Prognostic value of multi-PLD ASL-based cerebral perfusion ASPECTS in acute ischemic stroke.

Introduction: We aimed to verify the application value of the Alberta Stroke Program Early CT Score (ASPECTS) based on multiple post-labeling delay (multi-PLD) arterial spin labeling (ASL) for outcome assessment in acute ischemic stroke (AIS) patients. Method: The endpoint was modified Rankin scale score at 90 days (90-day mRS). Patients were divided into the good outcome (0-2) and poor outcome (3-6) groups. The independent samples t-test, Mann-Whitney U-test, and χ2-test were used to compare clinical and imaging parameters between groups. We used partial correlation analysis to evaluate the relationships between ASPECTS and outcomes. Multivariate logistic regression analysis was used to examine potential independent prognostic indicators. The receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the independent prognostic indicators in predicting outcomes. Results: Fifty-five AIS patients were included. The good outcome group had a lower baseline National Institutes of Health Stroke Scale (NIHSS; Z = -3.413, P < 0.001) and infarct core volume (ICV; Z = -3.114, P = 0.002) as well as higher cerebral blood flow (CBF)-ASPECTS (Z = -3.835, P < 0.001) and cerebral blood volume (CBV)-ASPECTS (Z = -4.099, P < 0.001). Higher CBF-ASPECTS (r = -0.459, P = 0.001), and CBV-ASPECTS (r = -0.502, P < 0.001) were associated with a lower 90-day mRS. The baseline NIHSS, CBF-ASPECTS, and CBV-ASPECTS were identified as independent prognostic indicators. The AUCs of the baseline NIHSS, CBF-ASPECTS, and CBV-ASPECTS were 83.3, 87.4, and 89.9%, respectively. Combining NIHSS with CBF-ASPECTS and CBV-ASPECTS, the AUC significantly improved to 96.3%. The combined three factors showed a significant difference compared to the baseline NIHSS (Z = 2.039, P = 0.041) and CBF-ASPECTS (Z = 2.099, P = 0.036), but no difference with CBV-ASPECTS (Z = 1.176, P = 0.239). Conclusions: The ASPECTS based on multi-PLD ASL is a valuable tool for identifying independent prognostic indicators and assessing clinical outcomes in AIS patients. The baseline NIHSS, combined with CBF-ASPECTS and CBV-ASPECTS, enhances the predictive efficacy of clinical outcomes in AIS patients. The CBV-ASPECTS alone can offer comparable predictive efficacy to the combination.

Circulating immune cells and apolipoprotein A mediation: a Mendelian randomization study on hypertensive disorder of pregnancy.

Background: Studies using observational epidemiology have indicated that inflammation and immunological dysregulation are important contributors to placental and renal failure, which ultimately results in maternal hypertension. The potential causal relationships between the immunophenotypes and hypertensive disorder of pregnancy (HDP) are yet unclear. Methods: We conducted two-sample Mendelian randomization (MR) analyses to thoroughly examine the relationship between immunophenotypes and HDP. The GWAS data on immunological traits was taken from public catalog for 731 immunophenotypes and the summarized GWAS data in 4 types of HDP were retrieved from FinnGen database. The link between immune cell traits and HDP was examined through our study methodology, taking into account both direct relationships and mediation effects of apolipoprotein A (apoA). The inverse variance weighted (IVW) method served as the main analysis, while sensitivity analysis was carried out as a supplement. Results: We identified 14 highly correlative immunophenotypes and 104 suggestive possible factors after investigating genetically predicted immunophenotype biomarkers. According to the IVW analysis, there was a strong correlation between HDP and HLA DR on DC and plasmacytoid DC. Reverse MR analysis showed that there was no statistically significant effect of HDP on immune cells in our investigation. Mediation analysis confirmed that apoA mediates the interaction between HLA DR on DC and HDP. Conclusion: Our results highlight the complex interplay of immunophenotypes, apoA, and HDP. Moreover, the pathophysiological link between HLA DR on DC and HDP was mediated by the level of apoA.

Novel bispecific antibody-drug conjugate targeting PD-L1 and B7-H3 enhances antitumor efficacy and promotes immune-mediated antitumor responses.

