Sensing of individual stalled 80S ribosomes by Fap1 for nonfunctional rRNA turnover.

Cells can respond to stalled ribosomes by sensing ribosome collisions and employing quality control pathways. How ribosome stalling is resolved without collisions, however, has remained elusive. Here, focusing on noncolliding stalling exhibited by decoding-defective ribosomes, we identified Fap1 as a stalling sensor triggering 18S nonfunctional rRNA decay via polyubiquitination of uS3. Ribosome profiling revealed an enrichment of Fap1 at the translation initiation site but also an association with elongating individual ribosomes. Cryo-EM structures of Fap1-bound ribosomes elucidated Fap1 probing the mRNA simultaneously at both the entry and exit channels suggesting an mRNA stasis sensing activity, and Fap1 sterically hinders the formation of canonical collided di-ribosomes. Our findings indicate that individual stalled ribosomes are the potential signal for ribosome dysfunction, leading to accelerated turnover of the ribosome itself.

Two modes of Cue2-mediated mRNA cleavage with distinct substrate recognition initiate no-go decay.

Ribosome collisions are recognized by E3 ubiquitin ligase Hel2/ZNF598, leading to RQC (ribosome-associated quality control) and to endonucleolytic cleavage and degradation of the mRNA termed NGD (no-go decay). NGD in yeast requires the Cue2 endonuclease and occurs in two modes, either coupled to RQC (NGDRQC+) or RQC uncoupled (NGDRQC-). This is mediated by an unknown mechanism of substrate recognition by Cue2. Here, we show that the ubiquitin binding activity of Cue2 is required for NGDRQC- but not for NGDRQC+, and that it involves the first two N-terminal Cue domains. In contrast, Trp122 of Cue2 is crucial for NGDRQC+. Moreover, Mbf1 is required for quality controls by preventing +1 ribosome frameshifting induced by a rare codon staller. We propose that in Cue2-dependent cleavage upstream of the collided ribosomes (NGDRQC-), polyubiquitination of eS7 is recognized by two N-terminal Cue domains of Cue2. In contrast, for the cleavage within collided ribosomes (NGDRQC+), the UBA domain, Trp122 and the interaction between Mbf1 and uS3 are critical.

Methyl-CpG-binding protein 2 regulates CYP27A1-induced myometrial contraction during preterm labor.

Persistent and intense uterine contraction is a risk factor for preterm labor. We previously found that methyl-CpG-binding protein 2 (MeCP2), as a target of infection-related microRNA miR-212-3p, may play an inhibitory role in regulating myometrium contraction. However, the molecular mechanisms by which MeCP2 regulates myometrial contraction are still unknown. In this study, we found that MeCP2 protein expression was lower in myometrial specimens obtained from preterm labor cases, compared to those obtained from term labor cases. Herein, using RNA sequence analysis of global gene expression in human uterine smooth muscle cells (HUSMCs) following siMeCP2, we show that MeCP2 silencing caused dysregulation of the cholesterol metabolism pathway. Notably, MeCP2 silencing resulted in the upregulation of CYP27A1, the key enzyme involved in regulating cholesterol homeostasis, in HUSMCs. Methylation-specific PCR, chromatin immunoprecipitation, and dual luciferase reporter gene technology indicated that MeCP2 could bind to the methylated CYP27A1 promoter region and repress its transcription. Administration of siCYP27A1 in a lipopolysaccharide (LPS)-induced preterm labor mouse model delayed the onset of preterm labor. Human preterm myometrium and the LPS-induced preterm labor mouse model both showed lower expression of MeCP2 and increased expression of CYP27A1. These results demonstrated that aberrant upregulation of CYP27A1 induced by MeCP2 silencing is one of the mechanisms facilitating inappropriate myometrial contraction. CYP27A1 could be exploited as a novel therapeutic target for preterm birth.

Effects and mechanisms of glyphosate as phosphorus nutrient on element stoichiometry and metabolism in the diatom Phaeodactylum tricornutum.

