The effect of fasting plasma glucose on in-hospital mortality after acute myocardial infarction in patients with and without diabetes: findings from a prospective, nationwide, and multicenter registry.

OBJECTIVES: To evaluate the predictive value of fasting plasma glucose (FPG) for in-hospital mortality in patients with acute myocardial infarction (AMI) with different glucose metabolism status. METHODS: We selected 5,308 participants with AMI from the prospective, nationwide, multicenter CAMI registry, of which 2,081 were diabetic and 3,227 were nondiabetic. Patients were divided into high FPG and low FPG groups according to the optimal cutoff values of FPG to predict in-hospital mortality for diabetic and nondiabetic cohorts, respectively. The primary endpoint was in-hospital mortality. RESULTS: Overall, 94 diabetic patients (4.5%) and 131 nondiabetic patients (4.1%) died during hospitalization, and the optimal FPG thresholds for predicting in-hospital death of the two cohorts were 13.2 mmol/L and 6.4 mmol/L, respectively. Compared with individuals who had low FPG, those with high FPG were significantly associated with higher in-hospital mortality in diabetic cohort (10.1% vs. 2.8%; odds ratio [OR] = 3.862, 95% confidence interval [CI]: 2.542-5.869) and nondiabetic cohort (7.4% vs. 1.7%; HR = 4.542, 95%CI: 3.041-6.782). After adjusting the potential confounders, this significant association was not changed. Furthermore, FPG as a continuous variable was positively associated with in-hospital mortality in single-variable and multivariable models regardless of diabetic status. Adding FPG to the original model showed a significant improvement in C-statistic and net reclassification in diabetic and nondiabetic cohorts. CONCLUSIONS: This large-scale registry indicated that there is a strong positive association between FPG and in-hospital mortality in AMI patients with and without diabetes. FPG might be useful to stratify patients with AMI.

Potential effects of aerosol generation and transmission during bedside endoscope cleaning.

Airborne transmission is among the most frequent types of nosocomial infection. Recent years have witnessed frequent outbreaks of airborne diseases, such as severe acute respiratory syndrome (SARS) in 2002, Middle East respiratory syndrome (MERS) in 2012, and coronavirus disease 2019 (COVID-19), with the latter being on the rampage since the end of 2019 and bringing the effect of aerosols on health back to the fore (Gralton et al., 2011; Wang et al., 2021). An increasing number of studies have shown that certain highly transmissible pathogens can maintain long-term stability and efficiently spread through aerosols (Leung, 2021; Lv et al., 2021). As reported previously, influenza viruses that can spread efficiently through aerosols remain stable for a longer period compared to those that cannot. The World Health Organization (WHO) has stated that aerosol-generating procedures (AGPs) play an important role in aerosol transmission in hospitals (Calderwood et al., 2021). AGPs, referring to medical procedures that produce aerosols, including dental procedures, endotracheal intubation, sputum aspiration, and laparoscopic surgeries, have been reported to be significantly associated with an increased risk of nosocomial infection among medical personnel (Hamilton, 2021).

Impact Analysis of COVID-19 Pandemic on Hospital Reviews on Dianping Website in Shanghai, China: Empirical Study.