BACKGROUND: Antibody-drug conjugates (ADCs) offer a promising approach, combining monoclonal antibodies with chemotherapeutic drugs to target cancer cells effectively while minimizing toxicity. METHODS: This study examined the therapeutic efficacy and potential mechanisms of a bispecific ADC (BsADC) in laryngeal squamous cell carcinoma. This BsADC selectively targets the immune checkpoints programmed cell death ligand-1 (PD-L1) and B7-H3, and the precise delivery of the small-molecule toxin monomethyl auristatin E. RESULTS: Our findings demonstrated that the BsADC outperformed its bispecific antibody and PD-L1 or B7-H3 ADC counterparts, particularly in terms of in vitro/in vivo tumor cytotoxicity, demonstrating remarkable immune cytotoxicity. Additionally, we observed potent activation of tumor-specific immunity and significant induction of markers of immunogenic cell death (ICD) and potential endoplasmic reticulum stress. CONCLUSION: In conclusion, this novel BsADC, through immune checkpoint inhibition and promotion of ICD, amplified durable tumor immune cytotoxicity, providing novel insights and potential avenues for future cancer treatments and overcoming resistance.

High-risks drug adverse events associated with Cetirizine and Loratadine for the treatment of allergic diseases: A retrospective pharmacovigilance study based on the FDA adverse event reporting system database.

BACKGROUND: Cetirizine and Loratadine are the two best-selling second-generation antihistamines for allergic diseases. This study aims to provide a comparative analysis of the differences in adverse drug events (ADEs) between these two medications, which can assist clinicians in making appropriate treatment decisions. METHODS: ADE reports related to Cetirizine and Loratadine obtained from the FDA adverse event reporting system (FAERS) database were analyzed using disproportionality analysis and Bayesian analysis to evaluate and compare the ADE signals of both drugs. RESULTS: A total of 28,051 and 28,073 ADE reports were retrieved from the FAERS database related to Cetirizine and Loratadine, respectively, with both drugs showing a predominance of middle-aged females. Specifically, Loratadine was associated with respiratory symptoms, mainly nasal symptoms such as rhinorrhea (n = 326, ROR 6.75), sneezing (n = 251, ROR 15.24), and nasal congestion (n = 185, ROR 4.25), while Cetirizine did not show this association. Notably, both drugs exhibited strong signals for somnolence in the nervous and psychiatric systems, especially Cetirizine (Cetirizine, n = 2556, ROR 10.52 vs. Loratadine, n = 1200, ROR 7.76). Additionally, Cetirizine itself showed strong signals for attention disturbance (n = 233, ROR 3.3), while Loratadine was associated with nervousness (n = 145, ROR 3.3). Further exploration revealed more severe adverse reactions closely associated with Cetirizine, including hallucinations, aggression, and abnormal behavior. Importantly, Cetirizine was significantly associated with the occurrence of pericarditis (n = 138, ROR 8.13), potentially leading to serious adverse consequences. CONCLUSION: Compared to Loratadine, Cetirizine poses a greater potential risk in the nervous and psychiatric systems. Additionally, this study reveals previously underestimated potential cardiac toxicity of Cetirizine; albeit at a relatively low incidence rate, the high signal intensity warrants further attention and exploration. These findings highlight the need for enhanced patient monitoring and therapy optimization when prescribing these medications, ensuring better management of allergic diseases while minimizing risks.

Multiomics analysis reveals the potential of LPCAT1-PC axis as a therapeutic target for human intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is a highly prevalent musculoskeletal disorder that is associated with considerable morbidity. However, there is currently no drug available that has a definitive therapeutic effect on IDD. In this study, we aimed to identify the molecular features and potential therapeutic targets of IDD through a comprehensive multiomics profiling approach. By integrating transcriptomics, proteomics, and ultrastructural analyses, we discovered dysfunctions in various organelles, including mitochondria, the endoplasmic reticulum, the Golgi apparatus, and lysosomes. Metabolomics analysis revealed a reduction in total phosphatidylcholine (PC) content in IDD. Through integration of multiple omics techniques with disease phenotypes, a pivotal pathway regulated by the lysophosphatidylcholine acyltransferase 1 (LPCAT1)-PC axis was identified. LPCAT1 exhibited low expression levels and exhibited a positive correlation with PC content in IDD. Suppression of LPCAT1 resulted in inhibition of PC synthesis in nucleus pulposus cells, leading to a notable increase in nucleus pulposus cell senescence and damage to cellular organelles. Consequently, PC exhibits potential as a therapeutic agent, as it facilitates the repair of the biomembrane system and alleviates senescence in nucleus pulposus cells via reversal of downregulation of the LPCAT1-PC axis.

