Sprint Interval Training Improves Brain-Derived Neurotropic Factor-Induced Benefits in Brain Health-A Possible Molecular Signaling Intervention.

Physical exercise can significantly impact our bodies, affecting our functional capacity, structure establishment, and molecular makeup. The magnitude of these changes depends on the specific exercise protocols used. For instance, low-to-moderate-intensity exercise can activate important molecular targets in the short term, such as BDNF-mediated signaling, while high-intensity exercise can maintain these signaling molecules in the active state for a longer term. This makes it challenging to recommend specific exercises for obtaining BDNF-induced benefits. Additionally, exercise-induced molecular signaling targets can have positive and negative effects, with some exercises blunting these targets and others activating them. For example, increasing BDNF concentration through exercise can be beneficial for brain health, but it may also have a negative impact on conditions such as bipolar disorder. Therefore, a deeper understanding of a specific exercise-mediated mechanistic approach is required. This review will delve into how the sprint exercise-mediated activation of BDNF could help maintain brain health and explore potential molecular interventions.

Myelin modulates the process of isoflurane anesthesia through the regulation of neural activity.

AIMS: The mechanism underlying the reversible unconsciousness induced by general anesthetics (GA) remains unclear. Recent studies revealed the critical roles of myelin and oligodendrocytes (OLs) in higher functions of the brain. However, it is unknown whether myelin actively participates in the regulation of GA. The aim of this study is to investigate the roles and possible mechanisms of myelin in the regulation of consciousness alterations induced by isoflurane anesthesia. METHODS: First, demyelination models for the entire brain and specific neural nuclei were established to investigate the potential role of myelination in the regulation of GA, as well as its possible regional specificity. c-Fos staining was then performed on the demyelinated nuclei to verify the impact of myelin loss on neuronal activity. Finally, the activity of neurons during isoflurane anesthesia in demyelinated mice was recorded by optical fiber photometric calcium signal. The related behavioral indicators and EEG were recorded and analyzed. RESULTS: A prolonged emergence time was observed from isoflurane anesthesia in demyelinated mice, which suggested the involvement of myelin in regulating GA. The demyelination in distinct nuclei by LPC further clarified the region-specific roles of isoflurane anesthesia regulation by myelin. The effect of demyelination on isoflurane anesthesia in the certain nucleus was consistent with that in neurons towards isoflurane anesthesia. Finally, we found that the mechanism of myelin in the modulation of isoflurane anesthesia is possibly through the regulation of neuronal activity. CONCLUSIONS: In brief, myelin in the distinct neural nucleus plays an essential role in regulating the process of isoflurane anesthesia. The possible mechanism of myelin in the regulation of isoflurane anesthesia is neuronal activity modification by myelin integrity during GA. Our findings enhanced the comprehension of myelin function, and offered a fresh perspective for investigating the neural mechanisms of GA.

MiR-338-5p, a novel metastasis-related miRNA, inhibits triple-negative breast cancer progression by targeting the ETS1/NOTCH1 axis.

Breast cancer ranks as the most prevalent cancer globally, surpassing lung cancer, with recurrence/metastasis to be its main account for the cancer-related mortality. MicroRNAs (miRNAs) participate critically in various physiological and pathological processes through posttranscriptional regulation of downstream genes. Our preliminary findings identified miR-338-5p, potentially linked to metastasis in breast cancer, a previously unexplored area. Analysis of the GSE38867 dataset revealed the decreased miR-338-5p expression in metastatic breast cancer compared to normal tissues. Cellular function experiments and a xenograft tumor model demonstrated the inhibitory function of miR-338-5p on the progression of breast cancer in vitro and in vivo. Furthermore, it downregulated the expression of mesenchymal biomarkers and NOTCH1 significantly. With the predicting targets of miR-338-5p and transcription factors of the NOTCH1 gene, coupled with dual luciferase reporter assays, it is identified ETS1 as the interactor between miR-338-5p and NOTCH1. In breast cancer tissues, as well as in our xenograft tumor model, expression of ETS1 and NOTCH1 was positively correlated using immunohistochemical staining. This study reports, for the first time, on the miR-338-5p/ETS1/NOTCH1 axis and its pivotal role in breast cancer proliferation and metastasis. These findings propose a novel therapeutic strategy for breast cancer patients and lays a foundation for its clinical detection and treatment evaluation.

