SARS-CoV-2 RNAemia as a reliable predictor of long-term mortality among older adults hospitalized in pulmonary intermediate care units: a prospective cohort study.

BACKGROUND: SARS-CoV-2 viremia is associated with disease severity and high risk for in-hospital mortality. However, the impact of SARS-CoV-2 viremia on long-term outcomes in hospitalized patients with COVID-19 is poorly understood. METHODS: We conducted a prospective cohort study and recruited a group of older adult patients with COVID-19 admitted to pulmonary intermediate care units of Peking University Third Hospital during December 2022 and January 2023. The plasma level of SARS-CoV-2 RNA was determined by a standardized RT-PCR technique, and SARS-CoV-2 RNAemia was defined as a plasma viral load ≥ 50 copies/ml. In-hospital and follow-up (180-day) outcome data were collected. RESULTS: A total of 101 patients with an average of 80.4 years were recruited, and 63.4% of them were severe or very severe cases. Twenty-eight patients (27.7%) had SARS-CoV-2 RNAemia, with a median viral RNA load of 422.1 [261.3, 1085.6] copies/ml. Patients with SARS-CoV-2 RNAemia were more likely to develop critical cases and had a higher incidence of sepsis. Accordingly, they had a higher 180-day mortality (57.1% vs. 19.7%, P < 0.001), as well as in-hospital mortality (50.0% vs. 13.7%, P < 0.001), independent of age, disease severity, sepsis, lymphocyte count and C-Reactive protein. In addition, the risk for 180-day mortality increased with the SARS-CoV-2 RNA load in plasma. Plasma cytokines, including IL-6, IL-8 and IL-10, were higher in patients with SARS-CoV-2 RNAemia. CONCLUSIONS: Our study indicates that SARS-CoV-2 RNAemia serves as a useful biomarker for predicting mortality, especially long-term mortality, in older adult patients hospitalized in pulmonary intermediate care units. TRIAL REGISTRATION: Chinese Clinical Trial Registry website (No. ChiCTR2300067434).

Effects of rumen metabolite butyric acid on bovine skeletal muscle satellite cells proliferation, apoptosis and transcriptional states during myogenic differentiation.

Butyric acid, a pivotal short-chain fatty acid in rumen digestion, profoundly influences animal digestive and locomotor systems. Extensive research indicates its direct or indirect involvement in the growth and development of muscle and fat cells. However, the impact of butyric acid on the proliferation and differentiation of bovine skeletal muscle satellite cells (SMSCs) remains unclear. This study aimed to elucidate the effects of butyrate on SMSCs proliferation and differentiation. After isolating, SMSCs were subjected to varying concentrations of sodium butyrate (NaB) during the proliferation and differentiation stages. Optimal treatment conditions (1 mM NaB for 2 days) were determined based on proliferative force, cell viability, and mRNA expression of proliferation and differentiation marker genes. Transcriptome sequencing was employed to screen for differential gene expression between 1 mM NaB-treated and untreated groups during SMSCs differentiation. Results indicated that lower NaB concentrations (≤1.0 mM) inhibited proliferation while promoting differentiation and apoptosis after a 2-day treatment. Conversely, higher NaB concentrations (≥2.0 mM) suppressed proliferation and differentiation and induced apoptosis. Transcriptome sequencing revealed differential expression of genes(ND1, ND3, CYTB, COX2, ATP6, MYOZ2, MYOZ3, MYBPC1 and ATP6V0A4,etc.) were associated with SMSCs differentiation and energy metabolism, enriching pathways such as Oxidative phosphorylation, MAPK, and Wnt signaling. These findings offer valuable insights into the molecular mechanisms underlying butyrate regulation of bovine SMSCs proliferation and differentiation, as well as muscle fiber type conversion in the future study.

Artificial Intelligence Application for Anti-tumor Drug Synergy Prediction.

