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1.
Nat Sci Sleep ; 16: 503-515, 2024.
Article in English | MEDLINE | ID: mdl-38803507

ABSTRACT

Purpose: The prevalence of obstructive sleep apnea (OSA) is high worldwide. This study aimed to quantify the relationship between the incidence of OSA and sleep patterns and genetic susceptibility. Methods: A total of 355,133 white British participants enrolled in the UK Biobank between 2006 and 2010 with follow-up data until September 2021 were recruited. We evaluated sleep patterns using a customized sleep scoring method based on the low-risk sleep phenotype, defined as follows: morning chronotype, 7-8 hours of sleep per day, never/rarely experience insomnia, no snoring, no frequent daytime sleepiness, never/rarely nap, and easily getting up early. The polygenic risk score was calculated to assess genetic susceptibility to OSA. Cox proportional hazard models were used to evaluate the associations between OSA and sleep patterns and genetic susceptibility. Results: During a mean follow-up of 12.57 years, 4618 participants were diagnosed with OSA (age: 56.83 ± 7.69 years, women: 31.3%). Compared with those with a poor sleep pattern, participants with a normal (HR: 0.42, 95% CI: 0.38-0.46), ideal (HR: 0.21, 95% CI: 0.19-0.24), or optimal (HR: 0.15, 95% CI: 0.12-0.18) sleep pattern were significantly more likely to have OSA. The genetic susceptibility of 173,239 participants was calculated, and the results showed that poor (HR: 3.67, 95% CI: 2.95-4.57) and normal (HR: 1.89, 95% CI: 1.66-2.16) sleep patterns with high genetic susceptibility can increase the risk for OSA. Conclusion: This large-scale prospective study provides evidence suggesting that sleep patterns across seven low-risk sleep phenotypes may protect against OSA in individuals with varying degrees of genetic susceptibility.

2.
Biomedicines ; 12(5)2024 May 16.
Article in English | MEDLINE | ID: mdl-38791066

ABSTRACT

Neutrophils play a crucial role in host defense against infection. Aberrant neutrophil activation may induce tissue damage via sterile inflammation. Neutrophil accumulation has been identified as a feature of the inflammatory response observed in metabolic dysfunction-associated steatohepatitis (MASH) and has been associated with liver fibrosis and cirrhosis. Here, we performed the transcriptomic analysis of circulating neutrophils from mild and advanced MASH patients to identify the potential mechanism behind neutrophil contribution to MASH progression. Our findings demonstrated that circulating neutrophils from mild and advanced MASH display an increased activated transcriptional program, with the expression of pro-inflammatory factors and an amplified lifespan compared to cells from non-diseased controls. Our results also suggest that MASH progression is associated with a dynamic shift in the profile of circulating neutrophils. In the early stages of MASH, mature neutrophils predominate in the bloodstream. As hepatic inflammation and fibrosis progress, the premature release of immature neutrophils into the circulation occurs. These immature neutrophils exhibit a pro-inflammatory profile that may exacerbate inflammation and promote fibrosis in MASH.

3.
World J Hepatol ; 16(5): 684-687, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38818296

ABSTRACT

In this editorial we comment on the review by Zhou et al reviewing the landscape of nanomedicine in the treatment of hepatocellular carcinoma (HCC). We focus on the immense potential of nanotechnology, particularly ligand-receptor mediated nanotherapy, in revolutionizing the treatment landscape of HCC. Despite advancements in multidisciplinary treatment, HCC remains a significant global health challenge. Ligand-mediated nanotherapy offers the opportunity for precise drug delivery to tumor sites, targeting specific receptors overexpressed in HCC cells, thereby enhancing efficacy and minimizing side effects. Overcoming drug resistance and aggressive tumor biology is facilitated by nanomedicine, bypassing traditional hurdles encountered in chemotherapy. Examples include targeting glypican-3, asialoglycoprotein, transferrin receptor or folic acid receptors, capitalizing on their over-expression in tumor cells. The ability for multi-receptor targeting through dual-ligand nanoparticle modification holds the prospect of further enhancement in specificity and efficacy of directed therapy. However, challenges including immune responses, reproducibility in nanoparticle synthesis, and production scalability remain. Future directions involve refining targeting strategies, improving drug release mechanisms, and streamlining production processes to enable personalized and multifunctional nanotherapies. Overall, the integration of nanotherapy in HCC treatment holds immense promise, but continued partnership and effort are needed in offering hope for more effective, precise, and accessible clinical care in the management of HCC.

