A Plasma Exosomal Metabolic Profiling of Nonalcoholic Fatty Liver Disease Patients Complicated with Impaired Fasting Glucose.

BACKGROUND/AIMS: Nonalcoholic fatty liver disease is considered as the hepatic manifestation of metabolic syndrome. Detection of circulating exosomes together with metabolomic analysis of their cargo would provide early signals for metabolic derangements and complications associated with nonalcoholic fatty liver disease. Therefore, this study profiled exosomal metabolome of patients with nonalcoholic fatty liver disease and impaired fasting glucose. MATERIALS AND METHODS: Plasma exosomes were extracted from nonalcoholic fatty liver disease patients with or without impaired fasting glucose through differential ultracentrifugation. Their metabolite profiles were examined by ultrahigh-performance liquid chrom atography-quadrupole time-of-flight mass spectrometry. Pathway analysis was carried out on platform MetaboAnalyst 4.0. RESULTS: Thirty-nine patients were enrolled, including nonalcoholic fatty liver disease-alone group (n = 26) and age-and gender-comparable nonalcoholic fatty liver disease plus impaired fasting glucose group (n = 13). Although less than and different from their plasma counterparts, a total of 10 significantly differential exosomal metabolites were identified. Nonalcoholic fatty liver disease plus impaired fasting glucose group had higher concentrations of linoleic acid, palmitamide, stearamide, and oleamide, as well as a lower concentration of phosphatidylethanolamine [20:5(5Z,8Z,11Z,14Z,17Z)/20:5(5Z,8Z,11Z,14Z,17Z)]. Pathway analysis showed an obviously changed metabolism of linoleic acid. CONCLUSION: Metabolomic analysis of plasma exosomes revealed a distinct change in fatty acids and related pathways in nonalcoholic fatty liver disease patients with impaired fasting glucose. These preliminary results provide a metabolomic snapshot and basis for further investigation of exosome biology for these patients.

A Plasma Exosomal Metabolic Profiling of Nonalcoholic Fatty Liver Disease Patients Complicated with Impaired Fasting Glucose.

BACKGROUND/AIMS: Nonalcoholic fatty liver disease is considered as the hepatic manifestation of metabolic syndrome. Detection of circulating exosomes together with metabolomic analysis of their cargo would provide early signals for metabolic derangements and complications associated with nonalcoholic fatty liver disease. Therefore, this study profiled exosomal metabolome of patients with nonalcoholic fatty liver disease and impaired fasting glucose. MATERIALS AND METHODS: Plasma exosomes were extracted from nonalcoholic fatty liver disease patients with or without impaired fasting glucose through differential ultracentrifugation. Their metabolite profiles were examined by ultrahigh-performance liquid chrom atography-quadrupole time-of-flight mass spectrometry. Pathway analysis was carried out on platform MetaboAnalyst 4.0. RESULTS: Thirty-nine patients were enrolled, including nonalcoholic fatty liver disease-alone group (n = 26) and age-and gender-comparable nonalcoholic fatty liver disease plus impaired fasting glucose group (n = 13). Although less than and different from their plasma counterparts, a total of 10 significantly differential exosomal metabolites were identified. Nonalcoholic fatty liver disease plus impaired fasting glucose group had higher concentrations of linoleic acid, palmitamide, stearamide, and oleamide, as well as a lower concentration of phosphatidylethanolamine [20:5(5Z,8Z,11Z,14Z,17Z)/20:5(5Z,8Z,11Z,14Z,17Z)]. Pathway analysis showed an obviously changed metabolism of linoleic acid. CONCLUSIONS: Metabolomic analysis of plasma exosomes revealed a distinct change in fatty acids and related pathways in nonalcoholic fatty liver disease patients with impaired fasting glucose. These preliminary results provide a metabolomic snapshot and basis for further investigation of exosome biology for these patients.

Immunoregulation mechanism of VEGF signaling pathway inhibitors and its efficacy on the kidney.

