The Study of PIK3CA Hotspot Mutations and Co-Occurring with EGFR, KRAS, and TP53 Mutations in Non-Small Cell Lung Cancer.

Objective: PIK3CA-mutant non-small-cell lung cancer (NSCLC) is associated with other genetic mutations and may influence treatment strategies and clinical outcomes. We aimed to characterize PIK3CA mutations co-occurring with several major driver mutations using data from published cohorts and our medical center. Materials and Methods: We analyzed NSCLC patients harboring PIK3CA mutations from The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering (MSK) databases and retrospectively identified NSCLC patients with PIK3CA-mutants at a single medical center from our electronic records. The Log rank test was used to determine the association between PIK3CA mutations and overall survival (OS) in NSCLC patients. Results: Common hotspot mutations in PIK3CA were found in exon 9 (c.1633G > A, E545K, and c.1624G > A, E542K) and exon 20 (c.3140A > G, H1047R) in all cohorts. Co-occurring mutations of PIK3CA with EGFR, KRAS, and TP53 have been frequently observed in patients with NSCLC, with different percentages in these datasets generated by different background. PIK3CA mutations were observed to be significantly associated with poor OS in lung adenocarcinomas patients in the MSKCC cohort (hazard ratio [HR] = 0.519, 95% confidence interval [CI] = 0.301-0.896; P <0.05). Conclusion: PIK3CA co-occurring mutations in other genes may represent distinct subsets of NSCLC. Further elucidation of the roles of PIK3CA hotspot mutations combined with other driver mutations, including EGFR and KRAS, is needed to guide effective treatment in patients with advanced NSCLC.

Magnetite nanoparticles from representative coal fired power plants in China: Dust removal capture and their final atmospheric emission.

Information on the emission of coal combustion-sourced magnetite nanoparticles (MNPs) is lacking, which is critical for their health-related risks. In this study, MNPs in coal fly ashes (CFAs) from various coal-fired power plants (CFPPs) in China equipped with various dust removal devices were extracted and quantified using single particle ICP-MS. The number concentrations of MNPs in CFAs captured by dust removal increased with stage, while their size decreased. Among all the dust removal devices, electrostatic-fabric-integrated precipitators showed the best removal of MNPs. Furthermore, throughout all the coal combustion by-products in a typical CFPP, MNPs in EFA (fly ash escaped from the stack) showed the highest number concentration (1.2 × 107 particles/mg) and lowest size (78 nm). Although the mass of CFA escaping through the stack is extremely low, it still had an emission rate of 1.9 × 1015 particles/h, contributing 3.56 % of the total emissions of MNPs in number. In addition, the purity of MNPs and their associated toxic metals showed a size-dependent variation pattern. As the particle size of MNPs decreased, the proportion of Fe in MNPs increased from 43 % in bottom ash (BA) to 84 % in EFA, while the abundance of trace toxic metals in EFA was 3.3 times higher than that of BA. These MNPs with the highest purity can adsorb elevated concentrations of toxic metals, and can be discharged directly into the atmosphere, posing a risk of synergistic toxicity.

Constructing and validating pan-apoptosis-related features for predicting prognosis and immunotherapy response in hepatocellular carcinoma.

The study aimed to develop a prognostic model for Hepatocellular Carcinoma (HCC) based on pan-apoptosis-related genes, a novel inflammatory programmed cell death form intricately linked to HCC progression. Utilizing transcriptome sequencing and clinical data from the TCGA database, we identified six crucial pan-apoptosis-related genes through statistical analyses. These genes were then employed to construct a prognostic model that accurately predicts overall survival rates in HCC patients. Our findings revealed a strong correlation between the model's risk scores and tumor microenvironment (TME) status, immune cell infiltration, and immune checkpoint expression. Furthermore, we screened for drugs with potential therapeutic efficacy in high- and low-risk HCC groups. Notably, PPP2R5B gene knockdown was found to inhibit HCC cell proliferation and clonogenic capacity, suggesting its role in HCC progression. In conclusion, this study presents a novel pan-apoptosis gene-based prognostic risk model for HCC, providing valuable insights into patient TME status and guiding the selection of targeted therapies and immunotherapies.

Dynamics alteration of the gut microbiota and faecal metabolomes in very low or extremely low birth weight infants: a Chinese single-center, prospective cohort study.

