Unexpected rare uterine carcinosarcoma with neuroendocrine differentiation: Reflections on clinical diagnosis and treatment of a case report.

RATIONALE: Uterine carcinosarcoma (UCS) is a rare and highly invasive malignant tumor.It exhibits an ectopic growth pattern of the uterus,and its histological features are biphasic differentiation of malignant epithelial components (cancer) and malignant mesenchymal components (sarcoma). The pathological pattern of high-component neuroendocrine differentiation is extremely rare. Due to the inherent heterogeneity of tumors, it increases the difficulty of accurate identification and diagnosis. The author introduces a rare case of primary endometrial carcinosarcoma (heterologous) with small cell neuroendocrine carcinoma (SCNEC) components. There is limited literature on this rare pathological differentiation pattern and a lack of guidelines for the best treatment methods, which prompts reflection on the diagnosis, optimal treatment strategies, and how preoperative diagnosis can affect patient prognosis for endometrial carcinosarcoma with neuroendocrine differentiation. PATIENT CONCERNS: The patient is an elderly woman who presents with abnormal vaginal bleeding after menopause. Transvaginal ultrasound examination shows that the uterus is slightly enlarged, and there is a lack of homogeneous echogenicity in the uterine cavity. Subsequently, a hysteroscopic curettage was performed, and a space-occupying lesion was observed on the anterior wall of the uterine cavity. DIAGNOSES: Preoperative endometrial biopsy revealed SCNEC of the endometrium. The patient underwent radical hysterectomy, and the postoperative pathological results showed that UCS (heterologous) was accompanied by SCNEC components (about 80%). INTERVENTION: The patient received radical hysterectomy, followed by adjuvant chemotherapy. OUTCOME: After 7 months of follow-up, no tumor recurrence or metastasis was found at the time of writing this article. LESSONS: The histological type of UCS (heterologous) with cell neuroendocrine carcinoma components is rare and highly invasive, with a high misdiagnosis rate in preoperative biopsy. There are currently no effective treatment guidelines for this type of case. The unusual appearance of SCNEC components in this case poses a challenge for both pathologists and surgeon. The rare differentiation pattern of this case exposes the complexity of its management and the necessity of prospective trials to determine the optimal treatment plan.

Effect of recombinant human brain natriuretic peptide on efficacy, hemodynamics and NT-proBNP in elderly patients with heart failure.

AIM: To investigate the effects of recombinant human brain natriuretic peptide (rhBNP) on efficacy, hemodynamics, and N-terminal pro-brain natriuretic peptide (NT-proBNP) in elderly patients with heart failure (HF). METHODS: In this retrospective analysis, the clinical data of 112 HF patients who visited the First Affiliated Hospital of Anhui University of Chinese Medicine between March 2019 and October 2022 were analyzed. On the basis of standard HF treatment, 52 patients additionally treated with milrinone intravenous were set as the control group (Con) and 60 patients with rhBNP were set as the observation group (Obs). The therapeutic efficacy and pre- and post-treatment echocardiographic indexes, NT-proBNP and hemodynamics were recorded and compared, and the adverse drug reactions and quality of life scores after treatment were counted. RESULTS: The Obs group showed a markedly higher post-treatment overall response rate than the Con (P=0.002). Besides, more obvious improvement of NT-proBNP and hemodynamic indexes were determined in the Obs group compared to the Con (P=0.000). Evidently ameliorated left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD) and left ventricular end-systolic diameter (LVESD) were observed in both groups after treatment, with more pronounced improvement in the Obs group (all P=0.000). The Obs group also exhibited an evidently lower incidence of adverse reactions and a better quality of life than the Con after treatment (P=0.000). CONCLUSIONS: rhBNP can effectively improve the cardiac function and hemodynamics in elderly HF patients, with high safety and few adverse reactions.

Competent blastocyst and receptivity endometrium improved clinical pregnancy in fresh embryo transfer cycles: a retrospective cohort study.