Angiogenesis and immunosuppression are closely related pathophysiologic processes. Widely prescribed in malignant tumor and proliferative retinal lesions, VEGF signaling pathway inhibitors may cause hypertension and renal injury in some patients, presenting with proteinuria, nephrotic syndrome, renal failure and thrombotic microangiopathy. VEGF signaling pathway inhibitors block the action of both VEGF-A and VEGF-C. However, VEGF-A and VEGF-C produced by podocytes are vital to maintain the physiological function of glomerular endothelial cells and podocytes. There is still no effective treatment for kidney disease associated with VEGF signaling pathway inhibitors and some patients have progressive renal failure even after withdrawal of the drug. Recent studies reveal that blocking of VEGF-A and VEGF-C can activate CD4 +and CD8+ T cells, augment antigen-presenting function of dendritic cells, enhance cytotoxicity of macrophages and initiate complement cascade activation. VEGF and VEGFR are expressed in immune cells, which are involved in the immunosuppression and cross-talk among immune cells. This review summarizes the expression and function of VEGF-A and VEGF-C in the kidney. The current immunoregulation mechanisms of VEGF signaling pathway inhibitors are reviewed. Finally, combinate strategies are summarized to highlight the proposal for VEGF signaling pathway inhibitors.

Effects of the Education and Training Programme for Excellent Physicians in China on medical students' academic performance: a cross-sectional study.

OBJECTIVES: To evaluate the effect of the Education and Training Programme for Excellent Physicians in China on medical students' academic performance. DESIGN: This study is a secondary analysis of data from a cross-sectional survey of China Medical Student Survey (CMSS, 2021) and administrative data of the first-stage Medical Licensing Examination-the Standardised Competence Test for Clinical Medicine Undergraduates (the Test, 2021). CMSS used a stratified sampling process, with all undergraduate clinical medicine students participating voluntarily. SETTING: This programme is implemented at the class level within reformed medical schools, targeting undergraduate students in 5-year clinical medicine in China. The reformed medical schools run pilot classes and traditional classes simultaneously. The analytic sample was a total of 12 243 observations from pilot and traditional classes in 34 medical schools which implemented the reform across 19 provinces in China. METHODS: This study applied the propensity score matching method to estimate the effect of the reform by comparing the scores of the Test between pilot and traditional classes within the same medical schools. We further explored the potential mechanisms driving the effect from two facets of the Test: medical knowledge modules and cognitive levels. RESULTS: Pilot classes outperformed traditional classes by 0.104 SD on the Test (95% CI 0.037 to 0.171). Improvements were seen in basic medicine and clinical medicine modules (0.109 and 0.101 SD, respectively) and cognitive levels of memorisation and application (0.116 and 0.111 SD, respectively). CONCLUSION: These results suggest that the reform had a significant positive impact on medical students' academic performance. Based on the components of this reform and the potential mechanism analysis of the two facets, this study indicates that curriculum reform in integrated learning and teaching methods reform in the adoption of problem-based learning may have been the possible drivers of this positive impact.

Supreme laryngeal mask airway for cesarean section under general anesthesia: a 10-year retrospective cohort study.

Background: Previous research showed the use of supraglottic airways in obstetric anesthesia. The relevant evidence of laryngeal mask airway (LMA) on maternal and neonatal outcomes is still limited. We aimed to assess the maternal and neonatal outcomes when the LMA Supreme was used for cesarean section under general anesthesia. Methods: We included all patients who underwent general anesthesia for cesarean section between January 2010 and December 2019. Propensity score matching was used to reduce potential bias from non-random selection of airway intervention. The primary outcome was adverse maternal and neonatal outcomes defined as maternal regurgitation, aspiration, hypoxemia, and low neonatal Apgar scores. Secondary outcomes included patient admission to the intensive care unit, neonate required tracheal intubation, external cardiac massage, and admission to the neonatal intensive care unit. Results: A total of 723 patients were included in the analysis; of whom, 221 received Supreme laryngeal mask airway (LMA group) and 502 were intubated with an endotracheal tube (ETT group). After propensity score matching, 189 patients remained in each group. No episode of regurgitation and aspiration occurred in both groups. There was no difference in the rates of Apgar score below 7 at 1 min (14.3% LMA group vs. 15.3% ETT group, OR 0.931, 95% CI 0.574 to 1.510, P = 0.772) and 5 min (3.7% vs. 4.2%, OR 0.875, 95% CI 0.324 to 2.365, P = 0.792). No difference was observed in the secondary outcomes between the two groups. Conclusion: The LMA Supreme was not associated with higher adverse maternal and neonatal outcomes when compared to an endotracheal tube for cesarean section under general anesthesia. It might be considered an alternative to tracheal intubation in obstetric practice.

