Investigating age-related differences in muscles of Kazakh horse through transcriptome analysis.

This study conducted transcriptome sequencing on the skeletal muscles of three different anatomical locations across various growth stages to investigate the impact of ages on crucial candidate genes and molecular mechanisms associated with muscle development in Kazakh horses. Sixteen Kazakh horses were selected, and they were divided into four age groups, each with four biological replicates. Tissue samples from the longest dorsal muscle, abdominal muscle, and diaphragm muscle were collected for analysis. The results revealed differential mRNA expression in the longest dorsal muscle between the eight-month group (Group O) and the 10-year group (Group F), with 434 up-regulated and 322 down-regulated genes. In the abdominal muscle, there were 125 up-regulated and 127 down-regulated genes, while in the diaphragm muscle, there were 73 up-regulated and 70 down-regulated genes. In this study, GO enrichment analysis focused on biological processes. KEGG pathway analysis highlighted the Oxidative Phosphorylation pathway for the longest dorsal muscle, annotating 37 differentially expressed genes (DEGs), including ATP5PF, NDUFB8, and ATP5MG, all of which were down-regulated. For the abdominal muscle, the ECM-receptor interaction pathway was enriched, annotating 7 DEGs such as COL4A2, COL4A1, and ITGA5. In the diaphragm muscle, the Hippo signaling pathway was enriched, annotating 6 DEGs, including SERPINE1, RASSF1, and FZD10. This study provides robust data support and a theoretical foundation for a comprehensive understanding of the influence of age on skeletal muscle development in horses.

Differential age-related transcriptomic analysis of ovarian granulosa cells in Kazakh horses.

Introduction: The Kazakh horse, renowned for its excellence as a breed, exhibits distinctive reproductive traits characterized by early maturity and seasonal estrus. While normal reproductive function is crucial for ensuring the breeding and expansion of the Kazakh horse population, a noteworthy decline in reproductive capabilities is observed after reaching 14 years of age. Methods: In this study, ovarian granulosa cells (GCs) were meticulously collected from Kazakh horses aged 1, 2, 7, and above 15 years old (excluding 15 years old) for whole transcriptome sequencing. Results: The analysis identified and selected differentially expressed mRNAs, lncRNAs, miRNAs, and circRNAs for each age group, followed by a thorough examination through GO enrichment analysis. The study uncovered significant variations in the expression profiles of mRNAs, lncRNAs, miRNAs, and circRNAs within GCs at different stages of maturity. Notably, eca-miR-486-3p and miR-486-y exhibited the highest degree of connectivity. Subsequent GO, KEGG, PPI, and ceRNA network analyses elucidated that the differentially expressed target genes actively participate in signaling pathways associated with cell proliferation, apoptosis, and hormonal regulation. These pathways include but are not limited to the MAPK signaling pathway, Hippo signaling pathway, Wnt signaling pathway, Calcium signaling pathway, Aldosterone synthesis and secretion, Cellular senescence, and NF-kappa B signaling pathway-essentially encompassing signal transduction pathways crucial to reproductive processes. Discussion: This research significantly contributes to unraveling the molecular mechanisms governing follicular development in Kazakh horses. It establishes and preliminarily validates a differential regulatory network involving lncRNA-miRNA-mRNA, intricately associated with processes such as cell proliferation, differentiation, and apoptosis and integral to the developmental intricacies of stromal follicles. The findings of this study provide a solid theoretical foundation for delving deeper into the realm of reproductive aging in Kazakh mares, presenting itself as a pivotal regulatory pathway in the context of horse ovarian development.

Transcriptome identification of differential mammary genes of Kazakh horses during early pregnancy.

Kazakh mares have attracted widespread attention with their outstanding lactation traits. Lactation is a complex dynamic process regulated by multiple factors. The extensive application of transcriptome sequencing technology enables researchers to further explore this biological issue. This study selected three pregnant and three non-pregnant Kazakh mares as the research subject. Their mammary glands were taken for transcriptome sequencing. The results show that there are 9 lncRNAs and 122 mRNAs differentially expressed between the two groups. GO enrichment analysis shows that there are 175 molecular functions, 59 cellular components, and 555 biological processes, including cellular hormone metabolic process, hormone catabolic process, and I-kappaB kinase/NF-kappaB signaling. KEGG enrichment analysis exhibits that these differential genes are mainly enriched in the NF-kappa B signaling pathway, steroid hormone biosynthesis, breast cancer, ECM-receptor interaction, and MAPK signaling pathway. WNT4, DPP4, and NFKBIA are key nodes regulating breast activation. Conclusions: Through the comparative analysis of the transcriptome data of mammary tissues of pregnant and non-pregnant mares, relevant differentially expressed genes are screened and analyzed. This study provides valuable fundamental data for investigating candidate genes related to the lactation regulation and mammogenesis of Kazakh horses.