Oropharyngeal microbiome profiling and its association with age and heart failure in the elderly population from the northernmost province of China.

Respiratory tract infections are the most common triggers for heart failure in elderly people. The healthy respiratory commensal microbiota can prevent invasion by infectious pathogens and decrease the risk of respiratory tract infections. However, upper respiratory tract (URT) microbiome in the elderly is not well understood. To comprehend the profiles of URT microbiota in the elderly, and the link between the microbiome and heart failure, we investigated the oropharyngeal (OP) microbiome of these populations in Heilongjiang Province, located in the North-East of China, a high-latitude and cold area with a high prevalence of respiratory tract infection and heart failure. Taxonomy-based analysis showed that six dominant phyla were represented in the OP microbial profiles. Compared with young adults, the OP in the elderly exhibited a significantly different microbial community, mainly characterized by highly prevalent Streptococcus, unidentified_Saccharibacteria, Veillonella, unidentified_Pre votellaceae, and Neisseria. While unidentified_Prevotellaceae dominated in the young OP microbiome. There was competition for niche dominance between Streptococcus and member of Prevotellaceae in the OP. Correlation analysis revealed that the abundance of unidentified_Saccharibacteria was positive, while Streptococcus was negatively correlated to age among healthy elderly. The bacterial structure and abundance in the elderly with heart failure were much like healthy controls. Certain changes in microbial diversity indicated the potential OP microbial disorder in heart failure patients. These results presented here identify the respiratory tract core microbiota in high latitude and cold regions, and reveal the robustness of OP microbiome in the aged, supplying the basis for microbiome-targeted interventions.IMPORTANCETo date, we still lack available data on the oropharyngeal (OP) microbial communities in healthy populations, especially the elderly, in high latitude and cold regions. A better understanding of the significantly changed respiratory tract microbiota in aging can provide greater insight into characteristics of longevity and age-related diseases. In addition, determining the relationship between heart failure and OP microbiome may provide novel prevention and therapeutic strategies. Here, we compared OP microbiome in different age groups and elderly people with or without heart failure in northeastern China. We found that OP microbial communities are strongly linked to healthy aging. And the disease status of heart failure was not a powerful factor affecting OP microbiome. The findings may provide basic data to reveal respiratory bacterial signatures of individuals in a cold geographic region.

Shirebi granules ameliorate acute gouty arthritis by inhibiting NETs-induced imbalance between immunity and inflammation.

BACKGROUND: Acute gouty arthritis (AGA) is classified as 'arthritis' in traditional Chinese medicine (TCM) theory. Shirebi granules (SGs), derived from the classic prescription SiMiaoWan, exerts satisfying therapeutic efficacy in ameliorating AGA clinically. However, the underlying mechanisms of SGs against AGA remain unclarified. METHODS: AGA-related biological processes, signal pathways and biomarker genes were mined from the GEO database through bioinformatics. SGs components were systematically recognized using the UPLC-Q-TOF-MS/MS. A correlation network was established based on the biomarker genes and the chemical components, from which the signal pathway used for further study was selected. Finally, we established an AGA model using SD rats injected with monosodium urate (MSU) in the ankle joint for experimental validation. A combination of behavioral tests, H&E, safranin O- fast green, western blotting, and immunofluorescence were employed to reveal the mechanism of action of SGs on AGA. RESULTS: The deterioration of AGA was significantly related to the imbalance between immunity and inflammation, neutrophil chemotaxis and inflammatory factor activation. HDAC5, PRKCB, NFκB1, MPO, PRKCA, PIK3CA were identified to be the candidate targets of SGs against AGA, associated with neutrophil extracellular traps (NETs) signal pathway. Animal experiments demonstrated that SGs effectively repaired cartilage damage, blocked TLR4 activation, and inhibited the expression of NETs indicators and inflammatory factors. In addition, SGs prominently alleviated joint redness and swelling, improved joint dysfunction, inhibited inflammatory infiltration of AGA rats. CONCLUSION: Our data reveal that SGs may effectively alleviate the disease severity of AGA by suppressing NETs-promoted imbalance between immunity and inflammation.