Metagenomic analysis reveals hidden links between gut microbes and habitat adaptation among cave and surface dwelling Sinocyclocheilus species.

Intestinal microbes are closely related to vital host functions such as digestion and nutrient absorption, which play important roles in enhancing host adaptability. As a natural "laboratory", caves provide an outstanding model for understanding the significance of gut microbes and feeding habits in the habitat adaptability of hosts. However, research on the relationship between gut microbes, feeding habits, and the adaptability of troglobites remains insufficient. In this study, we compared the characteristics of the intestinal microbes of Sinocyclocheilus cavefish and surface fish and further established the relationship between intestinal and habitat microbes. Furthermore, we conducted environmental DNA (eDNA) (metabarcoding) analysis of environmental samples to clarify the composition of potential food resources in the habitats of the Sinocyclocheilus cavefish and surface fish. Results showed that the structure of the Sinocyclocheilus gut microbes was more related to ecological type (habitat type) than phylogenetic relationships. While horizontal transfer of habitat microbes was a source of gut microbes, hosts also showed strong selection for inherent microbes as dominant microorganisms. Differences in the composition and structure of gut microbes, especially dominant microbes, may enhance the adaptability of the two Sinocyclocheilus fish types from the perspectives of food intake, nutrient utilization, and harmful substance metabolism, suggesting that food resources, predation patterns, intestinal flora, digestive and absorptive capacity, and feeding habits and preferences are linked to habitat adaptability. These results should facilitate our understanding of the significance of fish gut microbes to habitat adaptation and provide a new perspective for studying the adaptive mechanisms of cavefish.

The effect of an information intervention on the career commitment of medical students: evidence from a randomized experiment.

Introduction: The needs-based shortage of healthcare workers is severe worldwide and it would be exacerbated if many medical students switch to other careers after graduation. Maintaining and improving the career commitment of medical students, which could be a feasible, effective, and scalable way to reduce the attrition rate, is essential in medical education. We designed a randomized experiment to test whether an information intervention based on role modeling could enhance medical students' career commitment. Methods: In the randomized experiment, the sample (N = 36,482) was divided into the treatment group (N = 18,070) and the control group (N = 18,412). The intervention information consisted of image-text messages on Zhong Nanshan, who is an inspiring role model for he went to the frontline of COVID-19 in the most critical circumstances and received praise and affirmation from the public. Α difference-in-differences model was employed to identify the effect of the information intervention. Heterogeneous treatment effects were identified using sub-sample analyses. Results: The results showed that the information intervention statistically significantly reduced medical students' dropout intention by 2.7 percentage points (95% CI: -0.037 to -0.016, t = -4.95, p < 0.001), equivalent to 14.6% of the control group mean. This estimate indicates that the information intervention could significantly increase the career commitment of medical students. Finally, male and senior students were influenced more than their female and junior counterparts, which can be explained by their relatively high dropout intention. Conclusion: Role model-based information intervention improves the career commitment of medical students. The underlying behavioral model is that, when students use a role model as their reference point, they consider dropout as a substantial welfare loss. Role modeling is an effective way to improve the career commitment of medical students, especially for males and senior students.

Comparison of two frailty indices in predicting life-threatening morbidity and mortality among older patients undergoing elective high-risk abdominal surgery.