BACKGROUND: In the era of the internet, individuals have increasingly accustomed themselves to gathering necessary information and expressing their opinions on public web-based platforms. The health care sector is no exception, as these comments, to a certain extent, influence people's health care decisions. During the onset of the COVID-19 pandemic, how the medical experience of Chinese patients and their evaluations of hospitals have changed remains to be studied. Therefore, we plan to collect patient medical visit data from the internet to reflect the current status of medical relationships under specific circumstances. OBJECTIVE: This study aims to explore the differences in patient comments across various stages (during, before, and after) of the COVID-19 pandemic, as well as among different types of hospitals (children's hospitals, maternity hospitals, and tumor hospitals). Additionally, by leveraging ChatGPT (OpenAI), the study categorizes the elements of negative hospital evaluations. An analysis is conducted on the acquired data, and potential solutions that could improve patient satisfaction are proposed. This study is intended to assist hospital managers in providing a better experience for patients who are seeking care amid an emergent public health crisis. METHODS: Selecting the top 50 comprehensive hospitals nationwide and the top specialized hospitals (children's hospitals, tumor hospitals, and maternity hospitals), we collected patient reviews from these hospitals on the Dianping website. Using ChatGPT, we classified the content of negative reviews. Additionally, we conducted statistical analysis using SPSS (IBM Corp) to examine the scoring and composition of negative evaluations. RESULTS: A total of 30,317 pieces of effective comment information were collected from January 1, 2018, to August 15, 2023, including 7696 pieces of negative comment information. Manual inspection results indicated that ChatGPT had an accuracy rate of 92.05%. The F1-score was 0.914. The analysis of this data revealed a significant correlation between the comments and ratings received by hospitals during the pandemic. Overall, there was a significant increase in average comment scores during the outbreak (P<.001). Furthermore, there were notable differences in the composition of negative comments among different types of hospitals (P<.001). Children's hospitals received sensitive feedback regarding waiting times and treatment effectiveness, while patients at maternity hospitals showed a greater concern for the attitude of health care providers. Patients at tumor hospitals expressed a desire for timely examinations and treatments, especially during the pandemic period. CONCLUSIONS: The COVID-19 pandemic had some association with patient comment scores. There were variations in the scores and content of comments among different types of specialized hospitals. Using ChatGPT to analyze patient comment content represents an innovative approach for statistically assessing factors contributing to patient dissatisfaction. The findings of this study could provide valuable insights for hospital administrators to foster more harmonious physician-patient relationships and enhance hospital performance during public health emergencies.

Analysis of the effects of eating and emotions on reproductive axis function in patients with functional hypothalamic amenorrhea.

Objective: To investigate the effects of eating and emotions on reproductive axis function in patients with functional hypothalamic amenorrhea (FHA).Methods: A retrospective cohort study was conducted to summarize the clinical and endocrine characteristics of 58 patients with FHA at initial diagnosis and to follow up the recovery of ovulation and spontaneous menstruation in the patients to investigate these biochemical indicators and their effects on recovery outcomes.Results: Among patients with FHA, 13.8% (8/58) and 15.5% (9/58) had above moderately severe depressive and severe anxiety symptoms respectively, and 25.9% (15/58) were at high risk for eating disorders. 34.5% (20/58) were included assessed as having recovered. The non-recovered group had higher scores on the Patient Health Questionnaire (PHQ-9) (p = .022) and higher scores on the Eating Attitude Test-26 (EAT-26) (p = .03) as well as bulimia and food preoccupation (p = .041). Follicle diameter >5 mm at initial diagnosis was an independent factor influencing recovery of reproductive axis function (odds ratio = 7.532; 95% confidence interval, 1.321-42.930; p = .023).Conculsions: Mood disorders and a certain risk of eating disorders were present in FHA.These, together with weight loss, endocrine and follicle size, could influence the outcome.

Discovery of a Covalent Inhibitor That Overcame Resistance to Venetoclax in AML Cells Overexpressing BFL-1.

Clinical and biological studies have shown that overexpression of BFL-1 is one contributing factor to venetoclax resistance. The resistance might be overcome by a potent BFL-1 inhibitor, but such an inhibitor is rare. In this study, we show that 56, featuring an acrylamide moiety, inhibited the BFL-1/BID interaction with a Ki value of 105 nM. More interestingly, 56 formed an irreversible conjugation adduct at the C55 residue of BFL-1. 56 was a selective BFL-1 inhibitor, and its MCL-1 binding affinity was 10-fold weaker, while it did not bind BCL-2 and BCL-xL. Mechanistic studies showed that 56 overcame venetoclax resistance in isogenic AML cell lines MOLM-13-OE and MV4-11-OE, which both overexpressed BFL-1. More importantly, 56 and venetoclax combination promoted stronger apoptosis induction than either single agent. Collectively, our data show that 56 overcame resistance to venetoclax in AML cells overexpressing BFL-1. These attributes make 56 a promising candidate for future optimization.