BACKGROUND: Embryo quality is usually regarded as a key predictor of successful implantation and clinical pregnancy potential. The identification of embryos that have the capacity to implant and result in a healthy pregnancy is a crucial part of in vitro fertilization (IVF). Usually, morphologically high-quality embryos are chosen for embryo transfer in IVF treatment. The aim of this study was to assess the association between the available blastocyst formation rate and the clinical pregnancy outcome following the first fresh embryo transfer cycle and provide systematic individual treatment to adjust endometrial receptivity for the next transfer cycle. METHODS: This retrospective, single-center study included 512 fresh embryo transfers conducted between 11/2019 and 08/2021, which consisted of 385 cleavage-stage (Day 3) and 127 blastocyst-stage (Day 5) embryo transfers. The two groups were divided into a clinical pregnancy group and a nonclinical pregnancy group for comparison. The association between the available blastocyst formation rate and the clinical pregnancy rate in the Day 3 and Day 5 transfer groups were considered. RESULTS: In the Day 3 group, there were 275 clinical pregnancies, and the clinical pregnancy rate was 71.43%. Although the two pronuclei (2PN) oocyte rate and available embryo rate at Day 3 were significantly higher in the clinical pregnancy group than the nonclinical pregnancy group (P < 0.05), the blastocyst formation rate and the available blastocyst formation rate were not significantly different between the clinical pregnancy group and the nonclinical pregnancy group (P > 0.05). In the Day 5 group, there were 81 clinical pregnancies, and the clinical pregnancy rate was 63.78%. No baseline characteristics showed any obvious differences between the clinical pregnancy group and nonclinical pregnancy group (P > 0.05). The blastocyst formation rate in the nonclinical pregnancy group was higher than that in the clinical pregnancy group, but the difference was not statistically significant (81.06% vs. 77.03%, P = 0.083). Interestingly, the available blastocyst formation rate and the Day 5 available blastocyst formation rate were significantly higher in the nonclinical pregnancy group than the clinical pregnancy group (66.19% vs. 60.79%, P = 0.014; 54.58% vs. 46.98%, P = 0.007). CONCLUSIONS: In fresh cycles, the available blastocyst formation rate was not associated with the clinical pregnancy outcome for Day 3 embryo transfers, and the available blastocyst formation rate was not positively correlated with the clinical pregnancy outcome for Day 5 embryo transfers.

Day 2 versus day 3 embryo transfer in patients with in vitro fertilization and only one zygote with two pronuclei.

OBJECTIVE: This study aimed to compare the pregnancy outcomes of Day 2 (D2) fresh embryo transfer and D3 fresh embryo transfer in women with only one zygote with two pronuclei (2PN). METHODS: Data on 432 in vitro fertilization-embryo transfer cycles with only one 2PN zygote from January 2016 to January 2022 were retrospectively collected. A total of 302 fresh embryo transfers on D2 (n = 193) and D3 (n = 109) were analyzed, and pregnancy outcomes were compared. RESULTS: The patients' characteristics were not different between D2 and D3 embryo transfer. There were no significant differences in the rates of clinical pregnancy, early abortion, or live birth between D2 and D3 embryo transfer. A multivariate logistic regression model controlling for age, the fertilization method, the number of oocytes harvested, and the number of high-quality embryos transferred showed that the live birth rate was similar between D2 and D3 embryo transfer. CONCLUSION: In in vitro fertilization-embryo transfer cycles with only one 2PN zygote, D2 fresh embryo transfer may provide similar pregnancy outcomes to those of D3 embryo transfer. D2 embryo transfer may be an option because of the risk of cycle cancellation due to the absence of viable embryos on D3.

The influence of bootleg innovation on individual innovation performance: The mediating effect of cognitive flexibility and the moderating effect of leadership's emotional intelligence.