The ability to utilize dissolved organic phosphorus (DOP) gives phytoplankton competitive advantages in P-limited environments. Our previous research indicates that the diatom Phaeodactylum tricornutum could grow on glyphosate, a DOP with carbon-phosphorus (C-P) bond and an herbicide, as sole P source. However, direct evidence and mechanism of glyphosate utilization are still lacking. In this study, using physiological and isotopic analysis, combined with transcriptomic profiling, we demonstrated the uptake of glyphosate by P. tricornutum and revealed the candidate responsible genes. Our data showed a low efficiency of glyphosate utilization by P. tricornutum, suggesting that glyphosate utilization costs energy and that the alga possessed an herbicide-resistant type of 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase. Compared to the P-limited cultures, the glyphosate-grown P. tricornutum cells up-regulated genes involved in DNA replication, cell growth, transcription, translation, carbon metabolism, and many genes encoding antioxidants. Additionally, cellular C and silicon (Si) increased remarkably while cellular nitrogen (N) declined in the glyphosate-grown P. tricornutum, leading to higher Si:C and Si:N ratios, which corresponded to the up-regulation of genes involved in the C metabolism and Si uptake and the down-regulation of those encoding N uptake. This has the potential to enhance C and Si export to the deep sea when P is limited but phosphonate is available. In sum, our study documented how P. tricornutum could utilize the herbicide glyphosate as P nutrient and how glyphosate utilization may affect the element content and stoichiometry in this diatom, which have important ecological implications in the future ocean.IMPORTANCEGlyphosate is the most widely used herbicide in the world and could be utilized as phosphorus (P) source by some bacteria. Our study first revealed that glyphosate could be transported into Phaeodactylum tricornutum cells for utilization and identified putative genes responsible for glyphosate uptake. This uncovers an alternative strategy of phytoplankton to cope with P deficiency considering phosphonate accounts for about 25% of the total dissolved organic phosphorus (DOP) in the ocean. Additionally, accumulation of carbon (C) and silicon (Si), as well as elevation of Si:C ratio in P. tricornutum cells when grown on glyphosate indicates glyphosate as the source of P nutrient has the potential to result in more C and Si export into the deep ocean. This, along with the differential ability to utilize glyphosate among different species, glyphosate supply in dissolved inorganic phosphorus (DIP)-depleted ecosystems may cause changes in phytoplankton community structure. These insights have implications in evaluating the effects of human activities (use of Roundup) and climate change (potentially reducing DIP supply in sunlit layer) on phytoplankton in the future ocean.

A General Concept for the Electronic and Steric Modification of 1-Metallacyclobuta-2,3-dienes: A Case Study of Group 4 Metallocene Complexes.

The synthesis of group 4 metal 1-metallacyclobuta-2,3-dienes as organometallic analogues of elusive 1,2-cyclobutadiene has so far been limited to SiMe3 substituted examples. We present the synthesis of two Ph substituted dilithiated ligand precursors for the preparation of four new 1-metallacyclobuta-2,3-dienes [rac-(ebthi)M] (M=Ti, Zr; ebthi=1,2-ethylene-1,10-bis(η5-tetrahydroindenyl)). The organolithium compounds [Li2(RC3Ph)] (1 b: R=Ph, 1 c: R=SiMe3) as well as the metallacycles of the general formula [rac-(ebthi)M(R1C3R2)] (2 b: M=Ti, R1=R2=Ph, 2 c: M=Ti, R1=Ph, R2=SiMe3; 3 b: M=Zr, R1=R2=Ph; 3 c: M=Zr, R1=Ph, R2=SiMe3) were fully characterised. Single crystal X-ray diffraction and quantum chemical bond analysis of the Ti and Zr complexes reveal ligand influence on the biradicaloid character of the titanocene complexes. X-band EPR spectroscopy of structurally similar Ti complexes [rac-(ebthi)Ti(Me3SiC3SiMe3)] (2 a), 2 b, and 2 c was carried out to evaluate the accessibility of an EPR active triplet state. Cyclic voltammetry shows that introduction of Ph groups renders the complexes easier to reduce. 13C CPMAS NMR analysis provides insights into the cause of the low field shift of the resonances of metal-bonded carbon atoms and provides evidence of the absence of the ß-C-Ti interaction.

Stress-induced mucin 13 reductions drive intestinal microbiome shifts and despair behaviors.