Caries trajectories from childhood to adolescence: Analysis of data from a nationwide school dental service.

OBJECTIVES: The aim of the study was to assess patterns of longitudinal changes in caries status among school-going children in Singapore. METHODS: Dental records for a single cohort of students who received dental examinations in six standard examination years between 2009 and 2017 were analysed (n = 24 699). Group-based trajectory modelling with a zero-inflated Poisson distribution was carried out to determine dental caries trajectories in the permanent dentition. Associations between sociodemographic factors and trajectory group membership were assessed using multinomial logistic regression. RESULTS: The predicted population distribution across the four caries trajectory groups identified was 65.0% ('none'), 16.8% ('low'), 14.8% ('medium') and 3.4% ('high'). The 'none' trajectory group had a decayed, missing and filled teeth (DMFT) score of 0 throughout the 8 years. Higher baseline DMFT counts and nonlinear increases in DMFT scores were noted for the 'low', 'medium' and 'high' trajectory groups. The correlation coefficient between DMFT counts in years 6 and 8 was 0.91, as compared to 0.77 between baseline and year 1. Factors associated with the 'high' caries trajectory include lower socio-economic status, female gender, Chinese race (compared to the Indian race), enrolment in primary schools in the Eastern and Western regions of Singapore, and enrolment in public secondary schools. CONCLUSIONS: Under a nationwide school dental service, four trajectory patterns of caries counts in the permanent dentition were identified over 8 years. Among students in the 'low', 'medium' and 'high' trajectory groups, greater caries increment was noted during the transition from primary to secondary school. The correlation between DMFT counts in successive examinations was stronger in older than younger ages.

Tianhe Zhuifeng Gao reverses inflammatory response and attenuates bone/cartilage destruction in rheumatoid arthritis via PSMC2-RUNX2-COL1A1 axis based on transcriptional regulatory network analysis and experimental validation.

BACKGROUND: Tianhe Zhuifeng Gao (TZG) is an authorized Chinese patent drug with satisfying clinical efficacy, especially for RA patients with cold-dampness syndrome. However, its underlying pharmacological mechanisms remain unclear. METHOD: Anti-arthritic effects of TZG were evaluated using an adjuvant-induced arthritis (AIA) rat model. Transcriptional regulatory network analysis based on synovial tissues obtained from AIA rats, combining with our previous analysis based on whole blood samples from RA patients with cold-dampness syndrome and co-immunoprecipitation were performed to identify involved dominant pathways, which were experimentally verified using AIA-wind-cold-dampness stimulation modified (AIA-M) animal model. RESULTS: TZG treatment dramatically attenuated joint injury and inflammatory response in AIA rats, and PSMC2-RUNX2-COL1A1 axis, which was closely associated with bone/cartilage damage, was inferred to be one of therapeutic targets of TZG against RA. Experimentally, TZG displayed obvious pharmacological effects for alleviating the joint inflammation and destruction through reinstating the body weight, reducing the arthritis score, the limbs diameters, the levels of RF and CRP, and the inflammatory cytokines, recovering the thymus and spleen indexes, diminishing bone and cartilage destruction, as well elevating the pain thresholds of AIA-M rats. In addition, TZG markedly reversed the abnormal energy metabolism in AIA-M rats through enhancing articular temperature, daily water consumption, and regulating expression levels of energy metabolism parameters and hormones. Moreover, TZG also significantly modulated the abnormal expression levels of PSMC2, RUNX2 and COL1A1 proteins in the ankle tissues of AIA-M rats. CONCLUSION: TZG may exert the bone protective effects in RA therapy via regulating bone and cartilage damage-associated PSMC2-RUNX2-COL1A1 axis.

Renal denervation alleviates vascular remodeling in spontaneously hypertensive rats by regulating perivascular adipose tissue.