Based Correctly handling the creativity of employees who have not been adopted is not only conducive to continuously stimulating employees' creativity and improving individual innovation performance, but also conducive to making the best use of organizational resources. This study integrates conservation of resource theory (COR) and social information processing theory to explore the influence of bootleg innovation behavior in organizations on individual innovation performance, as well as the mediating role of cognitive flexibility and the moderating role of leadership emotional intelligence. A three-stage time-lagged research design is used to obtain a valid sample of 327 employees from China. The PROCESS macro for SPSS was applied to test the hypothesized relationships. Findings demonstrated that bootleg innovation is positively related to individual innovation performance; cognitive flexibility mediates the relationship between bootleg innovation and individual innovation performance. Moreover, leadership emotional intelligence moderates the relationship between bootleg innovation and individual innovation performance and between bootleg innovation and cognitive flexibility and between cognitive flexibility and individual innovation performance respectively. The conclusion of the study not only provides a theoretical basis for individuals and leaders to deal with employees' creative abortion, but also provides a new thinking mode for how to maximize the effectiveness of unaccepted ideas and promote individual innovation performance.

Effectiveness and safety of probiotics on patients with severe acute pancreatitis: A systematic review and meta-analysis.

BACKGROUND: This meta-analysis aimed to assess the efficacy and safety of probiotics in conjunction with early enteral nutrition for the treatment of severe acute pancreatitis (SAP). This study focused on multiple clinical endpoints, including mortality rate, risk of organ failure, and duration of hospital stay. METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The study adhered to the Patient, Intervention, Comparison, Outcome framework and utilized randomized controlled trials to examine the impact of probiotics on patients with SAP. Data extraction and quality assessment were conducted independently by 2 evaluators, with discrepancies resolved collaboratively, or by a third adjudicator. Statistical analyses were performed using chi-square statistics, I2 metrics, and both fixed- and random-effects models, as dictated by heterogeneity levels. RESULTS: The meta-analysis covered 6 randomized controlled trials. Compared to control groups (placebo or standard care without probiotics), probiotics did not significantly reduce mortality rates or organ failure risk. However, they notably shortened hospital stays by a weighted mean difference of -5.49 days (95% confidence interval: -10.40 to -0.58; P = .010). The overall bias risk was low to moderate. CONCLUSIONS: Probiotics combined with early enteral nutrition did not significantly improve mortality rates or reduce the risk of organ failure in patients with SAP, but shortened hospital stays. Further studies are required to corroborate these findings.

Primary synovial sarcoma and acinar adenocarcinoma of prostate rarely occur simultaneously: A case report.

RATIONALE: Primary synovial sarcoma of the prostate is an extremely rare mesenchymal malignant soft tissue tumor with unique morphological features. Synovial sarcoma often occurs in the pararticular tissues of limbs in young people, but rarely occurs in prostate. Because it is very rare, it is easily misdiagnosed as benign prostatic hyperplasia or prostate cancer clinically. A case of synchronous acinar adenocarcinoma of the prostate has not been reported. In this article, we report a unique case of primary prostatic synovial sarcoma with acinar adenocarcinoma. PATIENT CONCERNS: A 58-year-old male patient was found to have a prostate mass during physical examination. Prostate ultrasound examination showed an increase in prostate volume of 5.2 × 3.3 × 3.3 cm, mixed echo mass can be seen on the left side of the prostate, with a size of approximately 4.9 × 4.3 cm, left seminal vesicle compressed. DIAGNOSES: Prostatic synovial sarcoma (biphasic type) combined with prostatic acinar adenocarcinoma (Gleason 3 + 3). INTERVENTION: The patient received radical prostatectomy, followed by adjuvant chemotherapy and radiotherapy. OUTCOME: After 2 months of follow-up, at the time of writing this article, the patient received a comprehensive treatment plan of adjuvant chemotherapy and radiotherapy for 2 months, and no recurrence or metastasis was found. LESSONS: Primary prostatic synovial sarcoma (biphasic type) combined with prostatic acinar adenocarcinoma is a very unique and rare case, and effective treatment guidelines are not yet clear, posing new challenges to clinical treatment. Making full use of pathological and imaging examinations, early diagnosis and radical surgery combined with multidisciplinary treatment seem to be still a positive method.

Inhibition of PRMT1 alleviates sepsis-induced acute kidney injury in mice by blocking the TGF-ß1 and IL-6 trans-signaling pathways.

