Transcriptomic analysis reveals Cilostazol's role in ameliorating cardiovascular disease: Inhibition of monocyte-to-macrophage differentiation and reduction of endothelial cell reactive oxygen species production.

Background: Cardiovascular diseases (CVDs) are the leading global cause of death, with atherosclerosis as the primary cause. Chronic inflammation, endothelial dysfunction, and the role of molecules like nitric oxide and reactive oxygen species are crucial in this context. Our previous research indicated that cilostazol and ginkgo biloba extract could enhance the ability of endothelial cells to dissolve blood clots, but the effects of cilostazol on monocytes remain unexplored. Method: This study utilized peripheral blood mononuclear cells from 10 healthy donors, treated ex vivo with cilostazol. RNA-sequencing, over-representation analysis, xCell stromal cell analysis, and Gene Set Enrichment Analysis were employed to investigate the gene expression changes and biological pathways affected by cilostazol treatment. Results: The study identified specific gene sets and pathways that were enriched or reduced in response to cilostazol treatment, providing insights into its effects on monocytes and potential therapeutic applications in CVD. The analysis also revealed the potential impact of cilostazol on the stromal cell compartment, further broadening our understanding of its multifaceted role. Conclusion: The findings offer a nuanced understanding of the advantages and mechanisms of cilostazol in CVD, uncovering novel therapeutic targets and strategies to enhance the clinical application of cilostazol and contributing to the broader implications of this therapy in cardiovascular health.

Gallbladder carcinosarcoma with a poor prognosis: A case report.

BACKGROUND: Carcinosarcoma of the gallbladder is a rare malignant tumor with a very poor prognosis. To date, only approximately 100 patients have been reported in the English literature. The prognosis of this tumor type is poor, the preoperative diagnosis is difficult, and there is a possibility of a misdiagnosis. We present an unsuccessful case of carcinosarcoma of the gallbladder with a preoperative misdiagnosis and rapid early postoperative recurrence. Therefore, we have a deeper understanding of the poor prognosis of gallbladder carcinosarcoma (GBC) patients. CASE SUMMARY: The patient is a 65-year-old male. He was admitted to the hospital because of right upper abdomen distending pain and discomfort for half a month. Abdominal magnetic resonance imaging revealed a polycystic mass in the right lobe of the liver and the fossa of the gallbladder. After admission, the patient was diagnosed with a liver abscess, which was treated by abscess puncture drainage. Obviously, this treatment was unsuccessful. Hepatectomy and cholecystectomy were performed one month after the puncture. Postoperative pathologic examination revealed carcinosarcoma of the gallbladder, and the resected specimen contained two tumor components. One month after surgery, the patient's tumor recurred in situ and started to compress the duodenum, resulting in duodenal obstruction and bleeding. The treatment was not effective. The patient died of gastrointestinal hemorrhage and hypovolemic shock. CONCLUSION: Carcinosarcoma of the gallbladder is a rare malignant tumor that is easily misdiagnosed preoperatively and has a poor prognosis.

Different Impacts of Traffic-Related Air Pollution on Early-Onset and Late-Onset Asthma.

Background: Early-onset asthma (EOA) and late-onset asthma (LOA) are two distinct phenotypes. Air pollution has been associated with an increase in poorer asthma outcomes. The objective of this study was to examine the effects of traffic-related air pollution (TRAP) on asthma outcomes in EOA and LOA patients. Methods: A cross-sectional study was conducted on 675 asthma patients (LOA: 415) recruited from a major medical center in Taiwan. The land-use regression (LUR) model was used to estimate the level of exposure to PM10, PM2.5, NO2, and O3 on an individual level. We investigated the association between TRAP and asthma outcomes in EOA and LOA patients, stratified by allergic sensitization status, using a regression approach. Results: An increase in PM10 was associated with younger age of onset, increased asthma duration, and decreased lung function in EOA patients (p<0.05). An increase in PM10 was associated with older age of onset, and decreased asthma duration, eosinophil count, and Asthma Control Test (ACT) score in LOA patients. An increase in PM2.5 was associated with younger age of onset, increased asthma duration, decreased eosinophil count, and lung function in EOA patients (p<0.05). An increase in PM2.5 was associated with decreased lung function and ACT score in LOA patients. An increase in NO2 was associated with increased eosinophil count and decreased lung function in EOA patients (p<0.05). An increase in O3 was associated with decreased lung function in LOA patients (p<0.05). In addition, associations of TRAP with age of onset and eosinophil counts were mainly observed in both EOA and LOA patients with allergic sensitization, and an association with ACT was mainly observed in LOA patients without allergic sensitization. Conclusion: The impact of TRAP on age of onset, eosinophil count, and lung function in EOA patients, and ACT in LOA patients, was affected by the status of allergic sensitization.