Establishing a course to train ICU nurses on prone position mechanical ventilation: A Delphi study.

AIM: To develop a comprehensive training course for training ICU nurses in prone positioning. DESIGN: A mixed study combining semi-structured interviews and two rounds of Delphi surveys. METHODS: We constructed a questionnaire after collecting data through a literature review and semi-structured interviews. We used the Delphi expert correspondence method to conduct two rounds of research among 17 experts in the field of critical illness. Data collection took place between May and August 2022. RESULTS: The effective questionnaire recovery rate was 88.2%. The expert authority coefficient was 0.876; the Kendall coordination coefficient was 0.402; the average importance score for each index ranged from 4.00 to 4.93; and the coefficient of variation for each index ranged from 0.05 to 0.19. We established 13 second-level indicators and 41 third-level indicators on prone position ventilation training according to three aspects: training contents, training methods and training assessment. The training system of prone mechanical ventilation for ICU nurses established in this study will provide an effective framework for training and evaluating the practical ability of prone mechanical ventilation for ICU nurses.

Preoperative and postoperative MRI-based models versus clinical staging systems for predicting early recurrence in hepatocellular carcinoma.

BACKGROUND: To predict the early recurrence of HCC patients who received radical resection using preoperative variables based on Gd-EOB-DTPA enhanced MRI, followed by the comparison with the postoperative model and clinical staging systems. METHODS: One hundred and twenty-nine HCC patients who received radical resection were categorized into the early recurrence group (n = 48) and the early recurrence-free group (n = 81). Through COX regression analysis, statistically significant variables of laboratory, pathologic, and Gd-EOB-DTPA enhanced MRI results were identified. The preoperative and postoperative models were established to predict early recurrence, and the prognostic performances and differences were compared between the two models and clinical staging systems. RESULTS: Six variables were incorporated into the preoperative model, including alpha-fetoprotein (AFP) level, aspartate aminotransferase/platelet ratio index (APRI), rim arterial phase hyperenhancement (rim APHE), peritumoral hypointensity on hepatobiliary phase (HBP), CERHBP (tumor-to-liver SI ratio on hepatobiliary phase imaging), and ADC value. Moreover, the postoperative model was developed by adding microvascular invasion (MVI) and histological grade. The C-index of the preoperative model and postoperative model were 0.889 and 0.901 (p = 0.211) respectively. Using receiver operating characteristic curve analysis (ROC) and decision curve analysis (DCA), it was determined that the innovative models we developed had superior predictive capabilities for early recurrence in comparison to current clinical staging systems. HCC patients who received radical resection were stratified into low-, medium-, and high-risk groups on the basis of the preoperative and postoperative models. CONCLUSION: The preoperative and postoperative MRI-based models built in this study were more competent compared with clinical staging systems to predict the early recurrence in hepatocellular carcinoma.

Synthesis and biological evaluation of panaxadiol ester derivatives possessing pyrazole and pyrrole moiety as HIF-1α inibitors.

Hypoxia-inducing factor-1α (HIF-1α) is overexpressed in variety of tumor patients and plays an important role in the regulation of hypoxia response in tumor cells. Therefore, its inhibitors have become one of the targets for the treatment of a variety of cancers. Two series of panaxadiol (PD) ester derivatives containing pyrazole (18a-j) and pyrrole (19a-n) moiety were synthesized and their HIF-1α inhibitory activities were evaluated. Among all the target compouds, compounds 18c, 19d, and 19n (IC50 = 8.70-10.44 µM) showed better HIF-1α inhibitory activity than PD (IC50 = 13.35 µM). None of these compounds showed cytotoxicity above 100 µM and inhibited HIF-1α transcription in a dose-dependent manner. These compounds showed good antitumor activity and provide lead compounds for further design and activity study of PD ester derivatives.

Strategic disruption of cancer's powerhouse: precise nanomedicine targeting of mitochondrial metabolism.

