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1.
Front Genet ; 15: 1425370, 2024.
Article in English | MEDLINE | ID: mdl-39092429

ABSTRACT

Background: Genome-wide association studies (GWASs) have identified 38 loci associated with ulcerative colitis (UC) susceptibility, but the risk genes and their biological mechanisms remained to be comprehensively elucidated. Methods: Multi-marker analysis of genomic annotation (MAGMA) software was used to annotate genes on GWAS summary statistics of UC from FinnGen database. Genetic analysis was performed to identify risk genes. Cross-tissue transcriptome-wide association study (TWAS) using the unified test for molecular signatures (UTMOST) was performed to compare GWAS summary statistics with gene expression matrix (from Genotype-Tissue Expression Project) for data integration. Subsequently, we used FUSION software to select key genes from the individual tissues. Additionally, conditional and joint analysis was conducted to improve our understanding on UC. Fine-mapping of causal gene sets (FOCUS) software was employed to accurately locate risk genes. The results of the four genetic analyses (MAGMA, UTMOST, FUSION and FOCUS) were combined to obtain a set of UC risk genes. Finally, Mendelian randomization (MR) analysis and Bayesian colocalization analysis were conducted to determine the causal relationship between the risk genes and UC. To test the robustness of our findings, the same approaches were taken to verify the GWAS data of UC on IEU. Results: Multiple correction tests screened PIM3 as a risk gene for UC. The results of Bayesian colocalization analysis showed that the posterior probability of hypothesis 4 was 0.997 and 0.954 in the validation dataset. MR was conducted using the inverse variance weighting method and two single nucleotide polymorphisms (SNPs, rs28645887 and rs62231924) were included in the analysis (p < 0.001, 95%CI: 1.45-1.89). In the validation dataset, MR result was p < 0.001, 95%CI: 1.19-1.72, indicating a clear causal relationship between PIM3 and UC. Conclusion: Our study validated PIM3 as a key risk gene for UC and its expression level may be related to the risk of UC, providing a novel reference for further improving the current understanding on the genetic structure of UC.

2.
Medicine (Baltimore) ; 103(30): e38747, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39058887

ABSTRACT

This study aims to develop and validate a machine learning (ML) predictive model for assessing mortality in patients with malignant tumors and hyperkalemia (MTH). We extracted data on patients with MTH from the Medical Information Mart for Intensive Care-IV, version 2.2 (MIMIC-IV v2.2) database. The dataset was split into a training set (75%) and a validation set (25%). We used the Least Absolute Shrinkage and Selection Operator (LASSO) regression to identify potential predictors, which included clinical laboratory indicators and vital signs. Pearson correlation analysis tested the correlation between predictors. In-hospital death was the prediction target. The Area Under the Curve (AUC) and accuracy of the training and validation sets of 7 ML algorithms were compared, and the optimal 1 was selected to develop the model. The calibration curve was used to evaluate the prediction accuracy of the model further. SHapley Additive exPlanations (SHAP) and Local Interpretable Model-agnostic Explanations (LIME) enhanced model interpretability. 496 patients with MTH in the Intensive Care Unit (ICU) were included. After screening, 17 clinical features were included in the construction of the ML model, and the Pearson correlation coefficient was <0.8, indicating that the correlation between the clinical features was small. eXtreme Gradient Boosting (XGBoost) outperformed other algorithms, achieving perfect scores in the training set (accuracy: 1.000, AUC: 1.000) and high scores in the validation set (accuracy: 0.734, AUC: 0.733). The calibration curves indicated good predictive calibration of the model. SHAP analysis identified the top 8 predictive factors: urine output, mean heart rate, maximum urea nitrogen, minimum oxygen saturation, minimum mean blood pressure, maximum total bilirubin, mean respiratory rate, and minimum pH. In addition, SHAP and LIME performed in-depth individual case analyses. This study demonstrates the effectiveness of ML methods in predicting mortality risk in ICU patients with MTH. It highlights the importance of predictors like urine output and mean heart rate. SHAP and LIME significantly enhanced the model's interpretability.


Subject(s)
Hyperkalemia , Intensive Care Units , Machine Learning , Neoplasms , Humans , Hyperkalemia/diagnosis , Hyperkalemia/mortality , Female , Male , Intensive Care Units/statistics & numerical data , Middle Aged , Prognosis , Neoplasms/mortality , Neoplasms/complications , Aged , Hospital Mortality , Algorithms
3.
Ecol Evol ; 14(7): e11641, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38957699