A novel SLC3A2-targeting antibody-drug conjugate exerts potent antitumor efficacy in head and neck squamous cell cancer.

The development of innovative therapeutic strategies for head and neck squamous cell carcinoma (HNSCC) is a critical medical requirement. Antibody-drug conjugates (ADC) targeting tumor-specific surface antigens have demonstrated clinical effectiveness in treating hematologic and solid malignancies. Our investigation revealed high expression levels of SLC3A2 in HNSCC tissue and cell lines. This study aimed to develop a novel anti-SLC3A2 ADC and assess its antitumor effects on HNSCC both in vitro and in vivo. This study developed a potent anti-SLC3A2 ADC (19G4-MMAE) and systematically investigated its drug delivery potential and antitumor efficacy in preclinical models. This study revealed that 19G4-MMAE exhibited specific binding to SLC3A2 and effectively targeted lysosomes. Moreover, 19G4-MMAE induced a significant accumulation of reactive oxygen species (ROS) and apoptosis in SLC3A2-positive HNSCC cells. The compound demonstrated potent antitumor effects derived from MMAE against SLC3A2-expressing HNSCC in preclinical models, displaying a favorable safety profile. These findings suggest that targeting SLC3A2 with an anti-SLC3A2 ADC could be a promising therapeutic approach for treating HNSCC patients.

Palmitic acid induces lipid droplet accumulation and senescence in nucleus pulposus cells via ER-stress pathway.

Intervertebral disc degeneration (IDD) is a highly prevalent musculoskeletal disorder affecting millions of adults worldwide, but a poor understanding of its pathogenesis has limited the effectiveness of therapy. In the current study, we integrated untargeted LC/MS metabolomics and magnetic resonance spectroscopy data to investigate metabolic profile alterations during IDD. Combined with validation via a large-cohort analysis, we found excessive lipid droplet accumulation in the nucleus pulposus cells of advanced-stage IDD samples. We also found abnormal palmitic acid (PA) accumulation in IDD nucleus pulposus cells, and PA exposure resulted in lipid droplet accumulation and cell senescence in an endoplasmic reticulum stress-dependent manner. Complementary transcriptome and proteome profiles enabled us to identify solute carrier transporter (SLC) 43A3 involvement in the regulation of the intracellular PA level. SLC43A3 was expressed at low levels and negatively correlated with intracellular lipid content in IDD nucleus pulposus cells. Overexpression of SLC43A3 significantly alleviated PA-induced endoplasmic reticulum stress, lipid droplet accumulation and cell senescence by inhibiting PA uptake. This work provides novel integration analysis-based insight into the metabolic profile alterations in IDD and further reveals new therapeutic targets for IDD treatment.

Prognostic effects of different treatment modalities for hypopharyngeal squamous cell carcinoma: Experience of two tertiary hospitals in Southwestern China.

Background: The prognostic effects of different treatment modalities on patients with hypopharyngeal squamous cell carcinoma (HPSCC) remain unclear. Methods: HPSCC patients diagnosed and treated at either West China Hospital or Sichuan Cancer Hospital between January 1, 2009, and December 31, 2019, were enrolled in this retrospective, real-world study. Survival rates were presented using Kaplan-Meier curves and compared using log-rank tests. Univariable and multivariable Cox proportional hazards regression models were used to identify the predictors of overall survival (OS). Subgroup analyses were conducted for patients with advanced-stage HPSCC (stages III and IV and category T4). Results: A total of 527 patients with HPSCC were included. Patients receiving SRC (surgery, radiotherapy [RT], and chemotherapy) showed the best OS (p < 0.0001). In comparison with RT alone, both surgery alone (all cases: hazard ratio [HR] = 0.39, p = 0.0018; stage IV cases: HR = 0.38, p = 0.0085) and surgery-based multimodality treatment (SBMT; all cases: HR = 0.27, p < 0.0001; stage IV cases: HR = 0.30, p = 0.00025) showed prognostic benefits, while SBMT also showed survival priority over chemoradiotherapy (CRT; all cases: HR = 0.52, p < 0.0001; stage IV cases: HR = 0.59, p = 0.0033). Moreover, patients who underwent surgery alone had comparable OS to those who underwent SBMT (all patients: p = 0.13; stage IV cases: p = 0.34), while CRT yielded similar prognostic outcomes as RT alone (all patients: p = 0.054; stage IV cases: p = 0.11). Conclusions: Surgery alone was comparable to SBMT and superior to RT/CRT in terms of OS in patients with HPSCC. We suggest that surgery should be encouraged for the treatment of HPSCC, even in patients with advanced-stage disease.