Mitochondria occupy a central role in the biology of most eukaryotic cells, functioning as the hub of oxidative metabolism where sugars, fats, and amino acids are ultimately oxidized to release energy. This crucial function fuels a variety of cellular activities. Disruption in mitochondrial metabolism is a common feature in many diseases, including cancer, neurodegenerative conditions and cardiovascular diseases. Targeting tumor cell mitochondrial metabolism with multifunctional nanosystems emerges as a promising strategy for enhancing therapeutic efficacy against cancer. This review comprehensively outlines the pathways of mitochondrial metabolism, emphasizing their critical roles in cellular energy production and metabolic regulation. The associations between aberrant mitochondrial metabolism and the initiation and progression of cancer are highlighted, illustrating how these metabolic disruptions contribute to oncogenesis and tumor sustainability. More importantly, innovative strategies employing nanomedicines to precisely target mitochondrial metabolic pathways in cancer therapy are fully explored. Furthermore, key challenges and future directions in this field are identified and discussed. Collectively, this review provides a comprehensive understanding of the current state and future potential of nanomedicine in targeting mitochondrial metabolism, offering insights for developing more effective cancer therapies.

Unraveling the Role of the Liriodendron Thioredoxin (TRX) Gene Family in an Abiotic Stress Response.

Thioredoxin (TRX) is a small protein with REDOX activity that plays a crucial role in a plant's growth, development, and stress resistance. The TRX family has been extensively studied in Arabidopsis, rice, and wheat, and so it is likely that its members have similar biological functions in Liriodendron that have not been reported in Liriodendron. In this study, we performed the genome-wide identification of the TRX gene family based on the Liriodendron chinense genome, leading to a total of 42 LcTRX gene members. A phylogenetic analysis categorized these 42 LcTRX proteins into 13 subfamilies. We further characterized their chromosome distributions, gene structures, conserved protein motifs, and cis-elements in the promoter regions. In addition, based on the publicly available transcriptome data for Liriodendron hybrid and following RT-qPCR experiments, we explored the expression patterns of LhTRXs to different abiotic stressors, i.e., drought, cold, and heat stress. Notably, we found that several LhTRXs, especially LhTRX-h3, were significantly upregulated in response to abiotic stress. In addition, the subcellular localization assay showed that LhTRX-h3 was mainly distributed in the cytoplasm. Subsequently, we obtained LhTRX-h3 overexpression (OE) and knockout (KO) callus lines in Liriodendron hybrid. Compared to the wild type (WT) and LhTRX-h3-KO callus proliferation of LhTRX-h3-OE lines was significantly enhanced with reduced reactive oxygen species (ROS) accumulation under drought stress. Our findings that LhTRX-h3 is sufficient to improve drought tolerance. and underscore the significance of the TRX gene family in environmental stress responses in Liriodendron.

Role of obesity in lower mortality risk in sepsis: a meta-analysis of observational studies.

This meta-analysis aims to explore the correlation between obesity and mortality in patients with sepsis. Data were gathered from various sources, including PubMed, the Cochrane Library, and Embase (no language restrictions). Clinical studies, both retrospective and prospective ones, were selected to analyze mortality due to sepsis in patients with or without obesity. The Newcastle-Ottawa Scale was used to assess the quality of the studies included. In data synthesis, odds ratio (OR) and 95% confidence interval (CI) were meta-analyzed using the DerSimonian-Laird random-effects model, followed by sensitivity and heterogeneity analyses. Two cohort studies were included to investigate survival in inpatients with obesity and sepsis, with pooled analysis indicating a lowered mortality rate (OR=0.88; 95% CI: 0.81-0.95; I2=0.00%; P=0.000). This meta-analysis lends support to the obesity paradox, suggesting a reduced mortality from sepsis in obese patients. However, further prospective trials and research on mechanisms are needed to test this hypothesis.

24-hour movement behaviors time allocation and depression among Chinese community-dwelling older adults: A latent profile analysis.

