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1.
J Comput Biol ; 31(6): 486-497, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38837136

ABSTRACT

Automatic radiology medical report generation is a necessary development of artificial intelligence technology in the health care. This technology serves to aid doctors in producing comprehensive diagnostic reports, alleviating the burdensome workloads of medical professionals. However, there are some challenges in generating radiological reports: (1) visual and textual data biases and (2) long-distance dependency problem. To tackle these issues, we design a visual recalibration and gating enhancement network (VRGE), which composes of the visual recalibration module and the gating enhancement module (gating enhancement module, GEM). Specifically, the visual recalibration module enhances the recognition of abnormal features in lesion areas of medical images. The GEM dynamically adjusts the contextual information in the report by introducing gating mechanisms, focusing on capturing professional medical terminology in medical text reports. We have conducted sufficient experiments on the public datasets of IU X-Ray to illustrate that the VRGE outperforms existing models.


Subject(s)
Artificial Intelligence , Humans , Radiology/methods , Algorithms
2.
J Med Chem ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38913701

ABSTRACT

UC and ALI are inflammatory diseases with limited treatment in the clinic. Herein, fragment-based anti-inflammatory agent designs were carried out deriving from cyclohexylamine/cyclobutylamine and several fragments from anti-inflammatory agents in our lab. AF-45 (IC50 = 0.53/0.60 µM on IL-6/TNF-α in THP-1 macrophages) was identified as the optimal molecule using ELISA and MTT assays from the 33 synthesized compounds. Through mechanistic studies and a systematic target search process, AF-45 was found to block the NF-κB/MAPK pathway and target IRAK4, a promising target for inflammation and autoimmune diseases. The selectivity of AF-45 targeting IRAK4 was validated by comparing its effects on other kinase/nonkinase proteins. In vivo, AF-45 exhibited a good therapeutic effect on UC and ALI, and favorable PK proprieties. Since there are currently no clinical or preclinical trials for IRAK4 inhibitors to treat UC and ALI, AF-45 provides a new lead compound or candidate targeting IRAK4 for the treatment of these diseases.

3.
J Cell Mol Med ; 28(11): e18405, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38842134

ABSTRACT

Prostate cancer (PCa), a prevalent malignancy among elderly males, exhibits a notable rate of advancement, even when subjected to conventional androgen deprivation therapy or chemotherapy. An effective progression prediction model would prove invaluable in identifying patients with a higher progression risk. Using bioinformatics strategies, we integrated diverse data sets of PCa to construct a novel risk model predicated on gene expression and progression-free survival (PFS). The accuracy of the model was assessed through validation using an independent data set. Eight genes were discerned as independent prognostic factors and included in the prediction model. Patients assigned to the high-risk cohort demonstrated a diminished PFS, and the areas under the curve of our model in the validation set for 1-year, 3-year, and 5-year PFS were 0.9325, 0.9041 and 0.9070, respectively. Additionally, through the application of single-cell RNA sequencing to two castration-related prostate cancer (CRPC) samples and two hormone-related prostate cancer (HSPC) samples, we discovered that luminal cells within CRPC exhibited an elevated risk score. Subsequent molecular biology experiments corroborated our findings, illustrating heightened SYK expression levels within tumour tissues and its contribution to cancer cell migration. We found that the knockdown of SYK could inhibit migration in PCa cells. Our progression-related risk model demonstrated the potential prognostic value of SYK and indicated its potential as a target for future diagnosis and treatment strategies in PCa management.