Depression is a prevalent psychological condition with limited treatment options. While its etiology is multifactorial, both chronic stress and changes in microbiome composition are associated with disease pathology. Stress is known to induce microbiome dysbiosis, defined here as a change in microbial composition associated with a pathological condition. This state of dysbiosis is known to feedback on depressive symptoms. While studies have demonstrated that targeted restoration of the microbiome can alleviate depressive-like symptoms in mice, translating these findings to human patients has proven challenging due to the complexity of the human microbiome. As such, there is an urgent need to identify factors upstream of microbial dysbiosis. Here we investigate the role of mucin 13 as an upstream mediator of microbiome composition changes in the context of stress. Using a model of chronic stress, we show that the glycocalyx protein, mucin 13, is selectively reduced after psychological stress exposure. We further demonstrate that the reduction of Muc13 is mediated by the Hnf4 transcription factor family. Finally, we determine that deleting Muc13 is sufficient to drive microbiome shifts and despair behaviors. These findings shed light on the mechanisms behind stress-induced microbial changes and reveal a novel regulator of mucin 13 expression.

Distinguishing the effects of systemic CSF1R inhibition by PLX3397 on microglia and peripheral immune cells.

Microglia, the primary immune cells of the central nervous system (CNS), are derived from the yolk sac and populate the brain during development. Once microglia migrate to the CNS, they are self-renewing and require CSF1R signaling for their maintenance. Pexidartinib (PLX3397, PLX), a small molecule inhibitor of the CSF1R, has been shown to effectively deplete microglia since microglial maintenance is CSF1R-dependent. There have, however, been several conflicting reports that have shown the potential off-target effects of PLX on peripheral immune cells particularly those of lymphoid origin. Given this controversy in the use of the PLX family of drugs, it has become important to ascertain to what extent PLX affects the peripheral immune profile in lymphoid (spleen, and bone marrow) and non-lymphoid (kidney, lungs, and heart) organs. PLX3397 chow treatment at 660 mg/kg for 7 days significantly reduced CD45+ macrophages, CX3CR1-GFP cells, CD11b+CD45intermediate cells, and P2RY12 expression in the brain. However, there were minimal effects on peripheral immune cells from both lymphoid and non-lymphoid organs except in the heart where there was a significant decrease in CD3+ cells, inflammatory and patrolling monocytes, and CD11b+Ly6G+ neutrophils. We then stimulated the immune system with 1 mg/kg of LPS which resulted in a significant reduction in the number of innate immune cells. In this context, PLX did not alter the cytokine profile in the serum and the brain of naïve mice but did so in the LPS-stimulated group resulting in a significant reduction in TNFα, IL-1α, IFN-γ and IL-1ß. Furthermore, PLX did not alter locomotor activity in the open field test suggesting that microglia do not contribute to LPS-induced sickness behavior. Our results provide an assessment of immune cell populations with PLX3397 treatment on brain, lymphoid and non-lymphoid organs without and during LPS treatment that can serve as a resource for understanding consequences of such approaches.

A novel strategy for therapeutic drug monitoring: application of biosensors to quantify antimicrobials in biological matrices.

Over the past few years, therapeutic drug monitoring (TDM) has gained practical significance in antimicrobial precision therapy. Yet two categories of mainstream TDM techniques (chromatographic analysis and immunoassays) that are widely adopted nowadays retain certain inherent limitations. The use of biosensors, an innovative strategy for rapid evaluation of antimicrobial concentrations in biological samples, enables the implementation of point-of-care testing (POCT) and continuous monitoring, which may circumvent the constraints of conventional TDM and provide strong technological support for individualized antimicrobial treatment. This comprehensive review summarizes the investigations that have harnessed biosensors to detect antimicrobial drugs in biological matrices, provides insights into the performance and characteristics of each sensing form, and explores the feasibility of translating them into clinical practice. Furthermore, the future trends and obstacles to achieving POCT and continuous monitoring are discussed. More efforts are necessary to address the four key 'appropriateness' challenges to deploy biosensors in clinical practice, paving the way for personalized antimicrobial stewardship.

Association between health literacy and dysphagia in the community-dwelling older population: a cross-sectional study.