Currently, the main therapeutic methods for cancer include surgery, radiation therapy, and chemotherapy. However, chemotherapy still plays an important role in tumor therapy. Due to the variety of pathogenic factors, the development process of tumors is complex and regulated by many factors, and the treatment of a single drug is easy to cause the human body to produce a drug-resistant phenotype to specific drugs and eventually leads to treatment failure. In the process of clinical tumor treatment, the combination of multiple drugs can produce stronger anti-tumor effects by regulating multiple mechanisms and can reduce the problem of tumor drug resistance while reducing the toxic side effects of drugs. Therefore, it is still a great challenge to construct an efficient and accurate screening method that can systematically consider the synergistic anti- tumor effects of multiple drugs. However, anti-tumor drug synergy prediction is of importance in improving cancer treatment outcomes. However, identifying effective drug combinations remains a complex and challenging task. This review provides a comprehensive overview of cancer drug synergy therapy and the application of artificial intelligence (AI) techniques in cancer drug synergy prediction. In addition, we discuss the challenges and perspectives associated with deep learning approaches. In conclusion, the review of the AI techniques' application in cancer drug synergy prediction can further advance our understanding of cancer drug synergy and provide more effective treatment plans and reasonable drug use strategies for clinical guidance.

Empagliflozin ameliorates ventricular arrhythmias by inhibiting sympathetic remodeling via nerve growth factor/tyrosine kinase receptor A pathway inhibition.

BACKGROUND AND AIMS: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) can ameliorate arrhythmias; however, the mechanisms underlying their antiarrhythmic effect remain unclear. Therefore, we aimed to test the hypothesis that the SGLT2i empagliflozin (EMPA) ameliorates ventricular arrhythmias caused by myocardial infarction (MI) by inhibiting sympathetic remodeling. METHODS: Male nondiabetic Sprague-Dawley rats were divided into Sham ( n  = 10), MI ( n  = 13), low-EMPA (10 mg/kg/day; n  = 13), and high-EMPA (30 mg/kg/day; n  = 13) groups. Except for the Sham group, MI models were established by ligation of the left anterior descending coronary artery. After 4 weeks, the hearts were removed. Echocardiography, electrical stimulation, hematoxylin-eosin staining and Masson's staining, Western blotting, immunohistochemistry (IHC), and ELISA were performed. RESULTS: Except for left ventricular posterior wall thickness (LVPWT), EMPA treatment significantly ameliorated the left ventricular anterior wall thickness (LVAWT), interventricular septum thickness (IVST), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), and left ventricular ejection fraction (LVEF) in MI rats; there was no statistical difference between the low-EMPA and high-EMPA groups. The threshold for ventricular fibrillation induction and myocardial fibrosis was significantly ameliorated in EMPA-treated rats, and there was no statistical difference between the high-EMPA and low-EMPA groups. EMPA decreased the expression of nerve growth factor (NGF), tyrosine kinase receptor A (TrkA), tyrosine hydroxylase, and growth-associated protein 43 (GAP43) in the left ventricular infarction margin myocardium of MI rats, especially in the high-EMPA group, with a statistically significant difference between the high-EMPA and low-EMPA groups. High-EMPA significantly decreased noradrenaline (NE) levels in the blood of MI rats; however, there was no statistical difference between the low-EMPA and MI groups. CONCLUSION: EMPA ameliorated the occurrence of ventricular arrhythmias in MI rats, which may be related to a reduction in sympathetic activity, inhibition of the NGF/TrkA pathway, inhibition of sympathetic remodeling, and improvement in cardiac function and cardiac structural remodeling.

The role of iron overload and ferroptosis in arrhythmia pathogenesis.

Ferroptosis is a newly discovered form of programmed cell death triggered by intracellular iron overload, which leads to the accumulation of lipid peroxides in various cells. It has been implicated in the pathogenesis and progression of various diseases, including tumors, neurological disorders, and cardiovascular diseases. The intricate mechanism underlying ferroptosis involves an imbalance between the oxidation and antioxidant systems, disturbances in iron metabolism, membrane lipid peroxidation, and dysregulation of amino acid metabolism. We highlight the key molecular mechanisms governing iron overload and ferroptosis, and discuss potential molecular pathways linking ferroptosis with arrhythmias.

A study on the relationship between gut microbiota and intrahepatic cholestasis of pregnancy.