Vascular remodeling is the main pathological process that causes the damage of the target organ of hypertension. Perivascular adipose tissue (PVAT) surrounds blood vessels and plays a key role in the pathogenesis of various cardiovascular diseases. This study aimed to investigate the effects of renal denervation (RDN) on hypertensive vascular remodeling and to elucidate the role of PVAT in this process. Male spontaneously hypertensive rat (SHR) and Wistar-Kyoto (WKY) rat were selected. Aortic vascular remodeling was evaluated using hematoxylin and eosin (H&E) staining and Masson's trichrome staining. Morphological changes in the PVAT were observed through H&E and Oil Red O staining. Dihydroethidium was used to measure oxidative stress levels in PVAT, while western blot analysis was used to determine the expression levels of proteins associated with vascular remodeling. The results showed that the aortic medial thickness, media thickness/lumen diameter, collagen volume fraction, and reactive oxygen species (ROS) level in PVAT were significantly higher in the SHR group than in the WKY group. The indexes mentioned above were lower in the SHR-RDN group than in the SHR group. H&E staining revealed that fat droplets in PVAT in the SHR-RDN group became smaller and browning occurred. Moreover, the protein expression of uncoupling protein-1 (UCP-1) and neuregulin 4 (Nrg4) was significantly increased in the SHR-RDN group. In addition, the expression of adiponectin increased and the expression of leptin decreased in the SHR-RDN group compared to the SHR group. In conclusion, RDN can relieve hypertensive vascular remodeling, which may be associated with PVAT.

Efficacy and safety of simple analgesics for acute treatment of episodic tension-type headache in adults: a network meta-analysis.

OBJECTIVE: Tension-type headache is the most common type of primary headache and results in a huge socioeconomic burden. This network meta-analysis (NMA) aimed to compare the efficacy and safety of simple analgesics for the treatment of episodic tension-type headache (ETTH) in adults. METHODS: We searched the Cochrane Library, PubMed, Web of Science, Embase, Chinese BioMedical Literature database and International Clinical Trials Registry Platform databases for eligible randomized clinical trials reporting the efficacy and/or safety of simple analgesics. A Bayesian NMA was performed to compare relative efficacy and safety. The surface under the cumulative ranking curve (SUCRA) was calculated to rank interventions. PROSPERO registration number: CRD42018090554. RESULTS: We highlighted six studies including 3507 patients. For the 2 h pain-free rate, the SUCRA ranking was ibuprofen > diclofenac-K > ketoprofen > acetaminophen > naproxen > placebo. All drugs except naproxen reported a higher 2 h pain-free rate than placebo, with a risk ratio (RR) of 2.86 (95% credible interval, CrI: 1.62-5.42) for ibuprofen and 2.61 (1.53-4.88) for diclofenac-K. For adverse events rate, the SUCRA ranking was: metamizol > diclofenac-K > ibuprofen > lumiracoxib > placebo > aspirin > acetaminophen > naproxen > ketoprofen. The adverse event rates of all analgesics were no higher than those of placebo, except for ketoprofen. Moreover, all drugs were superior to placebo in the global assessment of efficacy. In particular, the RR of lumiracoxib was 2.47 (1.57-4.57). Global heterogeneity I2 between the studies was low. CONCLUSIONS: Simple analgesics are considered more effective and safe as a placebo for ETTH in adults. Our results suggest that ibuprofen and diclofenac-K may be the two best treatment options for patients with ETTH from a comprehensive point of view (both high-quality evidence).

To our knowledge, this is the first network meta-analysis comparing the available data on adult patients with episodic tension-type headache (ETTH) treated with different simple analgesics recommended by the current guidelines.Ibuprofen (400 mg) and diclofenac-K (12.5 mg, 25 mg) are potentially the most effective and safe treatment options, supported by high-quality evidence.

Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma.

Background: To date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials. Aim: To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life. Methods: This was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers. Results: Overall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R2: 0.751), compared to BEC (adjusted R2: 0.747) or FeNO alone (adjusted R2: 0.743) (p=0.005 and <0.001, respectively); however, this prediction was not improved by the addition of IgE. Conclusions: The ability of higher baseline BEC, FeNO and their combination to predict biologic-associated lung function improvement may encourage earlier intervention in patients with impaired lung function or at risk of accelerated lung function decline.