This study explored the combination characteristics of physical activity, sedentary behavior, and sleep among older adults during a 24-hour time allocation and analyzed the correlations between different combinations and depression. We recruited 648 older adults (mean age 72.65±7.03) from three communities in urban areas of central China and measured their physical activity, sedentary behavior, sleep quality, and depression. We used latent profile analysis to classify the time allocation of 24 h of movement behavior and binary logistic regression to analyze associations between different subgroups and depression. We found four classes of 24-hour movement behavior: moderately active-moderate sleepers (32.9 %), active-sedentary-short sleepers (17.8 %), sedentary-long sleepers (8.6 %), and active-short sleepers (40.7 %). Compared with moderately active-moderate sleepers, active-sedentary-short and sedentary-long sleepers were 2.953 and 4.813 times more likely to have depression, respectively. There was no statistically significant difference between active-short and moderately active-moderate sleepers. The results can inform preventive measures for depression in older adults.

Epigenetic Reprogramming Potentiates ICAM1 Antibody Drug Conjugates in Preclinical Models of Melanoma.

Therapeutic benefits and underlying biomechanism(s) of antibody drug conjugates (ADC) in combination with other targeted therapeutics are largely unknown. Here, the synergy between ADC and epigenetic drug decitabine (DAC), a clinically approved DNA methylation inhibitor, in multiple preclinical models of melanoma specifically investigated. Mechanistically, the underlying biomechanisms of how DAC cooperatively worked with ICAM1 antibody conjugated DNA topoisomerase I inhibitor DXd (I1-DXd) is elucidated. DAC treatment significantly enhanced anti-tumor efficacy of I1-DXd by upregulating antigen expression, enhancing antibody internalization and potentiating tumor sensitivity by epigenetically reprogramming of melanoma. Meanwhile, I1-DXd/DAC combination also exerted regulatory effects on tumor microenvironment (TME) by enhancing tumor infiltration of innate and adaptive immune cells and improving penetration of ADCs with a boosted antitumor immunity. This study provides a rational ADC combination strategy for solid tumor treatment.

Decoding the ribosome's hidden language: rRNA modifications as key players in cancer dynamics and targeted therapies.

Ribosomal RNA (rRNA) modifications, essential components of ribosome structure and function, significantly impact cellular proteomics and cancer biology. These chemical modifications transcend structural roles, critically shaping ribosome functionality and influencing cellular protein profiles. In this review, the mechanisms by which rRNA modifications regulate both rRNA functions and broader cellular physiological processes are critically discussed. Importantly, by altering the translational output, rRNA modifications can shift the cellular equilibrium towards oncogenesis, thus playing a key role in cancer development and progression. Moreover, a special focus is placed on the functions of mitochondrial rRNA modifications and their aberrant expression in cancer, an area with profound implications yet largely uncharted. Dysregulation in these modifications can lead to metabolic dysfunction and apoptosis resistance, hallmark traits of cancer cells. Furthermore, the current challenges and future perspectives in targeting rRNA modifications are highlighted as a therapeutic approach for cancer treatment. In conclusion, rRNA modifications represent a frontier in cancer research, offering novel insights and therapeutic possibilities. Understanding and harnessing these modifications can pave the way for breakthroughs in cancer treatment, potentially transforming the approach to combating this complex disease.

Exploring the Therapeutic Potential of Baicalin: Mitigating Anxiety and Depression in Epileptic Rats.