4.
Int J Ophthalmol ; 17(4): 736-747, 2024.
Article in English | MEDLINE | ID: mdl-38638264

ABSTRACT

AIM: To analysis of research hotspots and trends on the application of premium intraocular lens (PIOLs) in the past 2 decades. METHODS: The literature search was performed on the Web of Science and included PIOLs studies published between January 2000 and December 2022. The retrieved literature was collated and analyzed by R-tool's Bibliometrix package, CitNetExplorer, CiteSpace and other software. RESULTS: A total of 1801 articles about PIOLs were obtained, most of which were published in Spain and the United States. The organization that published the most articles was the University of Valencia in Spain. Alió JL, and Montés-Micó R, from Spain were the most influential authors in this field. The Journal of Cataract and Refractive Surgery and Journal of Refractive Surgery were the core journals for this field; the top 10 cited articles mainly focus on postoperative satisfaction with multifocal intraocular lens (IOLs) and postoperative results of toric IOLs. Through the keyword analysis, we found that trifocal IOLs, astigmatism and extended depth of focus (EDoF) IOLs are the most discussed topics at present, and the importance of astigmatism and the clinical application of the new generation of PIOLs are the emerging research trends. CONCLUSION: Bibliometric analysis can effectively help to identify multilevel concerns in PIOLs research and the prevailing research trends in the realm of PIOLs encompass the adoption of EDoF IOLs, trifocal IOLs, and their respective Toric models.

5.
Nat Genet ; 56(5): 846-860, 2024 May.
Article in English | MEDLINE | ID: mdl-38641644

ABSTRACT

Methylation quantitative trait loci (mQTLs) are essential for understanding the role of DNA methylation changes in genetic predisposition, yet they have not been fully characterized in East Asians (EAs). Here we identified mQTLs in whole blood from 3,523 Chinese individuals and replicated them in additional 1,858 Chinese individuals from two cohorts. Over 9% of mQTLs displayed specificity to EAs, facilitating the fine-mapping of EA-specific genetic associations, as shown for variants associated with height. Trans-mQTL hotspots revealed biological pathways contributing to EA-specific genetic associations, including an ERG-mediated 233 trans-mCpG network, implicated in hematopoietic cell differentiation, which likely reflects binding efficiency modulation of the ERG protein complex. More than 90% of mQTLs were shared between different blood cell lineages, with a smaller fraction of lineage-specific mQTLs displaying preferential hypomethylation in the respective lineages. Our study provides new insights into the mQTL landscape across genetic ancestries and their downstream effects on cellular processes and diseases/traits.


Subject(s)
DNA Methylation , East Asian People , Quantitative Trait Loci , Female , Humans , Male , East Asian People/genetics , Genetic Predisposition to Disease , Genome-Wide Association Study/methods , Multifactorial Inheritance , Polymorphism, Single Nucleotide
6.
Sci Total Environ ; 921: 171052, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38373459

