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1.
Front Nutr ; 11: 1386361, 2024.
Article in English | MEDLINE | ID: mdl-38832098

ABSTRACT

Background: Patients with nasopharyngeal carcinoma are notably susceptible to high nutritional risks. If not addressed, this susceptibility can lead to malnutrition, resulting in numerous adverse clinical outcomes. Despite the significance of this issue, there is limited comprehensive research on the topic. Objective: The objective of our study was to identify nutritional risk factors in patients with nasopharyngeal carcinoma. Methods: For this cross-sectional study, we recruited a total of 377 patients with nasopharyngeal carcinoma. The Nutritional Risk Screening 2002 tool was used to assess their nutritional risk. These patients were divided into a well-nourished group (n = 222) and a nutritional risk group (n = 155). Potential risk factors were screened out using univariate analysis (p < 0.1). These factors were subsequently analyzed with multivariate logistic regression analysis (p < 0.05) to identify the nutritional risk factors for these patients. Results: Our findings indicated that increasing age (OR = 1.085, 95%CI: 1.053-1.117, p < 0.001), high number of radiation treatments (OR = 1.103, 95%CI: 1.074-1.132, p < 0.001), low BMI (OR = 0.700, 95%CI: 0.618-0.793, p < 0.001), and low albumin levels (OR = 0.852, 95%CI: 0.789-0.921, p < 0.001) are significant nutritional risk factors in patients with nasopharyngeal carcinoma. Conclusion: Increasing age, high number of radiation treatments, low BMI, and low albumin levels are significant nutritional risk factors in patients with nasopharyngeal carcinoma.

2.
Front Endocrinol (Lausanne) ; 15: 1385143, 2024.
Article in English | MEDLINE | ID: mdl-38699391

ABSTRACT

Background and aims: Most studies have analyzed the relationship between resting heart rate (RHR) measured at only one time point and future clinical events. The current study aims to investigate the impact of long-term RHR changes on future clinical outcomes in a decade-long cohort with type 2 diabetes mellitus (T2DM). Methods: The two-staged follow-up involved 2,513 T2DM participants. The first stage (2008-2014) intended to identify levels and trends in RHR changes, while the second stage (2014-2018) attempted to collect new occurrence records of clinical results. Cox proportional hazards models were applied to predict hazard ratios (HRs), along with 95% confidence interval (CI) for the correlation between RHR changes and future events. Results: There is no significant correlation between baseline RHR levels and long-term clinical events. According to the range of RHR change, compared with the stable RHR group, the adjusted HRs for cardiovascular events and all-cause death in the large increase group were 3.40 (95% CI: 1.33-8.71, p=0.010) and 3.22 (95% CI: 1.07-9.64, p=0.037), respectively. While the adjusted HRs for all-cause death and major adverse cardiac and cerebrovascular events (MACCE) in the moderate decrease group were 0.55 (95% CI: 0.31-0.96, p=0.037) and 0.51 (95% CI: 0.26-0.98, p=0.046). According to the trend of RHR, compared with the normal-normal group, the adjusted HRs for composite endpoint events and cerebrovascular events in the normal-high group were 1.64 (95% CI: 1.00-2.68, p=0.047) and 2.82 (95% CI: 1.03-7.76, p=0.043), respectively. Conclusion: Changes in RHR had predictive value for long-term clinical events in diabetic populations. Individuals with significantly elevated RHR over a particular period of time showed an increased risk of adverse events.


Subject(s)
Diabetes Mellitus, Type 2 , Heart Rate , Humans , Male , Female , Heart Rate/physiology , Diabetes Mellitus, Type 2/physiopathology , Middle Aged , Follow-Up Studies , Aged , Prognosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/physiopathology , Rest/physiology , Adult , Risk Factors , Time Factors
3.
Science ; 384(6697): 767-775, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38753792

ABSTRACT

The efficiency and longevity of metal-halide perovskite solar cells are typically dictated by nonradiative defect-mediated charge recombination. In this work, we demonstrate a vapor-based amino-silane passivation that reduces photovoltage deficits to around 100 millivolts (>90% of the thermodynamic limit) in perovskite solar cells of bandgaps between 1.6 and 1.8 electron volts, which is crucial for tandem applications. A primary-, secondary-, or tertiary-amino-silane alone negatively or barely affected perovskite crystallinity and charge transport, but amino-silanes that incorporate primary and secondary amines yield up to a 60-fold increase in photoluminescence quantum yield and preserve long-range conduction. Amino-silane-treated devices retained 95% power conversion efficiency for more than 1500 hours under full-spectrum sunlight at 85°C and open-circuit conditions in ambient air with a relative humidity of 50 to 60%.