BACKGROUND: Epilepsy is a serious neurological disorder that affects millions of people each year, often leading to cognitive issues and reduced quality of life. Medication is the main treatment, but many patients experience negative side effects. Male Sprague-Dawley (SD) rats were chosen as experimental animals for this experiment due to their physiological and genetic similarities to humans, cost-effectiveness, and ease of handling in a laboratory setting. AIMS: The objective of this study was to assess the neuroprotective properties of baicalin (BA) in relation to its impact on anxiety and depressive-like behaviors in the epilepsy model. METHODS: Thirty male Sprague-Dawley (SD) rats were selected for this experiment. Pentylenetetrazol (PTZ) kindling (40 mg/kg; i.p.) was utilized to establish an epilepsy model. The effect of BA (50 mg/kg; gavage) on seizure severity (assessed using the Racine scale), anxiety, and depressive- like behaviors (evaluated through open field experiments and forced swimming tests) was examined. Histological examinations, including hematoxylin and eosin (HE) staining and Nissl staining, were conducted to assess neuronal damage. Furthermore, the neuroprotective properties of BA were examined through the analysis of Doublecortin (DCX), MKI67 (KI67), and Brain-Derived Neurotrophic Factor (BDNF) levels in the hippocampus of rats. The inhibitory impact of BA on neuroinflammation was assessed via dual labeling for NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and the microglial marker ionized calcium- binding adapter molecule 1 (Iba-1). The influence of BA on the expression of P2X7 receptor (P2X7R), NLRP3, and Interleukin-1ß (IL-1ß) was also assessed by reverse transcription quantitative PCR (RT-qPCR) in the brain. Finally, we employed a molecular docking model to assess the extent of receptor-ligand binding. RESULTS: Epilepsy models exhibited significant anxiety and depressive-like behaviors, and BA significantly reduced the severity of seizures in these rats while also alleviating their anxiety and depressive-like behaviors. Moreover, neuronal loss and damage were observed in the hippocampus of epileptic rats, but BA was able to effectively counteract this issue by enhancing BDNF expression and promoting neurogenesis within the hippocampus, especially in the DG region. The co-localization of Iba-1 with NLRP3 indicated the activation of NLRP3 inflammasome in microglia. Subsequent RT-PCR revealed that BA may alleviate anxiety and depressive-like behaviors in epileptic rats by activating the P2RX7/NLRP3/ IL-1ß signaling pathway. The final molecular docking results indicated that BA had a good binding affinity with proteins, such as P2RX7, NLRP3, and IL-1ß. CONCLUSION: This study confirmed the effectiveness of BA in improving anxiety and depressivelike behaviors associated with epilepsy. Moreover, it provides theoretical support for the neuroprotective role demonstrated by BA.

Predicting prognosis and immunotherapy response in colorectal cancer by pericytes insights from single-cell RNA sequencing.

Immunotherapy has revolutionized the treatment of tumors, but there are still a large number of patients who do not benefit from immunotherapy. Pericytes play an important role in remodeling the immune microenvironment. However, how pericytes affect the prognosis and treatment resistance of tumors is still unknown. This study jointly analyzed single-cell RNA sequencing (scRNA-seq) data and bulk RNA sequencing data of multiple cancers to reveal pericyte function in the colorectal cancer microenvironment. Analyzing over 800 000 cells, it was found that colorectal cancer had more pericyte enrichment in tumor tissues than other cancers. We then combined the TCGA database with multiple public datasets and enrolled more than 1000 samples, finding that pericyte may be closely related to poor prognosis due to the higher epithelial-mesenchymal transition (EMT) and hypoxic characteristics. At the same time, patients with more pericytes have higher immune checkpoint molecule expressions and lower immune cell infiltration. Finally, the contributions of pericyte in poor treatment response have been demonstrated in multiple immunotherapy datasets (n = 453). All of these observations suggest that pericyte can be used as a potential biomarker to predict patient disease progression and immunotherapy response.

Application of 18ß-glycyrrhetinic acid in the structural modification of natural products: a review.

18ß-Glycyrrhetinic acid (GA) is an oleane-type pentacyclic triterpene saponin obtained from glycyrrhizic acid by removing 2 glucuronic acid groups. GA and its analogues are active substances of glycyrrhiza aicd, with similar structure and important pharmacological effects such as anti-inflammatory, anti-diabetes, anti-tumor and anti-fibrosis. Although GA combined compounds are in the clinical trial stages, its application potential is severely restricted by its low bioavailability, water solubility and membrane permeability. In this article, synthetic methods and structure-activity relationships (SARs) of GA derivatives from 2018 to present are reviewed based on pharmacological activity. It is hoped that this review can provide reference for the future development of potential GA preclinical candidate compounds, and furnish ideas for the development of pentacyclic triterpenoid lead compounds.

High-Performance Contact-Doped WSe2 Transistors Using TaSe2 Electrodes.