Laryngeal paraganglioma: The analysis of misdiagnosed cases and literature review.

Laryngeal paraganglioma (LP) is an exceptionally rare neuroendocrine tumor, underscoring importance of accurate identification to preclude misdiagnoses. In this review, we presented two typical misdiagnosed LPs, and offered reviews of LP cases reported over the preceding decade and all documented misdiagnosed LP cases. Furthermore, we systematically investigated the underlying causes of misdiagnosis and elucidated key points for effective differentiation. A retrospective analysis of 28 LP cases revealed a predominant occurrence in middle-aged women, with an average history of 25.1 months. Through an analysis of all misdiagnosed cases (n = 37), supraglottic LPs were frequently misidentified as laryngeal carcinomas and vascular tumors, while subglottic LPs were often misdiagnosed as thyroid cancers. And the occurrence of misdiagnosis resulted in delayed and inappropriate treatments, contributing to the deterioration of LP patients (14 cases, 37.8%). In conclusion, this review endeavored to heighten awareness of LPs, with the ultimate goal of advancing diagnostic precision and enhancing patient outcomes.

Diagnostic value of renal biopsy in anti-phospholipase A2 receptor antibody-positive patients with proteinuria in China.

Renal biopsy remains the gold standard for diagnosing membranous nephropathy (MN). Recent studies have suggested that renal biopsy can be replaced with the serum phospholipase A2 receptor (PLA2R) antibody test for MN diagnosis in patients with nephrotic syndrome. However, this test has not been validated in the Chinese population. In this study, we investigated whether renal biopsy provides additional diagnostic information on patients with proteinuria who are seropositive for PLA2R antibodies (SAb +). We retrospectively reviewed the clinicopathological characteristics of SAb + adult patients (aged ≥ 18 years) with proteinuria (≥ 0.5 g/24 h) assessed at the Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, from June 2021 to March 2022. Among a total of 801 SAb + patients who received renal biopsy, those with incomplete pathological data, diabetes or any potential cause of secondary MN were excluded. Among the 491 remaining patients, 474 had primary MN (PMN), 16 had atypical MN (AMN, 9 patients with "full house" and 2 patients with HBsAg + /HBcAg + immunofluorescence results), and 1 had focal segmental glomerulosclerosis. In patients with an eGFR of ≥ 60 mL/min/1.73 m2 (n = 451), 436 had PMN, and 71 (16.3%) exhibited additional biopsy findings, with obesity-related glomerulopathy being the most common. In patients with an impaired eGFR (n = 40), 38 had PMN, and 31 (81.6%) showed additional findings, with acute tubular injury being the most common. In conclusion, anti-PLA2R antibody positivity is highly predictive of PMN in Chinese adults but often coexists with other pathological diagnoses. The advantages of renal biopsy for detecting other pathologies should be weighed against the potential risks of the biopsy procedure.

Development and validation of a diagnostic nomogram model for predicting monoclonal gammopathy of renal significance.

In patients with kidney disease, the presence of monoclonal gammopathy necessitates the exploration of potential causal relationships. Therefore, in this study, we aimed to address this concern by developing a nomogram model for the early diagnosis of monoclonal gammopathy of renal significance (MGRS). Univariate and multivariate logistic regression analyses were employed to identify risk factors for MGRS. Verification and evaluation of the nomogram model's differentiation, calibration, and clinical value were conducted using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis. The study encompassed 347 patients who underwent kidney biopsy, among whom 116 patients (33.4%) were diagnosed with MGRS and 231 (66.6%) with monoclonal gammopathy of undetermined significance. Monoclonal Ig-related amyloidosis (n = 86) and membranous nephropathy (n = 86) was the most common renal pathological type in each group. Notably, older age, abnormal serum-free light chain ratio, and the absence of microscopic hematuria were identified as independent prognostic factors for MGRS. The areas under the ROC curves for the training and verification sets were 0.848 and 0.880, respectively. In conclusion, the nomogram model demonstrated high accuracy and clinical applicability for diagnosing MGRS, potentially serving as a valuable tool for noninvasive early MGRS diagnosis.