ABSTRACT

Listening to natural sounds, both live and recorded, in either a natural or built environment is considered natural sound exposure (NSE). Sound is closely related to daily life, and research on the restorative effects of natural sounds is expanding. However, there is a lack of quantitative and comprehensive analysis on the impact of NSE on health recovery. This study systematically reviewed and conducted a meta-analysis on the impact of NSE on health recovery. Fifteen studies (1285 participants) were selected for the meta-analysis out of the 1157 literatures about the recovery of the NSE, searched from the Web of Science and Science Direct. The results indicate that NSE has certain positive effects: (a) In terms of emotional changes, NSE significantly reduces anxiety as measured by both the Visual Analog Scale (VAS) -2.31 (95 % CI -2.83, -1.79) and the State Anxiety Inventory (SAI) -12.22 (95 % CI -22.46, -1.98). (b) In terms of physiological reaction, NSE resulted in reduced heart rate (HR) -5.46 (95 % CI -9.62, -1.31), systolic blood pressure (SBP) -11.74 (95 % CI -15.51, -7.97), diastolic blood pressure (DBP) -13.98 (95 % CI -24.96, -2.99) and respiratory rate (RR) -1.58 (95 % CI -3.06, -0.10). (c) While the potential for restoration of cognitive performance by NSE was found, no consistent conclusions have been reached yet. However, there was significant heterogeneity between studies, primarily attributed to variations in study populations and methodologies. Because of the limited literature, we did not conduct subgroup analysis and meta-regression analysis. It is recommended that future studies address this heterogeneity by including more and higher-quality literature and employing rigorous methodologies to establish a robust foundation for evidence-based medicine. This will be of great significance for the application natural sounds in landscape planning and medical rehabilitation environments, and has the potential to promote improvements in public health.


Subject(s)
Anxiety , Emotions , Sound , Humans , Public Health
7.
Dig Dis Sci ; 69(4): 1403-1410, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38363522

ABSTRACT

BACKGROUND: Obesity and metabolic syndrome (MetS) have been implicated as rising risk factors for the development of colorectal cancers. A rapid increase in the prevalence of obesity and severe obesity among Hispanic patients in the United States may present substantially increased risk for advanced colorectal neoplasia in this population. Currently, there is very little research in this area. AIMS: We sought to identify metabolic risk factors for advanced adenomas (AA) in Hispanic Americans. METHODS: We retrospectively reviewed data from the Los Angeles General (LAG) Medical Center of asymptomatic Hispanic patients above 45 years of age who underwent their first colonoscopies following a positive screening FBT. Patient demographics, metabolic characteristics, as well as colon polyp size and histology were recorded. Polyps were classified as adenomas or AA (including both high-risk adenomas and high-risk serrated polyps). Relative risk for AA was assessed by multivariate logistical regression analyses. RESULTS: Of the 672 patients in our study, 41.4% were male, 67% had adenomas, and 16% had AA. The mean BMI was 31.2 kg/m2. The mean HDL-C was 49.5 mg/dL (1.28 mmol/L) and the mean triglyceride level was 151 mg/dL. 44.6% had diabetes and 64.1% had hypertension. When comparing patients with AA to patients with no adenoma, male sex, BMI > 34.9 kg/m2, and elevated fasting triglyceride levels were associated with an increased risk of AA. FIB-4 ≥1.45 was also associated with an increased risk of AA in males. There was no significant difference in the risk of AA with diabetes, hypertension, FIB-4 score, LDL-C level, and HDL-C level. CONCLUSIONS: Hispanic patients with a positive FBT were observed to have a high incidence of AA. Class II obesity (BMI ≥ 35 kg/m2), elevated triglyceride levels were identified as risk factors among males in our study. Early interventions to address these modifiable risk factors in at-risk populations, such as multi-disciplinary weight management programs for the treatment of obesity and related co-morbidities, could potentially lead to risk reduction and CRC prevention.