Two-dimensional (2D) transitional metal dichalcogenides (TMDs) have garnered significant attention due to their potential for next-generation electronics, which require device scaling. However, the performance of TMD-based field-effect transistors (FETs) is greatly limited by the contact resistance. This study develops an effective strategy to optimize the contact resistance of WSe2 FETs by combining contact doping and 2D metallic electrode materials. The contact regions were doped using a laser, and the metallic TaSe2 flakes were stacked on doped WSe2 as electrodes. Doping the contact areas decreases the depletion width, while introducing the TaSe2 contact results in a lower Schottky barrier. This method significantly improves the electrical performance of the WSe2 FETs. The doped WSe2/TaSe2 contact exhibits an ultralow Schottky barrier height of 65 meV and a contact resistance of 11 kΩ·µm, which is a 50-fold reduction compared to the conventional Cr/Au contact. Our method offers a way on fabricating high-performance 2D FETs.

New frontiers in salivary extracellular vesicles: transforming diagnostics, monitoring, and therapeutics in oral and systemic diseases.

Salivary extracellular vesicles (EVs) have emerged as key tools for non-invasive diagnostics, playing a crucial role in the early detection and monitoring of diseases. These EVs surpass whole saliva in biomarker detection due to their enhanced stability, which minimizes contamination and enzymatic degradation. The review comprehensively discusses methods for isolating, enriching, quantifying, and characterizing salivary EVs. It highlights their importance as biomarkers in oral diseases like periodontitis and oral cancer, and underscores their potential in monitoring systemic conditions. Furthermore, the review explores the therapeutic possibilities of salivary EVs, particularly in personalized medicine through engineered EVs for targeted drug delivery. The discussion also covers the current challenges and future prospects in the field, emphasizing the potential of salivary EVs in advancing clinical practice and disease management.

Gegen Qinlian tablets delay Alzheimer's disease progression via inhibiting glial neuroinflammation and remodeling gut microbiota homeostasis.

BACKGROUND: Current therapeutic agents for AD have limited efficacy and often induce undesirable side effects. Gegen Qinlian tablets (GGQLT) are a well-known clearingheat formula used in clinical treatment of inflammatory diseases. Based on traditional Chinese medicine (TCM) theory, the strategy of clearing-heat is then compatible with the treatment of AD. However, it remains unknown whether GGQLT can exert neuroprotective effects and alleviate neuroinflammation in AD. PURPOSE: This study aimed to evaluate the anti-AD effects of GGQLT and to decipher its intricate mechanism using integrative analyses of network pharmacology, transcriptomic RNA sequencing, and gut microbiota. METHODS: The ingredients of GGQLT were analyzed using HPLC-ESI-Q/TOF-MS. The AD model was established by bilateral injection of Aß1-42 into the intracerebroventricular space of rats. The Morris water maze was used to evaluate the cognitive function of the AD rats. The long-term toxicity of GGQLT in rats was assessed by monitoring their body weights and pathological alterations in the liver and kidney. Reactive astrocytes and microglia were assessed by immunohistochemistry by labeling GFAP and Iba-1. The levels of inflammatory cytokines in the hippocampus were evaluated using ELISA kits, RT-PCR, and Western blot, respectively. The potential anti-AD mechanism was predicted by analyses of RNA-sequencing and network pharmacology. Western blot and immunohistochemistry were utilized to detect the phosphorylation levels of IκBα, NF-κB p65, p38, ERK and JNK. The richness and composition of gut bacterial and fungal microflora were investigated via 16S rRNA and ITS sequencing. RESULTS: Typical ingredients of GGQLT were identified using HPLC-ESI-Q/TOF-MS. GGQLT significantly improved the cognitive function of AD rats by suppressing the activation of microglia and astrocytes, improving glial morphology, and reducing the neuroinflammatory reactions in the hippocampus. RNA-sequencing, network and experimental pharmacological studies demonstrated that GGQLT inhibited the activation of NF-κB/MAPK signaling pathways in the hippocampus. GGQLT could also restore abnormal gut bacterial and fungal homeostasis and no longer-term toxicity of GGQLT was observed. CONCLUSIONS: Our findings, for the first time, demonstrate GGQLT exhibit anti-AD effects and is worthy of further exploration and development.