Background: Frailty predicts an increased risk of postoperative morbidity and mortality. Comparison of the predictive performance between two deficit accumulation models of frailty, the modified frailty index (mFI) and the revised-Risk Analysis Index (RAI-rev), is poorly understood. This study compared the predictive abilities of the above two frailty indices in predicting life-threatening morbidity and mortality among older patients following elective high-risk abdominal surgery. Methods: This retrospective cohort study extracted perioperative data of older patients (age ≥65 years) undergoing elective high-risk abdominal surgery at a single institution between January 2018 and December 2020. Preoperative frailty was screened by mFI and RAI-rev scoring systems. The primary outcome was the composite of postoperative life-threatening morbidity and mortality during hospitalization. Multivariable logistic regression analyses were performed to investigate the association of the two frailty indices with the primary outcome. Receiver-operating characteristic (ROC) curve was employed to test the predictive performances of the two frailty instruments in predicting the composite primary outcome. The difference between the area under the curves (AUCs) was assessed by DeLong's test. Results: 1,132 older patients (mean age, 73.4 ± 6.2 years; 63.9% male) were included. Of these, 107 (9.5%) developed postoperative life-threatening morbidity and mortality. In multivariable logistic regression analyses, rising continuous frailty scores (mFI: adjusted OR 1.319 per 0.09-point increase in score, 95% CI 1.151-1.511, p < 0.001; RAI-rev: adjusted OR 1.052 per 1-point increase in score, 95% CI 1.018-1.087, p = 0.002) as well as dichotomized frailty measures (mFI ≥0.27: adjusted OR 2.059, 95% CI 1.328-3.193, p = 0.001; RAI-rev ≥45: adjusted OR 1.862, 95% CI 1.188-2.919, p = 0.007) were associated with increased odds of the primary outcome separately. ROC curve analysis showed that the discrimination of mFI and RAI-rev scores for the life-threatening morbidity and mortality was poor and comparable (AUC: 0.598 [95% CI 0.569-0.627] vs. 0.613 [95% CI 0.583-0.641]; DeLong's test: Z = 0.375, p = 0.7075). Conclusion: High mFI and RAI-rev scores were associated with an increased risk of life-threatening morbidity and mortality in older patients undergoing elective high-risk abdominal surgery. However, both frailty indices displayed poor discrimination for postoperative life-threatening morbidity and mortality.

The Effects of Diatomite as an Additive on the Macroscopic Properties and Microstructure of Concrete.

Diatomite is a siliceous sedimentary rock containing amorphous silica, which can be used as a green mineral admixture to improve the properties of concrete. This study investigates the affecting mechanism of diatomite on concrete performance by macro and micro tests. The results indicate that diatomite can reduce the fluidity of concrete mixture and change its water absorption, compressive strength, resistance to chloride penetration (RCP), porosity, and microstructure. The low fluidity of concrete mixture containing diatomite can reduce workability. With increasing diatomite as partial replacement for cement in concrete, water absorption of concrete decreases before increasing, while compressive strength and RCP rise first and then drop. When diatomite is added to the cement at a content of 5% by weight, the concrete has the lowest water absorption and the highest compressive strength and RCP. Through the mercury intrusion porosimetry (MIP) test, we determined that the addition of 5% diatomite reduces the porosity of concrete from 12.68% to 10.82% and changes the proportion of pores with different sizes in concrete, the proportion of harmless and less harmful pores increases, and the proportion of harmful pores reduces. Based on the microstructure analysis, the SiO2 in diatomite can react with CH and produce C-S-H. C-S-H is responsible for developing concrete because it fills pores and cracks, forms a platy structure, and makes the concrete much denser, thereby improving its macroscopic performance and microstructure.

Genome-Wide DNA Methylation Differences between Bos indicus and Bos taurus.