4.
Nutr Cancer ; : 1-11, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38757365

ABSTRACT

It is critical to screen and assess malnutrition in cancer patients early. However, there is no uniform standard for nutritional risk screening and malnutrition assessment. We aimed to analyze the effects of the Nutrition Risk Screening 2002 (NRS2002) in screening for nutritional risk among adult cancer patients, using the Patient-Generated Subjective Global Assessment (PG-SGA) as the reference standard. A systematic search was performed using PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, and China Science and Technology Journal Database (VIP). Studies comparing NRS2002 with PG-SGA in adult cancer patients were included. To assess the quality of the included studies, the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used. The combined sensitivity, specificity, diagnostic odds ratio (DOR), and the area under the receiver-operating characteristic curve (AUC) were calculated. In addition, sensitivity, subgroup, and publication bias analyses were performed. Thirteen articles involving 3,373 participants were included. The combined sensitivity, specificity, DOR, and AUC were 0.62 (95% CI, 0.60-0.64), 0.86 (95% CI, 0.84-0.88), 11.23 (95% CI, 8.26-15.27), and 0.85 (95% CI, 0.82-0.88), respectively. For adult cancer patients, NRS2002 has moderate sensitivity, high specificity, and high AUC in screening for nutritional risk.

5.
World J Pediatr ; 2024 May 24.
Article in English | MEDLINE | ID: mdl-38789720

ABSTRACT

BACKGROUND: Autism spectrum disorder (ASD) is a complex group of neurodevelopmental disorders. Research has highlighted a close association between the retinoic acid (RA) signaling pathway and ASD. This study investigates alterations in the vitamin A (VA, retinol) to RA metabolic pathway in children with ASD and speculates on the underlying reasons for these changes. We propose a subtype characterized by downregulated RA signaling in ASD, laying the groundwork for precise diagnosis and treatment research. METHODS: We included 489 children with ASD and 280 typically developing (TD) children. Those with ASD underwent evaluations of core symptoms and neuro-developmental levels, which were conducted by professional developmental behavior physicians using assessment scales. Serum VA and all-trans RA (atRA) levels were determined by high-performance liquid chromatography and ultra-high-performance liquid chromatography-tandem mass spectrometry. The expression levels and concentrations of enzyme molecules such as retinol dehydrogenase 10 were assessed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Children with ASD exhibited reduced serum atRA, accompanied by a downregulation of atRA synthesis enzymes. The reduction in serum atRA levels was linked not only to VA levels but also to the aberrant expression of metabolic enzymes responsible for atRA. Furthermore, the serum atRA levels in children with ASD were more strongly correlated with core symptoms and neurodevelopmental levels than VA levels. CONCLUSION: Children with ASD exhibited a dual regulation of reduced serum atRA levels, influenced by both VA levels and abnormal expression of atRA metabolic enzymes.

6.
Cardiovasc Diabetol ; 23(1): 177, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38783270

ABSTRACT

BACKGROUND: Numerous meta-analyses have explored the association between the triglyceride-glucose (TyG) index and diverse health outcomes, yet the comprehensive assessment of the scope, validity, and quality of this evidence remains incomplete. Our aim was to systematically review and synthesise existing meta-analyses of TyG index and health outcomes and to assess the quality of the evidence. METHODS: A thorough search of PubMed, EMBASE, and Web of Science databases was conducted from their inception through to 8 April 2024. We assessed the quality of reviews using A Measurement Tool to Assess Systematic Reviews (AMSTAR) and the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. This study was registered with PROSPERO (CRD: 42024518587). RESULTS: Overall, a total of 95 associations from 29 meta-analyses were included, investigating associations between TyG index and 30 health outcomes. Of these, 83 (87.4%) associations were statistically significant (P < 0.05) according to the random effects model. Based on the AMSTAR tool, 16 (55.2%) meta-analyses were high quality and none was low quality. The certainty of the evidence, assessed by the GRADE framework, showed that 6 (6.3%) associations were supported by moderate-quality evidence. When compared with the lowest category of the TyG index, the risk of contrast-induced nephropathy (CIN) [relative risk (RR) = 2.25, 95%CI 1.82, 2.77], the risk of stroke in patients with diabetes mellitus (RR = 1.26, 95%CI 1.18, 1.33) or with acute coronary syndrome disease (RR = 1.56, 95%CI 1.06, 2.28), the prognosis of coronary artery disease (CAD)-non-fatal MI (RR = 2.02, 95%CI 1.32, 3.10), and the severity of CAD including coronary artery stenosis (RR = 3.49, 95%CI 1.71, 7.12) and multi-vessel CAD (RR = 2.33, 95%CI 1.59, 3.42) increased with high TyG index. CONCLUSION: We found that the TyG index was positively associated with many diseases including the risk of CIN and stroke, the prognosis of CAD, and the severity of CAD which were supported by moderate-quality evidence. TyG index might be useful to identify people at high-risk for developing these diseases.