Objective: The aim of this study is to comprehensively investigate the temporal dynamics of faecal gut microbiota and metabonomics in early postnatal with a focus on very low or extremely low birth weight (VLBW/ELBW) infants. Methods: We collected faecal samples from 157 VLBW/ELBW infants at three time points: days 1, 14, and 28 in a prospective cohort study. The faecal microbial diversity, abundance, composition, and metabolomic analyses were determined using 16S rRNA sequencing and liquid chromatography tandem mass spectrometry (LC-MS/MS). Microbiome functional analyses were conducted utilizing PICRUSt2. The ecological association networks were employed to investigate the interactions between gut microbiota and identify the core genus within 28 days of birth, as well as to unveil correlations between taxa and metabolites. Result: (1) The alpha diversity of gut microbiota significantly decreased from D1 to D28, accompanied by an interrupted trajectory lacking obligate anaerobes. At the phylum level, the 16S RNA sequencing results showed an increase in Proteobacteria and a decrease in Firmicutes and Bacteroidota from D1 to D28. At the genus level, there was a decrease in the relative abundance of Staphylococcus, Acinetobacter and Ureaplasma, with Klebsiella and Enterococcus emerging as the most abundant genera. (2) The analysis revealed a total of 561 metabolic markers that exhibited significant and distinct alterations between D1 and D14. (3) Ecological association networks revealed that the gut microbiota in D1 exhibited a significantly higher degree of microbial interactions compared to those in D14 and D28. Additionally, Enterococcus, Klebsiella, and Enterobacter were major contributors to the co-occurring network at these three time points. (4) Steroid hormone biosynthesis, including tetrahydrocortisone, androsterone glucuronide, androstenedione and etiocholanolone glucuronide, decreased within 28 days after birth. Conclusion: We have successfully demonstrated a significant dysbiosis in the gut microbiota and a subsequent decrease in its diversity within 4 weeks postpartum in VLBW/ELBW infants. Monitoring the gut microbiota of VLBW/ELBW infants and promptly rectifying dysbiosis in the early stages may represent a potential therapeutic strategy.

Fibroblast growth factor 2 promotes osteo/odontogenic differentiation in stem cells from the apical papilla by inhibiting PI3K/AKT pathway.

Fibroblast growth factor 2 (FGF2) is a crucial factor in odontoblast differentiation and dentin matrix deposition, which facilitates pulpodentin repair and regeneration. Nevertheless, the specific biological function of FGF2 in odontoblastic differentiation remains unclear because it is controlled by complex signalling pathways. This study aimed to investigate the mechanism underlying the effect of FGF2 on osteo/odontogenic differentiation of stem cells from the apical papilla (SCAP). SCAP were pretreated with conditioned media containing FGF2 for 1 week, followed by culturing in induced differentiation medium for another week. RNA sequencing (RNA-seq) combined with quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to evaluate the pathways affected by FGF2 in SCAP. Osteo/odontogenic differentiation of SCAP was determined using Alizarin red S staining, alkaline phosphatase staining, RT-qPCR, and western blotting. Pretreatment with FGF2 for 1 week increased the osteo/odontogenic differentiation ability of SCAP. RNA-seq and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that phosphatidylinositol 3-kinase (PI3K)/AKT signalling is involved in the osteogenic function of FGF2. RT-qPCR results indicated that SCAP expressed FGF receptors, and western blotting showed that p-AKT was reduced in FGF2-pretreated SCAP. The activation of the PI3K/AKT pathway partially reversed the stimulatory effect of FGF2 on osteo/odontogenic differentiation of SCAP. Our findings suggest that pretreatment with FGF2 enhances the osteo/odontogenic differentiation ability of SCAP by inhibiting the PI3K/AKT pathway.

Proton pump inhibitors may increase the risk of cisplatin-induced acute kidney injury in patients with nasopharyngeal carcinoma: a prospective cohort study.