ABSTRACT

Although brood parasitism has been well documented among bird species, interspecific alloparenting, which is parenting behavior of adult individuals of one species toward the progeny of another species, is increasingly being reported. However, compared with the many reports of interspecific alloparenting behavior in North America and Europe, this phenomenon is less well known in China, with only two prior cases of interspecific alloparenting behavior in birds having been recorded. On June 23, 2022, we observed an instance of interspecific alloparental care provided by a mountain bulbul (Ixos mcclellandii) towards silver-eared mesia (Leiothrix argentauris) nestlings in Caihu Village, Jingdong County, Yunnan Province, southwestern China. We recorded 19.5 h of footage during the period in which the mountain bulbul provided care for the nestlings with the aim of documenting detailed observations of interspecific alloparenting to contribute to our overall understanding of this behavior. The alloparenting behavior of the mountain bulbul lasted for at least 5 days. During this period, both silver-eared mesia parents fed their nestlings 157 times and removed their nestlings' fecal sacs 5 times, while the mountain bulbul fed the nestlings 30 times and removed the nestlings' fecal sacs 4 times. In addition, the male silver-eared mesia parent chased the mountain bulbul away during nestling feeding. As there was no life history information for the mountain bulbul at that time, we were unable to directly determine why it exhibited interspecific alloparental care. Regardless of the reason for the mountain bulbul's behavior, these findings provide valuable information for future studies on the reproductive ecology of these two bird species.

4.
Int J Nanomedicine ; 19: 5173-5191, 2024.
Article in English | MEDLINE | ID: mdl-38855733

ABSTRACT

Purpose: Acne vulgaris is a chronic inflammatory skin disorder centered on hair follicles, making hair follicle-targeted delivery of anti-acne drugs a promising option for acne treatment. However, current researches have only focused on the delivering to healthy hair follicles, which are intrinsically different from pathologically clogged hair follicles in acne vulgaris. Patients and Methods: Azelaic acid (AZA) micro/nanocrystals with different particle sizes were prepared by wet media milling or high-pressure homogenization. An experiment on AZA micro/nanocrystals delivering to healthy hair follicles was carried out, with and without the use of physical enhancement techniques. More importantly, it innovatively designed an experiment, which could reveal the ability of AZA micro/nanocrystals to penetrate the constructed clogged hair follicles. The anti-inflammatory and antibacterial effects of AZA micro/nanocrystals were evaluated in vitro using a RAW264.7 cell model stimulated by lipopolysaccharide and a Cutibacterium acnes model. Finally, both the anti-acne effects and skin safety of AZA micro/nanocrystals and commercial products were compared in vivo. Results: In comparison to commercial products, 200 nm and 500 nm AZA micro/nanocrystals exhibited an increased capacity to target hair follicles. In the combination group of AZA micro/nanocrystals and ultrasound, the ability to penetrate hair follicles was further remarkably enhanced (ER value up to 9.6). However, toward the clogged hair follicles, AZA micro/nanocrystals cannot easily penetrate into by themselves. Only with the help of 1% salicylic acid, AZA micro/nanocrystals had a great potential to penetrate clogged hair follicle. It was also shown that AZA micro/nanocrystals had anti-inflammatory and antibacterial effects by inhibiting pro-inflammatory factors and Cutibacterium acnes. Compared with commercial products, the combination of AZA micro/nanocrystals and ultrasound exhibited an obvious advantage in both skin safety and in vivo anti-acne therapeutic efficacy. Conclusion: Hair follicle-targeted delivery of AZA micro/nanocrystals provided a satisfactory alternative in promoting the treatment of acne vulgaris.


Subject(s)
Acne Vulgaris , Anti-Bacterial Agents , Dicarboxylic Acids , Hair Follicle , Nanoparticles , Acne Vulgaris/drug therapy , Animals , Mice , Dicarboxylic Acids/chemistry , Dicarboxylic Acids/pharmacology , Hair Follicle/drug effects , RAW 264.7 Cells , Nanoparticles/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Humans , Particle Size , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/administration & dosage , Drug Delivery Systems/methods , Skin/drug effects , Skin/metabolism
5.
Front Pharmacol ; 15: 1396133, 2024.
Article in English | MEDLINE | ID: mdl-38828460

ABSTRACT

Objective: Growth differentiation factor 15 (GDF-15) is a stress-responsive cytokine that regulates myocardial injury, cardiac overloading pressure, and inflammation and is related to the risk of cardiovascular diseases and events. The current study aimed to investigate the correlation of GDF-15 levels with clinical features, biochemical indices, and especially the risk of cardiotoxicity in breast cancer patients receiving neoadjuvant dual anti-HER2 therapy. Methods: A total of 103 HER2-positive breast cancer patients who underwent neoadjuvant dual anti-HER2 therapy (trastuzumab and pertuzumab plus chemotherapy) were included. Serum GDF-15 levels before neoadjuvant treatment were detected by enzyme-linked immunosorbent assay. Cardiotoxicity was evaluated during neoadjuvant therapy by referring to a decline of ≥10 percentage points in the left ventricular ejection fraction from baseline to an absolute level less than 50%. Results: GDF-15 exhibited a skewed distribution, with a median level of 714 (range: 207-1805) pg/mL. GDF-15 was positively correlated with age (p = 0.037), diabetes (p = 0.036), and the N-terminal pro-brain natriuretic peptide level (p = 0.013) and positively correlated with the total cholesterol level (p = 0.086) and troponin T level (p = 0.082), but these correlations were not statistically significant. A total of 6.8% of patients experienced cardiotoxicity during neoadjuvant therapy. By comparison, the GDF-15 level was greater in patients who experienced cardiotoxicity than in those who did not (p = 0.008). A subsequent receiver operating characteristic curve revealed that GDF-15 predicted cardiotoxicity risk, with an area under the curve of 0.803 (95% CI: 0.664-0.939). After multivariate adjustment, GDF-15 independently predicted a greater risk of cardiotoxicity (p = 0.020). Conclusion: GDF-15 is a candidate biomarker for increased risk of cardiotoxicity in breast cancer patients receiving neoadjuvant dual anti-HER2 therapy.