BACKGROUND: Dysphagia, or swallowing disorders, has become a growing concern due to the aging population, and health literacy plays a crucial role in active aging. However, the relationship between them remains unclear. AIMS: To investigate the association between health literacy and dysphagia among community-dwelling older adults in China. METHODS: A survey was conducted on 4462 older adults aged 65 and above in a community in Yiwu City, China, from May 2021 to January 2022. Swallowing problems were assessed using a 30 ml water swallowing test (WST) and the Eating Assessment Tool-10 questionnaire (EAT-10). The participants' health literacy was evaluated using the Chinese Health Literacy Scale (CHLS). Logistic regression and t tests were employed to measure the association between them. RESULTS: The prevalence of dysphagia was 5.70% and 7.85% as determined by EAT-10 and 30 ml-WST, respectively. The health literacy level of community-dwelling older adults was 24.4 ± 4.93 (9-45). Participants with dysphagia exhibited lower levels of health literacy (p < 0.05). The logistic regression model demonstrated an inverse association between health literacy and dysphagia (OR = 0.94, 95%CI = 0.91-0.96 for EAT-10, and OR = 0.93, 95%CI = 0.92-0.95 for WST). Moreover, this association remained significant even after adjusting for covariates. DISCUSSION: Older adults with dysphagia have lower levels of health literacy, particularly in terms of their ability to seek medical advice, acquire and evaluate medical information, and access social support resources. CONCLUSIONS: Health literacy is associated with dysphagia among community-dwelling older adults. Effective interventions should be implemented to provide support in terms of both medical services and social support for this population.

Exploring the impacts of ecosystem services on human well-being in Qinghai Province under the framework of the sustainable development goals.

Ecosystem services (ESs) play vital roles in meeting the needs of human well-being and supporting sustainable development. However, there is limited research on how the types, amounts, interactions, and changes of the ESs collectively impact human well-being under the context of sustainable development goals (SDGs) of the United Nations. This study selected Qinghai Province of China as the study area and intended to make such an attempt to fill this gap in terms of the following aspects: (1) analyzing the spatial patterns and changing trends of ten ESs (food supply, water supply, carbon sink, soil retention, sand fixation, hydrological regulation, flood mitigation，cultural service，net primary productivity, and habitat quality) in Qinghai Province from 2000 to 2018; (2)constructing a multi-level index system of human well-being under the framework of the SDGs, and setting the criteria to assess the level of local human well-being; and (3) building a structural equation model to explore the direct and indirect impacts of the types, amounts, interactions and changes of the ESs on actual human well-being and the gaps between actual and targeted human well-being. The findings revealed that: (1) most of the ecosystem services fluctuated with significant downward or upward trends during 2000-2018, except for four ESs (i.e., carbon sink, soil retention, flood mitigation, and habitat quality); (2) only a few indicators of local residents' well-being such as meat production, milk production, the numbers of medical technical personnel in hospitals and health centers, and the numbers of scientific and technical personnel met the SDG criteria in most time, while other indicators remained at low levels and there were large gaps between them and the SDG criteria; (3) actual human well-being and the gaps between actual and targeted human well-being were affected by the types, amounts, interactions and changes of the ESs with different degrees directly or indirectly. The approaches and results in this study are instructive for other regions of the world to make certain the roles of ESs in promoting human well-being and substantiating the SDGs.

Using Potassium Bicarbonate to Improve the Water-Holding Capacity, Gel and Rheology Characteristics of Reduced-Phosphate Silver Carp Batters.

To study the use of partial or total potassium bicarbonate (PBC) to replace sodium tripolyphosphate (STPP) on reduced-phosphate silver carp batters, all the batters were composed of silver carp surimi, pork back fat, ice water, spices, sugar, and sodium chloride. Therein, the sample of T1 contained 4 g/kg STPP; T2 contained 1 g/kg PBC, 3 g/kg STPP; T3 contained 2 g/kg PBC, 2 g/kg STPP; T4 contained 3 g/kg PBC, 1 g/kg STPP; T5 contained 4 g/kg PBC, and they were all produced using a bowl chopper. The changes in pH, whiteness, water- and oil-holding capacity, gel and rheological properties, as well as protein conformation were investigated. The pH, cooking yield, water- and oil-holding capacity, texture properties, and the G' values at 90 °C of the reduced-phosphate silver carp batters with PBC significantly increased (p < 0.05) compared to the sample without PBC. Due to the increasing pH and enhanced ion strength, more ß-sheet and ß-turns structures were formed. Furthermore, by increasing PBC, the pH significantly increased (p < 0.05) and the cooked silver carp batters became darkened. Meanwhile, more CO2 was generated, which destroyed the gel structure, leading the water- and oil-holding capacity, texture properties, and G' values at 90 °C to be increased and then decreased. Overall, using PBC partial as a substitute of STPP enables reduced-phosphate silver carp batter to have better gel characteristics and water-holding capacity by increasing its pH and changing its rheology characteristic and protein conformation.