Effects of PEG in patients with esophageal squamous cell carcinoma during concurrent chemoradiotherapy: a prospective study.

BACKGROUND AND AIMS: This prospective study aimed to compare the changes in nutritional status and adverse events among patients with esophageal squamous cell carcinoma who received enteral nutrition through oral intake, PEG, and an enteral nasogastric tube (NGT) during concurrent chemoradiotherapy (CCRT). METHODS: Of 141 included patients, 38, 74, and 29 patients were fed through oral intake, PEG, and NGTs, respectively. The clinical characteristics and baseline nutritional status of the 3 groups were recorded and analyzed. The Patient-Generated Subjective Global Assessment score, skeletal muscle index, and quality of life were evaluated before and after CCRT; the incidence of adverse events during feeding using PEG and NGTs was also recorded. The correlations among the different nutritional pathways and the CCRT-related adverse events (eg, radiation esophagitis and myelosuppression) were assessed. RESULTS: At baseline, the oral intake group had a significantly better nutritional status and lower disease stage than those in the PEG and NGT groups. However, during CCRT, the oral intake group exhibited the most significant decreases in weight and skeletal muscle index. The synchronous chemotherapy completion rate was the highest in the PEG group. Multivariate analysis showed that the planning tumor volume and oral intake and NGT feeding pathways were associated with radiation esophagitis of at least grade 2. CONCLUSIONS: We found that PEG effectively maintained the body weight and skeletal muscle index of patients with esophageal cancer during CCRT. PEG also improved the synchronous chemotherapy completion rate and reduced the occurrence of at least grade 2 radiation esophagitis. (Clinical trial registration number: NCT04199832.).

Artificial-intelligence-based computed tomography histogram analysis predicting tumor invasiveness of lung adenocarcinomas manifesting as radiological part-solid nodules.

Background: Tumor invasiveness plays a key role in determining surgical strategy and patient prognosis in clinical practice. The study aimed to explore artificial-intelligence-based computed tomography (CT) histogram indicators significantly related to the invasion status of lung adenocarcinoma appearing as part-solid nodules (PSNs), and to construct radiomics models for prediction of tumor invasiveness. Methods: We identified surgically resected lung adenocarcinomas manifesting as PSNs in Peking University People's Hospital from January 2014 to October 2019. Tumors were categorized as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) by comprehensive pathological assessment. The whole cohort was randomly assigned into a training (70%, n=832) and a validation cohort (30%, n=356) to establish and validate the prediction model. An artificial-intelligence-based algorithm (InferRead CT Lung) was applied to extract CT histogram parameters for each pulmonary nodule. For feature selection, multivariate regression models were built to identify factors associated with tumor invasiveness. Logistic regression classifier was used for radiomics model building. The predictive performance of the model was then evaluated by ROC and calibration curves. Results: In total, 299 AIS/MIAs and 889 IACs were included. In the training cohort, multivariate logistic regression analysis demonstrated that age [odds ratio (OR), 1.020; 95% CI, 1.004-1.037; p=0.017], smoking history (OR, 1.846; 95% CI, 1.058-3.221; p=0.031), solid mean density (OR, 1.014; 95% CI, 1.004-1.024; p=0.008], solid volume (OR, 5.858; 95% CI, 1.259-27.247; p = 0.037), pleural retraction sign (OR, 3.179; 95% CI, 1.057-9.559; p = 0.039), variance (OR, 0.570; 95% CI, 0.399-0.813; p=0.002), and entropy (OR, 4.606; 95% CI, 2.750-7.717; p<0.001) were independent predictors for IAC. The areas under the curve (AUCs) in the training and validation cohorts indicated a better discriminative ability of the histogram model (AUC=0.892) compared with the clinical model (AUC=0.852) and integrated model (AUC=0.886). Conclusion: We developed an AI-based histogram model, which could reliably predict tumor invasiveness in lung adenocarcinoma manifesting as PSNs. This finding would provide promising value in guiding the precision management of PSNs in the daily practice.