Objective: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease associated with a high incidence of complications in the mid and late stages of gestation. This study investigates differences in the composition of intestinal flora among pregnant women diagnosed with ICP, employing Illumina MiSeq high-throughput sequencing technology. Methods: This case-control study obtained patient data from the hospital information system (HIS) and the laboratory information system (LIS). Fecal samples were collected from 25 pregnant women who did not undergo intestinal preparation before delivery between December 2020 and March 2021. Whole-genome analysis was performed. PCR was used to amplify the 16S rRNA V3-V4 variable region, which was then sequenced. Alpha and beta diversity were computed, and the maternal intestinal flora's abundance and composition characteristics were analyzed. Differences in intestinal flora between the two sample groups were examined. Results: Bacteroides and Proteobacteria exhibited positive correlations with TBIL and IBIL. Betaproteobacteria, Gammaproteobacteria, and Erysipeiotrichi showed positive correlations with TBIL, IBIL, and DBIL, while Lactobacillus, Delftia, and Odoribacter demonstrated positive correlations with ALT. Conclusion: The ICP group displayed significantly higher levels of total bile acid and ALT compared to the control group. The intestinal flora composition comprised four primary phyla: Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria. ICP patients exhibited a lower relative abundance of intestinal flora across different levels of community composition when compared to the control group. Specific correlations between certain intestinal flora and clinical liver parameters were identified.

Elevated CD4+ T Cell Senescence Associates with Impaired Immune Responsiveness in Severe COVID-19.

Aging is a critical risk factor for unfavorable clinical outcomes among COVID-19 patients and may impact vaccine efficacy. However, whether the senescence of T cells is associated with severe COVID-19 outcome in elderly individuals is unclear. Using flow cytometry, we analyzed the frequency of senescent T cells (Tsens) in peripheral blood from 100 hospitalized elderly COVID-19 patients and compared differences between those with mild/moderate and severe/critical illness. We also assessed correlations between the percentage of Tsens and the quantity and quality of spike-specific antibodies by ELISA, neutralizing antibody test kit, and ELISPOT assay respectively, the cytokine production profile of COVID-19 reactive T cells, and plasma soluble factors by cytometric bead array (CBA). Our study found a significantly elevated level of CD4+ Tsens in patients with severe/critical disease compared to those with mild/moderate illness. Patients with a higher level of CD4+ Tsens (>19.78%) showed a decreased survival rate compared to those with a lower level (≤19.78%). This is more pronounced among patients with breakthrough infections. The percentage of CD4+ Tsens was negatively correlated with spike-specific antibody titers, neutralization ability, and COVID-19 reactive IL-2+CD4+ T cells. In addition, spike-specific antibody levels were positively correlated with IL-2 producing T cells and plasma IL-2 amount. Mechanistically, with defective CD40L, T cells from patients with CD4+ Tsens >19.78% were unable to support B cell proliferation and differentiation. Our data demonstrate that the percentage of CD4+ Tsens in peripheral blood may serve as a reliable biomarker for the prognosis of severe COVID-19 patients, especially in breakthrough infections. Therefore, restoring the immune response of CD4+ Tsens may be key to preventing severe illness and improving vaccine efficacy in older adults.

Agreement of zero-heat-flux thermometry with the oesophageal and tympanic core temperature measurement in patient receiving major surgery.

To identify and prevent perioperative hypothermia, most surgical patients require a non-invasive, accurate, convenient, and continuous core temperature method, especially for patients undergoing major surgery. This study validated the precision and accuracy of a cutaneous zero-heat-flux thermometer and its performance in detecting intraoperative hypothermia. Adults undergoing major non-cardiac surgeries with general anaesthesia were enrolled in the study. Core temperatures were measured with a zero-heat-flux thermometer, infrared tympanic membrane thermometer, and oesophagal monitoring at 15-minute intervals. Taking the average value of temperature measured in the tympanic membrane and oesophagus as a reference, we assessed the agreement using the Bland-Altman analysis and linear regression methods. Sensitivity, specificity, and predictive values of detecting hypothermia were estimated. 103 patients and one thousand sixty-eight sets of paired temperatures were analyzed. The mean difference between zero-heat-flux and the referenced measurements was -0.03 ± 0.25 °C, with 95% limits of agreement (-0.52 °C, 0.47 °C) was narrow, with 94.5% of the differences within 0.5 °C. Lin's concordance correlation coefficient was 0.90 (95%CI 0.89-0.92). The zero-heat-flux thermometry detected hypothermia with a sensitivity of 82% and a specificity of 90%. The zero-heat-flux thermometer is in good agreement with the reference core temperature based on tympanic and oesophagal temperature monitoring in patients undergoing major surgeries, and appears high performance in detecting hypothermia.