Subject(s)
Adenoma , Colonic Polyps , Colorectal Neoplasms , Female , Humans , Male , Adenoma/diagnosis , Colonic Polyps/diagnosis , Colonoscopy , Colorectal Neoplasms/diagnosis , Diabetes Mellitus , Hispanic or Latino , Hypertension , Obesity/complications , Retrospective Studies , Risk Factors , Triglycerides
9.
J Ethnopharmacol ; 319(Pt 3): 117350, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-37907144

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Viola yedoensis Makino (VYM) is a traditional Chinese herbal medicine widely distributed in China. It has many pharmacological effects such as anti-inflammatory, immune regulation and anti-oxidation. However, the protective effect of VYM on the spleen and thymus of broilers induced by heat stress has rarely been reported. AIM OF THE STUDY: We established a heat stress model of broilers to explore the protective effect of VYM on spleen and thymus of broilers. MATERIALS AND METHODS: In this experiment, a heat stress model was made by adjusting the feeding temperature of broilers. The protective effect of VYM on the spleen and thymus of heat-stressed broilers were evaluated by detecting immune organ coefficient, histological observation, Enzyme-Linked Immunosorbent Assay, production of antioxidant enzymes and peroxides, TUNEL Staining, Quantitative Real-time PCR. RESULTS: In this study, 60 healthy male AA broilers were divided into 6 groups: Control, 4.5% VYM, HS, HS + 0.5% VYM, HS + 1.5% VYM, HS + 4.5% VYM. After 42 days of feeding, serum, spleen and thymus were collected for detection and analysis. The study revealed that heat stress can lead to pathological damage in the spleen and thymus of broilers, reduce the content of immunoglobulin and newcastle disease (ND), infectious bursal disease (IBD) antibody levels, increase the expression of inflammatory factors IL-1ß, INF-γ, heat shock 70 kDa protein (HSP70), heat shock 90 kDa protein (HSP90). Heat stress inhibits the activity of antioxidant enzymes CAT and SOD, promotes the production of MDA, and then lead to oxidative damage of the spleen and thymus. In addition, apoptotic cells and the ratio of Bax/Bcl-2 was increased. However, the addition of VYM to the feed can alleviate the adverse effects of heat stress on the spleen and thymus of broilers. CONCLUSIONS: This study showed that the addition of VYM to the diet could inhibit oxidative stress and apoptosis, and reduce the inflammatory damage of heat stress on the spleen and thymus of broilers. This study provides a basis for further exploring the regulatory role of VYM in heat stress-induced immune imbalance in broilers. In addition, this study also provides a theoretical basis for the development of VYM as a feed additive with immunomodulatory effects.


Subject(s)
Spleen , Viola , Male , Animals , Chickens , Antioxidants/pharmacology , Oxidative Stress , Apoptosis , Inflammation , Heat-Shock Proteins , Heat-Shock Response
10.
Sci Rep ; 13(1): 20539, 2023 11 23.
Article in English | MEDLINE | ID: mdl-37996736

ABSTRACT

As of 2021, over 2.8 million small-incision lenticule extraction (SMILE) procedures have been performed in China. However, knowledge regarding the selection of intraocular lens (IOL) power calculation formula for post-SMILE cataract patients remains limited. This study included 52 eyes of 26 myopic patients from northern China who underwent SMILE at Tianjin Eye Hospital from September 2022 to February 2023 to investigate the suitability of multiple IOL calculation formulas in post-SMILE patients using a theoretical surgical model. We compared the postoperative results obtained from three artificial intelligence (AI)-based formulas and six conventional formulas provided by the American Society of Cataract and Refractive Surgery (ASCRS). These formulas were applied to calculate IOL power using both total keratometry (TK) and keratometry (K) values, and the results were compared to the preoperative results obtained from the Barrett Universal II (BUII) formula for the SMILE patients. Among the evaluated formulas, the results obtained from the Emmetropia Verifying Optical 2.0 Formula with TK (EVO-TK) (0.40 ± 0.29 D, range 0-1.23 D), Barrett True K with K formula (BTK-K, 0.41 ± 0.26 D, range 0.01-1.19 D), and Masket with K formula (Masket-K, 0.44 ± 0.33 D, range 0.02-1.39 D) demonstrated the closest proximity to BUII. Notably, the highest proportion of prediction errors within 0.5 D was observed with the BTK-K (71.15%), EVO-TK (69.23%), and Masket-K (67.31%), with the BTK-K showing a significantly higher proportion than the Masket-K (p < 0.001). Our research indicates that in post-SMILE patients, the EVO-TK, BTK-K, and Masket-K may yield more accurate calculation results. At their current stage in development, AI-based formulas do not demonstrate significant advantages over conventional formulas. However, the application of historical data can enhance the performance of these formulas.