Cisplatin is the most commonly used platinum-based treatment for nasopharyngeal carcinoma (NPC). However, its clinical application is limited owing to its nephrotoxicity and gastrointestinal reactions. Proton pump inhibitors (PPIs) have been reported to increase nephrotoxicity risk in previous studies. We aimed to evaluate whether PPIs increase cisplatin-induced nephrotoxicity in patients with NPC. In total, 295 patients were included in this prospective cohort study: 145 in the PPIs group and 150 in the non-PPIs group. All patients underwent cisplatin-based induction chemotherapy, followed by cisplatin-based concurrent chemoradiotherapy. The PPIs group received 40 mg of intravenous esomeprazole sodium for 7 days in each chemotherapy cycle. Chi-squared test and logistic regression analyses with odds ratios and 95% confidence intervals were applied to assess the association between PPIs and the risk of acute kidney injury (AKI). AKI incidence in the PPIs group was significantly higher than that in the non-PPIs group (P = 0.005). After adjusting for various confounders including demographic features, clinical features, and renal function indices, PPIs use was significantly associated with a higher AKI risk (odds ratio: 2.775; 95% confidence interval 1.280-6.020; P = 0.010). The incidences of acute and chronic kidney diseases were similar between both groups (P > 0.05), whereas the incidence of nausea was lower in the PPIs group than in the non-PPIs group (P = 0.029). This study has shown that PPIs use may increase the risk of cisplatin-induced acute nephrotoxicity in patients with NPC.

Effect of combining batroxobin with acupuncture treatment on hearing recovery in patients with sudden sensorineural hearing loss.

BACKGROUND: The effect of batroxobin on hearing recovery in patients with Sudden Sensorineural Hearing Loss (SSNHL) is still controversial, and acupuncture shows auxiliary benefits for SSNHL. OBJECTIVES: To investigate the effectiveness of combining acupuncture with batroxobin therapy for patients with SSNHL. MATERIAL AND METHODS: One hundred and fifty-six patients with SSNHL were retrospectively enrolled in this study, and categorized into the control group (only batroxobin treatment) and observation group (batroxobin and acupuncture treatment). Pure Tone Audiograms (PTA) threshold and clinical outcomes of hearing recovery were compared. Logistic regression analysis was used to evaluate the association between hearing recovery and potential risk factors. RESULTS: Compared to the control group, the observation group had a higher overall effective rate (p = 0.006) and improvement in PTA threshold (p = 0.007). Among SSNHL patients with high-frequency and flat-type hearing loss, observation group demonstrated superior hearing recovery post-treatment compared to the control group (p < 0.05). Additionally, hearing recovery in patient with SSNHL were associated with SSNHL types, disease duration, neutrophil count and acupuncture (p < 0.05). CONCLUSIONS AND SIGNIFICANCE: Combining batroxobin and acupuncture treatments enhences the improvement of hearing recovery in SSNHL patients compared to only batroxobin treatments, especially high-frequency and flat-type hearing loss.

[Analysis of saliva and intestinal microbial community in children with severe caries based on 16S rDNA high-throughput sequencing technology].

PURPOSE: The characteristics of saliva and intestinal microbial community in children with high caries and no caries were analyzed by 16S rDNA high-throughput sequencing. METHODS: Among 431 children aged 3-5 years old in Zunyi City who were investigated previously by our team, 25 children in the high caries group and the same in the caries-free group were selected for fecal and saliva samples. 16S rDNA high-throughput sequencing was used to analyze the bacterial flora structure of the samples and identify the species with different relative abundance at the species level. SPSS 18.0 software package was used for data analysis. RESULTS: The diversity of intestinal flora in the high caries group was higher than that in the caries-free group, and the difference was statistically significant(P＜0.05). The diversity of salivary flora in the high caries group was more than that in the caries-free group, with no significant difference(P＞0.05). At phylum level,there was no significant difference in intestinal and salivary flora between children with high caries and children without caries. At gene level, Blautia, [Eubacterium] hallii group and [Eubacterium] eligens group in the intestine of caries-free group were significantly higher than those of high caries group(P＜0.05), while Parasutterella and Christensenellaceae R-7 group were significantly lower than those of high caries group(P＜0.05). At gene level, Peptostreptococcus in saliva of caries-free group was significantly higher than that in high caries group(P＜0.05). Dialister, Kingella, Escherichia-Shigella and Treponema in saliva of caries-free group were significantly lower than those in high caries group(P＜0.05). CONCLUSIONS: There are significant differences in species composition of intestinal flora but no in salivary flora between children with high caries and children without caries.

Association of healthy diet score and adiposity with risk of colorectal cancer: findings from the UK Biobank prospective cohort study.