Subject(s)
Biomarkers , Blood Glucose , Meta-Analysis as Topic , Observational Studies as Topic , Systematic Reviews as Topic , Triglycerides , Humans , Triglycerides/blood , Blood Glucose/metabolism , Biomarkers/blood , Risk Assessment , Prognosis , Predictive Value of Tests , Cardiovascular Diseases/blood , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Risk Factors , Female , Male
7.
BMC Med ; 22(1): 206, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769523

ABSTRACT

BACKGROUND: Numerous studies have been conducted to investigate the relationship between ABO and Rhesus (Rh) blood groups and various health outcomes. However, a comprehensive evaluation of the robustness of these associations is still lacking. METHODS: We searched PubMed, Web of Science, Embase, Scopus, Cochrane, and several regional databases from their inception until Feb 16, 2024, with the aim of identifying systematic reviews with meta-analyses of observational studies exploring associations between ABO and Rh blood groups and diverse health outcomes. For each association, we calculated the summary effect sizes, corresponding 95% confidence intervals, 95% prediction interval, heterogeneity, small-study effect, and evaluation of excess significance bias. The evidence was evaluated on a grading scale that ranged from convincing (Class I) to weak (Class IV). We assessed the certainty of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation criteria (GRADE). We also evaluated the methodological quality of included studies using the A Measurement Tool to Assess Systematic Reviews (AMSTAR). AMSTAR contains 11 items, which were scored as high (8-11), moderate (4-7), and low (0-3) quality. We have gotten the registration for protocol on the PROSPERO database (CRD42023409547). RESULTS: The current umbrella review included 51 systematic reviews with meta-analysis articles with 270 associations. We re-calculated each association and found only one convincing evidence (Class I) for an association between blood group B and type 2 diabetes mellitus risk compared with the non-B blood group. It had a summary odds ratio of 1.28 (95% confidence interval: 1.17, 1.40), was supported by 6870 cases with small heterogeneity (I2 = 13%) and 95% prediction intervals excluding the null value, and without hints of small-study effects (P for Egger's test > 0.10, but the largest study effect was not more conservative than the summary effect size) or excess of significance (P < 0.10, but the value of observed less than expected). And the article was demonstrated with high methodological quality using AMSTAR (score = 9). According to AMSTAR, 18, 32, and 11 studies were categorized as high, moderate, and low quality, respectively. Nine statistically significant associations reached moderate quality based on GRADE. CONCLUSIONS: Our findings suggest a potential relationship between ABO and Rh blood groups and adverse health outcomes. Particularly the association between blood group B and type 2 diabetes mellitus risk.


Subject(s)
ABO Blood-Group System , Meta-Analysis as Topic , Observational Studies as Topic , Rh-Hr Blood-Group System , Systematic Reviews as Topic , Humans , Systematic Reviews as Topic/methods , Observational Studies as Topic/methods
8.
J Med Internet Res ; 26: e55121, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38820583

ABSTRACT

BACKGROUND: As an important platform for researchers to present their academic findings, medical journals have a close relationship between their evaluation orientation and the value orientation of their published research results. However, the differences between the academic impact and level of disruptive innovation of medical journals have not been examined by any study yet. OBJECTIVE: This study aims to compare the relationships and differences between the academic impact, disruptive innovation levels, and peer review results of medical journals and published research papers. We also analyzed the similarities and differences in the impact evaluations, disruptive innovations, and peer reviews for different types of medical research papers and the underlying reasons. METHODS: The general and internal medicine Science Citation Index Expanded (SCIE) journals in 2018 were chosen as the study object to explore the differences in the academic impact and level of disruptive innovation of medical journals based on the OpenCitations Index of PubMed open PMID-to-PMID citations (POCI) and H1Connect databases, respectively, and we compared them with the results of peer review. RESULTS: First, the correlation coefficients of the Journal Disruption Index (JDI) with the Journal Cumulative Citation for 5 years (JCC5), Journal Impact Factor (JIF), and Journal Citation Indicator (JCI) were 0.677, 0.585, and 0.621, respectively. The correlation coefficient of the absolute disruption index (Dz) with the Cumulative Citation for 5 years (CC5) was 0.635. However, the average difference in the disruptive innovation and academic influence rankings of journals reached 20 places (about 17.5%). The average difference in the disruptive innovation and influence rankings of research papers reached about 2700 places (about 17.7%). The differences reflect the essential difference between the two evaluation systems. Second, the top 7 journals selected based on JDI, JCC5, JIF, and JCI were the same, and all of them were H-journals. Although 8 (8/15, 53%), 96 (96/150, 64%), and 880 (880/1500, 58.67%) of the top 0.1%, top 1%, and top 10% papers selected based on Dz and CC5, respectively, were the same. Third, research papers with the "changes clinical practice" tag showed only moderate innovation (4.96) and impact (241.67) levels but had high levels of peer-reviewed recognition (6.00) and attention (2.83). CONCLUSIONS: The results of the study show that research evaluation based on innovative indicators is detached from the traditional impact evaluation system. The 3 evaluation systems (impact evaluation, disruptive innovation evaluation, and peer review) only have high consistency for authoritative journals and top papers. Neither a single impact indicator nor an innovative indicator can directly reflect the impact of medical research for clinical practice. How to establish an integrated, comprehensive, scientific, and reasonable journal evaluation system to improve the existing evaluation system of medical journals still needs further research.