Subject(s)
Computational Biology , Disease Progression , Gene Expression Regulation, Neoplastic , Prostatic Neoplasms , Male , Humans , Computational Biology/methods , Prognosis , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Prostatic Neoplasms/diagnosis , Gene Expression Profiling , Biomarkers, Tumor/genetics , Risk Factors , Cell Line, Tumor
4.
Gene ; 926: 148624, 2024 Oct 30.
Article in English | MEDLINE | ID: mdl-38824974

ABSTRACT

BACKGROUND: Allergic rhinitis (AR) is an allergic disease characterized by the dominant differentiation of T helper cell 2 (Th2). BACH2 plays a key role in regulating Th2 immune response. This study aimed to explore the association between BACH2 single nucleotide polymorphism (SNPs) and susceptibility to AR. METHODS: Han population from northern Shaanxi, China was chosen as subjects. After the DNA extraction from the peripheral blood of subjects, genotyping was completed through the Agena MassARRAY platform. Logistic regression analysis was used to assess the association. Multivariate dimensionality reduction (MDR) was used to evaluate the effect of the interaction between 'SNP-SNP' on susceptibility to AR. Using false-positive report probability (FPRP) analysis to test whether the significant results obtained in this study were noteworthy. RESULTS: BACH2-rs905670 and -rs2134814 were significantly associated with increased risk of AR. The mutant allele 'A' of rs905670 (OR = 1.36, p = 0.018) and mutant allele 'G' of rs2134814 (OR = 1.34, p = 0.027) were risk genetic factors for AR. The above genetic association was further observed in the stratified analysis: BACH2-rs905670 and-rs2134814 were significantly associated with an increased risk of AR in females, aging older than 43 years, and participants working and living in the loess hills (OR > 1, p < 0.05). CONCLUSION: BACH2-rs905670 and -rs2134814 are significantly associated with increasing AR risk.


Subject(s)
Basic-Leucine Zipper Transcription Factors , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Rhinitis, Allergic , Th2 Cells , Humans , Female , Male , Rhinitis, Allergic/genetics , Rhinitis, Allergic/immunology , Basic-Leucine Zipper Transcription Factors/genetics , Adult , Th2 Cells/immunology , Middle Aged , China , Case-Control Studies , Alleles , Young Adult , Genotype , Asian People/genetics , Adolescent , Risk Factors
5.
Nat Chem ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862641

ABSTRACT

Conjugated organic photoredox catalysts (OPCs) can promote a wide range of chemical transformations. It is challenging to predict the catalytic activities of OPCs from first principles, either by expert knowledge or by using a priori calculations, as catalyst activity depends on a complex range of interrelated properties. Organic photocatalysts and other catalyst systems have often been discovered by a mixture of design and trial and error. Here we report a two-step data-driven approach to the targeted synthesis of OPCs and the subsequent reaction optimization for metallophotocatalysis, demonstrated for decarboxylative sp3-sp2 cross-coupling of amino acids with aryl halides. Our approach uses a Bayesian optimization strategy coupled with encoding of key physical properties using molecular descriptors to identify promising OPCs from a virtual library of 560 candidate molecules. This led to OPC formulations that are competitive with iridium catalysts by exploring just 2.4% of the available catalyst formulation space (107 of 4,500 possible reaction conditions).

6.
Nat Commun ; 15(1): 5211, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890314

ABSTRACT

Photosystem II (PSII) catalyzes water oxidation and plastoquinone reduction by utilizing light energy. It is highly susceptible to photodamage under high-light conditions and the damaged PSII needs to be restored through a process known as the PSII repair cycle. The detailed molecular mechanism underlying the PSII repair process remains mostly elusive. Here, we report biochemical and structural features of a PSII-repair intermediate complex, likely arrested at an early stage of the PSII repair process in the green alga Chlamydomonas reinhardtii. The complex contains three protein factors associated with a damaged PSII core, namely Thylakoid Enriched Factor 14 (TEF14), Photosystem II Repair Factor 1 (PRF1), and Photosystem II Repair Factor 2 (PRF2). TEF14, PRF1 and PRF2 may facilitate the release of the manganese-stabilizing protein PsbO, disassembly of peripheral light-harvesting complexes from PSII and blockage of the QB site, respectively. Moreover, an α-tocopherol quinone molecule is located adjacent to the heme group of cytochrome b559, potentially fulfilling a photoprotective role by preventing the generation of reactive oxygen species.


