[An analysis on clinical characteristics and prognosis-related risk factors in patients with drug-induced liver injury].

Objective: To explore the drugs and clinical characteristics causing drug-induced liver injury (DILI) in recent years, as well as identify drug-induced liver failure, and chronic DILI risk factors, in order to better manage them timely. Methods: A retrospective investigation and analysis was conducted on 224 cases diagnosed with DILI and followed up for at least six months between January 2018 and December 2020. Univariate and multivariate logistic regression analyses were used to identify risk factors for drug-induced liver failure and chronic DILI. Results: Traditional Chinese medicine (accounting for 62.5%), herbal medicine (accounting for 84.3% of traditional Chinese medicine), and some Chinese patent medicines were the main causes of DILI found in this study. Severe and chronic DILI was associated with cholestatic type. Preexisting gallbladder disease, initial total bilirubin, initial prothrombin time, and initial antinuclear antibody titer were independent risk factors for DILI. Prolonged time interval between alkaline phosphatase (ALP) and alanine aminotransferase (ALT) falling from the peak to half of the peak (T(0.5ALP) and T(0.5ALT)) was an independent risk factor for chronic DILI [area under the receiver operating characteristic curve (AUC) = 0.787, 95%CI: 0.697~0.878, P < 0.001], with cutoff values of 12.5d and 9.5d, respectively. Conclusion: Traditional Chinese medicine is the main contributing cause of DILI. The occurrence risk of severe DILI is related to preexisting gallbladder disease, initial total bilirubin, prothrombin time, and antinuclear antibodies. T(0.5ALP) and T(0.5ALT) can be used as indicators to predict chronic DILI.

Effects of supplemented mode of emulsifier on growth performance, serum biochemical index, quality of meat and skin fat, and nutrient utilization in Pekin ducks.

In our previous experiment, we found that fats with pre-emulsification (PreE), a new supplemented mode of emulsifier, had an improved bioavailability for Pekin ducks than fats without PreE based on dietary EE utilization. Therefore, this study was conducted to investigate the effects of the supplemented mode of emulsifier (PreE vs. emulsifier direct supplementation) on the growth performance, serum biochemical index, quality of meat and skin fat, and nutrient utilization in Pekin ducks. A total of 640 healthy 10-day-old Pekin male ducks (408.65 ± 12.00 g) were randomly allocated into 4 treatments with 16 replicates of 10 birds each. The 4 dietary treatments were as follows: the positive control group (PC; the oil supplemented amount of 6%), the negative control group (NC; the oil supplemented amount of 5.4%), the emulsifier group (E; NC diet with an emulsifier added directly), and the oil pre-emulsification group (PreE; NC diet with oil PreE). The results showed reducing the amount of fat in the diet (NC vs. PC) significantly decreased growth performance and quality of skin fat, and affected serum lipid metabolism (P < 0.05). Interestingly, the body weight (BW), body weight gain (BWG), and the shear force of skin fat were increased, but the feed to gain ratio (F/G) was markedly decreased in the PreE group (P < 0.05) compared to those in the NC group, and these levels were similar to those in the PC group (P > 0.05). Additionally, the utilization of dietary dry matter (DM), ether extract (EE), and total phosphorous (TP) were increased, but the activity of aspartate aminotransferase (AST) in serum was decreased in the PreE group compared to those in the NC group (P < 0.05). Furthermore, compared to the E group, the F/G was decreased (P < 0.05), and the utilization of dietary EE, the shear force of skin fat and content of collagen in skin fat were markedly increased (P < 0.05) in the PreE group. However, no differences were observed (P > 0.05) in growth performance between the group administered a direct supplementation of emulsifier and the control groups (PC and NC). These results indicate that the negative effect of reducing the oil supplementation amount (-0.6%) in the diet can be restored by supplementation with emulsifier, especially by oil with PreE.

The association of coffee consumption with the risk of osteoporosis and fractures: a systematic review and meta-analysis.

To elucidate the association of coffee and bone health would help fracture risk reduction via dietary intervention. Although those who had higher coffee consumption were less likely to have osteoporosis, the associations between coffee consumption and fracture risk need further investigations with better study designs. INTRODUCTION: The associations between coffee consumption and the risk of osteoporosis and fracture remain inconclusive. We aimed to better quantify these associations by conducting meta-analyses of observational studies. METHODS: Relevant studies were systematically searched on PubMed, Web of Science, Cochrane library, and Embase Database up to November 25, 2021. The odds ratio (OR) or relative risk (RR) with 95% confidence intervals (CI) was pooled and a dose-response analysis was performed. RESULTS: Four studies with 7114 participants for osteoporosis and thirteen studies with 391,956 participants for fracture incidence were included in the meta-analyses. High versus low coffee consumption was associated with a lower risk of osteoporosis [pooled OR (95% CI): 0.79 (0.65-0.92)], while it was non-significantly associated with fracture incidence [pooled OR (95% CI): 0.86 (0.67-1.05) at hip and 0.89 (0.42-1.36) at non-hip]. A non-linear association between the level of coffee consumption and hip fracture incidence was shown (P = 0.004). The pooled RR (95% CI) of hip fracture risk in those who consumed 1, 2-3, 4, and ≥ 9 cups of coffee per day was 0.92 (0.87-0.97), 0.89 (0.83-0.95), 0.91 (0.85-0.98), and 1.10 (0.76-1.59), respectively. The significance in the association between coffee consumption and the hip fracture incidence decreased in those studies that had larger sample size, higher quality, and more adjustments. CONCLUSIONS: A dose-dependent relationship may exist between coffee consumption and hip fracture incidence. The effect of high versus low coffee consumption was influenced by study designs. Further studies with dedicated designs are needed to confirm the independent effects of coffee consumption on bone health.