PURPOSE: To explore the joint association of dietary patterns and adiposity with colorectal cancer (CRC), and whether adiposity mediates the relationship between dietary patterns and CRC risk, which could provide deeper insights into the underlying pathogenesis of CRC. METHODS: The data of 307,023 participants recruited between 2006 and 2010 were extracted from the UK Biobank study. Healthy diet scores were calculated based on self-reported dietary data at baseline, and participants were categorized into three groups, namely, low, intermediate, and high diet score groups. Cox regression models with hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the effects of the healthy diet score on CRC incidence, adjusting for various covariates. Furthermore, the mediation roles of obesity and central obesity between the healthy diet score and CRC risk were assessed using a counterfactual causal analysis based on Cox regression model. Additionally, joint association between dietary patterns and adiposity on CRC risks was assessed on the additive and multiplicative scales. RESULTS: Over a median 6.2-year follow-up, 3,276 participants developed CRC. After adjusting for sociodemographic and lifestyle factors, a lower risk of CRC incidence was found for participants with intermediate (HR = 0.83, 95% CI: 0.72 to 0.95) and high diet scores (HR = 0.73, 95% CI: 0.62 to 0.87) compared to those with low diet scores. When compared with the low diet score group, obesity accounted for 4.13% and 7.93% of the total CRC effect in the intermediate and high diet score groups, respectively, while central obesity contributed to 3.68% and 10.02% of the total CRC risk in the intermediate and high diet score groups, respectively. The mediating effect of adiposity on CRC risk was significant in men but not in women. Concurrent unhealthy diet and adiposity multiplied CRC risk. CONCLUSION: Adiposity-mediated effects were limited in the link between dietary patterns and CRC incidence, implying that solely addressing adiposity may not sufficiently reduce CRC risk. Interventions, such as improving dietary quality in people with adiposity or promoting weight control in those with unhealthy eating habits, may provide an effective strategy to reduce CRC risk.

Accuracy and clinical characteristics of robot-assisted cervical spine surgery: a systematic review and meta-analysis.

PURPOSE: To evaluate the accuracy and feasibility of robot-assisted cervical screw placement and factors that may affect the accuracy. METHODS: A comprehensive search was made on PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Wanfang Med for the selection of potential eligible literature. The outcomes were evaluated in terms of the relative risk (RR) or standardized mean difference (MD) and corresponding 95% confidence interval (CI). Subgroup analyses of the accuracy of screw placement at different cervical segments and with different screw placement approaches were performed. A comparison was made between robotic navigation and conventional freehand cervical screw placement. RESULTS: Six comparative cohort studies and five case series studies with 337 patients and 1342 cervical screws were included in this study. The perfect accuracy was 86% (95% CI, 82-89%) and the clinically acceptable rate was 98% (95% CI, 95-99%) in robot-assisted cervical screw placement. The perfect accuracy of robot-assisted C1 lateral mass screw placement was the highest (96%), followed by C6-7 pedicle screw placement (93%) and C2 pedicle screw placement (86%), and the lowest was C3-5 pedicle screw placement (75%). The open approach had a higher perfect accuracy than the percutaneous/intermuscular approach (91% vs 83%). Compared with conventional freehand cervical screw placement, robot-assisted cervical screw placement had a higher accuracy, a lower incidence of perioperative complications, and less intraoperative blood loss. CONCLUSION: With good collaboration between the operator and the robot, robot-assisted cervical screw placement is accurate and feasible. Robot-assisted cervical screw placement has a promising prospect.

Efficacy and safety of radiofrequency ablation versus surgical sympathectomy in palmar hyperhidrosis.

Radiofrequency ablation (RFA) comparative efficacy of treatments using video-assisted thoracoscopic sympathectomy (VATS) in the long term remains uncertain in patients with palmar hyperhidrosis (PHH). This study aimed to compare the efficacy and safety of RFA and VATS in patients with PHH. We recruited patients aged ≥ 14 years with diagnosed PHH from 14 centres in China. The treatment options of RFA or VATS were assigned to two cohort in patients with PHH. The primary outcome was the efficacy at 1-year. A total of 807 patients were enrolled. After propensity score matching, the rate of complete remission was lower in RFA group than VATS group (95% CI 0.21-0.57; p < 0.001). However, the rates of palmar dryness (95% CI 0.38-0.92; p = 0.020), postoperative pain (95% CI 0.13-0.33; p < 0.001), and surgery-related complications (95% CI 0.19-0.85; p = 0.020) were lower in RFA group than in VATS group, but skin temperature rise was more common in RFA group (95% CI 1.84-3.58; p < 0.001). RFA had a lower success rate than VATS for the complete remission of PHH. However, the symptom burden and cost are lower in patients undergoing RFA compared to those undergoing VATS.Trial Registration: ChiCTR2000039576, URL: http://www.chictr.org.cn/index.aspx .