Disease risk is a persistent problem in domestic cattle farming, while economic traits are the main concern. This study aimed to reveal the epigenetic basis for differences between zebu (Bos indicus) and taurine cattle (Bos taurus) in disease, disease resistance, and economic traits, and provide a theoretical basis for the genetic improvement of domestic cattle. In this study, whole genome bisulfite sequencing (WGBS) was used to analyze the whole-genome methylation of spleen and liver samples from Yunnan zebu and Holstein cattle. In the genome-wide methylation pattern analysis, it was found that the methylation pattern of all samples was dominated by the CG type, which accounted for >94.9%. The DNA methylation levels of different functional regions and transcriptional elements in the CG background varied widely. However, the methylation levels of different samples in the same functional regions or transcriptional elements did not differ significantly. In addition, we identified a large number of differentially methylation region (DMR) in both the spleen and liver groups, of which 4713 and 4663 were annotated to functional elements, and most of them were annotated to the intronic and exonic regions of genes. GO and KEGG functional analysis of the same differentially methylation region (DMG) in the spleen and liver groups revealed that significantly enriched pathways were involved in neurological, disease, and growth functions. As a result of the results of DMR localization, we screened six genes (DNM3, INPP4B, PLD, PCYT1B, KCNN2, and SLIT3) that were tissue-specific candidates for economic traits, disease, and disease resistance in Yunnan zebu. In this study, DNA methylation was used to construct links between genotypes and phenotypes in domestic cattle, providing useful information for further screening of epigenetic molecular markers in zebu and taurine cattle.

Birth-and-death evolution of ribonuclease 9 genes in Cetartiodactyla.

RNase9 plays a reproductive function and has been recognized as an important member of the ribonuclease (RNase) A superfamily, a gene family that is widely used as a model for molecular evolutionary studies. Here, we identified 178 RNase9 genes from 95 Cetartiodactyla species that represent all four lineages and 21 families of this clade. Unexpectedly, RNase9 experienced an evolutionary scenario of "birth and death" in Ruminantia, and expression analyses showed that duplicated RNase9A and RNase9B genes are expressed in reproductive tissues (epididymis, vas deferens or prostate). This expression pattern combined with the estimate that these genes duplicated during the middle Eocene, a time when Ruminantia become a successful lineage, suggests that the RNase9 gene duplication might have been advantageous for promoting sperm motility and male fertility as an adaptation to climate seasonality changes of this period. In contrast, all RNase9 genes were lost in the Cetacean lineage, which might be associated with their high levels of prostatic lesions and lower reproductive rates as adaptations to a fully aquatic environment and a balance to the demands of ocean resources. This study reveals a complex and intriguing evolutionary history and functional divergence for RNase9 in Cetartiodactyla, providing new insights into the evolution of the RNaseA superfamily and molecular mechanisms for organismal adaptations to the environment.

Genome-Wide Population Structure and Selection Signatures of Yunling Goat Based on RAD-seq.

Animal diseases impose a huge burden on the countries where diseases are endemic. Conventional control strategies of vaccines and veterinary drugs are to control diseases from a pharmaceutical perspective. Another alternative approach is using pre-existing genetic disease resistance or tolerance. We know that the Yunling goat is an excellent local breed from Yunnan, southwestern China, which has characteristics of strong disease resistance and remarkable adaptability. However, genetic information about the selection signatures of Yunling goats is limited. We reasoned that the genes underlying the observed difference in disease resistance might be identified by investigating selection signatures between two different goat breeds. Herein, we selected the Nubian goat as the reference group to perform the population structure and selection signature analysis by using RAD-seq technology. The results showed that two goat breeds were divided into two clusters, but there also existed gene flow. We used Fst (F-statistics) and π (pi/θπ) methods to carry out selection signature analysis. Eight selected regions and 91 candidate genes were identified, in which some genes such as DOK2, TIMM17A, MAVS, and DOCK8 related to disease and immunity and some genes such as SPEFI, CDC25B, and MIR103 were associated with reproduction. Four GO (Gene Ontology) terms (GO:0010591, GO:001601, GO:0038023, and GO:0017166) were associated with cell migration, signal transduction, and immune responses. The KEGG (Kyoto Encyclopedia of Genes and Genomes) signaling pathways were mainly associated with immune responses, inflammatory responses, and stress reactions. This study preliminarily revealed the genetic basis of strong disease resistance and adaptability of Yunling goats. It provides a theoretical basis for the subsequent genetic breeding of disease resistance of goats.