Reduced plasma cortistatin is related to clinical parameters in patients with essential hypertension.

BACKGROUND: Cortistatin (CST), an endogenous bioactive polypeptide, has been acknowledged for its protective effect against several cardiovascular diseases, but its relationship with hypertension remains unclear. Therefore, we aimed to investigate changes in plasma CST in hypertensive patients and further analyze correlations with blood pressure, metabolic parameters and left ventricular structure and function. METHODS: In this hospital-based study, basic information and plasma samples for evaluating clinically relevant indicators such as total cholesterol (TC), triglycerides (TGs), fasting blood glucose (FGB), serum creatinine (Scr) and CST were collected from 81 essential hypertension patients and 75 normotensive subjects. Plasma CST levels were examined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with normotensive subjects, plasma CST was significantly lower in hypertensive patients. Plasma CST levels in hypertensive patients without blood pressure control was significantly lower than those of hypertensive patients with blood pressure control. Plasma CST levels were significantly negatively correlated with SBP and serum creatinine (Scr) in the overall population. Furthermore, multivariate logistic regression analysis showed that the OR of CST for hypertension was 0.64 using the unadjusted model, and there was still statistical significance using the four-adjusted model. CONCLUSIONS: The circulating concentration of CST was significantly lower in hypertensive patients and was higher after blood pressure control, suggesting that CST may be a new endogenous protective target for hypertension.

Use of aspirin in cardiovascular disease prevention-the role of online information search.

OBJECTIVES: This study intends to examine influences of online information search on the use of aspirin in cardiovascular diseases (CVDs) prevention among the applicable adult population in the United States. METHODS: We used data of 2018 National Health Interview Survey (NHIS). Our study sample is limited to adults age 40 or older to be consistent with the American Heart Association/American College of Cardiology Foundation (AHA/ACCF) guidelines for aspirin use. Linear probability models were used to test the association between patient's aspirin use behaviors and the variables of interest in four separate models. RESULTS: Our results show that the use of aspirin for CVD prevention was associated with online health information seeking in different ways. When patients received doctors' advice to use aspirin, online information seeking has a negative influence, depending on whether the individual has CVD risk factors. However, for patients without recommendations from providers, the effects of online information seeking on self-initiated aspirin use depend on the different types of preventions (primary vs. secondary) and CVD risk factors. CONCLUSION: Overall, online health information might lead to both overuse and underuse of aspirin in CVD preventions. Findings in this study may lead to decision-making that is not consistent with advice from healthcare professionals and/or established clinical guidelines.

Effect of tissue factor pathway inhibitor on the pyroptosis of vascular smooth muscle cells induced by angiotensin II.

Background: In recent years, a mass of studies have shown that pyroptosis plays an important role in the proliferation of vascular smooth muscle cells (VSMCs). We investigated whether angiotensin II (Ang II) induces the pyroptosis of rat aortic VSMCs and the role of NOD-like receptor family pyrin domain containing 3 (NLRP3) in this process. Additionally, we explored the effect and related mechanism of recombinant tissue factor pathway inhibitor (rTFPI) in Ang II-induced VSMC pyroptosis. Methods: Cultured VSMCs were divided into five groups: control group, Ang II group (1×10-5 mol/L), MCC950 group (NLRP3 inhibitor, 15 nmol/L), Ang II + MCC950 group and Ang II + rTFPI (50 µg/L) group. Cell viability was measured by cell counting kit-8 (CCK8) assays and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays. Propidium iodide (PI) staining and immunofluorescence were performed to determine the pyroptosis of VSMCs. Changes in VSMC ultrastructure were evaluated through transmission electron microscopy. The expression levels of NLRP3, pro-caspase-1, gasdermin D-N (GSDMD-N), and interleukin-1ß (IL-1ß) were determined by western blot analysis. Results: The cell viability, the positive rate of PI staining, and the expression level of GSDMD detected by immunofluorescence in the Ang II group were higher than that in the control group, whereas they all decreased in Ang II + MCC950 group and Ang II + rTFPI group compared with Ang II group (P<0.05). Electron microscopy analysis revealed less extracellular matrix, increased myofilaments, and decreased endoplasmic reticulum, Golgi complex, and mitochondria in Ang II + rTFPI-treated VSMCs than in Ang II-treated VSMCs. The protein expression levels of the pyroptosis-related molecules NLRP3, pro-caspase-1, GSDMD-N, and IL-1ß in Ang II group showed an increasing trend compared with those in control group (P<0.05); however, these expression levels in Ang II + MCC950 and Ang II + rTFPI groups were significantly lower than those in Ang II group (P<0.05). Conclusions: Ang II may induce pyroptosis in VSMCs by activating NLRP3. rTFPI can inhibit Ang II-induced VSMC pyroptosis. Furthermore, rTFPI might exert this effect by inhibiting the NLRP3 pathway and therefore play an important role in the treatment of vascular remodeling induced by hypertension.