Sepsis-induced acute kidney injury (SI-AKI) causes renal dysfunction and has a high mortality rate. Protein arginine methyltransferase-1 (PRMT1) is a key regulator of renal insufficiency. In the present study, we explored the potential involvement of PRMT1 in SI-AKI. A murine model of SI-AKI was induced by cecal ligation and perforation. The expression and localization of PRMT1 and molecules involved in the transforming growth factor (TGF)-ß1/Smad3 and interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) signaling pathways were detected in mouse kidney tissues by western blot analysis, immunofluorescence, and immunohistochemistry. The association of PRMT1 with downstream molecules of the TGF-ß1/Smad3 and IL-6/STAT3 signaling pathways was further verified in vitro in mouse renal tubular epithelial cells. Cecal ligation and perforation caused epithelial-mesenchymal transition, apoptosis, and inflammation in renal tissues, and this was alleviated by inhibition of PRMT1. Inhibition of PRMT1 in SI-AKI mice decreased the expression of TGF-ß1 and phosphorylation of Smad3 in the renal cortex, and downregulated the expression of soluble IL-6R and phosphorylation of STAT3 in the medulla. Knockdown of PRMT1 in mouse renal tubular epithelial cells restricted the expression of Cox-2, E-cadherin, Pro-caspase3, and phosphorylated Smad3 (involved in the TGF-ß1-mediated signaling pathway), and also blocked IL-6/soluble IL-6R, inducing the expression of Cox-2 and phosphorylated-STAT3. In conclusion, our findings suggest that inhibition of PRMT1 mitigates SI-AKI by inactivating the TGF-ß1/Smad3 pathway in the cortex and the IL-6/STAT3 pathway in the medulla. Our findings may aid in the identification of potential therapeutic target molecules for SI-AKI.

Gαq-PKD/PKCµ signal regulating the nuclear export of HDAC5 to induce the IκB expression and limit the NF-κB-mediated inflammatory response essential for early pregnancy.

Decidualization, denoting the transformation of endometrial stromal cells into specialized decidual cells, is a prerequisite for normal embryo implantation and a successful pregnancy in human. Here, we demonstrated that knockout of Gαq lead to an aberrantly enhanced inflammatory state during decidualization. Furthermore, we showed that deficiency of Gαq resulted in over-activation of nuclear factor (NF)-κB signaling, due to the decreased expression of NFκBIA, which encode the IκB protein and is the negative regulator for NF-κB. Mechanistically, Gαq deficiency decreased the Protein kinase D (PKD, also called PKCµ) phosphorylation levels, leading to attenuated HDAC5 phosphorylation and thus its nuclear export. Aberrantly high level of nuclear HDAC5 retarded histone acetylation to inhibit the induced NFκBIA transcription during decidualization. Consistently, pharmacological activation of the PKD/PKCµ or inhibition of the HDAC5 restored the inflammatory state and proper decidual response. Finally, we disclosed that over-active inflammatory state in Gαq-deficient decidua deferred the blastocyst hatching and adhesion in vitro, and the decidual expression of Gαq was significantly lower in women with recurrent pregnancy loss compared with normal pregnancy. In brief, we showed here that Gαq as a key regulator of the inflammatory cytokine's expression and decidual homeostasis in response to differentiation cues, which is required for successful implantation and early pregnancy.

Exosomes from hepatitis B virus-infected hepatocytes activate hepatic stellate cells and aggravate liver fibrosis through the miR-506-3p/Nur77 pathway.