Study on Nursing Effect of Psychological Intervention on Uremic Hemodialysis Patients.

Aim: Patients in the hemodialysis stage are prone to psychological pressure of depression and anxiety and have resistance, which affects the clinical treatment effect. Effective psychological intervention plays a very important role in improving patients' psychological pressure and patients' compliance. The aim of this study is to explore the nursing effect of psychological intervention on uremic hemodialysis patients. Methods: There were 126 uremic hemodialysis patients admitted to the hospital from August 2020 to December 2021. The patients were randomly divided into the routine nursing care group (n = 63) and psychological intervention group (n = 63). The routine nursing care group received routine nursing care for uremia hemodialysis patients. The psychological intervention group implemented psychological intervention on uremia hemodialysis patients. The methods of psychological intervention mainly include establishing a good nurse-patient relationship, popularizing hemodialysis knowledge, timely psychological counseling for patients, and organizing patient communication meetings. The treatment compliance, Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) of the two groups were compared before and after nursing. SF-36 scale was used to evaluate the quality of life of patients. The incidence of complications and nursing satisfaction were compared between the two groups. Results: The treatment compliance rate and nursing satisfaction of hemodialysis uremic patients in the psychological intervention group were significantly higher than the routine nursing care group. The SAS and SDS of hemodialysis uremia patients in the psychological intervention group were significantly lower than the routine nursing care group after psychological intervention, and SF-36 scale was significantly higher than the routine nursing group. The main complications of uremic hemodialysis patients are hypotension, hyperkalemia, internal fistula occlusion, and infection. Compared with the routine nursing care group, the incidence of complications in the psychological intervention group was significantly reduced. Conclusion: The implementation of psychological nursing intervention for uremic hemodialysis patients have a very significant effect on reducing the incidence of complications and improving anxiety, depression, treatment compliance, and the quality of life and the nursing satisfaction.

Experimental study on deformation characteristics and pore characteristics variation of granite residual soil.

This paper investigates the regularity of microstructural evolution of Shenzhen granite residual soil in an attempt to determine its macrostructural deformation characteristics. The pore distribution and microstructure characteristics of granite residual soil are examined experimentally under different consolidation stresses, coupled with mercury injection tests and scanning electron microscopy. It is found that a microstructure exists in the granite residual soil and that the structural characteristics of granite residual soil in Shenzhen. The calculated pre-consolidation stress and structural yield strength of the granite residual soil are similar, indicating a phenomenon that resembles over-consolidation in the granite residual soil. This is fundamentally different from the mechanism of conventional over-consolidation in soil. It is also found that the relationship between the increment of mercury in soil samples and the stress of the mercury under different consolidation stresses is mainly trimodal. The significance of the research presented in this paper lies in the development of a clear understanding of the influence of the microstructure characteristics of granite residual soil on its macrostructural deformation, thereby providing a theoretical basis for engineering applications involving granite residual soil and the analysis of foundation deformation.

Whole-Genome Analysis Deciphers Population Structure and Genetic Introgression Among Bovine Species.

It is known that throughout history and presently, taurine (Bos taurus) and indicine/zebu (Bos indicus) cattle were crossed with other bovine species (e.g., gayal, gaur, banteng, yak, wisent, and bison). Information on the role of interspecific hybridization to facilitate faster adaptation of the newly arrived domestic species to new environments is poorly known. Herein, we collected 266 samples of bovine species of the taurine, zebu, yak, and gaur from West Europe, Southwest China, Indian subcontinent, and Southeast Asia to conduct the principal component analysis (PCA), admixture, gene flow, and selection signature analyses by using SNPs distributed across the bovine autosomes. The results showed that the genetic relationships between the zebu, yak, and gaur mirrored their geographical origins. Three ancestral components of the European taurine, East Asian taurine, and Indian zebu were found in domestic cattle, and the bidirectional genetic introgression between the Diqing cattle and Zhongdian yak was also detected. Simultaneously, the introgressed genes from the Zhongdian yak to the Diqing cattle were mainly enriched with immune-related pathways, and the ENPEP, FLT1, and PIK3CA genes related to the adaptation of high-altitude hypoxia were detected. Additionally, we found the genetic components of the Zhongdian yak had introgressed into Tibetan cattle. The 30 selected genes were detected in Tibetan cattle, which were significantly enriched in the chemokine signaling pathway. Interestingly, some genes (CDC42, SLC39A2, and EPAS1) associated with hypoxia response were discovered, in which CDC42 and SLC39A2 played important roles in angiogenesis and erythropoiesis, and heart function, respectively. This result showed that genetic introgression was one of the important ways for the environmental adaptation of domestic cattle.