The bidirectional associations between sarcopenia-related traits and cognitive performance.

While many studies have sought to explore the degree to which sarcopenia-related traits are associated with cognitive performance, these studies have yielded contradictory results without any clear indication of the causality of such relationships. In efforts to better understand associations between sarcopenia-related traits and cognitive ability, a series of multivariate linear regression assessments were carried out upon datasets derived through the National Health and Nutrition Examination Survey (NHANES). Of these, cognitive performance was assessed by the Digit Symbol Substitution Test (DDST), the Consortium to Establish a Registry for Alzheimer's Disease Immediate Recall Test (CERAD-IR), Delayed Recall Test (CERAD-DR) and Animal Fluency Test (AFT). Causal relationships between the two were further inferred via a two-sample Mendelian randomization (MR) analysis approach. Sarcopenia-related traits considered in these assessments included walking speed, appendicular skeletal muscle mass (ASM), and hand grip strength (HGS). Walking speed, ASM, and HGS were all significantly independently related to cognitive scores following adjustment for covariates. MR assessments also identified that each 1-SD higher walking speed and appendicular lean mass were causally and respectively associated with a 0.34 [standard error (SE) = 0.09; p < 0.001)] standardized score higher and a 0.07 (SE = 0.01; p < 0.001) standardized score higher cognitive score, whereas a higher hand grip strength was positively associated with a better cognitive performance. Reverse MR assessments also yielded similar findings. These data suggest that lower walking speed, muscle strength, and muscle mass were all closely related to lower cognitive performance irrespective of gender, and that there may be a mutually reinforcing relationship among these variables.

Discovery of anti-inflammatory agents from 3, 4-dihydronaphthalene-1(2H)-one derivatives by inhibiting NLRP3 inflammasome activation.

NLRP3 inflammatory vesicles are a polymer of cellular innate immunity composed of a pair of proteins. The continuous activation of NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammatory vesicles induces the occurrence and enhancement of inflammatory response. In this study, a series of 3, 4-dihydronaphthalene-1(2H)-one derivatives (DHNs, 6a-u, 7a-e, 8a-n) were synthesized and characterized by NMR and HRMS. We evaluated the cytotoxicity and anti-inflammatory activity of all compounds in vitro, and selected 7a substituted by 7-Br in A-ring and 2-pyridylaldehyde in C-ring as effective lead compounds. Specifically, 7a can block the assembly and activation of NLRP3 inflammasome by down-regulating the expression of NLPR3 and apoptosis-associated speck-like protein containing a CARD (ASC), and inhibiting the production of reactive oxygen species (ROS) and other inflammatory mediators. In addition, 7a inhibits the phosphorylation of inhibitor kappa B alpha (IκBα) and NF-κB/p65 and the nuclear translocation of p65, thereby inhibiting nuclear factor kappa-B (NF-κB) signaling. Molecular docking analysis confirmed that 7a could reasonably bind the active sites of NLRP3, ASC and p65 proteins. Therefore, 7a is predicted as a potential NLRP3 inflammatory vesicle inhibitor and deserves further research and development.

Urinary cadmium concentration is associated with the severity and clinical outcomes of COVID-19: a bicenter observational cohort study.