Teleconsultation dynamic scheduling with a deep reinforcement learning approach.

In this study, the start time of teleconsultations is optimized for the clinical departments of class A tertiary hospitals to improve service quality and efficiency. For this purpose, first, a general teleconsultation scheduling model is formulated. In the formulation, the number of services (NS) is one of the objectives because of demand intermittency and service mobility. Demand intermittency means that demand has zero size in several periods. Service mobility means that specialists move between clinical departments and the National Telemedicine Center of China to provide the service. For problem-solving, the general model is converted into a Markov decision process (MDP) by elaborately defining the state, action, and reward. To solve the MDP, deep reinforcement learning (DRL) is applied to overcome the problem of inaccurate transition probability. To reduce the dimensions of the state-action space, a semi-fixed policy is developed and applied to the deep Q network (DQN) to construct an algorithm of the DQN with a semi-fixed policy (DQN-S). For efficient fitting, an early stop strategy is applied in DQN-S training. To verify the effectiveness of the proposed scheduling model and the model solving method DQN-S, scheduling experiments are carried out based on actual data of teleconsultation demand arrivals and service arrangements. The results show that DQN-S can improve the quality and efficiency of teleconsultations by reducing 9%-41% of the demand average waiting time, 3%-42% of the number of services, and 3%-33% of the total cost of services.

A Redactable Blockchain-Based Data Management Scheme for Agricultural Product Traceability.

With the development of agricultural information technology, the Internet of Things and blockchain have become important in the traceability of agricultural products. Sensors collect real-time data in agricultural production and a blockchain provides a secure and transparent storage medium for these data, which improves the transparency and credibility of agricultural product traceability. However, existing agricultural product traceability solutions are limited by the immutability of the blockchain, making it difficult to delete erroneous data and modify the scope of data sharing. This damages the credibility of traceability data and is not conducive to the exchange and sharing of information among enterprises. In this article, we propose an agricultural product traceability data management scheme based on a redactable blockchain. This scheme allows agricultural enterprises to encrypt data to protect privacy. In order to facilitate the maintenance and sharing of data, we introduce a chameleon hash function to provide data modification capabilities. Enterprises can fix erroneous data and update the access permissions of the data. To improve the efficiency of block editing, our scheme adopts a distributed block editing method. This method supports threshold editing operations, avoiding single-point-of-failure issues. We save records of data modifications on the blockchain and establish accountability mechanisms to identify malicious entities. Finally, in this paper we provide a security analysis of our proposed solution and verify its effectiveness through experiments. Compared with the existing scheme, the block generating speed is improved by 42% and the block editing speed is improved by 29.3% at 125 nodes.

International Variation in Severe Exacerbation Rates in Patients With Severe Asthma.