[The application of 99Tcm-DTPA orbital SPECT/CT in staging evaluation of thyroid associated ophthalmopathy].

Objective: To explore the application value of 99Tcm-diethylenetriaminepentaacetic acid (DTPA) orbital single photon emission computed tomography/computed tomography (SPECT/CT) in staging evaluation of thyroid associated ophthalmopathy (TAO). Methods: A case-control study. A total of 40 patients with binocular TAO were recruited from May 2019 to December 2019 in the Second Hospital of Dalian Medical University. According to the clinical activity score (CAS) standard, 40 TAO patients were divided into the active group (15 cases) and the inactive group (25 cases), and 10 healthy volunteers were recruited as the control group. All subjects underwent 99Tcm-DTPA orbital SPECT/CT examination, and each subject's CAS, reading results and maximum standardized uptake value (SUVmax) were recorded. The Kruskal-Walis H test was used for the CAS comparison among the three groups. The analysis of variance was used for the SUVmax comparison among the three groups. The comparison between CAS and SUVmax before and after treatment was performed by paired samples Wilcoxon signed rank test and paired-sample t test, and Spearman correlation analysis was performed between SUVmax and CAS. The Kappa test was used to check the consistency between the reading result and CAS's judgment of TAO activity. The receiver operating characteristic curve was used to analyze the diagnostic value of the reading results and SUVmax for TAO. Results: The age difference among the three groups was not statistically significant, and the gender difference was not statistically significant (all P>0.05). The difference in CAS among the three groups was statistically significant (H=39.894; P<0.01). Patients with active TAO showed abnormal concentration and enhancement of nuclides in the orbital tissue, and the uptake of radionuclides was significantly increased, while patients with inactive TAO had a slight increase, and healthy volunteers had no significant or only mild uptake. The SUVmax of the active group (2.24±0.47) was highest, and that of the inactive group (1.57±0.43) was higher than the healthy control group (0.67±0.22). After pairwise comparison, there were statistical differences between groups (all P<0.05). According to Spearman correlation analysis, the SUVmax of all TAO patients was linearly, positively correlated with their CAS (r=0.753; P<0.05). In assessing the clinical activity of TAO, the reading results were consistent with CAS (Kappa value=0.737; P<0.05). Taking the reading results as the standard, the area under the receiver operating characteristic curve (AUC) of SUVmax was 0.992, and the threshold of SUVmax to distinguish between active and inactive periods was 1.850, with a sensitivity of 86.70% and a specificity of 76.00%. Taking CAS results as the standard, the AUC of SUVmax was 0.853, and the threshold of SUVmax to distinguish between active and inactive periods was 1.850, with a sensitivity of 100.00% and a specificity of 87.50%. Five patients had inconsistent SUVmax and CAS. The CAS was ≥3, but the orbits did not show any inflammatory lesions in two of them; the CAS was<3, but the orbits showed inflammatory lesions in three of them. Thirteen active TAO patients with 99Tcm-DTPA orbital SPECT/CT showing significant accumulation of nuclides were given hormone shock therapy 12 times. After treatment, the CAS 2.00 (2.00) was lower than the pre-treatment 3.00 (1.50) score, and the difference was statistically significant (Z=-3.100, P<0.01). The SUVmax after treatment (1.60±0.20) was lower than the pre-treatment value (2.17±0.34), and the difference was statistically significant (t=10.197, P<0.01). Conclusion: 99Tcm-DTPA orbital SPECT/CT can relatively accurately determine the state of orbital inflammation in patients with TAO, and can be used as a useful supplement to evaluate the clinical activity of TAO, helping to guide clinical treatment. (Chin J Ophthalmol, 2021, 57: 830-836).

Neuroprotective effect of gastrodin in methamphetamine-induced apoptosis through regulating cAMP/PKA/CREB pathway in cortical neuron.