Extracellular Vesicles from Urine-Derived Stem Cell for Tissue Engineering and Regenerative Medicine.

The potential of urine-derived stem cells (USCs) for tissue engineering and regenerative medicine has attracted much attention during the last few decades. However, it has been suggested that the effects of the USCs may be endowed by their paracrine extracellular vesicles (EVs) rather than their differentiation. Compared with the USCs, the USC-EVs can cross the barriers more easily and safely, and their inclusions may mediate intercellular communication and promote the tissue repair. This article has summarized the current knowledge and applications about the USC-EVs in tissue engineering and regenerative medicine, and discussed the prospects and challenges for using them as an alternative to cell therapy. Impact statement Urine-derived stem cells (USCs) represent a newly discovered type of stem cells, and studies have proved that the beneficial effects of the USCs may be manifested through their paracrine extracellular vesicles (EVs) rather than through their own differentiation, which opens up new avenues for tissue engineering and regenerative medicine strategies. Therefore, this review aims to summarize the latest research progress and potential clinical applications of the USC-EVs, highlighting the promising potential of the USC-EVs as a therapeutic option in kidney regeneration, genital regeneration, nerve regeneration, bone and cartilage regeneration, and wound healing.

Single-cell sequencing of head and neck carcinoma: Transcriptional landscape and prognostic model based on malignant epithelial cell features.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and the development of novel therapeutic strategies for HNSCC requires a profound understanding of tumor cells and the tumor microenvironment (TME). Additionally, HNSCC has a poor prognosis, necessitating the use of genetic markers for predicting clinical outcomes in HNSCC. In this study, we performed single-cell sequencing analysis on tumor tissues from seven HNSCC patients, along with one adjacent normal tissue. Firstly, the analysis of epithelial cell clusters revealed two clusters of malignant epithelial cells, characterized by unique gene expression patterns and dysregulated signaling pathways compared to normal epithelial cells. Secondly, the examination of the TME unveiled extensive crosstalk between fibroblasts and malignant epithelial cells, potentially mediated through ligand-receptor interactions such as COL1A1-SDC1, COL1A1-CD44, and COL1A2-SDC1. Furthermore, transcriptional heterogeneity was observed in immune cells present in the TME, including macrophages and dendritic cells. Finally, leveraging the gene expression profiles of malignant epithelial cells, we developed a prognostic model comprising six genes, which we validated using two independent datasets. These findings shed light on the heterogeneity within HNSCC tumors and the intricate interplay between malignant cells and the TME. Importantly, the developed prognostic model demonstrates high efficacy in predicting the survival outcomes of HNSCC patients.

The Role and Mechanism of Aspirin Combined with Rehabilitation Training in the Repair of Sciatic Nerve Injury and the Changes in the Schwannocytus (Schwann Cells) in Rats / Rol y Mecanismo de la Aspirina Combinados con Entrenamiento de Rehabilitación en la Reparación de la Lesión del Nervio Ciático y los Cambios en los Schwannocitos (Células de Schwann) en Ratas

SUMMARY: This study investigated the role and mechanism of aspirin combined with rehabilitation training in the nerve injury repair and Schwann cell changes in rats with sciatic nerve injury. Totally, 120 male healthy SD rats were randomly divided into sham, model, aspirin, and aspirin + rehabilitation groups, with 30 rats in each group. The sciatic nerve function index (SFI), photothermal pain tolerance threshold and inclined plane test results at 4, 6, and 8 weeks after operation were compared. The distance of sensory nerve regeneration and the expression of S100B protein in Schwann cells were analyzed. Compared with the sham group, the SFI of the model, aspirin, and aspirin+rehabilitation groups were significantly lower at 4, 6, and 8 weeks after operation. However, the aspirin and aspirin+rehabilitation groups had significantly higher SFI than the model group. The SFI at 6 and 8 weeks after operation was higher in the aspirin+rehabilitation group than that in the aspirin group (P<0.05). The photothermal pain tolerance threshold of the sham, aspirin, and aspirin+rehabilitation groups were significantly higher than those of the model group at 4, 6, and 8 weeks after operation (P<0.05). The inclination angles of the model, aspirin, and aspirin+rehabilitation groups were significantly lower than those of the sham group at 4, 6, and 8 weeks after operation, and the inclination angle of the aspirin+rehabilitation group was significantly higher than that of the model and aspirin groups (P<0.05). The sensory nerve regeneration distance in aspirin and aspirin+rehabilitation groups was higher than that in the sham and model groups (P<0.05). The expression of S100B protein in the aspirin and aspirin+rehabilitation groups was higher than that in the model group (P<0.05). Aspirin combined with rehabilitation training can promote the functional recovery of sciatic nerve injury, and the mechanism may be related to the increase of the expression of S100B protein in Schwann cells.