Expert consensus on difficulty assessment of endodontic therapy.

Endodontic diseases are a kind of chronic infectious oral disease. Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha. However, it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy (RCT). Recent research, encompassing bacterial etiology and advanced imaging techniques, contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT. Success in RCT hinges on factors like patients, infection severity, root canal anatomy, and treatment techniques. Therefore, improving disease management is a key issue to combat endodontic diseases and cure periapical lesions. The clinical difficulty assessment system of RCT is established based on patient conditions, tooth conditions, root canal configuration, and root canal needing retreatment, and emphasizes pre-treatment risk assessment for optimal outcomes. The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT. These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Effects of 24-hour urine-output trajectories on the risk of acute kidney injury in critically ill patients with cirrhosis: a retrospective cohort analysis.

BACKGROUND: Acute kidney injury (AKI) is one of the most common complications for critically ill patients with cirrhosis, but it has remained unclear whether urine output fluctuations are associated with the risk of AKI in such patients. Thus, we explored the influence of 24-h urine-output trajectory on AKI in patients with cirrhosis through latent category trajectory modeling. MATERIALS AND METHODS: This retrospective cohort study examined patients with cirrhosis using the MIMIC-IV database. Changes in the trajectories of urine output within 24 h after admission to the intensive care unit (ICU) were categorized using latent category trajectory modeling. The outcome examined was the occurrence of AKI during ICU hospitalization. The risk of AKI in patients with different trajectory classes was explored using the cumulative incidence function (CIF) and the Fine-Gray model with the sub-distribution hazard ratio (SHR) and the 95% confidence interval (CI) as size effects. RESULTS: The study included 3,562 critically ill patients with cirrhosis, of which 2,467 (69.26%) developed AKI during ICU hospitalization. The 24-h urine-output trajectories were split into five classes (Classes 1-5). The CIF curves demonstrated that patients with continuously low urine output (Class 2), a rapid decline in urine output after initially high levels (Class 3), and urine output that decreased slowly and then stabilized at a lower level (Class 4) were at higher risk for AKI than those with consistently moderate urine output (Class 1). After fully adjusting for various confounders, Classes 2, 3, and 4 were associated with a higher risk of AKI compared with Class 1, and the respective SHRs (95% CIs) were 2.56 (1.87-3.51), 1.86 (1.34-2.59), and 1.83 1.29-2.59). CONCLUSIONS: The 24-h urine-output trajectory is significantly associated with the risk of AKI in critically ill patients with cirrhosis. More attention should be paid to the dynamic nature of urine-output changes over time, which may help guide early intervention and improve patients' prognoses.

A Respiratory Motion Prediction Method Based on LSTM-AE with Attention Mechanism for Spine Surgery.

Respiratory motion-induced vertebral movements can adversely impact intraoperative spine surgery, resulting in inaccurate positional information of the target region and unexpected damage during the operation. In this paper, we propose a novel deep learning architecture for respiratory motion prediction, which can adapt to different patients. The proposed method utilizes an LSTM-AE with attention mechanism network that can be trained using few-shot datasets during operation. To ensure real-time performance, a dimension reduction method based on the respiration-induced physical movement of spine vertebral bodies is introduced. The experiment collected data from prone-positioned patients under general anaesthesia to validate the prediction accuracy and time efficiency of the LSTM-AE-based motion prediction method. The experimental results demonstrate that the presented method (RMSE: 4.39%) outperforms other methods in terms of accuracy within a learning time of 2 min. The maximum predictive errors under the latency of 333 ms with respect to the x, y, and z axes of the optical camera system were 0.13, 0.07, and 0.10 mm, respectively, within a motion range of 2 mm.

Effect of Long Non-coding RNA and DNA Methylation on Gene Expression in Dental Fluorosis.