OBJECTIVE: Methamphetamine (MA) abuse induces neurotoxicity and causes neuronal cell apoptosis. Gastrodin is a traditional Chinese herbal medicine used for the treatment of nerve injuries, spinal cord injuries, and some central nervous system diseases as well. The present study investigated the neuroprotective effects of gastrodin against MA-induced neurotoxicity in neuronal cells and its potential protective mechanism. METHODS: The primary cortex neuronal culture was divided into four groups (control group, MA group, MA + gastrodin group, and MA + gastrodin + small interfering RNA group). The neurotoxicity of MA was assessed by detecting apoptotic cells by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay and cell viability by cell counting kit 8 (CCK-8) method, the Tuj1-positive cells and the average axonal length were detected by immunofluorescence, and the expressions of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP-response element-binding (CREB), and brain-derived neurotrophic factor (BDNF) proteins were detected by Western blot. RESULTS: The results of CCK-8 assay showed that 0.5 mM MA was an optimal concentration that induced neurotoxicity (p < 0.01). Pretreatment with 25 mg/L gastrodin exerted maximum protective effects on neuronal cells. The expression levels of cAMP, PKA, phosphorylated PKA, CREB, phosphorylated CREB, and BDNF proteins were decreased in the MA group, and pretreatment with gastrodin upregulated the expression levels of these proteins (p < 0.01). The expressions of PKA and CREB proteins showed no significant changes in the control group, MA group, and gastrodin group. Compared the MA + gastrodin + small interfering RNA group with MA + gastrodin group, the Tuj1-positive cells and the average axonal length were decreased significantly, while the number of apoptotic cells was increased (p < 0.05). CONCLUSION: Gastrodin has neuroprotective effects against MA-induced neurotoxicity, which exerts neuroprotective effects via regulation of cAMP/PKA/CREB signaling pathway and upregulates the expression of BDNF.

[Analysis of imatinib trough concentration at steady state in adjuvant therapy of patients with high risk gastrointestinal stromal tumor].

Objective: To explore the features of imatinib mesylate (IM) plasma concentration during adjuvant therapy and clinical factors associated with IM plasma concentration in patients with high risk gastrointestinal stromal tumors (GIST), and to determine whether IM plasma concentration <1100 µg/L influences the efficacy of adjuvant therapy. Methods: A retrospective case control study method was used. Case inclusion criteria: (1) complete resection of lesion and GIST confirmed by pathology; (2) high risk classified according to modified National Institutes of Health classification system (2008); (3) administration of IM 400 mg/d for at least 1 month; (4) not taking the medication likely affecting IM pharmacokinetic, such as rifampicin, dilantin, and carbamazepine, within 1 month before blood collection. Data of GIST patients who visited GIST Disease - Oriented Outpatient, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 to December 2018 were retrospectively analyzed. After taking IM for 22-26 hours, 5 ml of peripheral venous blood was collected into EDTA anticoagulant tube. IM plasma concentration was detected by using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Patients were divided into <1100 µg/L group and ≥1100 µg/L group according to plasma concentration. Linear regression was used to analyze the relevance between clinical features and IM plasma concentration. Parameters with normal distribution were analyzed by Pearson correlation coefficient, and parameters with non-normal distribution were analyzed by Spearman correlation. Kaplan-Meier survival curves and COX regression model were used for survival analysis. Results: Among the 85 patients enrolled in the study, 49 patients (57.6%) were male and 36 (42.4%) were female, with mean age of (51.9±11.0) years. The body mass index was (22.5±2.9) kg/m(2) and body surface area was (1.6±0.2) m(2). Thirty patients received gene test, including 23 patients with c-Kit exon 11 mutation, 4 with c-Kit exon 9 mutation, 1 with c-Kit exon 11 and 17 mutation and 2 without c-Kit or PDGFRA gene mutation. The mean IM plasma concentration was (1391.4±631.3) µg/L, and there were 32 patients with plasma concentration <1100 µg/L and 53 patients with plasma concentration ≥1100 µg/L. There were no statistically significant differences between the two groups in gender, age, body mass index, body surface area, hematological examination (white blood cells, albumin, alanine aminotransferase, aspartate aminotransferase and serum creatinine), tumor location, tumor size, mitotic counts, duration of adjuvant therapy and methods of operation (all P>0.05). Positive correlation between IM plasma concentration and serum creatinine was observed in linear regression analysis (r=0.297, P=0.007), but there were no correlations between IM plasma concentration and age (r=0.044, P=0.686), body mass index (r=0.066, P=0.547), body surface area (r=-0.010, P=0.924), white blood cells (r=-0.080, P=0.478), albumin (r=-0.065, P=0.563), alanine aminotransferase (r=0.114, P=0.308), aspartate aminotransferase (r=0.170, P=0.127) and duration of adjuvant therapy (ρ=0.060, P=0.586). There was no statistically significant difference in IM plasma concentration between patients with different genders (t=0.336, P=0.738) and patients with different surgical methods (F=0.888, P=0.451). Up to March 1, 2019. the median follow-up time was 30 (range 4-49) months. Tumor recurrence was detected in two patients with plasma concentration <1100 µg/L and two with plasma concentration ≥1100 µg/L. One recurrent patient with plasma concentration <1100 µg/L was detected to harbor c-Kit exon 11 and exon 17 mutations, and the other did not receive gene detection. Two recurrent patients with plasma concentration ≥1100 µg/L were both detected to harbor c-Kit exon 9 mutation. The 3-year relapse-free survival rate was 96.4% in the cohort, 96.2% in patients with plasma concentration <1100 µg/L, and 96.6% in patients with plasma concentration ≥1100 µg/L. No significant difference in relapse-free survival was observed between the two groups (P=0.204). Univariate Cox analysis showed that IM plasma concentration <1100 µg/L was not a risk factor for patients with high risk GIST (HR=0.238, 95% CI: 0.022-2.637, P=0.242). Conclusions: IM plasma concentration of adjuvant therapy in patients with high risk GIST varies with individual. Patients with higher level of serum creatinine are more likely to have a higher plasma concentration. A blood drug concentration standard of less than 1100 µg/L for advanced GIST patients may not influence the prognosis of patients with high risk GIST.