BACKGROUND: Exacerbation frequency strongly influences treatment choices in patients with severe asthma. RESEARCH QUESTION: What is the extent of the variability of exacerbation rate across countries and its implications in disease management? STUDY DESIGN AND METHODS: We retrieved data from the International Severe Asthma Registry, an international observational cohort of patients with a clinical diagnosis of severe asthma. We identified patients aged ≥ 18 years who did not initiate any biologics prior to baseline visit. A severe exacerbation was defined as the use of oral corticosteroids for ≥ 3 days or asthma-related hospitalization/ED visit. A series of negative binomial models were applied to estimate country-specific severe exacerbation rates during 365 days of follow-up, starting from a naive model with country as the only variable to an adjusted model with country as a random-effect term and patient and disease characteristics as independent variables. RESULTS: The final sample included 7,510 patients from 17 countries (56% from the United States), contributing to 1,939 severe exacerbations (0.27/person-year). There was large between-country variation in observed severe exacerbation rate (minimum, 0.04 [Argentina]; maximum, 0.88 [Saudi Arabia]; interquartile range, 0.13-0.54), which remained substantial after adjusting for patient characteristics and sampling variability (interquartile range, 0.16-0.39). INTERPRETATION: Individuals with similar patient characteristics but coming from different jurisdictions have varied severe exacerbation risks, even after controlling for patient and disease characteristics. This suggests unknown patient factors or system-level variations at play. Disease management guidelines should recognize such between-country variability. Risk prediction models that are calibrated for each jurisdiction will be needed to optimize treatment strategies.

Small nucleolar RNA and its potential role in the oncogenesis and development of colorectal cancer.

Small nucleolar RNAs (snoRNAs) represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification, thereby contributing significantly to the maintenance of cellular functions related to protein synthesis. SnoRNAs have been discovered to possess the ability to influence cell fate and alter disease progression, holding immense potential in controlling human diseases. It is suggested that the dysregulation of snoRNAs in cancer exhibits differential expression across various cancer types, stages, metastasis, treatment response and/or prognosis in patients. On the other hand, colorectal cancer (CRC), a prevalent malignancy of the digestive system, is characterized by high incidence and mortality rates, ranking as the third most common cancer type. Recent research indicates that snoRNA dysregulation is associated with CRC, as snoRNA expression significantly differs between normal and cancerous conditions. Consequently, assessing snoRNA expression level and function holds promise for the prognosis and diagnosis of CRC. Nevertheless, current comprehension of the potential roles of snoRNAs in CRC remains limited. This review offers a comprehensive survey of the aberrant regulation of snoRNAs in CRC, providing valuable insights into the discovery of novel biomarkers, therapeutic targets, and potential tools for the diagnosis and treatment of CRC and furnishing critical cues for advancing research into CRC and the judicious selection of therapeutic targets.

Predictors of persistent poor control and validation of ASSESS score: Longitudinal 5-year follow-up of severe asthma cohort.

Background: Longitudinal predictors of persistent poor asthma control in severe asthma (SA) cohort remain scarce. The predictive value of the asthma severity scoring system (ASSESS) in the SA cohort outside the original study and in the Asian population is unknown. Objective: We sought to determine the 5-year longitudinal outcome of patients with SA and validate the use of ASSESS score in predicting future outcomes in SA. Methods: A prospective longitudinal observational study of patients with SA attending the multidisciplinary specialist SA clinic of the Singapore General Hospital from 2011 to 2021 was conducted. The number of exacerbations and asthma control test results were recorded yearly for 5 consecutive years. The ASSESS score was computed at baseline, and the area under the receiver-operating characteristic curve for predicting persistent poor asthma control was generated. Results: Of the 489 patients recruited into the study, 306 patients with 5-year follow-up data were analyzed. Seventy-three percent had type 2 inflammation with increased overall exacerbations over 5 years (rate ratio, 2.55; 95% CI, 1.31-4.96; P = .006) relative to non-type 2 SA. In the multivariate model, bronchiectasis, gastroesophageal reflux disease, and an asthma control test score of less than 20 were significantly associated with persistent poor asthma control over 5 years. ASSESS scores were good at predicting persistent poor asthma control with an area under the receiver-operating characteristic curve of 0.71 (95% CI, 0.57-0.84). Conclusions: Bronchiectasis and gastroesophageal reflux disease are predictors for persistent poor asthma control and targeted traits for precision medicine in SA. The ASSESS score has a good prediction for persistent poor asthma control over 5 years.