Severe functional impairment increases the risk of major morbidity and mortality in older patients after digestive tract surgery: a retrospective cohort study.

PURPOSE: The relationship between the severity of impairment in basic activities of daily living (ADLs) function and postoperative outcomes in older surgical patients remains unclear. This study aimed to clarify the association between the severity of preoperative functional impairment and the composite postoperative outcome of major morbidity and mortality in older patients undergoing digestive tract surgery. METHODS: This was a retrospective cohort study. We collected perioperative data of older patients (age ≥ 65 years) who underwent digestive tract surgery in our institution. The severity of functional impairment was assessed using the Barthel Index scale before surgery. The major morbidity and mortality were defined as Clavien-Dindo grade III or greater postoperative complications during hospital stay. The association between the severity of functional impairment and the major morbidity and mortality was assessed using a multivariable logistic regression model. RESULTS: 131 of 1076 patients (12.2%) developed major morbidity and mortality. After controlling for confounding factors, high Barthel Index scores were correlated with decreased risk of major morbidity and mortality (OR 0.986, 95% CI 0.976-0.997, P = 0.011); preoperative severe (OR 2.862, 95% CI 1.172-6.989, P = 0.021), but not mild or moderate (OR 1.019, 95% CI 0.602-1.726, P = 0.943) functional impairment was independently associated with an increased risk of major morbidity and mortality, when compared with independent functional status. CONCLUSIONS: Preoperative severe functional impairment in basic ADLs was independently associated with a higher risk of major postoperative morbidity and mortality in older patients undergoing digestive tract surgery.

Transcriptome Analysis of Liver Cancer Cell Huh-7 Treated With Metformin.

Metformin is a kind of widely used antidiabetic drug that regulates glucose homeostasis by inhibiting liver glucose production and increasing muscle glucose uptake. Recently, some studies showed that metformin exhibits anticancer properties in a variety of cancers. Although several antitumor mechanisms have been proposed for metformin action, its mode of action in human liver cancer remains not elucidated. In our study, we investigated the underlying molecular mechanisms of metformin's antitumor effect on Huh-7 cells of hepatocellular carcinoma (HCC) in vitro. RNA sequencing was performed to explore the effect of metformin on the transcriptome of Huh-7 cells. The results revealed that 4,518 genes (with log2 fold change > 1 or < -1, adjusted p-value < 0.05) were differentially expressed in Huh-7 cells with treatment of 25-mM metformin compared with 0-mM metformin, including 1,812 upregulated and 2,706 downregulated genes. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses identified 54 classical pathways that were significantly enriched, and 16 pathways are closely associated with cancer, such as cell cycle, DNA replication, extracellular matrix-receptor interaction, and so on. We selected 11 differentially expressed genes, which are closely associated with HCC, to validate their differential expressions through a quantitative real-time reverse transcription-polymerase chain reaction. The result exhibited that the genes of fatty acid synthase, mini-chromosome maintenance complex components 6 and 5, myristoylated alanine-rich C-kinase substrate, fatty acid desaturase 2, C-X-C motif chemokine ligand 1, bone morphogenetic protein 4, S-phase kinase-associated protein 2, kininogen 1, and proliferating cell nuclear antigen were downregulated, and Dual-specificity phosphatase-1 is significantly upregulated in Huh-7 cells with treatment of 25-mM metformin. These differentially expressed genes and pathways might play a crucial part in the antitumor effect of metformin and might be potential targets of metformin treating HCC. Further investigations are required to evaluate the metformin mechanisms of anticancer action in vivo.