6.
Integr Med Res ; 13(2): 101045, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38831890

ABSTRACT

Background: Post-viral olfactory dysfunction (PVOD) is the common symptoms of long COVID, lacking of effective treatments. Traditional Chinese medicine (TCM) is claimed to be effective in treating olfactory dysfunction, but the evidence has not yet been critically appraised. We conducted a systematic review to evaluate the effectiveness and safety of TCM for PVOD. Methods: We searched eight databases to identified clinical controlled studies about TCM for PVOD. The Cochrane risk of bias tools and GRADE were used to evaluate the quality of evidence. Risk ratio (RR), mean differences (MD), and 95 % confidence interval (CI), were used for effect estimation and RevMan 5.4.1 was used for data analysis. Results: Six randomized controlled trials (RCTs) (545 participants), two non-randomized controlled trials (non-RCTs) (112 participants), and one retrospective cohort study (30 participants) were included. The overall quality of included studies was low. Acupuncture (n = 8) and acupoint injection (n = 3) were the mainly used TCM therapies. Five RCTs showed a better effect in TCM group. Four trials used acupuncture, and three trials used acupoint injection. The results of two non-RCTs and one cohort study were not statistically significant. Two trials reported mild to moderate adverse events (pain and brief syncope caused by acupuncture or acupoint injection). Conclusions: Limited evidence focus on acupuncture and acupoint injection for PVOD and suggests that acupuncture and acupoint injection may be effective in improving PVOD. More well-designed trials should focus on acupuncture to confirm the benefit. Protocol registration: The protocol of this review was registered at PROSPERO: CRD42022366776.

7.
Eur J Pharm Biopharm ; 201: 114353, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38885911

ABSTRACT

The latent reservoir of human immunodeficiency virus (HIV) is a major obstacle in the treatment of acquired immune deficiency syndrome (AIDS). The "shock and kill" strategy has emerged as a promising approach for clearing HIV latent reservoirs. However, current latency-reversing agents (LRAs) have limitations in effectively and safely activating the latent virus and reducing the HIV latent reservoirs in clinical practice. Previously, EK-16A was extracted from Euphorbia kansui, which had the effect of interfering with the HIV-1 latent reservoir and inhibiting HIV-1 entry. Nevertheless, there is no suitable and efficient EK-16A oral formulation for in vivo delivery and clinical use. In this study, an oral EK-16A self-nanoemulsifying drug delivery system (EK-16A-SNEDDS) was proposed to "shock" the HIV-1 latent reservoir. This system aims to enhance the bioavailability and delivery of EK-16A to various organs. The composition of EK-16A-SNEDDS was optimized through self-emulsifying grading and ternary phase diagram tests. Cell models, pharmacokinetic experiments, and pharmacodynamics in HIV-1 latent cell transplant animal models suggested that EK-16A-SNEDDS could be absorbed by the gastrointestinal tract and enter the blood circulation after oral administration, thereby reaching various organs to activate latent HIV-1. The prepared EK-16A-SNEDDS demonstrated safety and efficacy, exhibited high clinical experimental potential, and may be a promising oral preparation for eliminating HIV-1 latent reservoirs.


Subject(s)
Emulsions , HIV-1 , Virus Latency , HIV-1/drug effects , Virus Latency/drug effects , Animals , Administration, Oral , Humans , Virus Activation/drug effects , Euphorbia/chemistry , HIV Infections/drug therapy , HIV Infections/virology , Plant Extracts/administration & dosage , Plant Extracts/pharmacology , Biological Availability , Nanoparticle Drug Delivery System , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/pharmacology , Anti-HIV Agents/pharmacokinetics , Male , Drug Delivery Systems/methods , Mice
8.
J Control Release ; 372: 69-84, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38866244