En este estudio se investigó el papel y el mecanismo que desempeña la aspirina combinada, con el entrenamiento de rehabilitación en la reparación de lesiones nerviosas y los cambios en los schwannocitos en ratas con lesiones en el nervio ciático. En total, 120 ratas SD macho sanas se dividieron aleatoriamente en cuatro grupos de 30 ratas en cada uno: simulación, modelo, aspirina y aspirina + rehabilitación. Se compararon el índice de función del nervio ciático (SFI), el umbral de tolerancia al dolor fototérmico y los resultados de la prueba del plano inclinado a las 4, 6 y 8 semanas después de la operación. Se analizó la distancia de regeneración del nervio sensorial y la expresión de la proteína S100B en los schwannocitos. En comparación con el grupo simulado, el SFI de los grupos modelo, aspirina y aspirina+rehabilitación fue significativamente menor a las 4, 6 y 8 semanas después de la operación. Sin embargo, los grupos de aspirina y aspirina + rehabilitación tuvieron un SFI significativamente más alto que el grupo modelo. El SFI a las 6 y 8 semanas después de la operación fue mayor en el grupo de aspirina + rehabilitación que en el grupo de aspirina (P<0,05). El umbral de tolerancia al dolor fototérmico de los grupos simulado, aspirina y aspirina+rehabilitación fue significativamente mayor que el del grupo modelo a las 4, 6 y 8 semanas después de la operación (P<0,05). Los ángulos de inclinación de los grupos modelo, aspirina y aspirina+rehabilitación fueron significativamente menores que los del grupo simulado a las 4, 6 y 8 semanas después de la operación, y el ángulo de inclinación del grupo aspirina+rehabilitación fue significativamente mayor que el de los grupos modelo y aspirina (P<0.05). La distancia de regeneración del nervio sensorial en los grupos de aspirina y aspirina+rehabilitación fue mayor que en los grupos simulado y modelo (P<0,05). La expresión de la proteína S100B en los grupos de aspirina y aspirina+rehabilitación fue mayor que en el grupo modelo (P<0,05). La aspirina combinada con el entrenamiento de rehabilitación puede promover la recuperación funcional de la lesión del nervio ciático, y el mecanismo puede estar relacionado con el aumento de la expresión de la proteína S100B en los schwannocitos.

Immune-checkpoint protein VISTA in allergic, autoimmune disease and transplant rejection.

Negative checkpoint regulators (NCRs) reduce the T cell immune response against self-antigens and limit autoimmune disease development. V-domain Ig suppressor of T cell activation (VISTA), a novel immune checkpoint in the B7 family, has recently been identified as one of the NCRs. VISTA maintains T cell quiescence and peripheral tolerance. VISTA targeting has shown promising results in treating immune-related diseases, including cancer and autoimmune disease. In this review, we summarize and discuss the immunomodulatory role of VISTA, its therapeutic potential in allergic, autoimmune disease, and transplant rejection, as well as the current therapeutic antibodies, to present a new method for regulating immune responses and achieving durable tolerance for the treatment of autoimmune disease and transplantation.

Antidepressants: A content analysis of healthcare providers' tweets.