[Transurethral bipolar plasmakinetic prostatectomy for benign prostatic hyperplasia in high-risk and senior patients in China: a systematic review and meta-analysis].

Objective: To evaluate the effectiveness and safety of transurethral bipolar plasmakinetic prostatectomy in the treatment of benign prostatic hyperplasia in high-risk and senior patients in China. Methods: The PubMed, Cochrane Library, CBM, CNKI and WanFang databases were searched with computer for collecting relevant interventional case series from establishment dates to September 14, 2018. After quality evaluation and data extraction independently conducted by two authors, the Meta-analysis was performed using the Comprehensive Meta-analysis V2 software. Results: Eighteen studies involving 1 899 patients are included. Maximum flow rate increased to 12.28 ml/s (95%CI: 8.42-16.14), 12.88 ml/s (95%CI: 9.85-15.92) ,14.32 ml/s (95%CI: 10.47-18.18), 14.93 ml/s (95%CI: 10.19-19.67) and 20.00 ml/s (95%CI: 19.08-20.92) in 1, 3, 6, 12 and 24 months after surgery, respectively. International prostate symptom score decreased to -18.60 (95%CI: -23.20--14.00), -17.62 (95%CI: -20.21--15.03), -19.14 (95%CI: -20.70--17.59), -19.06 (95%CI: -21.53--16.60) and -22.90 (95%CI: -24.26--21.54), respectively. Quality of life decreased to -2.38 (95%CI: -4.26--0.50), -3.39 (95%CI: -4.57--2.21),-3.75 (95%CI: -4.14--3.36), -3.36(95%CI: -4.56--2.16), and -4.58(95%CI: -4.75--4.41). Post void residual decreased to -231.16 ml (95%CI: -288.30--174.01), -76.10 ml (95%CI: -116.71--35.50), -159.90 ml(95%CI: -207.21--112.59) and -87.70 ml (95%CI: -91.91--83.48). The event rate of postoperative adverse reactions all were not high. Conclusion: Transurethral bipolar plasmakinetic prostatectomy has better clinical efficacy and no obvious side effects in the treatment of benign prostatic hyperplasia in high-risk and senior patients in China.

Modulation of broilers' caecal microflora and metabolites in response to a potential probiotic Bacillus amyloliquefaciens.

Studies have found that a dietary supplement of Bacillus amyloliquefaciens improved the growth performance, increased the nutrient digestibility of hosts and modulated the intestinal microflora. A total of 360 1-day-old Ross broilers were randomly divided into three treatments: a control group with a basal diet, an antibiotic group with a basal diet and added colistin sulphate, and a probiotics group with a basal diet and added Bacillus amyloliquefaciens. The HiSeq high-throughput sequencing analysis of 16S rRNA was used to investigate the differences in birds' caecal microflora, and metabolomics was used to analyse changes in caecal metabolites. Results showed that the supplementation of Bacillus amyloliquefaciens significantly improved the BW and ADG compared with the control birds. Results of sequencing indicated that (i) 645, 670, 596 unique operational taxonomic units (OTUs) were found in birds supplemented with Bacillus amyloliquefaciens on day 7, 21 and 42, separately, (ii) due to the diversity and relative abundance of the birds' caecal microflora, the OTUs of the caecal microflora clustered according to age and treatment, except on day 42, (iii) among the six predominate families (Ruminococcaceae, Lachnospiraceae, Enterobacteriaceae, Erysipelotrichaceae, Lactobacillaceae and Rikenellaceae), the supplementation of Bacillus amyloliquefaciens significantly increased Enterobacteriaceae on day 42, (iv) Bacillus amyloliquefaciens increased the relative abundance of Faecalibacterium and Ruminococcus on day 21, increased the Faecalibacterium and Blautia and decreased the Ruminococcus on day 42. The metabolomics of caecal metabolites showed that the dietary Bacillus amyloliquefaciens changed the caecal metabolites involved of amino acid metabolism and glyceride metabolism, and the antibiotics changed the caecal metabolites that were related to carbohydrates and amino acid metabolism on day 21.

[Holistic integrative medicine: application in prevention and treatment of oral mucosal diseases].

Holistic integrative medicine (HIM), as one of the important ideas in the field of medicine, arouses great concern recently. HIM regards the human body as a whole, turns data and evidence in medical research back to facts, integrates technologies and experience developed in clinical research into medical skills. The repeated practices at the levels of fact, experience, and medical skills will generate true knowledge to solve the wide spread problems brought by linearized thinking and fragmented knowledge. With the development of highly divided medical disciplines, how to utilize and practice HIM has become a common concern of the medical community. Specialization of stomatology, which is a first level discipline like medicine, has also become a trend for years. However, holistic concept cannot be overlooked, especially in the development of oral medicine. This article aims at the communication and exchange of knowledge about HIM among dental professionals. In order to serve the patients better, the authors look forward to practicing the HIM concept in the field of oral medicine through the efforts of us all.

Dietary supplemented antimicrobial peptide microcin J25 improves the growth performance, apparent total tract digestibility, fecal microbiota, and intestinal barrier function of weaned pigs.