BACKGROUND: Cadmium and nickel exposure can cause oxidative stress, induce inflammation, inhibit immune function, and therefore has significant impacts on the pathogenesis and severity of many diseases. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can also provoke oxidative stress and the dysregulation of inflammatory and immune responses. This study aimed to assess the potential associations of cadmium and nickel exposure with the severity and clinical outcomes of patients with coronavirus disease 2019 (COVID-19). METHODS: We performed a retrospective, observational, bicenter cohort analysis of patients with SARS-CoV-2 infection in Taiwan between June 2022 and July 2023. Cadmium and nickel concentrations in blood and urine were measured within 3 days of the diagnosis of acute SARS-CoV-2 infection, and the severity and clinical outcomes of patients with COVID-19 were analyzed. RESULTS: A total of 574 patients were analyzed and divided into a severe COVID-19 group (hospitalized patients) (n = 252; 43.9%), and non-severe COVID-19 group (n = 322; 56.1%). The overall in-hospital mortality rate was 11.8% (n = 68). The severe COVID-19 patients were older, had significantly more comorbidities, and significantly higher neutrophil/lymphocyte ratio, C-reactive protein, and interleukin-6 than the non-severe COVID-19 patients (all p < 0.05). Blood and urine cadmium and urine nickel concentrations were significantly higher in the severe COVID-19 patients than in the non-severe COVID-19 patients. Among the severe COVID-19 patients, those in higher urine cadmium/creatinine quartiles had a significantly higher risk of organ failure (i.e., higher APACHE II and SOFA scores), higher neutrophil/lymphocyte ratio, lower PaO2/FiO2 requiring higher invasive mechanical ventilation support, higher risk of acute respiratory distress syndrome, and higher 60-, 90-day, and all-cause hospital mortality (all p < 0.05). Multivariable logistic regression models revealed that urine cadmium/creatinine was independently associated with severe COVID-19 (adjusted OR 1.643 [95% CI 1.060-2.547], p = 0.026), and that a urine cadmium/creatinine value > 2.05 µg/g had the highest predictive value (adjusted OR 5.349, [95% CI 1.118-25.580], p = 0.036). CONCLUSIONS: Urine cadmium concentration in the early course of COVID-19 could predict the severity and clinical outcomes of patients and was independently associated with the risk of severe COVID-19.

Epidemiology and outcomes of multidrug-resistant bacterial infection in non-cystic fibrosis bronchiectasis.

PURPOSE: Multidrug-resistant (MDR) bacteria impose a considerable health-care burden and are associated with bronchiectasis exacerbation. This study investigated the clinical outcomes of adult patients with bronchiectasis following MDR bacterial infection. METHODS: From the Chang Gung Research Database, we identified patients with bronchiectasis and MDR bacterial infection from 2008 to 2017. The control group comprised patients with bronchiectasis who did not have MDR bacterial infection and were propensity-score matched at a 1:2 ratio. The main outcomes were in-hospital and 3-year mortality. RESULTS: In total, 554 patients with both bronchiectasis and MDR bacterial infection were identified. The types of MDR bacteria that most commonly affected the patients were MDR- Acinetobacter baumannii (38.6%) and methicillin-resistant Staphylococcus aureus (18.4%), Extended-spectrum-beta-lactamases (ESBL)- Klebsiella pneumoniae (17.8%), MDR-Pseudomonas (14.8%), and ESBL-E. coli (7.5%). Compared with the control group, the MDR group exhibited lower body mass index scores, higher rate of chronic bacterial colonization, a higher rate of previous exacerbations, and an increased use of antibiotics. Furthermore, the MDR group exhibited a higher rate of respiratory failure during hospitalization (MDR vs. control, 41.3% vs. 12.4%; p < 0.001). The MDR and control groups exhibited in-hospital mortality rates of 26.7% and 7.6%, respectively (p < 0.001); 3-year respiratory failure rates of 33.5% and 13.5%, respectively (p < 0.001); and 3-year mortality rates of 73.3% and 41.5%, respectively (p < 0.001). After adjustments were made for confounding factors, the infection with MDR and MDR bacteria species were determined to be independent risk factors affecting in-hospital and 3-year mortality. CONCLUSIONS: MDR bacteria were discovered in patients with more severe bronchiectasis and were independently associated with an increased risk of in-hospital and 3-year mortality. Given our findings, we recommend that clinicians identify patients at risk of MDR bacterial infection and follow the principle of antimicrobial stewardship to prevent the emergence of resistant bacteria among patients with bronchiectasis.

Connections between body composition and dysregulation of islet α- and ß-cells in type 2 diabetes.