In the process of tooth development, the interaction between genetic information, epigenetic inheritance, and environment jointly affects the teeth formation. At present, the mechanism of dental fluorosis is rarely studied from transcriptomics, and there is no report on epigenetic perspective. In the study, SD rats were randomly divided into dental fluorosis group and control group fed with NaF (150 mg/L) or distilled water for 8 weeks. After 3.5 days of birth, the RNAs or DNA of rat mandibular molars were detected by RNA-seq or MethylTarget, respectively. The results demonstrated that a total of 1723 differentially expressed genes (DEGs) and 2511 differential expression lncRNAs (DE-lncRNAs) were mainly involved in the ion channels, calcium ion transport, and immunomodulatory signaling pathways. ATP2C1 and Nr1d1, which were related to Ca2+ transport, cellular calcium homeostasis, endoplasmic reticulum stress and immunity, may be the key genes in the formation of dental fluorosis. Notably, we also found that the immune response plays an important role in the formation of dental fluorosis, and a large amount of DEGs was enriched in immune regulation and NF-κB signaling pathways. Furthermore, the methylation levels of 13 sites were increased in Ago4, Atf3, Atp2c1, Dusp1, Habp4, and Mycl, while methylation levels of 5 CpG sites decreased in Ago4, Atp2c1, Habp4, and Traf6, and conformably, the expression of these genes have been significantly changed. This study comprehensively analyzed the occurrence mechanism of dental fluorosis from transcriptomics and epigenetics, so as to provide theoretical reference for further research.

Mortality patterns of patients with tonsillar squamous cell carcinoma: a population-based study.

Objective: Tonsillar squamous cell carcinoma (TSCC) and second primary malignancies (SPMs) are the most common causes of mortality in patients with primary TSCC. However, the competing data on TSCC-specific death (TSD) or SPM-related death in patients with TSCC have not been evaluated. This study aimed to analyze the mortality patterns and formulate prediction models of mortality risk caused by TSCC and SPMs. Methods: Data on patients with a first diagnosis of TSCC were extracted as the training cohort from the 18 registries comprising the Surveillance, Epidemiology, and End Results (SEER) database. A competing risk approach of cumulation incidence function was used to estimate cumulative incidence curves. Fine and gray proportional sub-distributed hazard model analyses were performed to investigate the risk factors of TSD and SPMs. A nomogram was developed to predict the 5- and 10-year risk probabilities of death caused by TSCC and SPMs. Moreover, data from the 22 registries of the SEER database were also extracted to validate the nomograms. Results: In the training cohort, we identified 14,530 patients with primary TSCC, with TSCC (46.84%) as the leading cause of death, followed by SPMs (26.86%) among all causes of death. In the proportion of SPMs, the lungs and bronchus (22.64%) were the most common sites for SPM-related deaths, followed by the larynx (9.99%), esophagus (8.46%), and Non-Melanoma skin (6.82%). Multivariate competing risk model showed that age, ethnicity, marital status, primary site, summary stage, radiotherapy, and surgery were independently associated with mortality caused by TSCC and SPMs. Such risk factors were selected to formulate prognostic nomograms. The nomograms showed preferable discrimination and calibration in both the training and validation cohorts. Conclusion: Patients with primary TSCC have a high mortality risk of SPMs, and the competing risk nomogram has an ideal performance for predicting TSD and SPMs-related mortality. Routine follow-up care for TSCC survivors should be expanded to monitor SPMs.

Genetic Association Analysis of Copy Number Variations for Meat Quality in Beef Cattle.

Meat quality is an economically important trait for global food production. Copy number variations (CNVs) have been previously implicated in elucidating the genetic basis of complex traits. In this article, we detected a total of 112,198 CNVs and 10,102 CNV regions (CNVRs) based on the Bovine HD SNP array. Next, we performed a CNV-based genome-wide association analysis (GWAS) of six meat quality traits and identified 12 significant CNV segments corresponding to eight candidate genes, including PCDH15, CSMD3, etc. Using region-based association analysis, we further identified six CNV segments relevant to meat quality in beef cattle. Among these, TRIM77 and TRIM64 within CNVR4 on BTA29 were detected as candidate genes for backfat thickness (BFT). Notably, we identified a 34 kb duplication for meat color (MC) which was supported by read-depth signals, and this duplication was embedded within the keratin gene family including KRT4, KRT78, and KRT79. Our findings will help to dissect the genetic architecture of meat quality traits from the aspects of CNVs, and subsequently improve the selection process in breeding programs.

Thiamine administration may increase survival benefit in critically ill patients with myocardial infarction.