Subject(s)
Bibliometrics , Journal Impact Factor , Periodicals as Topic , Periodicals as Topic/statistics & numerical data , Humans , Biomedical Research/statistics & numerical data
9.
World J Gastroenterol ; 30(17): 2354-2368, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38813048

ABSTRACT

BACKGROUND: Difficulty in obtaining tetracycline, increased adverse reactions, and relatively complicated medication methods have limited the clinical application of the classic bismuth quadruple therapy. Therefore, the search for new alternative drugs has become one of the research hotspots. In recent years, minocycline, as a semisynthetic tetracycline, has demonstrated good potential for eradicating Helicobacter pylori (H. pylori) infection, but the systematic evaluation of its role remains lacking. AIM: To explore the efficacy, safety, and compliance of minocycline in eradicating H. pylori infection. METHODS: We comprehensively retrieved the electronic databases of PubMed, Embase, Web of Science, China National Knowledge Infrastructure, SinoMed, and Wanfang database as of October 30, 2023, and finally included 22 research reports on H. pylori eradication with minocycline-containing regimens as per the inclusion and exclusion criteria. The eradication rates of H. pylori were calculated using a fixed or a random effect model, and the heterogeneity and publication bias of the studies were measured. RESULTS: The single-arm meta-analysis revealed that the minocycline-containing regimens achieved good overall H. pylori eradication rates, reaching 82.3% [95% confidence interval (CI): 79.7%-85.1%] in the intention-to-treat analysis and 90.0% (95%CI: 87.7%-92.4%) in the per-protocol analysis. The overall safety and compliance of the minocycline-containing regimens were good, demonstrating an overall incidence of adverse reactions of 36.5% (95%CI: 31.5%-42.2%). Further by traditional meta-analysis, the results showed that the minocycline-containing regimens were not statistically different from other commonly used eradication regimens in eradication rate and incidence of adverse effects. Most of the adverse reactions were mild to moderate and well-tolerated, and dizziness was relatively prominent in the minocycline-containing regimens (16%). CONCLUSION: The minocycline-containing regimens demonstrated good efficacy, safety, and compliance in H. pylori eradication. Minocycline has good potential to replace tetracycline for eradicating H. pylori infection.


Subject(s)
Anti-Bacterial Agents , Drug Therapy, Combination , Helicobacter Infections , Helicobacter pylori , Minocycline , Humans , Minocycline/adverse effects , Minocycline/administration & dosage , Minocycline/therapeutic use , Helicobacter Infections/drug therapy , Helicobacter Infections/microbiology , Helicobacter pylori/drug effects , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage , Drug Therapy, Combination/methods , Treatment Outcome , Proton Pump Inhibitors/adverse effects , Proton Pump Inhibitors/therapeutic use , Proton Pump Inhibitors/administration & dosage , Medication Adherence
10.
Int Immunopharmacol ; 134: 112159, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38692018

ABSTRACT

CONTEXT: Medical treatment plays a critical role in pituitary neuroendocrine tumour (PitNET) treatment. Dopamine agonists and somatostatin receptor agonists are the only known drugs for effectively treating PitNET. Thus, the identification of potential therapeutic targets and drugs is urgently needed. OBJECTIVE: To discover potential drugs that can suppress PitNET growth and to further investigate the underlying mechanism involved. METHODS: High-throughput drug screening of primary cultures of 17 patient-derived PitNETs was performed to identify potential therapeutic compounds. Cell viability assays, Western blot analysis and flow cytometry were used to investigate pituitary neuroendocrine tumour cell lines and patient-derived PitNET cultures in vitro. In vivo drug efficacy was examined in a mouse xenograft model. RESULTS: Seventeen primary PitNET samples were collected for high-throughput drug screening, and a class of copper ionophores that can effectively inhibit cell growth, such as zinc pyrithione, elesclomol, and disulfiram (DSF), was identified. Subsequent experiments initially validated the dose-dependent cell growth-suppressing effect of these copper ionophores on AtT20, GH3, and MMQ cells and several primary PitNET cell lines. Moreover, we confirmed that the cytotoxic effect of DSF depends on the presence of copper. Additionally, we determined that cell death occurs via cuproptosis, with events such as Fe-S cluster protein loss, dihydrolipoyl transacetylase oligomerization and heat shock protein 70 upregulation. Finally, we verified the cytotoxic effects of DSF in vivo. CONCLUSION: The present study revealed copper ionophores as a potential class of drugs for PitNET treatment. DSF induced PitNET cell death via cuproptosis and might be a promising option for PitNET therapy.