Microcin J25 (MccJ25) is an antimicrobial peptide produced by a fecal strain of Escherichia coli containing 21 AA. This study was performed primarily to evaluate the effects of MccJ25 as a potential substitute for antibiotics (AB) on growth performance, nutrient digestibility, fecal microbiota, and intestinal barrier function in weaned pigs. In the present study, 180 weaned pigs (7.98 ± 0.29 kg initial BW) were randomly assigned to 1 of 5 treatments, including a basal diet (CON) and CON supplemented with AB (20 mg/kg colistin sulfate; ABD) or 0.5, 1.0, and 2.0 mg/kg MccJ25. On d 0 to 14, dietary supplementation with MccJ25 and ABD had positive effects on ADG, ADFI, diarrhea incidence, and G:F ( < 0.05). Pigs fed the 2.0 mg/kg MccJ25 diet had greater ADG ( < 0.05) and marginally greater G:F ( < 0.10) compared with pigs fed the ABD diet. Compared with the CON diet, the 2.0 mg/kg MccJ25 diet sharply improved ( < 0.05) ADG and G:F and decreased ( < 0.05) diarrhea incidence (d 15 to 28 and d 0 to 28). Apparent digestibility of nutrients in pigs fed 1.0 and 2.0 mg/kg MccJ25 was improved ( < 0.05) compared with that of pigs fed CON and ABD. The serum cytokines IL-6 and IL-1ß and tumor necrosis factor-α levels in pigs fed MccJ25 were greater than in pigs fed CON ( < 0.05). Additionally, the IL-10 concentration in pigs fed MccJ25 was sharply increased ( < 0.05) compared with that of pigs fed CON. Pigs fed 1.0 and 2.0 mg/kg MccJ25 diets had remarkably decreased lactate, diamine oxidase, and endotoxin concentrations and fecal numbers ( < 0.05) and improved fecal and numbers ( < 0.05). Compared with the ABD diet, the diet containing 2.0 mg/kg MccJ25 did not increase lactate, diamine oxidase, and endotoxin (d 14) concentrations ( < 0.05) or decrease the and (d 28) numbers ( < 0.05). The diets containing 1.0 and 2.0 mg/kg MccJ25 and ABD (d 28) improved lactate concentration and short-chain fatty acid concentrations, including acetate, propionate, and butyrate, in feces ( < 0.05). Moreover, the pigs fed 2.0 mg/kg MccJ25 had greater lactate, butyrate (d 14), and propionate concentrations than the pigs fed the ABD diet ( < 0.05). In conclusion, dietary supplemented MccJ25 effectively improved performance, attenuated diarrhea and systematic inflammation, enhanced intestinal barrier function, and improved fecal microbiota composition of weaned pigs. Therefore, MccJ25 could be a potential effective alternative to AB for weaned pigs.

An integrated optimization method for river water quality management and risk analysis in a rural system.

In this study, an interval-stochastic-based risk analysis (RSRA) method is developed for supporting river water quality management in a rural system under uncertainty (i.e., uncertainties exist in a number of system components as well as their interrelationships). The RSRA method is effective in risk management and policy analysis, particularly when the inputs (such as allowable pollutant discharge and pollutant discharge rate) are expressed as probability distributions and interval values. Moreover, decision-makers' attitudes towards system risk can be reflected using a restricted resource measure by controlling the variability of the recourse cost. The RSRA method is then applied to a real case of water quality management in the Heshui River Basin (a rural area of China), where chemical oxygen demand (COD), total nitrogen (TN), total phosphorus (TP), and soil loss are selected as major indicators to identify the water pollution control strategies. Results reveal that uncertainties and risk attitudes have significant effects on both pollutant discharge and system benefit. A high risk measure level can lead to a reduced system benefit; however, this reduction also corresponds to raised system reliability. Results also disclose that (a) agriculture is the dominant contributor to soil loss, TN, and TP loads, and abatement actions should be mainly carried out for paddy and dry farms; (b) livestock husbandry is the main COD discharger, and abatement measures should be mainly conducted for poultry farm; (c) fishery accounts for a high percentage of TN, TP, and COD discharges but a has low percentage of overall net benefit, and it may be beneficial to cease fishery activities in the basin. The findings can facilitate the local authority in identifying desired pollution control strategies with the tradeoff between socioeconomic development and environmental sustainability.

Branched-chain Amino Acids are Beneficial to Maintain Growth Performance and Intestinal Immune-related Function in Weaned Piglets Fed Protein Restricted Diet.