Subject(s)
Cataract , Lenses, Intraocular , Myopia , Phacoemulsification , Humans , Artificial Intelligence , Biometry/methods , East Asian People , Lens Implantation, Intraocular/methods , Myopia/surgery , Optics and Photonics , Phacoemulsification/methods , Refraction, Ocular , Retrospective Studies
12.
BMC Ophthalmol ; 23(1): 416, 2023 Oct 16.
Article in English | MEDLINE | ID: mdl-37845633

ABSTRACT

BACKGROUND: As the two most prevalent refractive surgeries in China, there is a substantial number of patients who have undergone Femtosecond Laser-assisted In Situ Keratomileusis (FS-LASIK) and Small Incision Lenticule Extraction (SMILE) procedures. However, there is still limited knowledge regarding the selection of intraocular lens (IOL) power calculation formulas for these patients with a history of FS-LASIK or SMILE. METHODS: A total of 100 eyes from 50 postoperative refractive surgery patients were included in this prospective cohort study, with 25 individuals (50 eyes) having undergone FS-LASIK and 25 individuals (50 eyes) having undergone SMILE. We utilized a theoretical surgical model to simulate the IOL implantation process in postoperative FS-LASIK and SMILE patients. Subsequently, we performed comprehensive biological measurements both before and after the surgeries, encompassing demographic information, corneal biometric parameters, and axial length. Various formulas, including the Barrett Universal II (BUII) formula, as a baseline, were employed to calculate IOL power for the patients. RESULTS: The Barrett True K (BTK) formula, demonstrated an mean absolute error (AE) within 0.5 D for both FS-LASIK and SMILE groups (0.28 ± 0.25 D and 0.36 ± 0.24 D, respectively). Notably, the FS-LASIK group showed 82% of results differing by less than 0.25 D compared to preoperative BUII results. The Barrett True K No History (BTKNH) formula, which also incorporates measured posterior corneal curvature, performed similarly to BTK in both groups. Additionally, the Masket formula, relying on refractive changes based on empirical experience, displayed promising potential for IOL calculations in SMILE patients compared with BTK (p = 0.411). CONCLUSION: The study reveals the accuracy and stability of the BTK and BTKNH formulas for IOL power calculations in myopic FS-LASIK/SMILE patients. Moreover, the Masket formula shows encouraging results in SMILE patients. These findings contribute to enhancing the predictability and success of IOL power calculations in patients with a history of refractive surgery, providing valuable insights for clinical practice. Further research and larger sample sizes are warranted to validate and optimize the identified formulas for better patient outcomes.


Subject(s)
Keratomileusis, Laser In Situ , Lenses, Intraocular , Humans , Keratomileusis, Laser In Situ/methods , Prospective Studies , Refraction, Ocular , Cornea/surgery , Models, Theoretical , Retrospective Studies , Lasers, Excimer/therapeutic use
13.
Int Ophthalmol ; 43(11): 4137-4150, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37552428