Sodium Butyrate Induces Mitophagy and Apoptosis of Bovine Skeletal Muscle Satellite Cells through the Mammalian Target of Rapamycin Signaling Pathway.

Sodium butyrate (NaB) is one of the short-chain fatty acids and is notably produced in large amounts from dietary fiber in the gut. Recent evidence suggests that NaB induces cell proliferation and apoptosis. Skeletal muscle is rich in plenty of mitochondrial. However, it is unclear how NaB acts on host muscle cells and whether it is involved in mitochondria-related functions in myocytes. The present study aimed to investigate the role of NaB treatment on the proliferation, apoptosis, and mitophagy of bovine skeletal muscle satellite cells (BSCs). The results showed that NaB inhibited proliferation, promoted apoptosis of BSCs, and promoted mitophagy in a time- and dose-dependent manner in BSCs. In addition, 1 mM NaB increased the mitochondrial ROS level, decreased the mitochondrial membrane potential (MMP), increased the number of autophagic vesicles in mitochondria, and increased the mitochondrial DNA (mtDNA) and ATP level. The effects of the mTOR pathway on BSCs were investigated. The results showed that 1 mM NaB inhibited the mRNA and protein expression of mTOR and genes AKT1, FOXO1, and EIF4EBP1 in the mTOR signaling pathway. In contrast, the addition of PP242, an inhibitor of the mTOR signaling pathway also inhibited mRNA and protein expression levels of mTOR, AKT1, FOXO1, and EIF4EBP1 and promoted mitophagy and apoptosis, which were consistent with the effect of NaB treatment. NaB might promote mitophagy and apoptosis in BSCs by inhibiting the mTOR signaling pathway. Our results would expand the knowledge of sodium butyrate on bovine skeletal muscle cell state and mitochondrial function.

Prognosis of a Chinese patient with chronic lymphocytic leukemia who acquired a TP53 mutation following treatment with a BTK inhibitor.

Chronic lymphocytic leukemia (CLL) is a common type of adult leukemia that occurs in Western countries, and its incidence has gradually increased in China in recent years. The characteristics of CLL are highly heterogeneous. Despite promising response rates achieved with targeted therapy, new targets still need to be expanded due to the heterogeneous of disease. Bruton's tyrosine kinase inhibitor (BTKi) has been used in the treatment of TP53 mutation. In this report, we present a case with myeloid differentiation primary response 88 (MYD88) mutation who developed a TP53 mutation after application of BTKi. Here, the patient was CLL unmutated (U-CLL) with MYD88 (L265P) mutation before initial treatment. After traditional treatment, the effect was not good, and BTKi was used for treatment, then TP53 mutation appeared. It is well known that immunoglobulin heavy chain unmutated (IGHV-U) and TP53 mutation in CLL indicate poor prognosis. The case suggests that whenever TP53 mutation occurs, BTKi is the best choice. This result is considered to be related to signal pathways. We aim to add to the collective knowledge by highlighting this rare cases of CLL with MYD88 (L265P) mutation in an Asian patient.

A randomized controlled trial of iliopsoas plane block vs. femoral nerve block for hip arthroplasty.