Cumulative evidence indicates the important role of Nur77 in organ fibrogenesis. However, the role of Nur77 in hepatitis B virus (HBV)-related liver fibrosis (LF) remains unclear. Cells were transfected with the microRNA mimic miRNA-506-3p or inhibitor, and pcDNA3.1-Nur77 or Nur77 guide RNA. Exosomes were isolated from HBV-infected HepG2-sodium taurocholate cotransporting polypeptide cells. The levels of miR-506-3p, Nur77, and LF-related genes and proteins were detected by quantitative polymerase chain reaction (qPCR) and western blot analysis, respectively. The pathology of the liver from HBV-infected patients was examined using hematoxylin-eosin and Masson's staining. The expression of Nur77 in liver tissue was determined by immunohistochemistry, and the LF score was assessed using the METAVIR system. The relationship between miR-506-3p/Nur77 and LF score was analyzed by correlation analysis. HBV infection downregulated miR-506-3p expression and upregulated Nur77 levels in hepatocytes. Exosomes from HBV-infected hepatocytes also displayed decreased gene expression of miR-506-3p and increased expressions of Nur77- and LF-related genes in stellate cells compared with exosomes from hepatocytes with mock infection. These changes were reversed by Nur77 guide RNA. Nur77 expression in liver tissue was strongly correlated with LF, whereas serum miR-506-3p was strongly negatively correlated with LF. Exosomes from HBV-infected hepatocytes activate stellate cells and aggravate LF through the miR-506-3p/Nur77 pathway. These exosomes may be the basis of a promising therapeutic strategy.

The relationship between vocational college students' liking of teachers and learning engagement: A moderated mediation model.

To clarify the relationship between higher vocational students' liking of teachers and their learning engagement, based on the theory of social exchange, 1,279 vocational students in the Yangtze River Delta and the Pearl River Delta in China are used as the research objects. From the perspective of students and teachers, SPSS and AMOS are used to conduct a two-stage linear regression analysis. The results show that (1) students' liking of their teachers has a positive effect on learning engagement; (2) liking positively affects students' psychological empowerment; (3) liking of teachers indirectly influences learning engagement through psychological empowerment; (4) teacher's support positively moderates the indirect relationship between liking of teachers and learning engagement through psychological empowerment. This study attempts to provide practical guidance for college students to provide learning engagement.

Workplace ostracism and employee wellbeing: A conservation of resource perspective.

Introduction: As a common phenomenon of workplace ostracism in corporate management, it is urgent to clarify how it affects employee well-being. Methods: Based on Conservation of Resource Theory, this study investigates the mechanisms of workplace ostracism on employee well-being and examines the mediating role of emotional exhaustion and the moderating role of team forgiveness climate by surveying 282 employees from 68 companies in mainland China. Results: The results show that (1) workplace ostracism negatively affects employee well-being; (2) emotional exhaustion plays a mediating role between workplace ostracism and employee well-being; (3) team forgiveness climate weakens the negative effect of workplace ostracism on emotional exhaustion and negatively moderates the indirect effect of workplace ostracism on employee well-being through emotional exhaustion. Discussion: It tries to provide theoretical basis and practical guidance for eliminating the negative effects of workplace ostracism and focusing on employee well-being.

Predictive value of serum HCG concentrations for outcomes of vitrified-warmed blastocyst transfers in women of different ages.

RESEARCH QUESTION: Can serum human chorionic gonadotrophin (HCG) concentrations on day 10 after single-blastocyst transfer (SBT) in cryopreserved transfer cycles help to predict the cycle outcome in patients of different maternal ages? DESIGN: The study included 772 vitrified-warmed SBT cycles. The initial maternal serum HCG concentrations measured on day 10 after blastocyst transfer were evaluated using receiver operating characteristic (ROC) curves to predict clinical pregnancy and live birth. Threshold values for predicting a clinical pregnancy were established in three different age groups: group A (21-29 years old, n = 360), group B (30-34 years old, n = 290) and group C (35-47 years old, n = 122). RESULTS: The areas under the ROC curves for clinical pregnancy and live birth were 0.986 and 0.922, and the corresponding cut-off values were 113.28 and 146.37 mIU/ml, respectively. The optimal threshold values for clinical pregnancy as indicated by Youden index values for the three age groups were 145.15, 126.25 and 94.44 mIU/ml, respectively. CONCLUSIONS: The study demonstrates that determination of initial serum ß-HCG concentrations on day 10 after SBT in cryopreserved transfer cycles can help to predict cycle outcome in women of different ages. The optimal threshold value for clinical pregnancy for patients over 35 years of age was lower than that for the younger age groups.

Xylooligosaccharide attenuates lipopolysaccharide-induced intestinal injury in piglets via suppressing inflammation and modulating cecal microbial communities.