ABSTRACT

PURPOSE: As an autoimmune disease, Vogt‒Koyanagi‒Harada disease (VKHD) is a main type of uveitis in many countries and regions, significantly impacting patient vision. At present, information regarding VKHD is still limited, and further research is needed. We conducted a bibliometric analysis to characterize the overall status, current trends, and current focus of VKHD research. METHOD: Literature published from 1975 to 2022 was obtained from the Web of Science core collection and analysed with the R-language packages Bibliometrix, VOSviewer, and CiteSpace software. RESULTS: A total of 1050 papers on VKHD were retrieved from 261 journals, and 16,084 references were obtained from the papers in the original search. The average annual number of published articles was approximately 21.9, and the number of publications rapidly increased after 2004. The journal Ocular Immunology and Inflammation published the most papers on VKHD, while the American Journal of Ophthalmology has the highest citation frequency. The leading countries were Japan, China (PRC), and the United States of America (USA). Yang PZ from Chongqing Medical University was the most prolific and cited author. The most frequently cited study discussed revision of VKHD diagnostic criteria. An analysis of the highest frequency keywords showed that most research focused on the treatment, diagnosis, and pathogenesis of VKHD and its relationship with other related diseases. At present, the most urgent research direction is in the relationship between COVID-19 or COVID-19 vaccines and VKHD and the corresponding mechanisms underlying it. CONCLUSION: Utilizing dynamic and visualization tools, bibliometrics provides a clear depiction of the research history, development trends, and research hotspots in VKHD It serves as a valuable tool for identifying research gaps and areas that necessitate further exploration. Our study revealed potential directions for future VKHD research, including investigating specific molecular mechanisms underlying the disease, exploring the clinical utility of optical coherence tomography angiography and other diagnostic techniques, and conducting clinical research on novel therapeutic drugs.


Subject(s)
Autoimmune Diseases , COVID-19 , Uveomeningoencephalitic Syndrome , Humans , Uveomeningoencephalitic Syndrome/diagnosis , COVID-19 Vaccines , Bibliometrics
14.
EClinicalMedicine ; 55: 101752, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36444212

ABSTRACT

Background: The initial dose of tacrolimus after liver transplantation (LT) is critical for rapidly achieving the steady state of the drug concentration, minimizing the potential adverse reactions and warranting long-term patient prognosis. We aimed to develop and validate a genotype-guided model for determining personalized initial dose of tacrolimus. Methods: By combining pharmacokinetic modeling, pharmacogenomic analysis and multiple statistical methods, we developed a genotype-guided model to predict individualized tacrolimus initial dose after LT in the discovery (n = 150) and validation cohorts (n = 97) respectively. This model was further validated in a prospective, randomized and single-blind clinical trial from August, 2021 to February, 2022 (n = 40, ChiCTR2100050288). Findings: Our model included donor's and recipient's genotypes, recipient's weight and total bilirubin, which achieved an area under the curve of receiver operating characteristic curve (AUC of ROC) of 0.88 and 0.79 in the discovery and validation cohorts, respectively. We found that patients who were given tacrolimus within the recommended concentration range (RCR) (4-10 ng/mL), the new-onset metabolic syndromes are lower, especially for new-onset diabetes (p = 0.043). In the clinical trial, compared to those in experience-based (EB) group, patients in the model-based (MB) group were more likely to achieving the RCR (75% vs 40%, p = 0.025) with a more variable individualized dose (0.023-0.096 mg/kg/day vs 0.045-0.057 mg/kg/day). Moreover, significantly fewer medication adjustments were required for the MB group than the EB group (2.75 ± 2.01 vs 6.05 ± 3.35, p = 0.001). Interpretation: Our genotype-based model significantly improved the initial dosing accuracy of tacrolimus and reduced the number of medication adjustments, which are critical for improving the prognosis of LT patients. Funding: National Natural Science Foundation of China, Shanghai three-year action plan, National Science and Technology Major Project of China.