ABSTRACT

Transcytosis-inducing nanomedicines have been developed to improve tumor extravasation. However, the fate during transcytosis across multicell layers and the structural integrity of the nanomedicines before reaching tumor cells could impact antitumor therapy. Here, a BAY 87-2243 (a hypoxia-inducible factor-1 inhibitor)-loaded liposomal system (HA-P-LBAY) modified by low molecular weight protamine (LMWP) and crosslinked by hyaluronic acid (HA) was constructed. This system could accomplish differentiate cellular transport in endothelial and tumor cells by fine-tuning its structural integrity, i.e. transcytosis across the endothelial cells while preserving structural integrity, facilitating subsequent retention and drug release within tumor cells via degradation-induced aggregation. In vitro cellular uptake and transwell studies demonstrated that HA-P-LBAY were internalized by endothelial cells (bEnd.3) via an active, caveolin and heparin sulfate proteoglycan (HSPG)-mediated endocytosis, and subsequently achieved transcytosis mainly through the ER/Golgi pathway. Moreover, the fluorescence resonance energy transfer (FRET) study showed that HA-crosslinking maintained higher integrity of HA-P-LBAY after transcytosis, more efficiently than electrostatic coating of HA (HA/P-LBAY). In addition, more HA-P-LBAY was retained in tumor cells (4T1) compared to HA/P-LBAY corresponding to its enhanced in vitro cytotoxicity. This may be attributed to better integrity of HA-P-LBAY post endothelial transcytosis and more degradation of HA in tumor cells, leading to more liposome aggregation and inhibition of their transcytosis, which was inferred by both TEM images and the HAase responsiveness assay proved by FRET. In vivo, HA-P-LBAY exhibited more potency in tumor suppression than the other formulations in both low and high permeability tumor models. This highlighted that fine-tuning of structural integrity of nanocarriers played a key role no matter whether the transcytosis of nanocarriers contributed to cellular transport. Collectively, this study provides a promising strategy for antitumor therapies by fine-tuning liposome integrity to achieve active trans-endothelial transport with structural integrity and selective aggregation for prolonged tumor retention.


Subject(s)
Antineoplastic Agents , Hyaluronic Acid , Liposomes , Protamines , Transcytosis , Animals , Hyaluronic Acid/chemistry , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacology , Protamines/chemistry , Humans , Cell Line, Tumor , Female , Mice, Inbred BALB C , Endothelial Cells/metabolism , Endothelial Cells/drug effects , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology , Mice , Drug Liberation
9.
Heliyon ; 10(11): e32460, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38933931

ABSTRACT

Objective: Recent studies have shown that gene alternative splicing (AS) and long noncoding RNAs (lncRNAs) are involved in diabetes mellitus (DM) and its complications. Currently, myo-inositol (MI) is considered as effective for the treatment of insulin resistance and lipid metabolism disorders in diabetes patients. We hope to better explore the potential roles of gene AS and lncRNAs in liver glucose and lipid metabolism in diabetes, as well as the effects of myo-inositol treatment, through transcriptome analysis. Methods: This study analysed glucose and lipid metabolism-related biochemical indicators and liver HE staining in four groups of mice: the control group (Ctrl group), the diabetes group (DM group), the myo-inositol treatment group (MI group), and the metformin treatment group (Met group). The changes in relevant gene-regulated alternative splicing events (RASEs) and lncRNAs were analysed by RNA sequencing of liver tissue, and coexpression analysis and functional enrichment analysis were used to predict the possible lncRNAs and RASEs involved in liver glucose and lipid metabolism. Result: Metformin and myo-inositol alleviated insulin resistance, lipid metabolism disorders, and hepatic steatosis in diabetic mice. Transcriptome sequencing analysis revealed differential splicing events of genes related to lipid metabolism and differentially expressed lncRNAs (DElncRNAs). Six different lncRNAs and their potentially interacting splicing events were predicted. Conclusion: The present study revealed novel changes in RASEs and lncRNAs in the livers of diabetic mice following treatment with myo-inositol, which may shed light on the potential mechanisms by which myo-inositol delays and treats the progression of hepatic glucose and lipid metabolism in diabetes.