Subject(s)
Antineoplastic Agents , Disulfiram , Neuroendocrine Tumors , Pituitary Neoplasms , Xenograft Model Antitumor Assays , Disulfiram/pharmacology , Disulfiram/therapeutic use , Animals , Pituitary Neoplasms/drug therapy , Pituitary Neoplasms/pathology , Humans , Neuroendocrine Tumors/drug therapy , Neuroendocrine Tumors/pathology , Cell Line, Tumor , Mice , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Female , Male , Middle Aged , Mice, Nude , Cell Proliferation/drug effects , Adult , Cell Survival/drug effects
11.
Transl Oncol ; 45: 101986, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38723299

ABSTRACT

Microvascular invasion (MVI) is an adverse prognostic indicator of tumor recurrence after surgery for hepatocellular carcinoma (HCC). Therefore, developing a nomogram for estimating the presence of MVI before liver resection is necessary. We retrospectively included 260 patients with pathologically confirmed HCC at the Fifth Medical Center of Chinese PLA General Hospital between January 2021 and April 2024. The patients were randomly divided into a training cohort (n = 182) for nomogram development, and a validation cohort (n = 78) to confirm the performance of the model (7:3 ratio). Significant clinical variables associated with MVI were then incorporated into the predictive nomogram using both univariate and multivariate logistic analyses. The predictive performance of the nomogram was assessed based on its discrimination, calibration, and clinical utility. Serum carnosine dipeptidase 1 ([CNDP1] OR 2.973; 95 % CI 1.167-7.575; p = 0.022), cirrhosis (OR 8.911; 95 % CI 1.922-41.318; p = 0.005), multiple tumors (OR 4.095; 95 % CI 1.374-12.205; p = 0.011), and tumor diameter ≥3 cm (OR 4.408; 95 % CI 1.780-10.919; p = 0.001) were independent predictors of MVI. Performance of the nomogram based on serum CNDP1, cirrhosis, number of tumors and tumor diameter was achieved with a concordance index of 0.833 (95 % CI 0.771-0.894) and 0.821 (95 % CI 0.720-0.922) in the training and validation cohorts, respectively. It fitted well in the calibration curves, and the decision curve analysis further confirmed its clinical usefulness. The nomogram, incorporating significant clinical variables and imaging features, successfully predicted the personalized risk of MVI in HCC preoperatively.

12.
Eur J Med Res ; 29(1): 218, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38576041

ABSTRACT

BACKGROUND: The objective of this investigation is to analyze the levels and clinical relevance of serum PYCARD (Pyrin and CARD domain-containing protein, commonly known as ASC-apoptosis-associated speck-like protein containing a caspase activation and recruitment domain), interleukin-38 (IL-38), and interleukin-6 (IL-6) in individuals afflicted with rheumatoid arthritis (RA). METHODS: Our study comprised 88 individuals diagnosed with RA who sought medical attention at the Affiliated Hospital of Chengde Medical University during the period spanning November 2021 to June 2023, constituting the test group. Additionally, a control group of 88 individuals who underwent health assessments at the same hospital during the aforementioned timeframe was included for comparative purposes. The study involved the assessment of IL-38, IL-6, PYCARD, anti-cyclic citrullinated peptide antibody (anti-CCP), and erythrocyte sedimentation rate (ESR) levels in both groups. The research aimed to explore the correlations and diagnostic efficacy of these markers, employing pertinent statistical analyses for comprehensive evaluation. RESULTS: The test group had higher expression levels of PYCARD, IL-6, and IL-38 than the control group (P < 0.05). Based on the correlation analysis, there was a strong relationship between PYCARD and IL-38 (P < 0.01). The receiver operating characteristic (ROC) curve analysis revealed area under the curve (AUC) values of 0.97, 0.96, and 0.96 when using combinations of PYCARD and anti-CCP, IL-38 and anti-CCP, and IL-6 and anti-CCP for predicting RA, respectively. Importantly, all three of these pairs demonstrated superior AUC values compared to PYCARD, IL-38, IL-6, ESR, or anti-CCP used as standalone diagnostic indicators. CONCLUSION: PYCARD, IL-6, and IL-38 exhibit promising potential as novel diagnostic markers and may constitute valuable tools for supporting the diagnosis of RA.


Subject(s)
Anti-Citrullinated Protein Antibodies , Arthritis, Rheumatoid , Humans , Interleukin-6 , Arthritis, Rheumatoid/diagnosis , Autoantibodies , ROC Curve , Peptides, Cyclic , Biomarkers , CARD Signaling Adaptor Proteins/genetics , Interleukins
13.
Acta Neuropathol Commun ; 12(1): 61, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38637883