BACKGROUND: Accompanying islet α- and ß-cell dysregulation in type 2 diabetes (T2D) at the microscopic scale, alterations in body composition at the macroscopic scale may affect the pathogenesis of T2D. However, the connections between body composition and islet α-cell and ß-cell functions in T2D have not been thoroughly explored. METHODS: For this cross-sectional study, we recruited a total of 729 Chinese Han patients with T2D in a consecutive manner. Dual-energy X-ray absorptiometry (DXA) was used to measure body composition, which included total bone-free mass, total fat and lean mass, trunk fat and lean mass and limb fat and lean mass. Every patient underwent an oral glucose tolerance test to simultaneously detect glucose, C-peptide and glucagon. The indices of islet α-cell function included fasting glucagon levels and the area under the curve of glucagon after a challenge (AUCglucagon), while the indices of ß-cell function included the insulin sensitivity index derived from C-peptide (ISIC-peptide) and the area under the curve of C-peptide after a challenge (AUCC-peptide). RESULTS: Among all patients, fat mass, especially trunk fat mass, was significantly correlated with ISIC-peptide and AUCC-peptide levels (r = - 0.330 and 0.317, respectively, p < 0.001), while lean mass, especially limb lean mass, was significantly correlated with fasting glucagon and AUCglucagon levels (r = - 0.196 and - 0.214, respectively, p < 0.001). Moreover, after adjusting for other relevant variables via multivariate linear regression analysis, increased trunk fat mass was independently associated with decreased ISIC-peptide (ß = - 0.247, t = - 3.628, p < 0.001, partial R2 = 10.9%) and increased AUCC-peptide (ß = 0.229, t = 3.581, p < 0.001, partial R2 = 8.2%), while decreased limb lean mass was independently associated with increased fasting glucagon (ß = - 0.226, t = - 2.127, p = 0.034, partial R2 = 3.8%) and increased AUCglucagon (ß = - 0.218, t = - 2.050, p = 0.041, partial R2 = 2.3%). Additionally, when separate analyses were performed with the same concept for both sexes, we found that increased trunk fat mass was still independently associated with decreased ISIC-peptide and increased AUCC-peptide, while decreased limb lean mass was still independently associated with increased fasting glucagon and AUCglucagon. CONCLUSIONS: Increased trunk fat mass may partly account for decreased insulin sensitivity and increased insulin secretion, while decreased limb lean mass may be connected to increased fasting glucagon and postprandial glucagon secretion.

Thrombin worsens extravascular lung water and outcomes of septic patients with acute respiratory distress syndrome: A case control study.

Endothelial cell (EC) activation may increase systemic vascular permeability, causing extravascular lung water (EVLW) in sepsis with acute respiratory distress syndrome (ARDS). However, the correlation between thrombin and EVLW in sepsis and ARDS has not yet been addressed. Patients with sepsis and ARDS were prospectively enrolled between 2014 and 2016, and EVLW and serum thrombin levels on days 1 and 3 were measured and compared between surviving and non-surviving patients. Additionally, morphological changes in human umbilical vein endothelial cells (HUVECs) in the serum of patients with high and low EVLW were evaluated. The levels of EVLW, endothelial cells, and thrombin may positively correlate with the survival of patients with severe sepsis and ARDS. Twenty-seven patients were enrolled, and baseline characteristics, including age, sex, Acute Physiology and Chronic Health Evaluation (APACHE) II, prior 24-h fluid balance, body mass index, and shock status, were similar between survivors and non-survivors; however, day 1 EVLW was higher in non-survivors (27.5 ±â€…8.4 vs 22 ±â€…6.5 mL/kg, P = .047). EVLW of survivors improved from day 1 to day 3 (22 ±â€…6.5 vs 11 ±â€…3.8 mL/kg, P < .001), but did not improve in non-survivors (27.5 ±â€…8.4 vs 28 ±â€…6.7 mL/kg, P = .086), which means that patients had significantly lower EVLW on day 3 than on day 1. Thrombin levels of survivors significantly improved (1.03 ±â€…0.55 vs 0.87 ±â€…0.25 U/mL, P = .04) but did not improve in non-survivors (1.97 ±â€…0.75 vs 2.2 ±â€…0.75 U/mL, P = .08) from day 1 to day 3. EVLW and thrombin levels were positively correlated (r2 = 0.71, P < .0001). In vitro, the morphology and junctions of HUVECs changed when the serum from patients with high EVLW was added. The intercellular distances among the control, high EVLW, and low EVLW groups were 5.25 ± 1.22, 21.33 ± 2.15, and 11.17 ± 1.64 µm, respectively (P < .05).