Expanded catalogue of metagenome-assembled genomes reveals resistome characteristics and athletic performance-associated microbes in horse.

BACKGROUND: As a domesticated species vital to humans, horses are raised worldwide as a source of mechanical energy for sports, leisure, food production, and transportation. The gut microbiota plays an important role in the health, diseases, athletic performance, and behaviour of horses. RESULTS: Here, using approximately 2.2 Tb of metagenomic sequencing data from gut samples from 242 horses, including 110 samples from the caecum and 132 samples from the rectum (faeces), we assembled 4142 microbial metagenome-assembled genomes (MAG), 4015 (96.93%) of which appear to correspond to new species. From long-read data, we successfully assembled 13 circular whole-chromosome bacterial genomes representing novel species. The MAG contained over 313,568 predicted carbohydrate-active enzymes (CAZy), over 59.77% of which had low similarity match in CAZy public databases. High abundance and diversity of antibiotic resistance genes (ARG) were identified in the MAG, likely showing the wide use of antibiotics in the management of horse. The abundances of at least 36 MAG (e.g. MAG belonging to Lachnospiraceae, Oscillospiraceae, and Ruminococcus) were higher in racehorses than in nonracehorses. These MAG enriched in racehorses contained every gene in a major pathway for producing acetate and butyrate by fibre fermentation, presenting potential for greater amount of short-chain fatty acids available to fuel athletic performance. CONCLUSION: Overall, we assembled 4142 MAG from short- and long-read sequence data in the horse gut. Our dataset represents an exhaustive microbial genome catalogue for the horse gut microbiome and provides a valuable resource for discovery of performance-enhancing microbes and studies of horse gut microbiome. Video Abstract.

Plasma Non-targeted Metabolomics Analysis of Yili Horses Raced on Tracks With Different Surface Hardness.

In this study, the plasma non-targeted metabolomics of Yili horses were characterized before and after exercise on tracks that differed in surface hardness to better understand exercise-related biochemical changes. Blood samples were obtained from eight trained Yili horses before and immediately after exercise. Samples were used for metabolomic analysis by ultra-performance liquid chromatography-Q-EXACTIVE mass spectrometry. In total, 938 significantly different metabolites involving sugar, lipid, and amino acid metabolism were detected in the plasma, with significant increases in glucose, glucoheptanoic acid, lactic acid, malic acid, and methylmalonic acid and significant decreases in creatinine, D-tryptophan, carnitine, and citric acid after exercise. Among these metabolites, acetylcarnitine, tuliposide, vitamin C, and methylmalonic acid showed regular changes in concentration after exercise on tracks that differed in surface hardness, providing new insights into equine exercise physiology. The findings indicated the potential of vitamin C and methylmalonic acid as novel biomarkers of equine locomotor injury.

Nutritional Risk and Assessment for Patients with Cancer Pain.