ABSTRACT

We aimed to identify the druggable cell-intrinsic vulnerabilities and target-based drug therapies for PitNETs using the high-throughput drug screening (HTS) and genomic sequencing methods. We examined 9 patient-derived PitNET primary cells in HTS. Based on the screening results, the potential target genes were analyzed with genomic sequencing from a total of 180 PitNETs. We identified and verified one of the most potentially effective drugs, which targeted the Histone deacetylases (HDACs) both in in vitro and in vivo PitNET models. Further RNA sequencing revealed underlying molecular mechanisms following treatment with the representative HDACs inhibitor, Panobinostat. The HTS generated a total of 20,736 single-agent dose responses which were enriched among multiple inhibitors for various oncogenic targets, including HDACs, PI3K, mTOR, and proteasome. Among these drugs, HDAC inhibitors (HDACIs) were, on average, the most potent drug class. Further studies using in vitro, in vivo, and isolated PitNET primary cell models validated HDACIs, especially Panobinostat, as a promising therapeutic agent. Transcriptional surveys revealed substantial alterations to the Nrf2 signaling following Panobinostat treatment. Moreover, Nrf2 is highly expressed in PitNETs. The combination of Panobinostat and Nrf2 inhibitor ML385 had a synergistic effect on PitNET suppression. The current study revealed a class of effective anti-PitNET drugs, HDACIs, based on the HTS and genomic sequencing. One of the representative compounds, Panobinostat, may be a potential drug for PitNET treatment via Nrf2-mediated redox modulation. Combination of Panobinostat and ML385 further enhance the effectiveness for PitNET treatment.


Subject(s)
Neuroendocrine Tumors , Pituitary Neoplasms , Humans , Panobinostat/pharmacology , Panobinostat/therapeutic use , NF-E2-Related Factor 2/genetics , Neuroendocrine Tumors/drug therapy , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylase Inhibitors/therapeutic use , Signal Transduction
14.
PhytoKeys ; 241: 91-101, 2024.
Article in English | MEDLINE | ID: mdl-38638580

ABSTRACT

Indigoferajintongpenensis, a new species of the subfamily Papilionoideae of Fabaceae, is described and illustrated from Yunnan, southwest China. The new species is characterised by having a prostrate habit, flexible stems and branches, as well as spreading, sub-basifixed, asymmetrically 2-branched trichomes covering the entire plant, discoid calyx, and racemose inflorescences 6-8-flowered, short, 1-2 (-3.5) cm in length, apparently shorter than the leaf. A distribution map and comparison of morphological diagnostic characters with its morphologically similar species are provided. Additionally, a preliminary conservation assessment of I.jintongpenensis is proposed following IUCN criteria.

15.
Pediatr Cardiol ; 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38662212

ABSTRACT

Anthracycline chemotherapy is associated with the left ventricular (LV) dysfunction, but the conventional echocardiographic parameter is insensitive in detecting subclinical cardiac dysfunction, and the role of echocardiography in children cancer survivors (CCSs) has not been well established. Here, the myocardial work (MW) was employed to evaluate the early effect of the anthracyclines on LV function in children lymphoma survivors, as well as to explore the clinical application value of this modality. 51 children lymphoma survivors treated with anthracyclines were included. During the treatments, the echocardiography was performed at baseline (T0 phase), the 3rd (T1 phase) and 6th (T2 phase) chemotherapeutic cycle, respectively. After that, the conventional echocardiographic parameters, LV global longitudinal strain (GLS), and global myocardial work (GMW) parameters were obtained. Finally, these echocardiographic parameters were compared to distinguish the differences among three groups, and correlation analysis was used to identify relationship between GMW parameters and LV GLS. Compared with the baseline, we found that there are no significant differences for LVEF and other conventional echocardiographic parameters after chemotherapy, but the value of LV lateral E/E' increased at T1 and T2 group. The GLS, global work index, global constructed work, and global work efficiency were decreased, while the global wasted work was increased after chemotherapy (all P < 0.05). The correlation analysis showed that the GLS has significant correlation with GMW parameters (all P < 0.001). The MW, as a new noninvasive echocardiography modality, could be used to quantitatively evaluate the LV MW in children lymphoma survivors treated with anthracyclines, which providing a sensitive method to early detect the children's LV dysfunction after the chemotherapy.

16.
Psychol Med ; : 1-10, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38571298

ABSTRACT

BACKGROUND: Extensive research has explored altered structural and functional networks in major depressive disorder (MDD). However, studies examining the relationships between structure and function yielded heterogeneous and inconclusive results. Recent work has suggested that the structure-function relationship is not uniform throughout the brain but varies across different levels of functional hierarchy. This study aims to investigate changes in structure-function couplings (SFC) and their relevance to antidepressant response in MDD from a functional hierarchical perspective. METHODS: We compared regional SFC between individuals with MDD (n = 258) and healthy controls (HC, n = 99) using resting-state functional magnetic resonance imaging and diffusion tensor imaging. We also compared antidepressant non-responders (n = 55) and responders (n = 68, defined by a reduction in depressive severity of >50%). To evaluate variations in altered and response-associated SFC across the functional hierarchy, we ranked significantly different regions by their principal gradient values and assessed patterns of increase or decrease along the gradient axis. The principal gradient value, calculated from 219 healthy individuals in the Human Connectome Project, represents a region's position along the principal gradient axis. RESULTS: Compared to HC, MDD patients exhibited increased SFC in unimodal regions (lower principal gradient) and decreased SFC in transmodal regions (higher principal gradient) (p < 0.001). Responders primarily had higher SFC in unimodal regions and lower SFC in attentional networks (median principal gradient) (p < 0.001). CONCLUSIONS: Our findings reveal opposing SFC alterations in low-level unimodal and high-level transmodal networks, underscoring spatial variability in MDD pathology. Moreover, hierarchy-specific antidepressant effects provide valuable insights into predicting treatment outcomes.