Research progress into the application of Mycobacterium phlei in veterinary medicine.

Mycobacterium phlei is a gram-positive acid-fast mycobacterium from the family Mycobacteriaceae. It is a valuable resource for both natural drugs and microecological preparations. It has been widely used in the field of human medicine; however, in the field of animal husbandry and veterinary medicine, the research and application of M. phlei is still in the preliminary exploration stage. This study aims to summarize the research progress of M. phlei in the field of veterinary medicine and provide a valuable reference for future research. Key words, such as 'M. phlei', 'veterinary field', 'immune balancer', 'genome' and other relevant words to this study, were used to search through PubMed, Web of Science, SciELO, Science Direct and Google Scholar databases. The results showed that the culture conditions of M. phlei were relatively simple, but its bacterial composition and genome sequence were relatively complex, and various components in the cell wall may have immunoregulatory effects. Therefore, the inactivated preparation made from M. phlei can have various applications in the veterinary field, such as growth regulation, immune regulation, antitumour, anti-parasite and asthma treatment. The literature review indicates that M. phlei preparation is an efficient and convenient immune system balance agent. Despite the challenges associated with the use of M. phlei preparations, it has a strong potential for application in veterinary medicine.

A hybrid model of modal decomposition and gated recurrent units for short-term load forecasting.

Electrical load forecasting is important to ensuring power systems are operated both economically and safely. However, accurately forecasting load is difficult because of variability and frequency aliasing. To eliminate frequency aliasing, some methods set parameters that depend on experiences. The present study proposes an adaptive hybrid model of modal decomposition and gated recurrent units (GRU) to reduce frequency aliasing and series randomness. This model uses average sample entropy and mutual correlation to jointly determine the modal number in the decomposition. Random adjustment parameters were introduced to the Adam algorithm to improve training speed. To assess the applicability and accuracy of the proposed hybrid model, it was compared with some state of the art forecasting methods. The results, which were validated by actual data sets from Shaanxi province, China, show that the proposed model had a higher accuracy and better reliability compared to the other forecasting methods.

Hippocampus protection from apoptosis by Baicalin in a LiCl-pilocarpine-induced rat status epilepticus model through autophagy activation.

BACKGROUND: Autophagy is associated with hippocampal injury following status epilepticus (SE) and is considered a potential therapeutic mechanism. Baicalin, an emerging multitherapeutic drug, has shown neuroprotective effects in patients with nervous system diseases due to its antioxidant properties. AIM: To investigate the potential role of autophagy in LiCl-pilocarpine-induced SE. METHODS: The drugs were administered 30 min before SE. Nissl staining showed that Baicalin attenuated hippocampal injury and reduced neuronal death in the hippocampus. Western blotting and terminal deoxynucleotidyl transferase dUTP nick end labeling assay confirmed that Baicalin reversed the expression intensity of cleaved caspase-3 and apoptosis in hippocampal CA1 following SE. Fur-thermore, western blotting and immunofluorescence staining were used to measure the expression of autophagy markers (p62/SQSTM1, Beclin 1, and LC3) and apoptotic pathway markers (cleaved caspase-3 and Bcl-2). RESULTS: Baicalin significantly upregulated autophagic activity and downregulated mitochondrial apoptotic pathway markers. Conversely, 3-methyladenine, a commonly used autophagy inhibitor, was simultaneously administered to inhibit the Baicalin-induced autophagy, abrogating the protective effect of Baicalin on the mitochondrial apoptotic level. CONCLUSION: We illustrated that Baicalin-induced activation of autophagy alleviates apoptotic death and protects the hippocampus of SE rats.

Exosomal miR-21 determines lung-to-brain metastasis specificity through the DGKB/ERK axis within the tumor microenvironment.