Cross-sectional study on dysphagia evaluation in community-dwelling older adults using the Eating Assessment Tool (EAT) -10, EAT-2, and Water Swallow Test.

BACKGROUND: Dysphagia is a health concern that causes severe complications and affects the life quality of the older population. This study aimed to determine the diagnostic performance of the Eating Assessment Tool (EAT)-2 compared with the EAT-10 and the Water Swallow Test (WST) in screening for dysphagia. METHODS: A cross-sectional study was conducted among 5,090 community-dwelling older adults. Dysphagia was evaluated using both a subjective measure, the 10-item EAT (EAT-10) and an objective measure, the WST. The kappa index in pairs were analyzed. The validity and reliability of EAT-2 were also assessed. RESULTS: The sensitivity and specificity of the EAT-2 were 96.3 % and 94.8 %, respectively. The kappa index between the EAT-2 and EAT-10 was 0.64, whereas it was 0.11 between the EAT-10 and WST. CONCLUSIONS: The EAT-2 was a simpler screening tool for dysphagia. Combining the subjective questionnaire (EAT-10 or EAT-2) and the objective test (WST) is recommended.

Symptom clusters and impact on quality of life in esophageal cancer patients.

BACKGROUND: Esophageal cancer patients can experience co-occurring, related symptoms labeled symptom clusters. This study aimed to identify symptom clusters and explore which SCs independently affect the quality of life (QoL) among esophageal cancer patients. METHODS: This cross-sectional study was performed in Shenyang, China, from February 2021 to February 2022. Finally, 118 esophageal cancer patients effectively completed the survey. Questionnaires' information included the Functional Assessment of Cancer Therapy-General (FACT-G), the MD Anderson Symptom Inventory Gastrointestinal Cancer Module (MDASI-GI), the Multidimensions Scale of Perceived Social Support, and demographic and clinical characteristics. Exploratory factor analysis with principal axis factoring was used to identify symptom clusters, and multiple regression analysis was employed to analyze the influencing factors of QoL. RESULTS: The mean score of FACT-G was 69.88 (SD = 17.85) among 118 esophageal cancer patients. Four symptom clusters were identified: psychological-somatic, dysphagia, fatigue-pain, and gastrointestinal symptom clusters. Results of regression analysis indicated a significant impact on QoL for chemotherapy (ß = 0.140, P < 0.045), psychological-somatic symptom cluster (ß = - 0.329, P = 0.013), and social support (ß = 0.409, P < 0.001) after adjusting demographic and clinical characteristics. The linear combination explained 47.8% of the variance in QoL. CONCLUSIONS: There is a critical need to emphasize the importance of psychological-somatic symptoms clusters management programs and increasing social support to improve QoL in esophageal cancer patients.

Modulation of gastrointestinal bacterial in chronic atrophic gastritis model rats by Chinese and west medicine intervention.

Chronic atrophic gastritis (CAG) is well-known related with multiple pathogenic factors and normally therapies comprised by western or Chinese medicines. The present study was designed to identify the bacterial community characterized by 16S rRNA amplicon sequencing and determine the modulate affection of bacterial composition response western and Chinese medicine Qinghuayin (QHY) as well as antibiotic on model rats. The result shown the overall structure alteration of bacterial appeared under medicine intervened, antibiotic caused a marked depletion in bacterial diversity and richness. The enrichments of Firmicutes (85.1-90.7%) in antibiotic-free converts into Bacteroidetes (30.7-34.6%) in antibiotic-added model rat were demonstrated. Firmicutes as the most dominant phylum in antibiotic-free treatments and significantly decreased till 21.9-68.5% in antibiotic-added treatments. Especially QHY-treated rats showed highest RA of Firmicutes (90.7%) and the amelioration of CAG using QHY attributed by beneficial bacterial enrichment, especially Ruminococcus, Lactobacillus and Bifidobacterium. In addition, alpha and beta diversity analysis also demonstrated the clear dispersion and aggregation that revealed the alteration and steady of bacterial community structures. In summary, QHY has potential application value in the treatment of CAG, which attributed to close relation with the modulatory of internal bacterial communities.