15.
Nat Commun ; 13(1): 7468, 2022 12 03.
Article in English | MEDLINE | ID: mdl-36463230

ABSTRACT

Treg cells acquire distinct transcriptional properties to suppress specific inflammatory responses. Transcription characteristics of Treg cells are regulated by epigenetic modifications, the mechanism of which remains obscure. Here, we report that Setd2, a histone H3K36 methyltransferase, is important for the survival and suppressive function of Treg cells, especially those from the intestine. Setd2 supports GATA3+ST2+ intestinal thymic-derived Treg (tTreg) cells by facilitating the expression and reciprocal relationship of GATA3 and ST2 in tTreg cells. IL-33 preferentially boosts Th2 cells rather than GATA3+ Treg cells in Foxp3Cre-YFPSetd2 flox/flox mice, corroborating the constraint of Th2 responses by Setd2 expression in Treg cells. SETD2 sustains GATA3 expression in human Treg cells, and SETD2 expression is increased in Treg cells from human colorectal cancer tissues. Epigenetically, Setd2 regulates the transcription of target genes (including Il1rl1) by modulating the activity of promoters and intragenic enhancers where H3K36me3 is typically deposited. Our findings provide mechanistic insights into the regulation of Treg cells and intestinal immunity by Setd2.


Subject(s)
Histone-Lysine N-Methyltransferase , Interleukin-1 Receptor-Like 1 Protein , Intestines , T-Lymphocytes, Regulatory , Animals , Humans , Mice , GATA3 Transcription Factor/genetics , GATA3 Transcription Factor/immunology , Histone Methyltransferases , Histone-Lysine N-Methyltransferase/genetics , Histone-Lysine N-Methyltransferase/immunology , Inflammation/genetics , Inflammation/immunology , Interleukin-1 Receptor-Like 1 Protein/genetics , Interleukin-1 Receptor-Like 1 Protein/immunology , T-Lymphocytes, Regulatory/immunology , Thymus Gland , Colorectal Neoplasms/genetics , Colorectal Neoplasms/immunology , Intestines/immunology
16.
Front Psychiatry ; 13: 980315, 2022.
Article in English | MEDLINE | ID: mdl-36081461

ABSTRACT

Tissue-specific gene expression has been found to be associated with multiple complex diseases including cancer, metabolic disease, aging, etc. However, few studies of brain-tissue-specific gene expression patterns have been reported, especially in psychiatric disorders. In this study, we performed joint analysis on large-scale transcriptome multi-tissue data to investigate tissue-specific expression patterns in major depressive disorder (MDD) and bipolar disorder (BP). We established the strategies of identifying tissues-specific modules, annotated pathways for elucidating biological functions of tissues, and tissue-specific genes based on weighted gene co-expression network analysis (WGCNA) and robust rank aggregation (RRA) with transcriptional profiling data from different human tissues and genome wide association study (GWAS) data, which have been expanded into overlapping tissue-specific modules and genes sharing with MDD and BP. Nine tissue-specific modules were identified and distributed across the four tissues in the MDD and six modules in the BP. In general, the annotated biological functions of differentially expressed genes (DEGs) in blood were mainly involved in MDD and BP progression through immune response, while those in the brain were in neuron and neuroendocrine response. Tissue-specific genes of the prefrontal cortex (PFC) in MDD-, such as IGFBP2 and HTR1A, were involved in disease-related functions, such as response to glucocorticoid, taste transduction, and tissue-specific genes of PFC in BP-, such as CHRM5 and LTB4R2, were involved in neuroactive ligand-receptor interaction. We also found PFC tissue-specific genes including SST and CRHBP were shared in MDD-BP, SST was enriched in neuroactive ligand-receptor interaction, and CRHBP shown was related to the regulation of hormone secretion and hormone transport.

17.
Clin Liver Dis (Hoboken) ; 19(3): 106-110, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35355841

ABSTRACT

Content available: Author Audio Recording.