BACKGROUND: Iliopsoas plane block (IPB) is a novel analgesic technique for hip surgery that retains quadriceps strength. However, evidence from randomized controlled trial is remains unavailable. We hypothesized that IPB, as a motor-sparing analgesic technique, could match the femoral nerve block (FNB) in pain management and morphine consumption, providing an advantage for earlier functional training in patients underwent hip arthroplasty. METHODS: We recruited ninety patients with femoral neck fracture, femoral head necrosis or hip osteoarthritis who were scheduled for unilateral primary hip arthroplasty were recruited and received either IPB or FNB. Primary outcome was the pain score during hip flexion at 4 h after surgery. Secondary outcomes included quadriceps strength and pain scores upon arrival at post anesthesia care unit (PACU) and at 2, 4, 6, 24, 48 h after surgery, the first time out of bed, total opioids consumption, patient satisfaction, and complications. RESULTS: There was no significant difference in terms of pain score during hip flexion at 4 h after surgery between the IPB group and FNB group. The quadriceps strength of patients receiving IPB was superior to those receiving FNB upon arrival at PACU and at 2, 4, 6 and 24 h after surgery. The IPB group showed a shorter first time out of bed compared to the FNB group. However, there were no significant differences in terms of pain scores within 48 h after surgery, total opioids consumption, patient satisfaction and complications between the two groups. CONCLUSION: IPB was not superior to FNB in terms of postoperative analgesia for hip arthroplasty. However, IPB could serve as an effective motor-sparing analgesic technique for hip arthroplasty, which would facilitate early recovery and rehabilitation. This makes IPB worth considering as an alternative to FNB. TRIAL REGISTRATION: The trial was registered prior to patient enrollment at the Chinese Clinical Trial Registry (ChiCTR2200055493; registration date: January 10, 2022; enrollment date: January 18, 2022; https://www.chictr.org.cn/searchprojEN.html ).

Multi-transcriptomics reveals RLMF axis-mediated signaling molecules associated with bovine feed efficiency.

The regulatory axis plays a vital role in interpreting the information exchange and interactions among mammal organs. In this study on feed efficiency, it was hypothesized that a rumen-liver-muscle-fat (RLMF) regulatory axis exists and scrutinized the flow of energy along the RLMF axis employing consensus network analysis from a spatial transcriptomic standpoint. Based on enrichment analysis and protein-protein interaction analysis of the consensus network and tissue-specific genes, it was discovered that carbohydrate metabolism, energy metabolism, immune and inflammatory responses were likely to be the biological processes that contribute most to feed efficiency variation on the RLMF regulatory axis. In addition, clusters of genes related to the electron respiratory chain, including ND (2,3,4,4L,5,6), NDUF (A13, A7, S6, B3, B6), COX (1,3), CYTB, UQCR11, ATP (6,8), clusters of genes related to fatty acid metabolism including APO (A1, A2, A4, B, C3), ALB, FG (A, G), as well as clusters of the ribosomal-related gene including RPL (8,18A,18,15,13, P1), the RPS (23,27A,3A,4X), and the PSM (A1-A7, B6, C1, C3, D2-D4, D8 D9, E1) could be the primary effector genes responsible for feed efficiency variation. The findings demonstrate that high feed efficiency cattle, through the synergistic action of the regulatory axis RLMF, may improve the efficiency of biological processes (carbohydrate metabolism, protein ubiquitination, and energy metabolism). Meanwhile, high feed efficiency cattle might enhance the ability to respond to immunity and inflammation, allowing nutrients to be efficiently distributed across these organs associated with digestion and absorption, energy-producing, and energy-storing organs. Elucidating the distribution of nutrients on the RLMF regulatory axis could facilitate an understanding of feed efficiency variation and achieve the study on its molecular regulation.

Blood transcriptome reveals immune and metabolic-related genes involved in growth of pasteurized colostrum-fed calves.