Xylooligosaccharide (XOS) has been considered to be an effective prebiotic, but its exact mechanisms remain unknown. This research was conducted to evaluate the effects of XOS on pig intestinal bacterial community and mucosal barrier using a lipopolysaccharide (LPS)-caused gut damage model. Twenty-four weaned pigs were assigned to 4 treatments in a 2 × 2 factorial design involving diet (with or without XOS) and immunological challenge (saline or LPS). After 21 d of feeding 0% or 0.02% commercial XOS product, piglets were treated with saline or LPS. After that, blood, small intestinal mucosa and cecal digesta were obtained. Dietary XOS enhanced intestinal mucosal integrity demonstrated by higher villus height, villus height-to-crypt depth ratio, disaccharidase activities and claudin-1 protein expression and lower crypt depth. XOS also caused down-regulation of the gene expression of toll-like receptor 4 and nucleotide-binding oligomerization domain protein signaling, accompanied with decreased pro-inflammatory cytokines and cyclooxygenase 2 contents or mRNA expression and increased heat shock protein 70 mRNA and protein expression. Additionally, increased Bacteroidetes and decreased Firmicutes relative abundance were observed in the piglets fed with XOS. At the genus level, XOS enriched the relative abundance of beneficial bacteria, e.g., Faecalibacterium, Lactobacillus, and Prevotella. Moreover, XOS enhanced short chain fatty acids contents and inhibited histone deacetylases. The correlation analysis of the combined datasets implied some potential connections between the intestinal microbiota and pro-inflammatory cytokines or cecal metabolites. These results suggest that XOS inhibits inflammatory response and beneficially modifies microbes and metabolites of the hindgut to protect the intestine from inflammation-related injury.

Digital PCR Detection of mtDNA/gDNA Ratio in Embryo Culture Medium for Prediction of Embryo Development Potential.

PURPOSE: The ratio of mitochondrial DNA to genomic DNA (mtDNA/gDNA) in embryo culture medium as a predictor of embryonic development is a new method of noninvasive embryo screening. However, current tests based on this concept have proven inconsistent. The aim of this study was to define the predictive value of the ratio of mtDNA/gDNA for embryonic developmental potential. MATERIALS AND METHODS: We used digital PCR to measure mtDNA/gDNA ratios in day 3 culture media of 223 embryos from 56 patients. We compared the relationship between the predictive value of mtDNA/gDNA ratio and each of embryo fragmentation, embryo morphological grade, and blastocyst formation. RESULTS: mtDNA/gDNA ratio decreased significantly with a decrease in embryo rating: 22.54 (44.66); 31.25 (36.97) and 46.33 (57.11); Grades A vs C, P = 0.006; B vs C, P = 0.015. mtDNA/gDNA ratio increased overall with an increase in embryo fragment content but did not differ significantly between high-, -medium, and poor-quality embryos. Interestingly, this trend differed from that of the unformed blastocysts. mtDNA/gDNA ratio of cleavage stage embryos forming blastocysts was lower (P=0.005). Trends of mtDNA/gDNA ratio differed according to inner cell mass (ICM) and trophectoderm (TE) levels, but not significantly. mtDNA/gDNA ratio in day 3 culture medium was not significantly improved over morphological scores. CONCLUSION: We hereby show the correlation of mtDNA/gDNA ratio in the culture medium of developing embryos. The correlation between the mtDNA/gDNA ratio and early embryonic development was controversial. Furthermore, an increase in mtDNA/gDNA ratio might indicate reduced development potential, but the difference remains insufficient for application as a clinical predictor.

Holly polyphenols alleviate intestinal inflammation and alter microbiota composition in lipopolysaccharide-challenged pigs.