10.
Front Pharmacol ; 15: 1383831, 2024.
Article in English | MEDLINE | ID: mdl-38863976

ABSTRACT

Background: The COVID-19 pandemic has had a profound global impact, although the majority of recently infected cases have presented with mild to moderate symptoms. Previous clinical studies have demonstrated that Shufeng Jiedu (SFJD) capsule, a Chinese herbal patent medicine, effectively alleviates symptoms associated with the common cold, H1N1 influenza, and COVID-19. This study aimed to assess the efficacy and safety of SFJD capsules in managing symptoms of mild to moderate COVID-19 infection. Methods: A randomized, double-blind, placebo-controlled trial was conducted from May to December 2022 at two hospitals in China. Mild and moderate COVID-19-infected patients presenting respiratory symptoms within 3 days from onset were randomly assigned to either the SFJD or placebo groups in a 1:1 ratio. Individuals received SFJD capsules or a placebo three times daily for five consecutive days. Participants were followed up for more than 14 days after their RT-PCR nucleoid acid test for SARS-CoV-2 turned negative. The primary outcome measure was time to alleviate COVID-19 symptoms from baseline until the end of follow-up. Results: A total of 478 participants were screened; ultimately, 407 completed the trial after randomization (SFJD, n = 203; placebo, n = 204). No statistically significant difference in baseline parameters was observed between the two groups. The median time to alleviate all symptoms was 7 days in the SFJD group compared to 8 days in the placebo group (p = 0.037). Notably, the SFJD group significantly attenuated fever/chills (p = 0.04) and headache (p = 0.016) compared to the placebo group. Furthermore, the median time taken to reach normal body temperature within 24 h was reduced by 7 hours in the SFJD group compared to the placebo group (p = 0.033). No deaths or instances of serious or critical conditions occurred during this trial period; moreover, no serious adverse events were reported. Conclusion: The trial was conducted in a unique controlled hospital setting, and the 5-day treatment with SFJD capsules resulted in a 1-day reduction in overall symptoms, particularly headache and fever/chills, among COVID-19-infected participants with mild or moderate symptoms. Compared to placebo, SFJD capsules were found to be safe with fewer side effects. SFJD capsules could potentially serve as an effective treatment for alleviating mild to moderate symptoms of COVID-19. Clinical Trial Registration: https://www.isrctn.com/, identifier ISRCTN14236594.

11.
J Cancer Res Clin Oncol ; 150(5): 234, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38710918

ABSTRACT

BACKGROUND: The pathogenesis and treatment of colorectal cancer (CRC) continue to be areas of ongoing research, especially the benefits of traditional Chinese medicine (TCM) in slowing the progression of CRC. This study was conducted to investigate the effectiveness and mechanism of action of modified Lichong decoction (MLCD) in inhibiting CRC progression. METHODS: We established CRC animal models using azoxymethane/dextran sodium sulfate (AOM/DSS) and administered high, medium, or low doses of MLCD or mesalazine (MS) for 9 weeks to observe MLCD alleviation of CRC. The optimal MLCD dose group was then subjected to metagenomic and RNA sequencing (RNA-seq) to explore the differentially abundant flora and genes in the control, model and MLCD groups. Finally, the mechanism of action was verified using WB, qRT‒PCR, immunohistochemistry and TUNEL staining. RESULTS: MLCD inhibited the progression of CRC, and the optimal effect was observed at high doses. MLCD regulated the structure and function of the intestinal flora by decreasing the abundance of harmful bacteria and increasing that of beneficial bacteria. The differentially expressed genes were mainly associated with the Wnt/ß-catenin pathway and the cell cycle. Molecular biology analysis indicated that MLCD suppressed the Wnt/ß-catenin pathway and the epithelial-mesenchymal transition (EMT), inhibited abnormal cell proliferation and promoted intestinal epithelial cell apoptosis. CONCLUSION: MLCD mitigated the abnormal growth of intestinal epithelial cells and promoted apoptosis, thereby inhibiting the progression of CRC. This inhibition was accomplished by modifying the intestinal microbiota and disrupting the Wnt/ß-catenin pathway and the EMT. Therefore, MLCD could serve as a potential component of TCM prescriptions for CRC treatment.


Subject(s)
Colorectal Neoplasms , Drugs, Chinese Herbal , Gastrointestinal Microbiome , Wnt Signaling Pathway , Wnt Signaling Pathway/drug effects , Gastrointestinal Microbiome/drug effects , Animals , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Drugs, Chinese Herbal/pharmacology , Mice , Humans , Male , Apoptosis/drug effects , Epithelial-Mesenchymal Transition/drug effects , Cell Proliferation/drug effects , Dextran Sulfate , beta Catenin/metabolism , Disease Models, Animal
12.
Front Pharmacol ; 15: 1359866, 2024.
Article in English | MEDLINE | ID: mdl-38803432