BACKGROUND: The incidence of nutritional risk and malnutrition are high in patients with cancer pain. It is very important to choose an effective tool to identify these patients promptly. However, few studies have discussed this issue. The primary objective of this study is to clarify the similarities and differences between the two nutritional screening and assessment tools, and to estimate the anthropometry and biochemical indicators of the patients with cancer pain, with a view to provide help for treatment of these patients. METHOD: Data of 146 patients with cancer pain were collected from August 2018 to May 2019 in the Pain Therapy Department of Tianjin Cancer Hospital. The information of numerical rating scale (NRS), nutritional risk screening-2002 (NRS-2002), patient-generated subjective global assessment (PG-SGA), anthropometry and biochemical indicators were collected for pain assessment, nutritional risk screening, and nutritional status assessment. RESULTS: NRS scores had a positive correlation with NRS-2002 (R = 0.273, P = 0.001) and PG-SGA (R = 0.341, P = 0.000) separately. NRS-2002 and PG-SGA had a significant positive correlation with each other (R = 0.468, P = 0.000). NRS-2002 was finished in a shorter time period (4.2 ± 0.8 min vs. 12.8 ± 0.8 min, P = 0.001), while PG-SGA had a higher detection rate of malnutrition (86.3% vs. 65.8%). In the stepwise multiple regression analysis, NRS (0.258, P = 0.001), PA (-0.297, P = 0.000), TP (0.178, P = 0.030) are the indicators of NRS-2002; and NRS (0.317, P = 0.000), PA (ß = 0.288, P = 0.000) and BMI (-0.281, P = 0.000) are the related variables of PG-SGA. The kappa coefficient was lower than 0.4 (kappa value = 0.396) when choosing the score of NRS-2002 ≥ 3 and PG-SGA ≥ 9 as the diagnostic criteria. If choosing the score of NRS-2002 ≥ 2 and PG-SGA ≥ 9, both the correlation coefficient (R = 0.699, P = 0.000) and the kappa coefficient (kappa value = 0.698, P = 0.000) became more coefficient. CONCLUSIONS: Both NRS-2002 and PG-SGA could identify patients with nutritional risk and malnutrition accurately. NRS-2002 is simpler and takes less time to finish, while PG-SGA is more cumbersome with a higher detection rate of malnutrition. NRS, PA, TP and BMI are the most important reference indicators predicting on nutritional risk index and malnutrition status. We recommend NRS-2002 ≥ 2 as the diagnostic criteria in order to avoid missing the patients with nutritional risk.

Enteral Nutrition Combined with Improved-Sijunzi Decoction Shows Positive Effect in Precachexia Cancer Patients: A Retrospective Analysis.

BACKGROUND: Cancer has been considered as the leading cause of death in the world. In patients with cancer, up to 80% display a cachectic period after diagnosis. Cachexia is known to have a negative impact on function, treatment tolerance, higher rates of hospitalizations, and mortality. Anorexia is often used as a warning sign of precachexia. Long-term anorexia may lead to malnutrition and, then, accelerate the occurrence of cachexia. A safe and effective treatment, which can both improve appetite and assist nutritional support for precachexia cancer patients shows its particular important role. METHODS: A retrospective analysis comparing the different therapeutic effects on precachexia cancer patients with anorexia-malnutrition. We recorded 46 patients with the improved-Sijunzi decoction combined with enteral nutrition emulsion (ISJZ group) and 35 patients with single enteral nutrition emulsion (SEN group). The different therapeutic effects of the two groups were observed by recording indicators before and 2 weeks after treatment, including patient-generated subjective global assessment score, quality of life score, Karnofsky performance status scale, Eastern cooperative oncology group scale standard and traditional Chinese medicine syndrome, daily total dietary intake, red blood cells, hemoglobin, prealbumin, albumin, total protein cholinesterase, C-reactive protein, leukocytes, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea nitrogen, and creatinine. RESULTS: ISJZ group exhibited prominent improvement of traditional Chinese medicine syndrome (TCMS), nutritional condition, and quality of life compared with the SEN group (QOL: p=0.0001, PG-SGA: p=0.019, dietary intake: p=0.0001, TCMS: p=0.0001). The levels of HGB (p=0.006), PAlb (p=0.001), Alb (p=0.0001), TP (p=0.008), and ChE (p=0.0001) in the ISJZ group were higher than the SEN group after treatment. Moreover, the ratios of CRP/ALB (p=0.028) and CRP/PALB (p=0.005) in the two groups have obvious differences; they were lower for the ISJZ group than the SEN group. CONCLUSIONS: Enteral nutrition combined with ISJZ decoction is an effective treatment in precachexia cancer patients for the prevention of cachexia. This treatment therapy can alleviate the inflammatory response, improve malnutrition state, and promote the performance status. Tianjin Medical University Cancer Institute and Hospital approved this study (Trial No. 1913).

Baseline nutritional status could be a predictor for radiation esophagitis in esophageal cancer patients undergoing radiotherapy.