The quality of colostrum is a key factor contributing to healthy calf growth, and pasteurization of colostrum can effectively reduce the counts of pathogenic microorganisms present in the colostrum. Physiological changes in calves fed with pasteurized colostrum have been well characterized, but little is known about the underlying molecular mechanisms. In this study, key genes and functional pathways through which pasteurized colostrum affects calf growth were identified through whole blood RNA sequencing. Our results showed that calves in the pasteurized group (n = 16) had higher body height and daily weight gain than those in the unpasteurized group (n = 16) in all months tested. Importantly, significant differences in body height were observed at 3 and 4 months of age (p < 0.05), and in daily weight gain at 2, 3, and 6 months of age (p < 0.05) between the two groups. Based on whole blood transcriptome data from 6-months old calves, 630 differentially expressed genes (DEGs), of which 235 were upregulated and 395 downregulated, were identified in the pasteurized compared to the unpasteurized colostrum groups. Most of the DEGs have functions in the immune response (e.g., CCL3, CXCL3, and IL1A) and metabolism (e.g., PTX3 and EXTL1). Protein-protein interaction analyses of DEGs revealed three key subnetworks and fifteen core genes, including UBA52 and RPS28, that have roles in protein synthesis, oxidative phosphorylation, and inflammatory responses. Twelve co-expression modules were identified through weighted gene co-expression network analysis. Among them, 17 genes in the two modules that significantly associated with pasteurization were mainly involved in the tricarboxylic acid cycle, NF-kappa B signaling, and NOD-like receptor signaling pathways. Finally, DEGs that underwent alternative splicing in calves fed pasteurized colostrum have roles in the immune response (SLCO4A1, AKR1C4, and MED13L), indicative of potential roles in immune regulation. Results from multiple analytical methods used suggest that differences in calf growth between the pasteurized and unpasteurized groups may be due to differential immune activity. Our data provide new insights into the impact of pasteurization on calf immune and metabolic-related pathways through its effects on gene expression.

Rumen and Fecal Microbiota Characteristics of Qinchuan Cattle with Divergent Residual Feed Intake.

Residual feed intake (RFI) is one of the indicators of feed efficiency. To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). The results of taxonomic annotation revealed that Bacteroidetes and Firmicutes were the most dominant phyla in rumen and feces. Prevotella was identified as a potential biomarker in the rumen of the LRFI group by the LEfSe method, while Turicibacter and Prevotella might be potential biomarkers of the HRFI and LRFI group in feces, respectively. Functional annotation revealed that the microbiota in the rumen of the HRFI group had a greater ability to utilize dietary polysaccharides and dietary protein. Association analysis of rumen microbes (genus level) with host genes revealed that microbiota including Prevotella, Paraprevotella, Treponema, Oscillibacter, and Muribaculum, were significantly associated with differentially expressed genes regulating RFI. This study discovered variances in the microbial composition of rumen and feces of beef cattle with different RFIs, demonstrating that differences in microbes may play a critical role in regulating the bovine divergent RFI phenotype variations.

Impact of cigarette smoking on rheumatoid arthritis-associated lung diseases: a retrospective case control study on clinical and radiological features and prognosis.

Our study aimed to investigate the clinical and radiological features and prognosis of male smoker patients with rheumatoid arthritis (RA). We consecutively enrolled male inpatients with RA who received chest HRCT during hospitalization in Peking University Third Hospital from Jan 1st, 2012 to August 1st, 2021. 154 male patients with RA were eligible for analysis, of whom 76.6% (n = 118) were current smokers or had a history of cigarette smoking. Compared to never-smokers, smoker patients had more respiratory symptoms, including cough (31.4% vs 5.6%, p = 0.002) and sputum production (26.3% vs 2.8%, p = 0.002), and a higher positive rate of rheumatoid factor (RF) (77.6% vs 58.8%, p = 0.030). A higher percentage of smoker patients showed emphysema (45.8% vs 16.7%, p = 0.002) and signs of lung fibrosis (51/54, 94.4% vs 7/13, 53.8%, p < 0.001) in those with interstitial lung disease (ILD, n = 67) on chest HRCT. The overall survival rate was different between smoker and never-smoker patients (p = 0.031), but instead of cigarette smoking, lung fibrosis on HRCT was the risk factor for survival of our patients. In conclusion, male patients with RA who were current smokers or had a history of cigarette smoking presented more respiratory symptoms and a higher positive rate of RF. They also showed more emphysema and signs of lung fibrosis on chest HRCT. Cigarette smoking impacted on the overall survival as a confounding factor in this cohort of male patients with RA.

Identification and characterization of hypothalamic circular RNAs associated with bovine residual feed intake.