Subject(s)
Chlamydomonas reinhardtii , Photosystem II Protein Complex , Photosystem II Protein Complex/metabolism , Chlamydomonas reinhardtii/metabolism , Chlamydomonas reinhardtii/genetics , Thylakoids/metabolism , Light-Harvesting Protein Complexes/metabolism , Light-Harvesting Protein Complexes/genetics , Plant Proteins/metabolism , Plant Proteins/genetics , Cytochrome b Group/metabolism , Cytochrome b Group/genetics , Oxidation-Reduction , Reactive Oxygen Species/metabolism , Light
7.
JAMA Netw Open ; 7(6): e2418072, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38904958

ABSTRACT

Importance: The associations between angiographic findings and post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) and their clinical relevance according to residual functional disease burden have not been thoroughly investigated. Objectives: To evaluate the association of angiographic and physiologic parameters according to residual functional disease burden after drug-eluting stent implantation. Design, Setting, and Participants: This cohort study population was from the International Post-PCI FFR registry, which incorporated 4 registries from Korea, China, and Japan. Patients who underwent angiographically successful second-generation drug-eluting stent implantation and post-PCI FFR measurement were included in the analysis. The patients were divided into 3 groups according to the residual disease burden (post-PCI FFR ≤0.80 [residual ischemia], 0.81-0.86 [suboptimal], and >0.86 [optimal]). The data were collected from August 23, 2018, to June 11, 2019, and the current analysis was performed from January 11, 2022, to October 7, 2023. Exposures: Angiographic parameters and post-PCI FFR. Main Outcomes and Measures: The primary outcome was target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction, and target vessel revascularization (TVR) at 2 years. Results: In this cohort of 2147 patients, the mean (SD) age was 64.3 (10.0) years, and 1644 patients (76.6%) were men. Based on the post-PCI physiologic status, 269 patients (12.5%) had residual ischemia, 551 (25.7%) had suboptimal results, and 1327 (61.8%) had optimal results. Angiographic parameters had poor correlations with post-PCI FFR (r < 0.20). Post-PCI FFR was isolated from all angiographic parameters in the unsupervised hierarchical cluster analysis. Post-PCI FFR was associated with the occurrence of TVF (adjusted hazard ratio [AHR] per post-PCI FFR 0.01 increase, 0.94 [95% CI, 0.92-0.97]; P < .001), but angiographic parameters were not. The residual ischemia group had a significantly higher rate of TVF than the suboptimal group (AHR, 1.75 [95% CI, 1.08-2.83]; P = .02) and the optimal group (AHR, 2.94 [95% CI, 1.82-4.73]; P < .001). The TVR in the residual ischemia group was predominantly associated with TVR in the nonstented segment (14 [53.8%]), unlike the other 2 groups (3 [10.0%] in the suboptimal group and 13 [30.2%] in the optimal group). Conclusions and Relevance: In this cohort study of the International Post-PCI FFR registry, a low degree of associations were observed between angiographic and physiologic parameters after PCI. Post-PCI FFR, unlike angiographic parameters, was associated with clinical events and the distribution of clinical events. The current study supports the use of post-PCI FFR as a procedural quality metric and further prospective study is warranted.


Subject(s)
Coronary Angiography , Fractional Flow Reserve, Myocardial , Percutaneous Coronary Intervention , Humans , Fractional Flow Reserve, Myocardial/physiology , Percutaneous Coronary Intervention/methods , Male , Female , Middle Aged , Aged , Coronary Artery Disease/physiopathology , Coronary Artery Disease/surgery , Coronary Artery Disease/diagnostic imaging , Registries , Drug-Eluting Stents , Cohort Studies , Republic of Korea , China/epidemiology , Treatment Outcome
9.
Article in English | MEDLINE | ID: mdl-38886269