ABSTRACT

Objective: This study aimed to conduct the first meta-analysis to comprehensively evaluate the clinical effectiveness and safety of Xiaochaihu Decoction in treating Cancer-related Fever (CRF). Methods: Eight databases were systematically searched in September 2023. The risk of bias (ROB) 2.0 tool recommended by Cochrane Handbook was applied to evaluate the ROB of the included randomized controlled trials (RCTs). Additionally, the quality of evidence was assessed using the Grading of recommendations assessment, development and evaluation (GRADE) tool. Results: We included 18 RCTs involving 1,424 patients. Compared to Western medicine or Xinhuang Tablets, Xiaochaihu Decoction significantly improved clinical effectiveness in CRF patients (risk ratio [RR] = 1.24, 95% confidence interval [CI]: 1.17, 1.32) and expedited the normalization of body temperature (mean difference [MD] = -5.29, 95%CI: -5.59, -4.99). It also demonstrated a reduction in tumor necrosis factor-α (TNF-α) levels (MD = -0.63, 95%CI: -0.84, -0.41) and an increase in IL-2 levels (MD = 1.42, 95%CI: -1.09, 1.74). Analysis of Karnofsky Performance Status (KPS) scores showed that the use of Xiaochaihu Decoction improved the quality of life in CRF patients (RR = 1.57, 95%CI: 1.11, 2.22) and reduced the incidence of adverse events. However, it is important to note that the majority of included studies showed "some concerns" in risk of bias based on ROB 2.0, and the evidence quality assessed by GRADE method was rated as "low". Conclusion: While this study suggests the clinical effectiveness and safety of Xiaochaihu Decoction in treating patients with CRF, confirming these findings will necessitate additional high-quality, large-scale RCTs in future research. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023484068.

14.
Asia Pac J Clin Nutr ; 33(2): 237-246, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38794983

ABSTRACT

BACKGROUND AND OBJECTIVES: This study aims to examine the causal relationship between dietary factors and ulcerative colitis (UC). METHODS AND STUDY DESIGN: The analysis utilized data from genome-wide association studies (GWAS). Dried fruit, vegetables, processed meat, fresh fruit, and cereal intake were examined as exposure factors. UC was considered the outcome. Two-sample Mendelian randomization (TSMR) analysis was performed using methods. Heterogeneity and horizontal pleiotropy assessments were conducted to ensure the robustness of our findings. Additionally, we applied False Discovery Rate (FDR) corrections for multiple tests. RESULTS: The analysis revealed a significant inverse causal relationship between dried fruit intake and UC risk (odds ratio [OR]: 0.488, 95% confidence interval [CI]: 0.261 to 0.915, p = 0.025). No significant association was observed between vegetable intake (OR: 1.742, 95% CI: 0.561 to 5.415, p = 0.337), processed meat intake (OR: 1.136, 95% CI: 0.552 to 2.339, p = 0.729), fresh fruit intake (OR: 0.977, 95% CI: 0.465 to 2.054, p = 0.952), cereal intake (OR: 1.195, 95% CI: 0.669 to 2.134, p = 0.547). The low heterogeneity observed across analyses and the confirmation of stability through leave-one-out analysis reinforce the reliability of these results. Moreover, after adjusting for multiple tests, none of the dietary factors reached a p-value below the conventional significance threshold of 0.05. CONCLUSIONS: This study provides evidence of a potential association between dried fruit intake and a reduced risk of UC. Further MR studies incorporating larger GWAS datasets are needed to confirm these findings.


Subject(s)
Colitis, Ulcerative , Diet , Fruit , Genome-Wide Association Study , Mendelian Randomization Analysis , Colitis, Ulcerative/genetics , Humans , Mendelian Randomization Analysis/methods , Diet/statistics & numerical data , Diet/methods , Vegetables , Risk Factors
15.
Integr Med Res ; 13(2): 101047, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38799120

ABSTRACT

This educational article explores the convergence of open science practices and traditional, complementary, and integrative medicine (TCIM), shedding light on the potential benefits and challenges of open science for the development, dissemination, and implementation of evidence-based TCIM. We emphasize the transformative shift in medical science towards open and collaborative practices, highlighting the limited application of open science in TCIM research despite its growing acceptance among patients. We define open science practices and discuss those that are applicable to TCIM, including: study registration; reporting guidelines; data, code and material sharing; preprinting; publishing open access; and reproducibility/replication studies. We explore the benefits of open science in TCIM, spanning improved research quality, increased public trust, accelerated innovation, and enhanced evidence-based decision-making. We also acknowledge challenges such as data privacy concerns, limited resources, and resistance to cultural change. We propose strategies to overcome these challenges, including ethical guidelines, education programs, funding advocacy, interdisciplinary dialogue, and patient engagement. Looking to the future, we envision the maturation of open science in TCIM, the development of TCIM-specific guidelines for open science practices, advancements in data sharing platforms, the integration of open data and artificial intelligence in TCIM research, and changes in the context of policy and regulation. We foresee a future where open science in TCIM leads to a better evidence base, informed decision-making, interdisciplinary collaboration, and transformative impacts on healthcare and research methodologies, highlighting the promising synergy between open science and TCIM for holistic, evidence-based healthcare solutions.