As a novel approach for disease control and prevention, nutritional modulation of the intestinal health has been proved. However, It is still unknown whether branched-chain amino acid (BCAA) is needed to maintain intestinal immune-related function. The objective of this study was to determine whether BCAA supplementation in protein restricted diet affects growth performance, intestinal barrier function and modulates post-weaning gut disorders. One hundred and eight weaned piglets (7.96±0.26 kg) were randomly fed one of the three diets including a control diet (21% crude protein [CP], CON), a protein restricted diet (17% CP, PR) and a BCAA diet (BCAA supplementation in the PR diet) for 14 d. The growth performance, plasma amino acid concentrations, small intestinal morphology and intestinal immunoglobulins were tested. First, average daily gain (ADG) (p<0.05) and average daily feed intake (ADFI) (p<0.05) of weaned pigs in PR group were lower, while gain:feed ratio was lower than the CON group (p<0.05). Compared with PR group, BCAA group improved ADG (p<0.05), ADFI (p<0.05) and feed:gain ratio (p<0.05) of piglets. The growth performance data between CON and BCAA groups was not different (p>0.05). The PR and BCAA treatments had a higher (p<0.05) plasma concentration of methionine and threonine than the CON treatment. The level of some essential and functional amino acids (such as arginine, phenylalanine, histidine, glutamine etc.) in plasma of the PR group was lower (p<0.05) than that of the CON group. Compared with CON group, BCAA supplementation significantly increased BCAA concentrations (p<0.01) and decreased urea concentration (p<0.01) in pig plasma indicating that the efficiency of dietary nitrogen utilization was increased. Compared with CON group, the small intestine of piglets fed PR diet showed villous atrophy, increasing of intra-epithelial lymphocytes (IELs) number (p<0.05) and declining of the immunoglobulin concentration, including jejunal immunoglobulin A (IgA) (p = 0.04), secreted IgA (sIgA) (p = 0.03) and immunoglobulin M (p = 0.08), and ileal IgA (p = 0.01) and immunoglobulin G (p = 0.08). The BCAA supplementation increased villous height in the duodenum (p<0.01), reversed the trend of an increasing IELs number. Notably, BCAA supplementation increased levels of jejunal and ileal immunoglobulin mentioned above. In conclusion, BCAA supplementation to protein restricted diet improved intestinal immune defense function by protecting villous morphology and by increasing levels of intestinal immunoglobulins in weaned piglets. Our finding has the important implication that BCAA may be used to reduce the negative effects of a protein restricted diet on growth performance and intestinal immunity in weaned piglets.

Estimation of the standardized ileal digestible valine to lysine ratio required for 25- to 120-kilogram pigs fed low crude protein diets supplemented with crystalline amino acids.

Four 28-d experiments were conducted to determine the standardized ileal digestible (SID) valine (Val) to lysine (Lys) ratio required for 26- to 46- (Exp. 1), 49- to 70- (Exp. 2), 71- to 92- (Exp. 3), and 94- to 119-kg (Exp. 4) pigs fed low CP diets supplemented with crystalline AA. The first 3 experiments utilized 150 pigs (Duroc × Landrace × Large White), while Exp. 4 utilized 90 finishing pigs. Pigs in all 4 experiments were randomly allocated to 1 of 5 diets with 6 pens per treatment (3 pens of barrows and 3 pens of gilts) and 5 pigs per pen for the first 3 experiments and 3 pigs per pen for Exp. 4. Diets for all experiments were formulated to contain SID Val to Lys ratios of 0.55, 0.60, 0.65, 0.70, or 0.75. In Exp. 1 (26 to 46 kg), ADG increased (linear, = 0.039; quadratic, = 0.042) with an increasing dietary Val:Lys ratio. The SID Val:Lys ratio to maximize ADG was 0.62 using a linear broken-line model and 0.71 using a quadratic model. In Exp. 2 (49 to 70 kg), ADG increased (linear, = 0.021; quadratic, = 0.042) as the SID Val:Lys ratio increased. G:F improved (linear, = 0.039) and serum urea nitrogen (SUN) decreased (linear, = 0.021; quadratic, = 0.024) with an increased SID Val:Lys ratio. The SID Val:Lys ratios to maximize ADG as well as to minimize SUN levels were 0.67 and 0.65, respectively, using a linear broken-line model and 0.72 and 0.71, respectively, using a quadratic model. In Exp. 3 (71 to 92 kg), ADG increased (linear, = 0.007; quadratic, = 0.022) and SUN decreased (linear, = 0.011; quadratic, = 0.034) as the dietary SID Val:Lys ratio increased. The SID Val:Lys ratios to maximize ADG as well as to minimize SUN levels were 0.67 and 0.67, respectively, using a linear broken-line model and 0.72 and 0.74, respectively, using a quadratic model. In Exp. 4 (94 to 119 kg), ADG increased (linear, = 0.041) and G:F was improved (linear, = 0.004; quadratic, = 0.005) as the dietary SID Val:Lys ratio increased. The SID Val:Lys ratio to maximize G:F was 0.68 using a linear broken-line model and 0.72 using a quadratic model. Carcass traits and muscle quality were not influenced by SID Val:Lys ratio. In conclusion, the dietary SID Val:Lys ratios required for 26- to 46-, 49- to 70-, 71- to 92-, and 94- to 119-kg pigs were estimated to be 0.62, 0.66, 0.67, and 0.68, respectively, using a linear broken-line model and 0.71, 0.72, 0.73, and 0.72, respectively, using a quadratic model.

The antimicrobial peptide sublancin ameliorates necrotic enteritis induced by Clostridium perfringens in broilers.