BACKGROUND: Brain metastasis affects 20-40 % of lung cancer patients, severely diminishing their quality of life. This research focuses on miR-21, overexpressed in these patients and inversely associated with DGKB in the ERK/STAT3 pathway, suggesting a dysregulated pathway with therapeutic potential. AIMS: The objective was to investigate miR-21's role in lung cancer patients with brain metastases and whether targeting this pathway could improve treatment outcomes. We also examined the miR-21 content in tumor spheres-derived extracellular vesicles (EVs) and their influence on ERK/STAT3 signaling and metastasis. MATERIALS AND METHODS: Tumor spheres were created from metastatic lung cancer cells. We studied miR-21 levels in these spheres, their impact on macrophage polarization, and the transition of nonmetastatic lung cancer cells. Furthermore, we analyzed miR-21 content in EVs derived from these spheres and their effect on ERK/STAT3 signaling and metastasis potential. KEY FINDINGS: We found tumor spheres had high miR-21 levels, promoting macrophage polarization and, epithelial-mesenchymal transition. These spheres-derived EVs, enriched with miR-21, accelerated ERK/STAT3 signaling and metastasis. Silencing miR-21 and inhibiting ERK signaling with ulixertinib notably mitigated these effects. Moreover, ulixertinib reduced brain metastasis incidence and increased survival in a mouse model and led to reduced tumor sphere generation and miR-21 levels in EVs. SIGNIFICANCE: Our study highlights the exacerbation of lung-to-brain metastasis via miR-21-rich EV secretion. This underlines the therapeutic promise of targeting the miR-21/ERK/STAT3 pathway with ulixertinib for managing brain metastasis from lung cancer.

Multifunctional xyloglucan-containing electrospun nanofibrous dressings for accelerating infected wound healing.

Preventing wound infection is a major challenge in biomedicine. Conventional wound dressings often have poor moisturizing and antimicrobial properties unfavorable for wound healing. In this study, we prepared a multifunctional electrospun nanofiber dressing (PCQX-M) containing xyloglucan, quaternized chitosan, Polyvinyl alcohol, and collagen. By applying the concept of wet healing, xyloglucan and quaternized chitosan polysaccharides with excellent water solubility were employed to improve the absorption and moisturizing properties and maintain a moist microenvironment for the wound healing process. PCQX-M demonstrated high mechanical, thermodynamic, and biocompatible properties, providing suitable healing conditions for wounds. In addition, PCQX-M showed exceptional antibacterial properties and a potential inhibitory effect on the growth of microorganisms in infected wounds. More intriguingly, the restorative healing effect was investigated on a mouse model of whole skin injury infected with Staphylococcus aureus. Wound healing, collagen deposition, and immunofluorescence results showed that PCQX-M significantly promoted cell proliferation and angiogenesis at the injury site and facilitated the healing of the infected wound. Our study suggests that PCQX-M has excellent potential for clinical application in infected wound healing.

TIG1 Inhibits the mTOR Signaling Pathway in Malignant Melanoma Through the VAC14 Protein.

BACKGROUND/AIM: Currently, there are few drug options available to treat malignant melanoma. Tazarotene-inducible gene 1 (TIG1) was originally isolated from skin tissue, but its function in skin tissue has not been clarified. The aim of this study was to elucidate the effect of TIG1 and mTOR signaling pathways associated with VAC14 on melanoma. MATERIALS AND METHODS: The expression of TIG1 and VAC14 in melanoma tissue was analyzed using a melanoma tissue cDNA array. The interaction between TIG1 and VAC14 was analyzed using immunoprecipitation and immunostaining. Western blot was used to investigate the molecular targets of TIG1 and VAC14 in melanoma cells. RESULTS: TIG1 was highly expressed in normal skin tissue but was low in malignant melanoma, while VAC14 showed the opposite trend. TIG1 inhibited insulin-induced cell proliferation and insulin-activated mammalian target of rapamycin complex 1 (mTORC1)-p70 S6 kinase but did not affect the level of phospho-AKT in A2058 melanoma cells. This suggests that the main target of TIG1 regulating cell growth is phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] rather than the PI(4,5)P2 signaling pathway. Additional TIG1 showed no additive effect on the inhibition of mTOR signaling in the absence of VAC14 expression, suggesting that TIG1 inhibited the activation of mTOR mainly by inhibiting VAC14. CONCLUSION: TIG1 may play an important role in preventing malignant melanoma through retinoic acid via VAC14.