16.
BMC Med Genomics ; 17(1): 124, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711024

ABSTRACT

BACKGROUND: Glycogen storage disease (GSD) is a disease caused by excessive deposition of glycogen in tissues due to genetic disorders in glycogen metabolism. Glycogen storage disease type I (GSD-I) is also known as VonGeirk disease and glucose-6-phosphatase deficiency. This disease is inherited in an autosomal recessive manner, and both sexes can be affected. The main symptoms include hypoglycaemia, hepatomegaly, acidosis, hyperlipidaemia, hyperuricaemia, hyperlactataemia, coagulopathy and developmental delay. CASE PRESENTATION: Here, we present the case of a 13-year-old female patient with GSD Ia complicated with multiple inflammatory hepatic adenomas. She presented to the hospital with hepatomegaly, hypoglycaemia, and epistaxis. By clinical manifestations and imaging and laboratory examinations, we suspected that the patient suffered from GSD I. Finally, the diagnosis was confirmed by liver pathology and whole-exome sequencing (WES). WES revealed a synonymous mutation, c.648 G > T (p.L216 = , NM_000151.4), in exon 5 and a frameshift mutation, c.262delG (p.Val88Phefs*14, NM_000151.4), in exon 2 of the G6PC gene. According to the pedigree analysis results of first-generation sequencing, heterozygous mutations of c.648 G > T and c.262delG were obtained from the patient's father and mother. Liver pathology revealed that the solid nodules were hepatocellular hyperplastic lesions, and immunohistochemical (IHC) results revealed positive expression of CD34 (incomplete vascularization), liver fatty acid binding protein (L-FABP) and C-reactive protein (CRP) in nodule hepatocytes and negative expression of ß-catenin and glutamine synthetase (GS). These findings suggest multiple inflammatory hepatocellular adenomas. PAS-stained peripheral hepatocytes that were mostly digested by PAS-D were strongly positive. This patient was finally diagnosed with GSD-Ia complicated with multiple inflammatory hepatic adenomas, briefly treated with nutritional therapy after diagnosis and then underwent living-donor liver allotransplantation. After 14 months of follow-up, the patient recovered well, liver function and blood glucose levels remained normal, and no complications occurred. CONCLUSION: The patient was diagnosed with GSD-Ia combined with multiple inflammatory hepatic adenomas and received liver transplant treatment. For childhood patients who present with hepatomegaly, growth retardation, and laboratory test abnormalities, including hypoglycaemia, hyperuricaemia, and hyperlipidaemia, a diagnosis of GSD should be considered. Gene sequencing and liver pathology play important roles in the diagnosis and typing of GSD.


Subject(s)
Glycogen Storage Disease Type I , Liver Neoplasms , Liver Transplantation , Humans , Glycogen Storage Disease Type I/genetics , Glycogen Storage Disease Type I/complications , Glycogen Storage Disease Type I/pathology , Female , Adolescent , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Liver Neoplasms/complications , Adenoma/genetics , Adenoma/complications , Adenoma/pathology , Adenoma, Liver Cell/genetics , Adenoma, Liver Cell/complications , Adenoma, Liver Cell/pathology , Inflammation/genetics , Inflammation/pathology , Inflammation/complications
17.
PLoS One ; 19(5): e0302384, 2024.
Article in English | MEDLINE | ID: mdl-38728341

ABSTRACT

Pneumonia is a major cause of morbidity and mortality in older adults. In the aging society, screening methods for predicting aspiration pneumonia are crucial for its prevention. Changes in the oropharyngeal morphology and hyoid bone position may increase the risk of aspiration pneumonia. This multicenter study aimed to investigate a simple and effective screening method for predicting dysphagia and aspiration pneumonia. Overall, 191 older adults (aged 65 years or older) were randomly sampled using the simple random sampling technique. Oropharyngeal morphology was assessed using the modified Mallampati classification, which reflects the size of the tongue in the oropharyngeal cavity. The hyoid position was measured as the distance between the menton and laryngeal prominence to evaluate aging-related changes in the muscles of the laryngopharynx. Dysphagia was assessed using the repetitive saliva swallowing test (RSST), which measures the number of swallowing movements in 30 seconds; dysphasia is defined as less than 3 swallowing movements in 30 seconds. The aspiration signs were assessed based on history of choking or coughing reflex during eating or drinking and medical history of pneumonia. The study findings revealed that the modified Mallampati classification was significantly correlated with a medical history of pneumonia. A higher incidence of pneumonia was evident in the lower Mallampati classification, which shows the smaller size of the tongue base in the oropharyngeal cavity. The results of this study suggest that the modified Mallampati classification may be a possible screening method to predict the occurrence of pneumonia.