Necroptosis and Apoptosis Contribute to Cisplatin and Aminoglycoside Ototoxicity.

Ototoxic side effects of cisplatin and aminoglycosides have been extensively studied, but no therapy is available to date. Sensory hair cells, upon exposure to cisplatin or aminoglycosides, undergo apoptotic and necrotic cell death. Blocking these cell death pathways has therapeutic potential in theory, but incomplete protection and lack of therapeutic targets in the case of necrosis, has hampered the development of clinically applicable drugs. Over the past decade, a novel form of necrosis, termed necroptosis, was established as an alternative cell death pathway. Necroptosis is distinguished from passive necrotic cell death, in that it follows a cellular program, involving the receptor-interacting protein kinase (RIPK) 1 and RIPK3. In this study, we used pharmacological and genetic interventions in the mouse to test the relative contributions of necroptosis and caspase-8-mediated apoptosis toward cisplatin and aminoglycoside ototoxicity. We find that ex vivo, only apoptosis contributes to cisplatin and aminoglycoside ototoxicity, while in vivo, necroptosis as well as apoptosis are involved in both sexes. Inhibition of necroptosis and apoptosis using pharmacological compounds is thus a viable strategy to ameliorate aminoglycoside and cisplatin ototoxicity.SIGNIFICANCE STATEMENT The clinical application of cisplatin and aminoglycosides is limited due to ototoxic side effects. Here, using pharmaceutical and genetic intervention, we present evidence that two types of programmed cell death, apoptosis and necroptosis, contribute to aminoglycoside and cisplatin ototoxicity. Key molecular factors mediating necroptosis are well characterized and druggable, presenting new avenues for pharmaceutical intervention.

Aryl Hydrocarbon Receptor Signaling Prevents Activation of Hepatic Stellate Cells and Liver Fibrogenesis in Mice.

BACKGROUND & AIMS: The role of aryl hydrocarbon receptor (AhR) in liver fibrosis is controversial because loss and gain of AhR activity both lead to liver fibrosis. The goal of this study was to investigate how the expression of AhR by different liver cell types, hepatic stellate cells (HSCs) in particular, affects liver fibrosis in mice. METHODS: We studied the effects of AhR on primary mouse and human HSCs, measuring their activation and stimulation of fibrogenesis using RNA-sequencing analysis. C57BL/6J mice were given the AhR agonists 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE); were given carbon tetrachloride (CCl4); or underwent bile duct ligation. We also performed studies in mice with disruption of Ahr specifically in HSCs, hepatocytes, or Kupffer cells. Liver tissues were collected from mice and analyzed by histology, immunohistochemistry, and immunoblotting. RESULTS: AhR was expressed at high levels in quiescent HSCs, but the expression decreased with HSC activation. Activation of HSCs from AhR-knockout mice was accelerated compared with HSCs from wild-type mice. In contrast, TCDD or ITE inhibited spontaneous and transforming growth factor ß-induced activation of HSCs. Mice with disruption of Ahr in HSCs, but not hepatocytes or Kupffer cells, developed more severe fibrosis after administration of CCl4 or bile duct ligation. C57BL/6J mice given ITE did not develop CCl4-induced liver fibrosis, whereas mice without HSC AhR given ITE did develop CCl4-induced liver fibrosis. In studies of mouse and human HSCs, we found that AhR prevents transforming growth factor ß-induced fibrogenesis by disrupting the interaction of Smad3 with ß-catenin, which prevents the expression of genes that mediate fibrogenesis. CONCLUSIONS: In studies of human and mouse HSCs, we found that AhR prevents HSC activation and expression of genes required for liver fibrogenesis. Development of nontoxic AhR agonists or strategies to activate AhR signaling in HSCs might be developed to prevent or treat liver fibrosis.