17.
World J Diabetes ; 15(4): 697-711, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38680694

ABSTRACT

BACKGROUND: The importance of age on the development of ocular conditions has been reported by numerous studies. Diabetes may have different associations with different stages of ocular conditions, and the duration of diabetes may affect the development of diabetic eye disease. While there is a dose-response relationship between the age at diagnosis of diabetes and the risk of cardiovascular disease and mortality, whether the age at diagnosis of diabetes is associated with incident ocular conditions remains to be explored. It is unclear which types of diabetes are more predictive of ocular conditions. AIM: To examine associations between the age of diabetes diagnosis and the incidence of cataract, glaucoma, age-related macular degeneration (AMD), and vision acuity. METHODS: Our analysis was using the UK Biobank. The cohort included 8709 diabetic participants and 17418 controls for ocular condition analysis, and 6689 diabetic participants and 13378 controls for vision analysis. Ocular diseases were identified using inpatient records until January 2021. Vision acuity was assessed using a chart. RESULTS: During a median follow-up of 11.0 years, 3874, 665, and 616 new cases of cataract, glaucoma, and AMD, respectively, were identified. A stronger association between diabetes and incident ocular conditions was observed where diabetes was diagnosed at a younger age. Individuals with type 2 diabetes (T2D) diagnosed at < 45 years [HR (95%CI): 2.71 (1.49-4.93)], 45-49 years [2.57 (1.17-5.65)], 50-54 years [1.85 (1.13-3.04)], or 50-59 years of age [1.53 (1.00-2.34)] had a higher risk of AMD independent of glycated haemoglobin. T2D diagnosed < 45 years [HR (95%CI): 2.18 (1.71-2.79)], 45-49 years [1.54 (1.19-2.01)], 50-54 years [1.60 (1.31-1.96)], or 55-59 years of age [1.21 (1.02-1.43)] was associated with an increased cataract risk. T2D diagnosed < 45 years of age only was associated with an increased risk of glaucoma [HR (95%CI): 1.76 (1.00-3.12)]. HRs (95%CIs) for AMD, cataract, and glaucoma associated with type 1 diabetes (T1D) were 4.12 (1.99-8.53), 2.95 (2.17-4.02), and 2.40 (1.09-5.31), respectively. In multivariable-adjusted analysis, individuals with T2D diagnosed < 45 years of age [ß 95%CI: 0.025 (0.009,0.040)] had a larger increase in LogMAR. The ß (95%CI) for LogMAR associated with T1D was 0.044 (0.014, 0.073). CONCLUSION: The younger age at the diagnosis of diabetes is associated with a larger relative risk of incident ocular diseases and greater vision loss.

18.
Genome Med ; 16(1): 60, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38658971

ABSTRACT

BACKGROUND: Pituitary neuroendocrine tumors (PitNETs) are common gland neoplasms demonstrating distinctive transcription factors. Although the role of immune cells in PitNETs has been widely recognized, the precise immunological environment and its control over tumor cells are poorly understood. METHODS: The heterogeneity, spatial distribution, and clinical significance of macrophages in PitNETs were analyzed using single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, spatial transcriptomics, immunohistochemistry, and multiplexed quantitative immunofluorescence (QIF). Cell viability, cell apoptosis assays, and in vivo subcutaneous xenograft experiments have confirmed that INHBA-ACVR1B influences the process of tumor cell apoptosis. RESULTS: The present study evaluated scRNA-seq data from 23 PitNET samples categorized into 3 primary lineages. The objective was to explore the diversity of tumors and the composition of immune cells across these lineages. Analyzed data from scRNA-seq and 365 bulk RNA sequencing samples conducted in-house revealed the presence of three unique subtypes of tumor immune microenvironment (TIME) in PitNETs. These subtypes were characterized by varying levels of immune infiltration, ranging from low to intermediate to high. In addition, the NR5A1 lineage is primarily associated with the subtype characterized by limited infiltration of immune cells. Tumor-associated macrophages (TAMs) expressing CX3CR1+, C1Q+, and GPNMB+ showed enhanced contact with tumor cells expressing NR5A1 + , TBX19+, and POU1F1+, respectively. This emphasizes the distinct interaction axes between TAMs and tumor cells based on their lineage. Moreover, the connection between CX3CR1+ macrophages and tumor cells via INHBA-ACVR1B regulates tumor cell apoptosis. CONCLUSIONS: In summary, the different subtypes of TIME and the interaction between TAM and tumor cells offer valuable insights into the control of TIME that affects the development of PitNET. These findings can be utilized as prospective targets for therapeutic interventions.