Residual feed intake (RFI) is crucial economic indicator used for calculating the feed efficiency of growing beef cattle. circRNA plays an important biological role in gene transcriptional regulation, but little is known about its potential functional regulation underlying RFI phenotypic variation. As the core center of regulation of animal feeding, the hypothalamus is closely associated with RFI. Therefore, the present study aimed to identify the key genes and functional pathways contributing to variance in cattle RFI phenotypes using RNA sequencing from hypothalamic tissue samples, in order to gain insight into the potential regulatory role of circRNAs in bovine RFI phenotypic variation. Differentially expressed genes were detected by RNA sequencing for beef cattle in the high and low RFI groups, followed by GO, KEGG enrichment, and circRNA-miRNA co-expression network analysis. A total of 257 circRNAs were differentially expressed between the two groups, with 128 significantly upregulated and 129 significantly downregulated genes in H group compared to L group. Among them, 9 unique circRNAs were present in group L and 4 unique circRNAs were present in group H. GO and KEGG enrichment analysis of the source genes of the differentially expressed circRNAs revealed that they were mainly involved in metabolic processes, such as cellular metabolic processes, cellular macromolecular metabolic processes, and regulatory pathways related to nutrient metabolism, including protein and amino acid metabolism, as well as vitamin metabolism and pancreatic secretion associated with the animal feeding behavior. The circRNAs detected in this study were mostly novel, and have not been investigated directly to be associated with the RFI phenotype. Interestingly, most miRNAs of differentially expressed circRNAs predicted based on the circRNA-miRNA co-expression network analysis by using top 50 differentially expressed circRNAs and 13 unique circRNAs, have been reported to be related to animal RFIs, implying that circRNAs in bovine hypothalamic tissue may regulate phenotypic variation in RFI through miRNAs. The study results illustrate the complex biological functions of the hypothalamus in regulating feed efficiency and showing the potential role of circRNAs in the feeding behavior regulation of livestock, which would contributing to expanding the understanding of circRNA.

Targeting Autophagy in Atrial Fibrillation.

Atrial fibrillation (AF) is the most common type of arrhythmia in clinical practice, and its incidence is positively correlated with risk factors that include advanced age, hypertension, diabetes, and heart failure. Although our understanding of the mechanisms that govern the occurrence and persistence of AF has been increasing rapidly, the exact mechanism of AF is still not fully understood. Autophagy is an evolutionarily highly conserved and specific physiological process in cells that has been suggested as a potential therapeutic target for several cardiovascular diseases including the pathophysiology of AF. The present article provides an updated review of the fast-progressing field of research surrounding autophagy in AF, and how regulating autophagy might be a therapeutic target to reduce the incidence of AF.

Anesthetic considerations for inadvertent severe hypertension in a patient with osteogenesis imperfecta during the perioperative period.

Osteogenesis imperfecta is a rare genetic syndrome caused by mutations of bone matrix protein type I collagen coding genes, which is characterized by increased bone fragility and recurrent fractures. We report a patient undergoing general anesthesia with additional nerve block for wrist and hip fracture repair. Preoperatively, we were confronted with an inadvertent severe hypertension without significant triggers and history, which prompted us to be vigilant for hypertensive emergencies due to the fragile vessel regulation capacity in osteogenesis imperfecta patients.

Bronchiectasis in patients with antineutrophil cytoplasmic antibody-associated vasculitis: a case control study on clinical features and prognosis.

BACKGROUND: Bronchiectasis was reported in 2%-40% of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), but there were no studies on the prevalence, risk factors and impact of AAV-associated bronchiectasis in Chinese patients. RESEARCH DESIGN AND METHODS: AAV patients were retrospectively enrolled. The clinical, laboratory and imaging features and the prognosis were analyzed and compared between those with and without bronchiectasis. RESULTS: Bronchiectasis was present in 48/212 (22.6%) of our AAV patients, among whom 41 were confirmed in 210 patients (19.5%) who received chest HRCT at the initial diagnosis of AAV. There were more women and fewer smokers in those with bronchiectasis as compared to those without. Cases with positive anti-MPO were more likely to have bronchiectasis (26.2%), and those with bronchiectasis were more likely to be anti-MPO positive (93.8%). Patients who had a diagnosis of bronchiectasis before AAV were more likely to have nervous system involvement, while patients without bronchiectasis had higher 24h proteinuria. The presence of bronchiectasis showed no significant effect on the 1, 3, 5-year survival. CONCLUSIONS: Nearly 20% of patients showed bronchiectasis on chest HRCT at the initial diagnosis of AAV, and positivity of anti-MPO was associated with bronchiectasis in a Chinese cohort of AAV patients.