Background: Antidepressants are the primary treatment for depression, and social support from social media may offer another support route. Whilst Twitter has become an interactive platform for healthcare providers and their patients, previous studies found low engagement of healthcare providers when discussing antidepressants on Twitter. This study aims to analyse the Twitter posts of healthcare providers related to antidepressants and to explore the healthcare providers' engagement and their areas of interest. Method: Tweets within a 10-day period were collected through multiple searches with a list of keywords within Twitter. The results were filtered against several inclusion criteria, including a manual screening to identify healthcare providers. A content analysis was conducted on eligible tweets where correlative themes and subthemes were identified. Key findings: Healthcare providers contributed 5.9% of the antidepressant-related tweets (n = 770/13,005). The major clinical topics referred to in the tweets were side effects, antidepressants for the treatment of COVID-19, and antidepressant studies of psychedelics. Nurses posted more tweets sharing personal experiences with commonly negative attitudes, in contrast to physicians. Links to external webpages were commonly used among healthcare providers, especially users representing healthcare organisations. Conclusions: A relatively low proportion of healthcare providers' engagement on Twitter regarding antidepressants (5.9%) was identified, with a minimal increase throughout the COVID-19 pandemic when compared to previous studies. The major clinical topics referred to in the tweets were side effects, antidepressants for the treatment of COVID-19 and antidepressant studies of psychedelics, which have been made publicly available. In general, the findings confirmed that social media platforms are a mechanism by which healthcare providers, organisations and students support patients, share information about adverse drug effects, communicate personal experiences, and share research. It is plausible that this could impact the belief and behaviours of people with lived experience of depression who may see these tweets.

The Relationship Between Sleep Traits and Tinnitus in UK Biobank: A Population-Based Cohort Study.

OBJECTIVES: Understanding the association between sleep traits and tinnitus could help prevent and provide appropriate interventions against tinnitus. Therefore, this study aimed to assess the relationship between different sleep patterns and tinnitus. DESIGN: A cross-sectional analysis using baseline data (2006-2010, n = 168,064) by logistic regressions was conducted to evaluate the association between sleep traits (including the overall health sleep score and five sleep behaviors) and the occurrence (yes/no), frequency (constant/transient), and severity (upsetting/not upsetting) of tinnitus. Further, a prospective analysis of participants without tinnitus at baseline (n = 9581) was performed, who had been followed-up for 7 years (2012-2019), to assess the association between new-onset tinnitus and sleep characteristics. Moreover, a subgroup analysis was also carried out to estimate the differences in sex by dividing the participants into male and female groups. A sensitivity analysis was also conducted by excluding ear-related diseases to avoid their confounding effects on tinnitus (n = 102,159). RESULTS: In the cross-sectional analysis, participants with "current tinnitus" (OR: 1.13, 95% CI: 1.04-1.22, p = 0.004) had a higher risk of having a poor overall healthy sleep score and unhealthy sleep behaviors such as short sleep durations (OR: 1.09, 95% CI: 1.04-1.14, p < 0.001), late chronotypes (OR: 1.09, 95% CI: 1.05-1.13, p < 0.001), and sleeplessness (OR: 1.16, 95% CI: 1.11-1.22, p < 0.001) than those participants who "did not have current tinnitus." However, this trend was not obvious between "constant tinnitus" and "transient tinnitus." When considering the severity of tinnitus, the risk of "upsetting tinnitus" was obviously higher if participants had lower overall healthy sleep scores (OR: 1.31, 95% CI: 1.13-1.53, p < 0.001). Additionally, short sleep duration (OR: 1.22, 95% CI: 1.12-1.33, p < 0.001), late chronotypes (OR: 1.13, 95% CI: 1.04-1.22, p = 0.003), and sleeplessness (OR: 1.43, 95% CI: 1.29-1.59, p < 0.001) showed positive correlations with "upsetting tinnitus." In the prospective analysis, sleeplessness presented a consistently significant association with "upsetting tinnitus" (RR: 2.28, p = 0.001). Consistent results were observed in the sex subgroup analysis, where a much more pronounced trend was identified in females compared with the males. The results of the sensitivity analysis were consistent with those of the cross-sectional and prospective analyses. CONCLUSIONS: Different types of sleep disturbance may be associated with the occurrence and severity of tinnitus; therefore, precise interventions for different types of sleep disturbance, particularly sleeplessness, may help in the prevention and treatment of tinnitus.

Development and validation of diagnostic models for immunoglobulin A nephropathy based on gut microbes.