Subject(s)
Deglutition Disorders , Pneumonia, Aspiration , Humans , Aged , Pneumonia, Aspiration/diagnosis , Male , Female , Aged, 80 and over , Deglutition Disorders/diagnosis , Oropharynx , Deglutition/physiology , Mass Screening/methods , Hyoid Bone/diagnostic imaging
18.
Adv Sci (Weinh) ; 11(28): e2403120, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38728591

ABSTRACT

The DNA-guided (gDNA) Argonaute from Thermus thermophilus (TtAgo) has little potential for nucleic acid detection and gene editing due to its poor dsDNA cleavage activity at relatively low temperature. Herein, the dsDNA cleavage activity of TtAgo is enhanced by using 2'-fluorine (2'F)-modified gDNA and developes a novel nucleic acid testing strategy. This study finds that the gDNA with 2'F-nucleotides at the 3'-end (2'F-gDNA) can promote the assembly of the TtAgo-guide-target ternary complex significantly by increasing its intermolecular force to target DNA and TtAgo, thereby providing ≈40-fold activity enhancement and decreasing minimum reaction temperature from 65 to 60 °C. Based on this outstanding advance, a novel nucleic acid testing strategy is proposed, termed FAST, which is performed by using the 2'F-gDNA/TtAgo for target recognition and combining it with Bst DNA polymerase for nucleic acid amplification. By integrating G-quadruplex and Thioflavin T, the FAST assay achieves one-pot real-time fluorescence analysis with ultra-sensitivity, providing a limit of detection up to 5 copies (20 µL reaction mixture) for miR-21 detection. In summary, an atom-modification-based strategy has been developed for enhancing the cleavage activity of TtAgo efficiently, thereby improving its practicability and establishing a TtAgo-based nucleic acid testing technology with ultra-sensitivity and high-specificity.


Subject(s)
DNA , Thermus thermophilus , Thermus thermophilus/genetics , Thermus thermophilus/metabolism , DNA/genetics , DNA/metabolism , DNA/chemistry , Argonaute Proteins/metabolism , Argonaute Proteins/genetics , Nucleic Acids/metabolism , Nucleic Acids/genetics , Fluorine/chemistry
19.
J Med Syst ; 48(1): 52, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38761230

ABSTRACT

This study aimed to analyze the current landscape of ChatGPT application in the medical field, assessing the current collaboration patterns and research topic hotspots to understand the impact and trends. By conducting a search in the Web of Science, we collected literature related to the applications of ChatGPT in medicine, covering the period from January 1, 2000 up to January 16, 2024. Bibliometric analyses were performed using CiteSpace (V6.2., Drexel University, PA, USA) and Microsoft Excel (Microsoft Corp.,WA, USA) to map the collaboration among countries/regions, the distribution of institutions and authors, and clustering of keywords. A total of 574 eligible articles were included, with 97.74% published in 2023. These articles span various disciplines, particularly in Health Care Sciences Services, with extensive international collaboration involving 73 countries. In terms of countries/regions studied, USA, India, and China led in the number of publications. USA ot only published nearly half of the total number of papers but also exhibits a highest collaborative capability. Regarding the co-occurrence of institutions and scholars, the National University of Singapore and Harvard University held significant influence in the cooperation network, with the top three authors in terms of publications being Wiwanitkit V (10 articles), Seth I (9 articles), Klang E (7 articles), and Kleebayoon A (7 articles). Through keyword clustering, the study identified 9 research theme clusters, among which "digital health"was not only the largest in scale but also had the most citations. The study highlights ChatGPT's cross-disciplinary nature and collaborative research in medicine, showcasing its growth potential, particularly in digital health and clinical decision support. Future exploration should examine the socio-economic and cultural impacts of this trend, along with ChatGPT's specific technical uses in medical practice.


Subject(s)
Artificial Intelligence , Bibliometrics
20.
Integr Med Res ; 13(2): 101039, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38746044

ABSTRACT

Background: Chronic fatigue is a predominant symptom of post COVID-19 condition, or long COVID. We aimed to evaluate the efficacy and safety of Traditional, Complementary and Integrative Medicine (TCIM) for fatigue post COVID-19 infection. Methods: Ten English and Chinese language databases and grey literature were searched up to 12 April 2023 for randomized controlled trials (RCTs). Cochrane "Risk of bias" (RoB) tool was applied. Evidence certainty was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Effect estimates were presented as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). Results: Thirteen RCTs with 1632 participants were included. One RCT showed that Bufei Huoxue herbal capsules reduced fatigue (n=129, MD -14.90, 95%CI -24.53 to -5.27), one RCT reported that Ludangshen herbal liquid lowered fatigue (n=184, MD -1.90, 95%CI -2.38 to -1.42), and the other one RCT shown that fatigue disappearance rate was higher with Ludangshen herbal liquid (n=184, RR 4.19, 95%CI 2.06 to 8.53). Compared to traditional Chinese medicine rehabilitation (TCM-rahab) alone, one RCT showed that fatigue symptoms were lower following Qingjin Yiqi granules plus TCM-rehab (n=388, MD -0.48, 95%CI -0.50 to -0.46). Due to concerns with RoB and/or imprecision, the certainty in this evidence was low to very low. No serious adverse events was reported. Conclusions: Limited evidence suggests that various TCIM interventions might reduce post COVID-19 fatigue. Larger, high quality RCTs of longer duration are required to confirm these preliminary findings. Study Registration: The protocol of this review has been registered at PROSPERO: CRD42022384136.

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