Efficacy of extracellular vesicles of different cell origins in traumatic brain injury: A systematic review and network meta-analysis.

Background: There was still no effective treatment for traumatic brain injury (TBI). Recently, many preclinical studies had shown promising efficacy of extracellular vesicles (EVs) from various cell sources. Our aim was to compare which cell-derived EVs were most effective in treating TBI through a network meta-analysis. Methods: We searched four databases and screened various cell-derived EVs for use in preclinical studies of TBI treatment. A systematic review and network meta-analysis were conducted for two outcome indicators, modified Neurological Severity Score (mNSS) and Morris Water Maze (MWM), and they were ranked by the surface under the cumulative ranking curves (SUCRA). Bias risk assessment was performed with SYRCLE. R software (version 4.1.3, Boston, MA, USA) was used for data analysis. Results: A total of 20 studies were included in this study, involving 383 animals. Astrocyte-derived extracellular vesicles (AEVs) ranked first in response to mNSS at day 1 (SUCRA: 0.26%), day 3 (SUCRA: 16.32%), and day 7 (SUCRA: 9.64%) post-TBI. Extracellular vesicles derived from mesenchymal stem cells (MSCEVs) were most effective in mNSS assessment on day 14 (SUCRA: 21.94%) and day 28 (SUCRA: 6.26%), as well as MWM's escape latency (SUCRA: 6.16%) and time spent in the target quadrant (SUCRA: 86.52%). The result of mNSS analysis on day 21 showed that neural stem cell-derived extracellular vesicles (NSCEVs) had the best curative effect (SUCRA: 6.76%). Conclusion: AEVs may be the best choice to improve early mNSS recovery after TBI. The efficacy of MSCEVs may be the best in the late mNSS and MWM after TBI. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023377350.

Risk Factors for Influenza-Induced Exacerbations and Mortality in Non-Cystic Fibrosis Bronchiectasis.

Influenza infection is a cause of exacerbations in patients with chronic pulmonary diseases. The aim of this study was to investigate the clinical outcomes and identify risk factors associated with hospitalization and mortality following influenza infection in adult patients with bronchiectasis. Using the Chang Gung Research Database, we identified patients with bronchiectasis and influenza-related infection (ICD-9-CM 487 and anti-viral medicine) between 2008 and 2017. The main outcomes were influenza-related hospitalization and in-hospital mortality rate. Eight hundred sixty-five patients with bronchiectasis and influenza infection were identified. Five hundred thirty-six (62%) patients with bronchiectasis were hospitalized for influenza-related infection and 118 (22%) patients had respiratory failure. Compared to the group only seen in clinic, the hospitalization group was older, with more male patients, a lower FEV1, higher bronchiectasis aetiology comorbidity index (BACI), and more acute exacerbations in the previous year. Co-infections were evident in 55.6% of hospitalized patients, mainly caused by Pseudomonas aeruginosa (15%), fungus (7%), and Klebsiella pneumoniae (6%). The respiratory failure group developed acute kidney injury (36% vs. 16%; p < 0.001), and shock (47% vs. 6%; p < 0.001) more often than influenza patients without respiratory failure. The overall mortality rate was 10.8% and the respiratory failure group exhibited significantly higher in-hospital mortality rates (27.1% vs. 6.2%; p < 0.001). Age, BACI, and previous exacerbations were independently associated with influenza-related hospitalization. Age, presence of shock, and low platelet counts were associated with increased hospital mortality. Influenza virus caused severe exacerbation in bronchiectasis, especially in those who were older and who had high BACI scores and previous exacerbations. A high risk of respiratory failure and mortality were observed in influenza-related hospitalization in bronchiectasis. We highlight the importance of preventing or treating influenza infection in bronchiectasis.

Clinical manifestations and outcomes of fungus-associated asthma: A multi-institution database study in Taiwan.