ABSTRACT

Air pollution can cause disease and has become a major global environmental problem. It is currently believed that air pollution may be related to the progression of SSNHL. As a rapidly developing city in recent years, Hefei has serious air pollution. In order to explore the correlation between meteorological variables and SSNHL admissions, we conducted this study. This study investigated the short-term associations between SSNHL patients admitted to the hospital and Hefei climatic variables. The daily data on SSNHL-related hospital admissions and meteorological variables containing mean temperature (T-mean; °C), diurnal temperature range (DTR; °C), atmospheric pressure (AP; Hp), and relative humidity (RH; %), from 2014 to 2021 (2558 days), were collected. A time-series analysis integrating distributed lag non-linear models and generalized linear models was used. PubMed, Embase, Cochrane Library, and Web of Science databases were searched. Literature published up to August 2023 was reviewed to explore the potential impact mechanisms of meteorological factors on SSNHL. The mechanisms were determined in detail, focusing on wind speed, air pressure, temperature, humidity, and air pollutants. Using a median of 50.00% as a baseline, the effect of exceedingly low T-mean in the single-day hysteresis effect model began at a lag of 8 days (RR = 1.032, 95% CI: 1.001 ~ 1.064). High DTR affected the admission rate for SSNHL on lag 0 day. The significance of the effect was the greatest on that day (RR = 1.054, 95% CI: 1.007 ~ 1.104) and then gradually decreased. High and exceedingly high RH affected the admission rate SSNHL on lag 0 day, and these effects lasted for 8 and 7 days, respectively. There were significant associations between all grades of AP and SSNHL. This is the first study to assess the effect of meteorological variables on SSNHL-related admissions in China using a time-series approach. Long-term exposures to high DTR, RH values, low T-mean values, and all AP grades enhance the incidence of SSNHL in residents. Limiting exposure to extremes of ambient temperature and humidity may reduce the number of SSNHL-related hospital visits in the region. It is advisable to maintain a suitable living environment temperature and avoid extreme temperature fluctuations and high humidity. During periods of high air pollution, it is recommended to stay indoors and refrain from outdoor exercise.

10.
Metabolism ; 157: 155954, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38878856

ABSTRACT

BACKGROUND: Metabolic diseases contribute significantly to premature mortality worldwide, with increasing burdens observed among the working-age population (WAP). This study assessed global, regional, and national trends in metabolic disorders and associated mortality over three decades in WAP. METHODS: Data from the Global Burden of Disease 2019 study were leveraged to assess global metabolism-associated mortality and six key metabolic risk factors in WAP from 1990-2019. An age-period-cohort model was employed to determine the overall percentage change in mortality. RESULTS: The 2019 global metabolic risk-related mortality rate in WAP rose significantly by 50.73%, while the age-standardized mortality rate declined by 21.5%. India, China, Indonesia, the USA, and the Russian Federation were the top contributing countries to mortality in WAP, accounting for 51.01% of the total. High systolic blood pressure (HSBP), high body mass index (HBMI), and high fasting plasma glucose (HFPG) were the top metabolic risk factors for the highest mortality rates. Adverse trends in HBMI-associated mortality were observed, particularly in lower sociodemographic index (SDI) regions. HFPG-related mortality declined globally but increased in older age groups in lower SDI countries. CONCLUSIONS: Despite a general decline in metabolic risk-related deaths in WAP, increasing HBMI- and HFPG-related mortality in lower SDI areas poses ongoing public health challenges. Developing nations should prioritize interventions addressing HBMI and HFPG to mitigate mortality risks in WAP.