Characterization and phylogenetic analysis of the complete mitochondrial genome of Sinocyclocheilus wenshanensis (Cypriniformes: Cyprinidae).

Sinocyclocheilus wenshanensis is a cyprinid fish species endemic to Southwestern China. In this study, we first sequenced and characterized the complete mitochondrial genome (mitogenome) of S. wenshanensis by next-generation sequencing method. The entire length of mitogenome is 16,595 base pairs (bp), containing 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and a control region. Its gene arrangement pattern was identical to other previously reported Sinocyclocheilus fishes. The overall base composition is 31.12% A, 16.63% G, 25.45% T, and 26.80% C, with AT content of 56.57%. Phylogenetic analysis using mitogenome of 26 Cyprinidae fishes showed that S. wenshanensis are closely related to S. aluensis and S. oxycephalus. This work would provide molecular information fundamental to future phylogenetic analyses among Sinocyclocheilus species.

Failure properties and stability monitoring of strip and column cemented gangue backfill bodies under uniaxial compression in constructional backfill mining.

The strip and column cemented gangue backfill bodies (CGBBs) are the main supporting components in the design of constructional backfill mining for coal mining, which determines the stability of goaf. Previous researches have mostly focused on the mechanical properties of column CGBB, but the mechanical properties of strip CGBB are still unclear. Herein, the uniaxial compression experiments for strip and column CGBBs were conducted to compare the failure properties. The acoustic emission (AE) and two types of resistivity monitoring were used to monitor the damage evolution. The effect of the length-height ratio on the mechanical characteristic of strip CGBB was analyzed by discrete element simulation. The results show that the strength and peak strain of strip CGBB under uniaxial compression is higher than those of column CGBB and the strip CGBB shows better ductility. The stress of column CGBB decreases significantly faster than that of strip CGBB at the post-peak stage. The strength and ductility of strip CGBB increase with the increase of length-height ratio. The strip CGBB is destroyed from both ends to the middle under uniaxial compression, and the core bearing area is reduced correspondingly. The AE signal evolution of CGBBs under uniaxial compression before the peak stress contains three stages, and the AE signals of strip CGBB at the peak stress will not rise sharply compared with column CGBB. The resistivity monitoring effect of the horizontally symmetrical conductive mesh is better than that of the axial. The horizontal resistivity increases gradually with the increase of stress under uniaxial compression, and increases sharply at the peak stress, and then drops after the peak stress. The damage constitutive models and the stability monitoring models of the CGBBs are established based on the experimental results. This work would be instructive for the design and stability monitoring of CGBB.

Effect of Fly Ash and Metakaolin on Properties and Microstructure of Magnesium Oxysulfate Cement.

To improve the mechanical performance and lower the production cost of magnesium oxysulfate cement (MOSC), this article investigates the effects of single and compounded addition of metakaolin (MK) and/or fly ash (FA) on the setting time, mechanical strength, water resistance, hydration product, composition, and microstructure of the resulting cement. MOSC samples with different proportions, ranging from 0 to 30 wt.%, of FA and/or MK substituting magnesium oxide (MgO) were prepared. The microstructure was explored by scanning electron microscopy, X-ray diffraction, and mercury intrusion porosimetry. The findings suggest that adding FA can delay the setting of MOSC; however, the effect of adding MK to MOSC was reversed. Furthermore, the phase composition of the MOSC hydration products was unaltered upon adding FA and/or MK, but thicker and longer 517 phase crystals were observed. FA and MK can effectively fill the large pores of MOSC through filling and nucleation effects, reduce the pore size, and form a denser microstructure, thereby improving its mechanical properties. The optimal MOSC sample was found by substituting 10 wt.% of both FA and MK, resulting in a cement that exhibited a short setting time and an incredibly high mechanical strength and density. These findings will further the development of stronger, more cost-efficient, and more water-resistant MOSC products.