Formulation of traditional Chinese medicine and its application on intestinal flora of constipated rats.

In this study, the self-extracted constipation treatment of traditional Chinese medicine extracts was applied to constipated rats. To explore the mechanism and role of the Chinese medicine for the treatment of constipation, the 16S rRNA sequencing and qRT-PCR technology were used to analyze the intestinal flora. We found that the relative abundance of Firmicutes with constipation was significantly higher accounted for 86.7%, while the gut microbiota was significantly changed after taking a certain dose of Chinese medicine, greatly increased the relative abundance of Lactobacillus accounted for 23.1%, enhanced the symbiotic relationships of Lactobacillus with other intestinal flora. The total copies of intestinal bacteria in the constipated rats decreased after taking the traditional Chinese medicine. Finally, this study results provides a theoretical basis for the treatment and understand the mechanism and effect of traditional Chinese medicine on rate constipation.

Prognostic Role of the Prognostic Nutritional Index in Pancreatic Cancer: A Meta-analysis.

OBJECTIVE: The prognostic nutritional index (PNI) has been reported to play an important prognostic role in various malignancies. Here we performed a meta-analysis to explore the predictive value of PNI in pancreatic cancer (PC). METHODS: Clinical studies about PNI and prognosis in PC were retrieved from Pubmed, Embase, Web of Science and Cochrane Libarary updated on 31 December 2017. Stata 12 was used to compute pooled hazard radio (HR) and 95% confidence interval (CI) to estimate the relationship between PNI and overall survival (OS). RESULTS: Ten studies with 2064 patients were eligible for final analysis. The pooled HR (1.48, 95%CI: 1.32-1.66, I 2 = 25.5% P = 0.201）revealed that low PNI was related to poor prognosis in patients with PC. The significant relationship between PNI and prognosis was not affected by subgroup analysis based on tumor stage, treatment method, sample size, cutoff value, HR data source and study quality. CONCLUSION: Our meta-analysis suggests PNI maybe a potential prognostic indicator for patients with PC.

Establishing a balanced scorecard measurement system for integrated care organizations in China.

To address, among other issues, the regional and international challenges of the heavy health care burden caused by an aging population, integrated care organizations (ICOs) were proposed at the end of the 20th century for health care delivery. However, the implementation of ICOs has not progressed smoothly, and the current results have not eliminated the imbalance of medical service capabilities among hospitals of different levels. To make up for the deficiency in the current evaluation system at ICOs and offer suggestions for improved sustainable health planning and management, this study establishes a balanced scorecard based on a comprehensive measurement system valid for a Chinese ICO by surveying the staff at the West China Hospital ICO. This study collected valid responses from 216 professional staff members at the ICO via questionnaires. K-means clustering and the coefficient of variation method were used to evaluate the weights of the first- and second-level indicators. The results show the importance ranking of the core perspectives of the ICO balanced scorecard in the following order: patient, internal process, learning and growth, and financial. The weight-based analysis identified the importance ranking of all indicators and pointed to the areas that require close attention in future ICO planning and management.

Effect of Lactobacillus acidophilus KLDS 1.0738 on miRNA expression in in vitro and in vivo models of ß-lactoglobulin allergy.

This study aims to investigate the correlation between the ability of L. acidophilus to modulate miRNA expression and prevent Th17-dominated ß-lactoglobulin (ß-Lg) allergy. In vitro immunomodulation was evaluated by measuring splenocyte proliferation, Th17-related immune response and miRNA expression in ß-Lg-sensitized splenocytes cultured with live L. acidophilus. Next, the allergic mouse model was used to evaluate anti-allergy capability of lactobacilli. The ß-Lg challenge led to induction of up-regulation of miR-146a, miR-155, miR-21 and miR-9 expression in both in vivo and in vitro, along with increased Th17-related cytokine levels and mRNA expression of RORγt and IL-17. However, treatment of live L. acidophilus significantly suppressed hypersensitivity responses and Th17 cell differentiation. Moreover, administration of live L. acidophilus reduced expression of four miRNAs, especially miR-146a and miR-155. In addition, the decreased expression of the miRNAs in the spleen of the L. acidophilus-treated group was closely associated with decrease of IL-17 and RORγt mRNA expression.