11.
J Peripher Nerv Syst ; 29(2): 232-242, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705839

ABSTRACT

BACKGROUND AND AIMS: Mutations in ganglioside-induced differentiation-associated protein 1 (GDAP1) cause axonal or demyelinating Charcot-Marie-Tooth disease (CMT) with autosomal dominant or recessive inheritance. In this study, we aim to report the genotypic and phenotypic features of GDAP1-related CMT in a Chinese cohort. METHODS: Clinical, neurophysiological, genetic data, and available muscle/brain imaging information of 28 CMT patients with GDAP1 variants were retrospectively collected. RESULTS: We identified 16 GDAP1 pathogenic variants, among which two novel variants c.980dup(p.L328FfsX25) and c.480+4T>G were first reported. Most patients (16/28) presented with AR or AD CMT2K phenotype. Clinical characteristics in our cohort demonstrated that the AR patients presented earlier onset, more severe phenotype compared with the AD patients. Considerable intra-familial phenotypic variability was observed among three AD families. Muscle atrophy and fatty infiltration in the lower extremity were detected by Muscle magnetic resonance imaging (MRI) scans in four patients. MRI showed two AR patients showed more severe muscle involvement of the posterior compartment than those of the anterolateral compartment in the calf. One patient carrying Q38*/H256R variants accompanied with mild periventricular leukoaraiosis. CONCLUSIONS: In this study, we conducted an analysis of clinical features of the GDAP1-related CMT patients, expanded the mutation spectrum in GDAP1 by reporting two novel variants, and presented the prevalent occurrence of the H256R mutation in China. The screening of GDAP1 should be particularly emphasized in Chinese patients with CMT2, given the incomplete penetrance and pathogenic inheritance patterns involving dominant and recessive modes.


Subject(s)
Charcot-Marie-Tooth Disease , Mutation , Nerve Tissue Proteins , Humans , Charcot-Marie-Tooth Disease/genetics , Charcot-Marie-Tooth Disease/physiopathology , Charcot-Marie-Tooth Disease/diagnostic imaging , Male , Female , Adult , Adolescent , Young Adult , Child , Nerve Tissue Proteins/genetics , Middle Aged , Asian People/genetics , China , Retrospective Studies , Pedigree , Child, Preschool , Phenotype , East Asian People
12.
J Peripher Nerv Syst ; 29(2): 243-251, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38772550

ABSTRACT

BACKGROUND AND AIMS: This study aimed to report nine Charcot-Marie-Tooth disease (CMT) families with six novel IGHMBP2 mutations in our CMT2 cohort and to summarize the genetic and clinical features of all AR-CMT2S patients reported worldwide. METHODS: General information, clinical and neurophysiological data of 275 axonal CMT families were collected. Genetic screening was performed by inherited peripheral neuropathy related genes panel or whole exome sequencing. The published papers reporting AR-CMT2S from 2014 to 2023 were searched in Pubmed and Wanfang databases. RESULTS: In our CMT2 cohort, we detected 17 AR-CMT2S families carrying IGHMBP2 mutations and eight were published previously. Among these, c.743 T > A (p.Val248Glu), c.884A > G (p.Asp295Gly), c.1256C > A (p.Ser419*), c.2598_2599delGA (p.Lys868Sfs*16), c.1694_1696delATG (p.Asp565del) and c.2509A > T (p.Arg837*) were firstly reported. These patients prominently presented with early-onset typical axonal neuropathy and without respiratory dysfunction. So far, 56 AR-CMT2S patients and 57 different mutations coming from 43 families have been reported in the world. Twenty-nine of 32 missense mutations were clustered in helicase domain and ATPase region. The age at onset ranged from 0.11to 20 years (Mean ± SD: 3.43 ± 3.88 years) and the majority was infantile-onset (<2 years). The initial symptoms included weakness of limbs (19, 29.7%), delayed milestones (12, 18.8%), gait disturbance (11, 17.2%), feet deformity (8, 12.5%), feet drop (8, 12.5%), etc. INTERPRETATION: AR-CMT2S accounted for 6.2% in our CMT2 cohort. We firstly reported six novel IGHMBP2 mutations which expanded the genotypic spectrum of AR-CMT2S. Furthermore, 17 AR-CMT2S families could provide more resources for natural history study, drug research and development.