Background: Immunoglobulin A nephropathy (IgAN) is a highly prevalent glomerular disease. The diagnosis potential of the gut microbiome in IgAN has not been fully evaluated. Gut microbiota, serum metabolites, and clinical phenotype help to further deepen the understanding of IgAN. Patients and methods: Cohort studies were conducted in healthy controls (HC), patients of IgA nephropathy (IgAN) and non-IgA nephropathy (n_IgAN). We used 16S rRNA to measure bacterial flora and non-targeted analysis methods to measure metabolomics; we then compared the differences in the gut microbiota between each group. The random forest method was used to explore the non-invasive diagnostic value of the gut microbiome in IgAN. We also compared serum metabolites and analyzed their correlation with the gut microbiome. Results: The richness and diversity of gut microbiota were significantly different among IgAN, n_IgAN and HC patients. Using a random approach, we constructed the diagnosis model and analysed the differentiation between IgAN and n_IgAN based on gut microbiota. The area under the receiver operating characteristic curve for the diagnosis was 0.9899. The metabolic analysis showed that IgAN patients had significant metabolic differences compared with HCs. In IgAN, catechol, l-tryptophan, (1H-Indol-3-yl)-N-methylmethanamine, and pimelic acid were found to be enriched. In the correlation analysis, l-tryptophan, blood urea nitrogen and Eubacterium coprostanoligenes were positively correlated with each other. Conclusion: Our study demonstrated changes in the gut microbiota and established models for the non-invasive diagnosis of IgAN from HC and n_IgAN. We further demonstrated a close correlation between the gut flora, metabolites, and clinical phenotypes of IgAN. These findings provide further directions and clues in the study of the mechanism of IgAN.

Tacrolimus treatment after short-term intravenous methylprednisolone in incipient minimal change disease for adults: A retrospective analysis.

The present study aimed to investigate the efficacy and safety of tacrolimus for treating incipient minimal change disease in adults. The clinical data of 52 adult patients with minimal change disease of nephrotic syndrome diagnosed by renal biopsy in the First affiliated hospital of Zhengzhou University between August 2013 and August 2015 were retrospectively analyzed. According to the treatment plan, the patients were divided into a tacrolimus group and a glucocorticoid group. The efficacy and safety of tacrolimus in the treatment of minimal change disease in adult patients was analyzed and compared with that of glucocorticoids. The results revealed that the baseline characteristics of the two groups were similar (P>0.05). At 24 weeks, there was a significant difference in serum albumin between the two groups (P<0.01). The serum albumin levels of tacrolimus group was higher compared with the glucocorticoid group. In addition, the complete remission rates in the tacrolimus and glucocorticoid groups were 93.75 and 77.8%, respectively (P=0.095), and the mean complete remission time was 6.33±4.21 and 5.14±2.45 weeks, respectively (P=0.175). The relapse rate was 12.5 and 22.2% in the tacrolimus and glucocorticoid groups, respectively (P=0.368). During the follow-up, in tacrolimus group, the incidence of new onset diabetes or impaired glucose tolerance, osteoporosis, infection, abnormal liver function, Cushing's syndrome, acne and gastrointestinal symptoms were significantly less than those of glucocorticoids (P<0.05). In conclusion, tacrolimus treatment after short-time intravenous methylprednisolone is an effective treatment option with fewer adverse effects in adult onset minimal change disease.

Gut Microbiome Analysis Can Be Used as a Noninvasive Diagnostic Tool and Plays an Essential Role in the Onset of Membranous Nephropathy.

Membranous nephropathy (MN) is a common cause of nephrotic syndrome. The aim is to establish a non-invasive diagnostic model of MN using differential gut microbiome analysis, and to explore the relationship between the gut microbiome and MN pathogenesis in vivo. 825 fecal samples from MN patients and healthy participants are collected from multiple medical centers across China. Key operational taxonomic units (OTUs) obtained through 16S rRNA sequencing are used to establish a diagnostic model. A rat model of MN is developed to explore the relationship between the gut microbiome and the pathogenesis of MN. The diversity and richness of the gut microbiome are significantly lower in patients with MN than in healthy individuals. The diagnostic model based on seven OTUs achieves an excellent efficiency of 98.36% in the training group and also achieves high efficiency in cross-regional cohorts. In MN rat model, gut microbiome elimination prevents model establishment, but fecal microbiome transplantation restores the phenotype of protein urine. Gut microbiome analysis can be used as a non-invasive tool for MN diagnosis. The onset of MN depends on the presence of naturally colonized microbiome. Early intervention in the gut microbiome may help reduce urinary protein level in MN.