BACKGROUND: Differences in the clinical phenotypes and outcomes of fungus-associated asthma remain unclear. We aimed to investigate the presentation of asthmatics with fungal sensitization and/or positive fungal isolates. METHODS: Clinical characteristics, pulmonary function, microbiological data, allergy test reports, emergency department (ED) visits and hospitalizations were retrieved from the Chang Gung Research Database between 2010 and 2018; the largest electronic medical record-based database in Taiwan. Follow-up care was provided to each patient for 3 years. RESULTS: A total of 30,754 asthmatics were enrolled, and 7976 were eligible for analysis after applying the exclusion criteria. Of these patients, 694 had sputum examinations for fungi. The patients were divided into four groups: group 1, neither fungal sensitization nor fungal isolates in the sputum (n = 386); group 2, positive fungal sensitization (n = 58); group 3, positive fungal isolates (n = 217); and group 4, concomitant positive fungal sensitization and positive fungal isolates (n = 33). Asthmatic patients with fungal sensitization (groups 2 and 4) demonstrated significantly higher IgE levels compared with those without (groups 1 and 3). Group 4 patients had a higher frequency of hospitalization. Amongst patients under Global Initiative for Asthma (GINA) step 4-5 therapies, group 4 asthmatics possessed significantly higher incidence of respiratory failure. CONCLUSIONS: The prevalence of fungal sensitization and fungal isolates from sputum were even across asthmatic severities, but the clinical impact of fungi may be more significant among patients with more severe disease.

Benign paroxysmal positional vertigo with congenital nystagmus: A case report.

BACKGROUND: Benign paroxysmal positional vertigo (BPPV) is a form of temporary vertigo induced by moving the head to a specific position. It is a self-limited, peripheral, vestibular disease and can be divided into primary and secondary forms. Congenital nystagmus (CN), an involuntary, rhythmic, binocular-symmetry, conjugated eye movement, is found at birth or within 3 mo of birth. According to the pathogenesis, CN can be divided into sensory-defect nystagmus and motor-defect nystagmus. The coexistence of BPPV and CN is rarely seen in the clinic. CASE SUMMARY: A 62-year-old woman presented to our clinic complaining of a 15-d history of recurrent positional vertigo. The vertigo lasting less than 1 min occurred when she turned over, sometimes accompanied by nausea and vomiting. Both the patient and her father had CN. Her spontaneous nystagmus was horizontal to right; however, the gaze test revealed variable horizontal nystagmus with the same degree when the eyes moved. The patient's Dix-Hallpike test was normal, except for persistent nystagmus, and the roll test showed severe variable horizontal nystagmus, which lasted for about 20 s in the same direction as her head movement to the right and left, although the right-side nystagmus was stronger than the left-side. Since these symptoms were accompanied by nausea, she was diagnosed with BPPV with CN and treated by manual reduction. CONCLUSION: Though rare, if BPPV with CN is correctly identified and diagnosed, reduction treatment is comparably effective to other vertigo types.

Increased levels of serum adenosine deaminase and increased risk of diabetic peripheral neuropathy in type 2 diabetes.

Background: Increased serum adenosine deaminase (ADA) levels have been shown to be involved in metabolic abnormalities and immune disequilibrium, which may in turn contribute to inflammatory diseases. This study aimed to determine whether increased serum ADA levels are related to diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2D). Methods: This study was part of a series exploring the potential risks for DPN. All patients received DPN assessment based on neuropathic symptoms, neuropathic signs, and nerve conduction studies to calculate the composite Z score of nerve latency, amplitude and conduction velocity (NCV). DPN was confirmed by both at least a presentation of neuropathic symptoms/signs and an abnormal nerve conduction index. Serum ADA levels were also synchronously detected. Results: A total of 384 eligible patients with T2D were recruited for this study, and 24.5% (n=94) were determined to have DPN. Increases in serum ADA levels were closely associated with increases in composite Z score of latency (ß=0.263, t=5.273, p<0.001) and decreases in composite Z score of amplitude (ß=-0.126, t=-2.352, p=0.019) and NCV (ß=-0.201, t=-3.841, p<0.001) after adjusting for other clinical covariates. Moreover, each 5 U/L increase in serum ADA levels was associated with a 1.781-fold increased adjusted odds ratio of having DPN (95% confidence interval: 1.271-2.495). Furthermore, the optimal cut-off value of serum ADA levels to discriminate DPN was ≥14.2 U/L (sensitivity=59.57%, specificity=75.52% and Youden index=0.351) after analysis by receiver operating characteristic curve. Conclusions: Increased serum ADA levels may be a potential risk factor for DPN in patients with T2D.