Subject(s)
Charcot-Marie-Tooth Disease , Genetic Association Studies , Humans , Charcot-Marie-Tooth Disease/genetics , Charcot-Marie-Tooth Disease/physiopathology , Female , Male , Adult , China/epidemiology , Cohort Studies , Adolescent , Child , Mutation , Transcription Factors/genetics , Young Adult , DNA-Binding Proteins/genetics , Middle Aged , Pedigree , Child, Preschool
13.
PLoS One ; 19(5): e0303198, 2024.
Article in English | MEDLINE | ID: mdl-38701057

ABSTRACT

The study of morphological characteristics and growth information in fish scales is a crucial component of modern fishery biological research, while it has been less studied in fossil materials. This paper presents a detailed morphological description and growth analysis of a fossil ctenoid scale obtained from the Upper Cretaceous Campanian lacustrine deposits in northeastern China. The morphological features of this fossil scale are well-preserved and consistent with the structures found in ctenoid scales of extant fish species and display prominent ring ornamentation radiating outward from the central focus, with grooves intersecting the rings. A comparative analysis of the morphological characteristics between the fossil ctenoid scale and those well-studied extant fish Mugilidae allows us to explore the applicability of modern fishery biological research methods to the field of fossil scales. The scale length, scale width, the vertical distance from the focus to the apex of the scale, and the total number of radii have been measured. The age of the fish that possessed this ctenoid scale has been estimated by carefully counting the annuli, suggesting an age equal to or more than seven years. The distribution of growth rings on the scale potentially reflects the warm paleoclimatic condition and fish-friendly paleoenvironment prevalent during that period. This paper, moreover, serves as a notable application of fishery biological methods in the examination of fossil materials.


Subject(s)
Fossils , China , Animals , Fishes/anatomy & histology , Fishes/growth & development , Animal Scales/anatomy & histology
14.
Cancer Lett ; 594: 216992, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38797231

ABSTRACT

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive cancer with an extremely poor prognosis, and new treatment options are needed. Recently, immunotherapy has emerged as an efficient treatment against malignant tumors, but less effective in iCCA. Activation of stimulator of interferon genes (STING) signaling could reignite immunologically inert tumors, but the expression and role of STING in iCCA remains to be determined. Here, we show STING is expressed in iCCA, and patients with high expression of STING in early-stage iCCA have a longer overall survival than those have low expression. Increased immune cell infiltration in early-stage iCCA corresponds to elevated STING expression. In mice iCCA models, treatment with the STING agonist MSA-2 show stage-specific inhibitory effects on tumors, with beneficial effects in early-stage tumors but not with advanced-stage cancer. This discrepancy was associated with greater programmed cell death ligand 1 (PD-L1) expression in advanced-stage tumors. Combination therapy targeting PD-L1 and MSA-2 strikingly reduced tumor burden in such tumors compared to either monotherapy. Cumulatively, these data demonstrate that STING agonism monotherapy improves the immune landscape of the tumor microenvironment in early-stage iCCA, while combination therapy ameliorates advanced-stage iCCA.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Membrane Proteins , Cholangiocarcinoma/immunology , Cholangiocarcinoma/genetics , Cholangiocarcinoma/pathology , Cholangiocarcinoma/drug therapy , Animals , Membrane Proteins/genetics , Membrane Proteins/metabolism , Membrane Proteins/agonists , Humans , Mice , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/immunology , Bile Duct Neoplasms/drug therapy , Bile Duct Neoplasms/genetics , B7-H1 Antigen/genetics , B7-H1 Antigen/metabolism , Neoplasm Staging , Cell Line, Tumor , Tumor Microenvironment/immunology , Male , Female , Signal Transduction
15.
J Diabetes ; 16(6): e13567, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38769875

ABSTRACT

BACKGROUND: Reportedly, the stress-hyperglycemia ratio (SHR) is closely associated with poor prognosis in patients with severe acute disease. However, the community-dwelling may also be in a state of stress due to environmental exposure. Our study aimed to explore the association between SHR and all-cause mortality in the community-dwelling population. METHODS: A total of 18 480 participants were included out of 82 091 from the NHANES 1999-2014 survey. The Kaplan-Meier survival analyses were used to assess the disparities in survival rates based on SHR, and the log-rank test was employed to investigate the distinctions between groups. The multivariate Cox regression analysis and restricted cubic spline (RCS) analysis were performed to assess the association of SHR with all-cause mortality. A subgroup analysis was also conducted. RESULTS: A total of 3188 deaths occurred during a median follow-up period of 11.0 (7.7; 15.4) years. The highest risk for all-cause mortality was observed when SHR≤ 0.843 or SHR ≥0.986 (log-rank p < .001). After adjusting for the confounding factors, compared with subjects in the second SHR quartile (Q2), participants in the highest (Q4, adjusted hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.28-1.73) and lowest quartiles (Q1, adjusted HR 1.37, 95% CI 1.16-1.60) have a higher probability of all-cause death. The RCS observed a dose-response U-shaped association between SHR and all-cause mortality. The U-shaped association between SHR and all-cause mortality was similar across subgroup analysis. CONCLUSIONS: The SHR was significantly associated with all-cause mortality in the community-dwelling population, and the relationship was U-shaped.