Subject(s)
Macrophages , Neuroendocrine Tumors , Pituitary Neoplasms , Single-Cell Analysis , Transcriptome , Tumor Microenvironment , Humans , Neuroendocrine Tumors/genetics , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/immunology , Neuroendocrine Tumors/metabolism , Pituitary Neoplasms/genetics , Pituitary Neoplasms/immunology , Pituitary Neoplasms/pathology , Pituitary Neoplasms/metabolism , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Animals , Mice , Macrophages/metabolism , Macrophages/immunology , Tumor-Associated Macrophages/metabolism , Tumor-Associated Macrophages/immunology , Gene Expression Regulation, Neoplastic , Gene Expression Profiling , Phenotype , Apoptosis/genetics , Cell Lineage/genetics
19.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(4): 371-377, 2024 Apr 15.
Article in Chinese | MEDLINE | ID: mdl-38660901

ABSTRACT

OBJECTIVES: To investigate the levels of serum folate and vitamin B12 (VB12) and their association with the level of neurodevelopment in preschool children with autism spectrum disorder (ASD). METHODS: A total of 324 ASD children aged 2-6 years and 318 healthy children aged 2-6 years were recruited. Serum levels of folate and VB12 were measured using chemiluminescent immunoassay. The Social Responsiveness Scale and the Childhood Autism Rating Scale were used to assess the core symptoms of ASD children, and the Gesell Developmental Schedule was employed to evaluate the level of neurodevelopment. RESULTS: The levels of serum folate and VB12 in ASD children were significantly lower than those in healthy children (P<0.05). Serum folate levels in ASD children were positively correlated with gross and fine motor developmental quotients (P<0.05), and serum VB12 levels were positively correlated with adaptive behavior, fine motor, and language developmental quotients (P<0.05). In ASD children aged 2 to <4 years, serum folate levels were positively correlated with developmental quotients in all domains (P<0.05), and serum VB12 levels were positively correlated with language developmental quotient (P<0.05). In male ASD children, serum VB12 levels were positively correlated with language and personal-social developmental quotients (P<0.05). CONCLUSIONS: Serum folate and VB12 levels in preschool ASD children are lower than those in healthy children and are associated with neurodevelopmental levels, especially in ASD children under 4 years of age. Therefore, maintaining normal serum folate and VB12 levels may be beneficial for the neurodevelopment of ASD children, especially in ASD children under 4 years of age.


Subject(s)
Autism Spectrum Disorder , Folic Acid , Vitamin B 12 , Humans , Autism Spectrum Disorder/blood , Autism Spectrum Disorder/etiology , Child, Preschool , Male , Female , Folic Acid/blood , Vitamin B 12/blood , Child , Child Development
20.
World J Surg ; 48(2): 446-455, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38686786

ABSTRACT

BACKGROUND: The diseased bile duct in bilobar congenital biliary dilatation is extensive and often requires major hepatectomy or liver transplantation associated with a higher risk. We aimed to evaluate the safety and benefit of modified mesohepatectomy, in comparison with trisectionectomy, to treat bilobar congenital biliary dilatation. METHODS: This study included 28 patients with type IV and V bilobar congenital biliary dilatation. An innovative mesohepatectomy comprising the hepatectomy technique beyond the P/U point and bile duct shaping was applied to 14 patients to address the extensively diseased bile duct and difficulty in hepaticojejunostomy. Another 14 patients received trisectionectomy. The perioperative and long-term outcomes of these patients were compared. RESULTS: The ratio of residual liver volume to standard liver volume in the mesohepatectomy group was higher (78.68% vs. 40.90%, p = 0.005), while the resection rate of the liver parenchyma was lower (28.25% vs. 63.97%, p = 0.000), than that in trisectionectomy group. The mesohepatectomy group had a lower severe complication (>Clavein III, 0% vs. 57.70%, p = 0.019) and incidence of posthepatectomy liver failure (7.14% vs. 42.86%, p = 0.038). No significant difference was observed in blood loss and bile leakage (p > 0.05). All the patients in the mesohepatectomy group achieved optimal results in the long-term follow-up. CONCLUSIONS: mesohepatectomy provides an efficient treatment option for bilobar congenital biliary dilatation and can achieve radical resection, retain more liver parenchyma, and reduce the difficulty of hepaticojejunostomy, especially for patients that are not eligible for major hepatectomy and liver transplantation.


Subject(s)
Hepatectomy , Humans , Hepatectomy/methods , Male , Female , Treatment Outcome , Retrospective Studies , Dilatation, Pathologic/surgery , Infant , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Child, Preschool
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