19.
Am J Gastroenterol ; 117(3): 433-444, 2022 03 01.
Article in English | MEDLINE | ID: mdl-35083985

ABSTRACT

INTRODUCTION: Nonalcoholic steatohepatitis (NASH) is one of the most common etiologies of liver transplantation (LT) in the United States. We investigated regional trends in waitlist candidates, LT rates, and recipient survival among patients with NASH. METHODS: Using the United Network for Organ Sharing database by Organ Procurement and Transplantation Network regions, we investigated waitlist registration, LT rates, and survival for NASH between January 2004 and December 2019. RESULTS: The absolute number and percentage of total LT performed for NASH increased substantially in all Organ Procurement and Transplantation Network regions. In 2019, region 11 had the highest percentage of NASH-related LT with 31.4% followed by region 10 (25.3%) and region 8 (23.1%). Between 2015 and 2019, region 5 had the highest rising percentage in LT for NASH at 208%, followed by region 1 (194%) and region 4 (183%). The proportion of NASH hepatocellular carcinoma (NASH-HCC) was the highest in region 9 at 37.7% and lowest in region 10 (19.2%), region 3 (20.6%), and region 11 (20.8%). In multivariate analysis, diabetes (HR 1.18, P < 0.001), dialysis before LT (hazard ratio [HR] 1.53, P < 0.001), HCC (HR 1.19, P < 0.00), portal vein thrombosis (HR 1.24, P < 0.001), donor age (HR 1.026, P = 0.03), and recipient age (HR 1.24, P = <0.001) were associated with worse survival. DISCUSSION: LT for patients with NASH has dramatically increased across all regions since 2004, but with substantial heterogeneity among regions in the proportion with HCC and post-LT survival. Identifying contributing factors to these regional differences is warranted.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Liver Transplantation , Non-alcoholic Fatty Liver Disease , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/surgery , Humans , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/surgery , Retrospective Studies , Risk Factors , United States/epidemiology
20.
Dig Dis Sci ; 67(7): 3340-3355, 2022 07.
Article in English | MEDLINE | ID: mdl-34173916

ABSTRACT

BACKGROUND AND AIMS: Most population-based studies of risk profiles for liver steatosis have relied upon serum markers (e.g., ALT or FIB-4) or ultrasound steatosis index to define cases. We sought to examine racial/ethnic differences in metabolic risk factors associated with liver steatosis and fibrosis at the population level using elastography-based measures. METHODS: In total, 4509 adults completed vibration-controlled transient elastography (VCTE) with controlled attenuated parameter (CAP) examinations in the 2017-2018 National Health and Nutrition Examinations Survey. Race/ethnicity was self-identified; metabolic parameters included waist circumference, obesity, diabetes, hypertension, and hyperlipidemia. Primary outcome was steatosis defined by CAP score ≥ 280 decibels per meter and secondary outcome significant fibrosis by VCTE median stiffness ≥ 8 kilopascals. Race-specific logistic regression models were performed to assess the relationship between metabolic parameters and hepatic steatosis and fibrosis. RESULTS: Prevalence of elastography-based hepatic steatosis was > 30% for all race/ethnicities. Steatosis was associated with increasing waist circumference for all race/ethnicities (OR ranging 1.7-2.3, p < 0.01). Steatosis was associated with diabetes for Whites (OR 2.4, 95% CI 1.2-4.7), Asians (OR 3.0, 1.4-6.3), and Hispanics (OR 2.2, 1.3-3.6), but not Blacks (OR 1.3, 0.8-2.2); hypertension for Whites (OR 1.7, 1.3-4.7) and Asians (OR 2.1, 1.1-3.8); and hyperlipidemia for Blacks only (OR 2.2, 1.3-3.7). Of metabolic risk factors, higher odds of fibrosis were demonstrated with higher waist circumference per 10 cm increase (OR 2.1, 1.8-2.4) and diabetes (OR 2.5, 1.6-3.7), but the effect of diabetes was present in all racial/ethnic groups except Blacks (p-interaction < 0.05). CONCLUSION: Blacks have a distinct metabolic phenotype for steatosis, while Asians, Whites, and Hispanics are more similar. Racial/ethnic differences in risk profiles are important to consider in prevention, screening strategies, and interventions for fatty liver disease.


Subject(s)
Elasticity Imaging Techniques , Hypertension , Non-alcoholic Fatty Liver Disease , Ethnicity , Humans , Hypertension/complications , Liver/diagnostic imaging , Liver/pathology , Liver Cirrhosis/complications , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/epidemiology , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Non-alcoholic Fatty Liver Disease/epidemiology
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