The effect of holly polyphenols (HP) on intestinal inflammation and microbiota composition was evaluated in a piglet model of lipopolysaccharide (LPS)-induced intestinal injury. A total of twenty-four piglets were used in a 2 × 2 factorial design including diet type and LPS challenge. After 16 d of feeding with a basal diet supplemented with or without 250 mg/kg HP, pigs were challenged with LPS (100 µg/kg body weight) or an equal volume of saline for 4 h, followed by analysis of disaccharidase activities, gene expression levels of several representative tight junction proteins and inflammatory mediators, the SCFA concentrations and microbiota composition in intestinal contents as well as proinflammatory cytokine levels in plasma. Our results indicated that HP enhanced intestinal disaccharidase activities and reduced plasma proinflammatory cytokines including TNF-α and IL-6 in LPS-challenged piglets. Moreover, HP up-regulated mRNA expression of intestinal tight junction proteins such as claudin-1 and occludin. In addition, bacterial 16S rRNA gene sequencing showed that HP altered hindgut microbiota composition by enriching Prevotella and enhancing SCFA production following LPS challenge. These results collectively suggest that HP is capable of alleviating LPS-triggered intestinal injury by improving intestinal disaccharidase activities, barrier function and SCFA production, while reducing intestinal inflammation.

Lentinan modulates intestinal microbiota and enhances barrier integrity in a piglet model challenged with lipopolysaccharide.

The intestinal microbiota plays a vital role in metabolism, pathogen resistance, and immune development in host cells, and is modifiable by dietary change. Lentinan (LNT), a type of mushroom polysaccharide, is known to ameliorate intestinal inflammation with the potential of therapeutic effect on digestive diseases. We hypothesized that LNT could alleviate Escherichia coli lipopolysaccharide (LPS)-induced intestinal injury via regulating the composition and metabolites of intestinal microbiota in a piglet model. Twenty-four weaned piglets were used in a 2 × 2 factorial design, and the main factors included a dietary treatment (basal or LNT diet) and immunological challenge (LPS or saline). After feeding basal or LNT diet for 21 days, pigs were injected with LPS or saline. At 4 h post-injection, pigs were killed and jejunum, ileum and cecal digesta were collected. LNT improved intestinal morphology and barrier function. LNT also inhibited inflammatory signaling pathways (toll-like receptor 4 and nucleotide binding oligomerization domain protein) and pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1ß and interleukin-6) expression, as well as up-regulated the heat shock protein 70 expression in small intestine. In addition, LNT enhanced the concentrations of propionate, butyrate, isobutyrate and isovalerate in cecal digesta, resulting in a significant increase in histone acetylation without affecting the protein level of G protein-coupled receptor 41 (GPR41), a short chain fatty acid receptor. Bacterial 16S rRNA gene pyrosequencing showed that LNT had a great impact on gut microbiota composition at different taxonomic levels. Moreover, the correlation analysis revealed some potential relationships between cecal metabolites and certain intestinal microbiota. These results indicate that LNT promotes intestinal health, in part, through altering intestinal microbiota composition and increasing the short chain fatty acid synthesis, which subsequently lead to a reduction in inflammation and hyper-acetylation of histones.

Tadalafil-loaded PLGA microspheres for pulmonary administration: preparation and evaluation

Tadalafil, a long-acting PED-5 inhibitor, is commonly used for the treatment of pulmonary arterial hypertension (PAH). However, its efficacy and clinical application are severely limited by the poor water solubility, low bioavailability and a series adverse effects (e.g. headaches, indigestion). In this study, tadalafil was prepared and loaded into biodegradable PLGA (poly(lactic-co-glycolic acid)) microspheres (TDF-PLGA-MS) via emulsification-solvent evaporation. The resulting microspheres were processed into pulmonary inhalant by freeze drying. The TDF-PLGA-MS was spherical and uniform, with an average particle diameter ~10.29 µm. The encapsulation efficiency and drug loading yield of TDF-PLGA-MS were 81.68% and 8.52%, respectively. The investigation of micromeritics showed that the TDF-PLGA-MS had low moisture content. The fluidity of powders was relatively good. The aerodynamic diameter and emptying rate of microspheres powders were 3.92 µm and 95.41%, respectively. Therefore, the microspheres powders were easy to be atomized, and can meet the requirements of pulmonary administration. In vitro release results showed that the microspheres group released slowly. The cumulative release in 24 h and 10 d was 46.87% and 84.06%, respectively. The in vitro release profile of TDF-PLGA-MS was in accordance with the Weibull model. The results of Pharmacokinetics showed that tadalafil from microspheres slowly released into the blood after intratracheal instillation. The pulmonary drug residue in 0.5 h was 3.5 times compared with solution group. The residual concentration in lung after 10d was still higher than that of solution group in 48 h. The t1/2β and MRT0-∞ were 3.10 times and 3.96 times that of solution group, respectively. Moreover, the Cmax and AUC of drug residues in lung ​​were 3.48 times and 16.36 times that of solution group, respectively. The results of tissue distribution showed that the Re in lung was 16.358, which indicated the lung targeting. In conclusion, the TDF-PLGA-MS for pulmonary administration in this study can significantly improve the pulmonary targeting, increase efficacy of tadalafil and reduce other non-target organs toxicity. This study will have an important clinical significance for PAH patients who need long-term drug therapy.

