum with EO addition.These favorable effects were maximized at medium dosage(200 mg/kg)of EO addition and intestinal microbial composition in the control and EO200 groups were assessed.Dietary EO addition increased(P<0.05)the abundances of Burkholderiales,Actinobacteria,Bifidobacteriales,Enterococcaceae and Bacillaceae,whereas decreased Shigella abundance in the ileum.Conclusions:Dietary EO addition could enhance digestive enzyme activity,improve gut morphology,epithelial barrier functions and modulate mucosal immune status by altering microbial composition,thus favoring feed efficiency and eggshell quality of late-phase laying hens.

Prognostic implications of ferroptosis-associated gene signature in colon adenocarcinoma

BACKGROUND Colon adenocarcinoma(COAD)is one of the most common and fatal malignant tumors,which increases the difficulty of prognostic predictions.Thus,new biomarkers for the diagnosis and prognosis of COAD should be explored.Ferroptosis is a recently identified programmed cell death process that has the characteristics of iron-dependent lipid peroxide accumulation.However,the predictive value of ferroptosis-related genes(FRGs)for COAD still needs to be further clarified.AIM To identify some critical FRGs and construct a COAD patient prognostic signature for clinical utilization.METHODS The Cancer Genome Atlas database(TCGA)and Gene Expression Omnibus databases were the data sources for mRNA expression and corresponding COAD patient clinical information.Differentially expressed FRGs were recognized using R and Perl software.We constructed a multi-FRG signature of the TCGA-COAD cohort by performing a univariate Cox regression and least absolute shrinkage and selection operator Cox regression analysis.COAD patients from the Gene Expression Omnibus cohort were utilized for verification.RESULTS Our research showed that most of the FRGs(85%)were differentially expressed between the corresponding adjacent normal tissues and cancer tissues in the TCGA-COAD cohort.Seven FRGs were related to overall survival(OS)in the univariate Cox analysis(all P<0.05).A model with five FRGs(AKR1C1,AKR1C3,ALOX12,CRYAB,and FDFT1)was constructed to divide patients into high-and low-risk groups.The OS of patients in the high-risk group was significantly lower than that of the low-risk group(all P<0.01 in the TCGA and Gene Expression Omnibus cohorts).The risk score was an independent prognosticator of OS in the multivariate Cox analysis(hazard ratio>1,P<0.01).The predictive capacity of the model was verified by a receiver operating characteristic curve analysis.In addition,a nomogram based on the expression of five hub FRGs and risk score can precisely predict the OS of individual COAD cancer patients.Immune correlation analysis and functional enrichment analysis results revealed that immunology-related pathways were abundant,and the immune states of the high-risk group and the low-risk group were different.CONCLUSION In conclusion,a novel five FRG model can be utilized for predicting prognosis in COAD.Targeting ferroptosis may be a treatment option for COAD.

Feeding Bacillus-based probiotics to gestating and lactating sows is an efficient method for improving immunity,gut functional status and biofilm formation by probiotic bacteria in piglets at weaning

The effects of dietary probiotic supplementation with viable Bacillus subtilis and Bacillus amyloliquefaciens spores on sow performance,immunity,gut functional status and biofilm formation by probiotic bacteria in piglets at weaning were investigated.Ninety-six sows reared in a continuous farrowing system for one full cycle were fed gestation diets during the first 90 d of pregnancy and lactation diets until the end of lactation.The sows were fed a basal diet without probiotics(control;n=48)or a diet supplemented with viable spores(1.1×10^(9)CFU/kg of feed)(probiotic;n=48).At 7 d of age,sucking piglets(n=12/group)were provided prestarter creep feed until weaning at 28 d of age.The piglets in the probiotic group were supplemented with the same probiotic and dosage as their dams.Blood and colostrum collected from sows and ileal tissues collected from piglets on the day of weaning were used for analyses.Probiotics increased the weight of piglets(P=0.077),improved the weaning weight(P=0.039)and increased both the total creep feed consumption(P=0.027)and litter gain(P=0.011).Probiotics also improved the faecal score in the second(P=0.013)week of life.The immunoglobulin G(IgG)concentrations in sow blood at farrowing and the IgM concentrations in piglet blood at weaning were higher in the probiotic group than in the control group(P=0.046).The piglets from the probiotic-treated sows showed a higher IgM concentration in the ileal mucosa(P=0.050)and a lower IgG concentration in the ileal mucosa(P=0.021)compared with the piglets from control sows.The probiotic-treated piglets had a thicker ileal mucosa(P=0.012)due to the presence of longer villi and larger Peyer's patches(P<0.001).B.subtilis and B.amyloliquefaciens were detected in the probiotic-treated piglets but not the control piglets;these bacteria were present in the digesta and villus structures and formed structures resembling biofilms.Overall,Bacillus-based probiotic supplementation improves the health indices of sows and their piglets.