Sublancin is an antimicrobial peptide produced by 168 containing 37 amino acids. The objective of this study was to investigate its inhibitory efficacy against both in vitro and in vivo. In the in vitro study, we determined that sublancin had a minimum inhibitory concentration of 8 µM against , which was much higher than the antibiotic lincomycin (0.281 µM). Scanning electron microscopy showed that sublancin damaged the morphology of . The in vivo study was conducted on broilers for a 28-d period using a completely randomized design. A total of 252 chickens at 1 d of age were randomly assigned to 1 of 6 treatments including an uninfected control; an infected control; 3 infected groups supplemented with sublancin at 2.88, 5.76, or 11.52 mg activity/L of water; and an infected group supplemented with lincomycin at 75 mg activity/L of water (positive control). Necrotic enteritis was induced in the broilers by oral inoculation of on d 15 through 21. Thereafter, the sublancin or lincomycin were administered fresh daily for a period of 7 days. The challenge resulted in a significant decrease in ADG ( < 0.05) and a remarkable deterioration in G:F ( < 0.05) during d 15 to 21 of the experiment. There was a sharp increase of numbers in the cecum ( < 0.05). The addition of sublancin or lincomycin reduced caecal counts ( < 0.05). The counts had a tendency to decrease in the lincomycin treatment ( = 0.051) but were the highest in the sublancin treatment (5.76 mg activity/L of water). A higher villus height to crypt depth ratio in the duodenum and jejunum as well as a higher villus height in the duodenum were observed in broilers treated with sublancin or lincomycin ( < 0.05) compared with infected control broilers. It was observed that sublancin and lincomycin decreased IL-1ß, IL-6, and tumor necrosis factor-α levels ( < 0.05) in the ileum compared with the infected control. In conclusion, although sublancin's minimum inhibitory concentration is much higher than lincomycin in vitro, less sublancin is needed to control necrotic enteritis induced by in vivo than lincomycin. These novel findings indicate that sublancin could be used as a potential antimicrobial agent to control necrotic enteritis.

The appropriate standardized ileal digestible tryptophan to lysine ratio improves pig performance and regulates hormones and muscular amino acid transporters in late finishing gilts fed low-protein diets.

This study investigated the effects of various standardized ileal digestible (SID) Trp to Lys ratios on the performance and carcass characteristics of late finishing gilts receiving low-CP (9.6%) diets supplemented with crystalline AA. Ninety gilts (89.1 ± 5.1 kg) were used in a dose-response study conducted for 35 d. Crystalline Trp (0, 0.1, 0.2, 0.4, or 0.6 g/kg) was added to a corn-wheat bran basal diet providing SID Trp to Lys ratios of 0.12, 0.15, 0.18, 0.21, or 0.24. Each diet was fed to 6 pens of pigs with 3 gilts per pen. At the end of the experiment, 30 gilts (1 pig per pen) were slaughtered to evaluate carcass traits and meat quality (BW = 121 kg). Increasing the SID Trp to Lys ratio increased ADG (linear and quadratic effect, < 0.05) and also improved G:F (linear and quadratic effect, < 0.05). Serum urea nitrogen (SUN) decreased as the SID Trp to Lys ratio increased (linear and quadratic effects, < 0.05). A quadratic effect of L* light and marbling in the longissimus dorsi was observed as the dietary SID Trp to Lys ratio increased ( < 0.05). Increasing the SID Trp to Lys ratio increased the level of serum GH (quadratic effect, < 0.05) and also increased the level of serum IGF-1 (linear and quadratic effect, < 0.05). Increasing the SID Trp to Lys ratio increased the protein abundance of the muscular AA transporter of sodium-coupled neutral amino acid transporter 2 (SNAT2) in the longissimus dorsi muscle (linear and quadratic effect, < 0.05). The optimum SID Trp to Lys ratios to maximize ADG and G:F as well as to minimize SUN levels were 0.16, 0.17, and 0.16 using a linear-breakpoint model and 0.20, 0.20, and 0.20 using a quadratic model. Tryptophan could influence serum GH and IGF-1 secretion and protein abundance of the muscular AA transporter of SNAT2 in the longissimus dorsi muscle in late finishing gilts fed low-protein diets.

Low-level laser therapy for orthodontic pain: a systematic review.

This review aimed to evaluate the clinical outcome of different lasers management on orthodontic pain. Cochrane Library (Issue 7, 2014) and MEDLINE (1966-2014.7) were searched to collect randomized controlled trials on lasers for orthodontic pain. Studies meeting the inclusion criteria were systematically evaluated. The Cochrane Collaboration tools RevMan5.1.7 and GRADEpro 3.6 were used in this systematic review and meta-analysis. As a result, 11 randomized controlled trials (RCTs) studying on low-level laser therapy (LLLT) for orthodontic pain control were included. Meta-analysis and risk of bias assessment were implemented using RevMan5.1.7, and level of evidence assessments was measured by GRADEpro 3.6. In the outcome of the score of the most painful day, the comparison of laser versus placebo (pain associated with tooth movement) demonstrated that LLLT reduced the pain score significantly compared with placebo groups (MD = -4.39, 95% CI range -5.9--2.88, P < 0.00001). In the same way, the most painful day was significantly brought forward in laser versus control group (MD = -0.42, 95% CI range -0.74--0.10, P = 0.009). Furthermore, the outcome of the end of pain day showed a trend of pain termination earlier in laser versus control and placebo groups, but without statistical significance (MD = -1.37, 95% CI range -3.37-0.64, P = 0.18 and MD = -1.04, 95% CI range -4.22-2.15, P = 0.52). However, for the reason of downgrade factors, all the GRADE level of evidences of eight comparisons for three outcomes showed a very low quality. Therefore, for the methodological shortcomings and risk of bias of RCTs included, insufficient evidence was submitted to judge whether LLLT was effective in relieving orthodontic pain. Further and more perfect researches should be done in order to recommend LLLT as a routine method for orthodontic pain.