Glutamate alleviates muscle protein loss by modulating TLR4, NODs, Akt/FOXO and mTOR signaling pathways in LPS-challenged piglets.

The experiment was conducted to study the effect of the glutamate (Glu) on muscle protein loss through toll-like receptor 4 (TLR4), nucleotide-binding oligomerization domain proteins (NODs), Akt/Forkhead Box O (Akt/FOXO) and mammalian target of rapamycin (mTOR) signaling pathways in LPS-challenged piglets. Twenty-four weaned piglets were assigned into four treatments: (1) Control; (2) LPS+0% Glu; (3) LPS + 1.0% Glu; (4) LPS + 2.0% Glu. The experiment was lasted for 28 days. On d 28, the piglets in the LPS challenged groups were injected with LPS on 100 µg/kg body weight (BW), and the piglets in the control group were injected with the same volume of 0.9% NaCl solution. After 4 h LPS or saline injection, the piglets were slaughtered and the muscle samples were collected. Glu supplementation increased the protein/DNA ratio in gastrocnemius muscle, and the protein content in longissimus dorsi (LD) muscle after LPS challenge (P<0.05). In addition, Glu supplementation decreased TLR4, IL-1 receptor-associated kinase (IRAK) 1, receptor-interacting serine/threonine-protein kinase (RIPK) 2, and nuclear factor-κB (NF-κB) mRNA expression in gastrocnemius muscle (P<0.05), MyD88 mRNA expression in LD muscle, and FOXO1 mRNA expression in LD muscle (P<0.05). Moreover, Glu supplementation increased p-Akt/t-Akt ratio (P<0.05) in gastrocnemius muscle, and p-4EBP1/t-4EBP1 ratio in both gastrocnemius and LD muscles (P<0.05). Glu supplementation in the piglets' diets might be an effective strategy to alleviate LPS-induced muscle protein loss, which might be due to suppressing the mRNA expression of TLR4 and NODs signaling-related genes, and modulating Akt/FOXO and mTOR signaling pathways.

[Isolation, Identification and Characterization of the Filamentous Microorganisms from Bulking Sludge].

To illustrate the species and characteristics of filamentous microorganisms in bulking sludge, culture method, microscopic examination and molecular biological analysis were conducted to isolate and identify the filamentous microorganisms existing in bulking sludge collected from municipal wastewater treatment plant. Filamentous microorganisms isolated by Gause's synthetic agar medium and starch agar fell into 18 genera, among which Streptomyces and Microbacterium belong to bacterial phylum Actinobacteria, all other isolates were classified into fungi. Penicillium, Cladosporium, Alternaria, Aspergillus and Trichosporon were the fungi with high occurrence frequency in culture medium. Trichosporon, Streptomyces, Penicillium and Alternaria could grow well at neutral pH or meta-acid condition. High concentration of NaCl could inhibit the growth of Trichosporon and Streptomyces, but had no obvious inhibitory effect on Penicillium and Alternaria. Except of Trichosporon, Streptomyces, Penicillium and Alternaria all could utilize saccharose, starch and cellulose. The increase of carbon source concentration could promote their growth. The results of high throughput sequencing of rDNA-ITS showed that a large number of unidentified fungi existed in bulking sludge.