Comprehensive analysis reveals an arachidonic acid metabolism-related gene signature in patients with pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma(PDAC)is highly heterogeneous,making its prognosis prediction difficult.The arachidonic acid(AA)cascade is involved in carcinogenesis.Therefore,the metabolic enzymes of the AA cascade consist of lipoxygenases(LOXs),phospholipase A2s(PLA2s),and cyclooxygenases(COXs)along with their metabolic products,including leukotrienes.Nevertheless,the prognostic potential of AA metabolism-associated PDAC has not been explored.Herein,the mRNA expression patterns and the matching clinical information of individuals with PDAC were abstracted from online data resources.We employed the LASSO Cox regression model to develop a multigene clinical signature in the TCGA queue.The GEO queue and the ICGC queue were employed as the validation queue.There was differential expression of a significant number of AA metabolism-associated genes(56.8%)between PDAC and neighboring nonmalignant tissues in the TCGA queue.Univariate Cox regression demonstrated that 13 of the differentially expressed genes(DEGs)were linked to overall survival(OS)(p<0.05).A 6-gene clinical signature was developed for stratifying the PDAC patients into two risk groups,with the high-risk group patients exhibiting remarkably lower OS than the low-risk group patients(p<0.001 in the TCGA data set and the ICGC queue,and p=0.001 in the GEO data set).The multivariate Cox data revealed the risk score as an independent OS predictor(HR>1,p<0.01).The receiver operating characteristic(ROC)curve verified the predictive potential of our signature.The expression and alteration of the six genes in PDAC were also validated using online databases.Functional analyses demonstrated that immune-linked cascades were enriched,and the immune status was remarkably different between the high-and low-risk groups.In summary,an AA metabolism-associated clinical gene signature can be applied for prognostic estimation in PDAC.

Effect of fermented total mixed rations on rumen microbial communities and serum metabolites in lambs

Background:Diet regulates rumen microbiota,which in turn affects animal health.The present study evaluated the response of rumen microbiota and the immune system of lambs to a fermented total mixed ration diet.Methods:A total of 30 lambs were assigned into two groups:a group fed an unfermented high-fiber diet(total mixed ration[TMR])and a group fed an fermented low-fiber diet(fermented TMR[FTMR]).Results:The results showed that FTMR markedly(p<0.05)increased average daily gain and dry matter intake compared to TMR.The FTMR diet increased the relative abundance of Veillonellaceae_UCG-001 and decreased the diversity of undesirable microbiota despite stable overall microbial community diversity.Serum metabolomic analysis combined with enrichment analysis showed that serum metabolites were affected by the FTMR and metabolic pathways,and the FTMR diet significantly(p<0.05)influenced amino acid metabolism of lambs.There was a decrease in inflammatory factors in the FTMR treatment,indicating that inflammatory factors followed the same trajectory as changes in microbial community structure and function.Conclusions:Overall,the FTMR diet reduced undesirable microbiota diversity,thereby regulating host amino acid metabolism and improving immune status.

Different plasma levels of interleukins and chemokines： comparison between children and adults with AIDS in China

Background The immunological differences between children and adults with AIDS in China are not well documented. Th1/Th2 cytokines and chemokines are two types of immune factors intimately involved in disease progression of HIV-1 infection. This study aimed to identify changes in plasma levels of Th1/Th2 cytokines inerleukin （IL）-18, IL-16, IL-10 and chemokines regulated on activation, normal T cell expressed and secreted （RANTES）, stromal cell-derived factor-1 （SDF-1） and monocyte chemoattractant protein-1 （MCP-1） in HIV-l-infected children and adults in China. Methods Seventy-five children with AIDS and 35 adult AIDS patients were recruited and clinical data were collected. CD4^＋ T lymphocyte counts were measured by flow cytometery and plasma HIV RNA levels were measured by quantitative RT-PCR. Plasma levels of IL-18, IL-10, IL-16, RANTES, MCP-1, SDF-1a and SDF-1β were quantified by enzyme-linked immunosorbent assay. The levels of β2-microglobulin （β2-MG） and soluble Fas （sFas） were measured to validate the level of humoral and cellular immune activation. Results The mean levels of all cytokines in pediatric and adult AIDS patients were significantly higher than in their healthy controls （P 〈0.01）. The mean levels of these cytokines were higher in pediatric patients than in adult patients （P 〈0.05, except for SDF-la and β2-MG）. Some of the cytokine levels in patients younger than 6 years old was higher than in older children and adults with AIDS （IL-10, IL-18, SDF-la, MCP, RANTES and sFas, P 〈0.05）. Levels of IL-18, IL-10, RANTES and β2-MG of pediatric patients increased as the levels of viral load increased （P 〈0.05）. Conclusions Abnormal immune activation can be measured in Chinese pediatric and adult patients with AIDS, and is higher in children than in adult patients. The cytokines levels coincide with disease progression of AIDS, but have no direct relationship with total CD4^＋ T cell count.