BACKGROUND: To investigate the relationship between baseline nutrition status and radiation esophagitis in patients with esophageal cancer treated by radiation therapy. METHODS: A retrospective study was performed on 100 patients with esophageal cancer who was treated with definitive chemoradiotherapy, preoperative chemoradiation and definitive radiotherapy at the Tianjin Medical University Cancer Institute and Hospital from October 2018 and October 2019. We documented the clinical characteristics of patients, including tumor location, clinical stage, treatment, radiation dose, gross tumor volume (GTV), planning tumor volume (PTV) and Atkinson's Dysphagia score (ADS), and we recorded the nutrition status before radiation, including Patient-Generated Subjective Global Assessment (PG-SGA), body mass index (BMI), weight loss percentage in 3 mouths (WL), the level of albumin (ALB), hemoglobin (HB), C-reactive protein (CRP) and Glasgow prognostic score (GPS). These factors were correlated with radiation esophagitis using univariate and multivariate regression analyses. RESULTS: Of 100 patients, 44% patients with PG-SGA score ≥9 at baseline, suggesting severe malnutrition, 41% patients developed grade ≥2 radiation esophagitis. In univariate analysis, dose >40 Gy (P=0.015), PTV ≥495 cm3 (P=0.049), PG-SGA score ≥9 (P=0.001), WL ≥10% (P=0.019) and ALB level <35 g/L (P=0.043) were significantly associated with grade ≥2 radiation esophagitis. Multivariate analysis revealed that PG-SGA score ≥9 (P=0.042) was the independent predictor of radiation esophagitis. CONCLUSIONS: Baseline nutritional status associated with development of grade ≥2 radiation esophagitis in patients with esophageal cancer undergoing radiotherapy.

Serum IGFBP2 Level Is a New Candidate Biomarker of Severe Malnutrition in Advanced Lung Cancer.

Objectives: This study aimed to analyze and evaluate serum insulin-like growth factor-binding protein 2 (IGFBP2) levels as a new biomarker of severe malnutrition in patients with advanced lung cancer.Design and methods: This prospective study involved 59 patients with advanced lung cancer. We detected serum IGFBP2 level by using enzyme-linked immunosorbent assay and analyzed its relationship to clinical characteristics, nutritional status, Glasgow prognostic score (GPS), and survival. Serum albumin and C-reactive protein (CRP) levels were measured, and nutritional status was assessed using Patient-Generated Subjective Global Assessment (PG-SGA). The best cutoff point value for serum IGFBP2 level was established using receiver operating characteristic analysis. Kaplan-Meier method was utilized to analyze the survival curves.Results: Serum IGFBP2 levels were elevated in patients with advanced lung cancer and severe malnutrition. The best cutoff value for serum IGFBP2 level was determined at 363 ng/ml, which could diagnose severe malnutrition with 73.3% sensitivity and 70.5% specificity and was found to be related to albumin, CRP, and GPS. Patients whose serum IGFBP2 levels were higher than 363 ng/ml had poor survival outcome.Conclusion: This study demonstrates the remarkably association between higher serum level of IGFBP2 and severe malnutrition, albumin, CRP, GPS, and survival. Hence, serum IGFBP2 level can be used as a potential biomarker for diagnosis of severe malnutrition in patients with advanced lung cancer.

Correlation Analysis Between Stride Characteristics and Racing Ability of 2-year-old Yili Horses in Track Conditions.

In this study, we aimed to explore correlations among stride characteristics, time records, and bonus amounts to identify relevant indices for evaluating racing abilities of 2-year-old Yili horses. In total, 41 and 26 Yili horses were enrolled in the 1600 and 3600 m races, respectively. This experiment was performed by measuring their stride characteristics using a high-speed video and collecting time records during the competition and the bonus amounts. The results showed that the 2-year-old Yili horses' stride length (SL), stride frequency (SF), middle SL (mid SL), hind limb SL (hind SL), forelimb SL (fore SL), aerial duration SL (AD SL), stride angle, and advanced placement (AP) between the leading hind limb and trailing forelimb (AP LH-TF) were significantly and positively correlated with the bonus (P < .01). The bonus group had significantly higher values for these variables than the nonbonus group (P < .05); the stance duration and the overlap between LH and TF (overlap LH-TF) were negatively correlated with the bonus (P < .01), and the bonus group had a significantly lower overlap LH-TF value than the non-bonus group (P < .01). These findings indicated that 2-year-old Yili horses with greater SL, SF, mid SL, fore SL, AD SL, and stride angle values have better racing abilities. Likewise, smaller stance and overlap LH-TF values correspond to better horse racing abilities. The swing trailing hind limb, mid SL, AP LH-TF, and SF were filtrated by stepwise regression analysis as the primary indices for evaluating the racing ability of 2-year-old Yili horses.