Dietary supplementation with Lactobacillus fermentum I5007 improves the anti-oxidative activity of weanling piglets challenged with diquat.

AIMS: To determine the effects of Lactobacillus fermentum I5007 on the redox state of piglets oxidatively stressed with diquat. METHODS AND RESULTS: Twenty-four, 28-day-old barrows were used in a 2 × 2 factorial design experiment with the main effects being Lact. fermentum supplementation and diquat challenge. Half of the pigs (n = 12) were orally administered with 20 ml of a solution containing 10(8 ) CFU ml(-1) of Lact. fermentum each morning of the 21-day trial, while the remainder received saline. On day 8, these two groups were further subdivided so that half of the pigs in each group (n = 6) were intraperitoneally injected with 10 mg kg(-1) BW diquat, while the remainder received saline. The diquat-injected pigs had significantly poorer performance and increased levels of plasma cortisol, adrenaline, carbonyl and malondialdehyde. Lactobacillus fermentum supplementation significantly increased superoxide dismutase and glutathione and increased the ability to inhibit superoxide anion production in liver and muscle. CONCLUSIONS: Lactobacillus fermentum improved the anti-oxidative defence system and alleviated damage caused by diquat. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactobacillus fermentum has the potential to alleviate oxidative stress and improve weaning pig performance.

Solid-phase low temperature steam-assisted synthesis of thermal stable alumina nanowires.

A simple steam-assisted solid phase synthesis method was developed for synthesis of boehmite nanowires in the presence of TEAOH surfactant. The boehmite nanowires had uniform diameters (12-16 nm) and length up to 1-2 microm. The morphology of the nanostructured wires was well preserved after being converted to pure gamma-Al2O3 by thermal treatment at 600 degrees C for 5 h. The nanowires of Al2O3 exhibited excellent thermal stability by retarding the phase transformation and maintaining the wires-like nanostructure after being aged up to 1300 degrees C by preventing sintering between particles at high temperatures. The surface areas of Al2O3 nanowires could be maintained as high as 68 m2/g at 1300 degrees C while the surface areas of Al2O3 micropowder shrank to 0.89 m2/g after same thermal treatment. Both in-situ XRD and 27Al NMR results indicated that the crystal structure of gamma-Al2O3 nanowires was not transformed to alpha-Al2O3 at 1300 degrees C whereas micropowder Al2O3 was fully converted to alpha-Al2O3 at 1100 degrees C.

Ginkgo biloba for acute ischaemic stroke.

BACKGROUND: Ginkgo biloba extract is widely used in the treatment of acute ischaemic stroke in China. We aimed to assess the evidence from randomised controlled trials and quasi-randomised controlled trials on the use of Ginkgo biloba extract in acute ischaemic stroke. OBJECTIVES: The primary objective was to determine whether Ginkgo biloba extract improves functional outcome without causing undue harm in patients with acute ischaemic stroke. Secondary objectives were to assess the effect of Ginkgo biloba extract on neurological impairment and quality of life. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched October 2004), the Trials Register of the Cochrane Complementary Medicine Field (last searched October 2004) and the Chinese Stroke Trials Register (last searched June 2004). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2004), MEDLINE (1966 to August 2004), EMBASE (1980 to June 2004), AMED (1985 to May 2002) and the China Biological Medicine Database (CBM-disc, 1979 to August 2004). We searched relevant clinical trials and research registers and contacted pharmaceutical companies and researchers in an effort to identify further published and unpublished studies. SELECTION CRITERIA: Randomised controlled trials or quasi-randomised controlled clinical trials comparing Ginkgo biloba extract with placebo or open control (no placebo) in patients with acute ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed trial quality and extracted the data. MAIN RESULTS: Fourteen trials were identified, of which 10 trials (792 patients) were included. Four trials are awaiting assessment. In the 10 included trials follow up was performed at 14 to 35 days after stroke. In all studies neurological outcome was assessed but none of them reported on disability (activities of daily living function) or quality of life. Only three trials reported adverse events. In nine trials, all of them assessed to be of inferior quality, significant improvement in neurological deficit at the end of the treatment was used as the outcome measure. When analysing these trials together, Ginkgo biloba extract was associated with a significant increase in the number of improved patients (Peto odds ratio (OR) 2.66; 95% confidence interval (CI) 1.79 to 3.94). One placebo-controlled trial, assessed to be of good quality, reported neurological outcome as a continuous variable. It failed to show an improvement of neurological deficit at the end of treatment (weighted mean difference (fixed) 0.81; 95% CI -8.9 to 10.52). No deaths or major adverse events were reported during the follow-up period. AUTHORS' CONCLUSIONS: There was no convincing evidence from trials of sufficient methodological quality to support the routine use of Ginkgo biloba extract to promote recovery after stroke. High-quality and large-scale randomised controlled trials are needed to test its efficacy.