Background: Myocardial infarction (MI) is a common cardiovascular disease (CVD) in critically ill patients, leading to 17% mortality in the intensive care unit (ICU) setting. Patients with CVD frequently suffer from thiamine insufficiency, thereby thiamine supplements may be helpful. Unfortunately, the relationship between thiamine treatment and survival outcomes in ICU patients with MI is still unknown. The purpose of the research is to demonstrate the survival advantage of thiamine application in these patients. Methods: The Medical Information Mart of Intensive Care-IV database served as the foundation for this retrospective cohort analysis. Depending on whether patients were given thiamine therapy during the hospital stay, critically ill MI patients were split into the thiamine and non-thiamine groups. The Kaplan-Meier (KM) method and Cox proportional hazard models were used to evaluate the relationship between thiamine use and the risk of in-hospital, 30-day, and 90-day mortality. To validate the results, a 1:2 closest propensity-score matching (PSM) was also carried out. Results: This study included 1782 patients for analysis with 170 and 1,612 individuals in the thiamine and non-thiamine groups, respectively. The KM survival analyses revealed that the risk of in-hospital, 30-day, and 90-day mortality was significantly lower in the thiamine group than the none-thiamine group. After modifying for a variety of confounding factors, the Cox regression models demonstrated substantial positive impacts of thiamine use on in-hospital, 30-d, and 90-d mortality risk among critically ill patients with MI with hazard ratio being 0.605 [95% confidence interval (CI): 0.397-0.921, p = 0.019], 0.618 (95% CI: 0.398-0.960, p = 0.032), and 0.626 (95% CI: 0.411-0.953, p = 0.028), respectively, in the completely modified model. PSM analyses also obtained consistent results. Conclusion: Thiamine supplementation is related to a decreased risk of mortality risk in critically ill patients with MI who are admitted to the ICU. More multicenter, large-sample, and well-designed randomized controlled trials are needed to validate this finding.

Evaluation of Linear Programming and Optimal Contribution Selection Approaches for Long-Term Selection on Beef Cattle Breeding.

The optimized selection method can maximize the genetic gain in offspring under the premise of controlling the inbreeding level of the population. At present, genetic gain has been largely improved by using genomic selection in multiple farm animals. However, the design of the optimal selection method and assessment of its effects during long-term selection in beef cattle breeding are yet to be fully explored. In this study, a simulated beef cattle population was constructed, and 15 generations of simulated breeding were carried out using the linear programming breeding strategy (LP) and optimal contribution selection strategy (OCS), respectively. The truncation selection strategy (TS-I and TS-II) was used as the control. During the breeding process, genetic parameters including genetic gain, average kinship coefficient, QTL effect variance, and average observed heterozygosity were calculated and compared across generations. Our results showed that the LP method can significantly improve the genetic gain in the population, especially the genetic performance of the traits with high heritability and the traits with high weight in the breeding process, but the inbreeding level of the population is higher under LP strategy. Although the genetic gain in the population under the OCS strategy is lower than the TS-II strategy, this method can effectively control the inbreeding level of the population. Our findings also suggest that the LP and OCS method can be used as an effective means to improve genetic gain, while the OCS method is a more ideal method to obtain sustainable genetic gain during long-term selection.

Crucial Factors Influencing the Involvement of Odontogenic Exosomes in Dental Pulp Regeneration.

Recent progress in exosome based studies has revealed that they possess several advantages over cells, including "cell-free" properties, low immunogenicity and ethical controversy, high biological safety and effective action. These characteristics confer exosomes significant advantages that allow them to overcome the limitations associated with traditional "cell therapy" by circumventing the issues of immune rejection, scarcity of donor cells, heterogeneity, and ethical concerns. Identification of a complete and effective radical treatment for irreversible pulpal disease, a common clinical problem, continues to pose challenges. Although traditional root canal therapy remains the primary clinical treatment, it does not fully restore the physiological functions of pulp. Although stem cell transplantation appears to be a relatively viable treatment strategy for pulp disease, issues such as cell heterogeneity and poor regeneration effects remain problematic. Dental pulp regeneration strategies based on "cell-free" exosome therapies explored by numerous studies appear to have shown significant advantages. In particular, exosomes derived from odontogenic stem cells have demonstrated considerable potential in tooth tissue regeneration engineering, and continue to exhibit superior therapeutic effects compared to non-odontogenic stem cell-derived exosomes. However, only a few studies have comprehensively summarised their research results, particularly regarding the critical factors involved in the process. Therefore, in this study, our purpose was to review the effects exerted by odontogenic exosomes on pulp regeneration and to analyse and discus crucial factors related to this process, thereby providing scholars with a feasible and manageable new concept with respect to regeneration schemes.