Subject(s)
Hyperglycemia , Independent Living , Nutrition Surveys , Humans , Male , Female , Middle Aged , Independent Living/statistics & numerical data , Hyperglycemia/mortality , Hyperglycemia/blood , Hyperglycemia/epidemiology , Adult , Aged , Cause of Death , Risk Factors , Mortality/trends , Stress, Physiological , United States/epidemiology , Prognosis , Kaplan-Meier Estimate
16.
Small ; : e2400311, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38804863

ABSTRACT

Polarization-sensitive photodetection grounded on low-symmetry 2D materials has immense potential in improving detection accuracy, realizing intelligent detection, and enabling multidimensional visual perception, which has promising application prospects in bio-identification, optical communications, near-infrared imaging, radar, military, and security. However, the majority of the reported polarized photodetection are limited by UV-vis response range and low anisotropic photoresponsivity factor, limiting the achievement of high-performance anisotropic photodetection. Herein, 2D t-InTe crystal is introduced into anisotropic systems and developed to realize broadband-response and high-anisotropy-ratio polarized photodetection. Stemming from its narrow band gap and intrinsic low-symmetry lattice characteristic, 2D t-InTe-based photodetector exhibits a UV-vis-NIR broadband photoresponse and significant photoresponsivity anisotropy behavior, with an exceptional in-plane anisotropic factor of 1.81@808 nm laser, surpassing the performance of most reported 2D counterparts. This work expounds the anisotropic structure-activity relationship of 2D t-InTe crystal, and identifies 2D t-InTe as a prospective candidate for high-performance polarization-sensitive optoelectronics, laying the foundation for future multifunctional device applications.

17.
Eur J Med Chem ; 272: 116487, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38759452

ABSTRACT

Acute lung injury (ALI) and inflammatory bowel disease (IBD) are common inflammatory illnesses that seriously affect people's health. Herein, a series of 4-hydroxylcoumarin (4-HC) derivatives were designed and synthesized. The inhibitory effects of these compounds on LPS-induced interleukin-6 (IL-6) release from J774A.1 cells were then screened via ELISA assay, compound B8 showed 3 times more active than the lead compound 4-HC. The most active compound B8 had the IC50 values of 4.57 µM and 6.51 µM for IL-6 release on mouse cells J774A.1 and human cells THP-1, respectively. Furthermore, we also found that B8 could act on the MAPK pathway. Based on the target prediction results of computer virtual docking, kinase inhibitory assay was carried out, and it revealed that targeting IRAK1 was a key mechanism for B8 to exert anti-inflammatory activity. Moreover, B8 exerted a good therapeutic effect on the dextran sulfate sodium (DSS)-induced colitis model and liposaccharide (LPS)-induced ALI mouse models. The acute toxicity experiments indicated that high-dose B8 caused no adverse reactions in mice, confirming its safety in vivo. Additionally, the preliminary pharmacokinetic (PK) parameters of B8 in SD rats were also examined, revealing a bioavailability (F) of 28.72 %. In conclusion, B8 is a potential candidate of drug for the treatment of ALI and colitis.


Subject(s)
4-Hydroxycoumarins , Acute Lung Injury , Colitis , Drug Design , Acute Lung Injury/drug therapy , Acute Lung Injury/chemically induced , Animals , Colitis/drug therapy , Colitis/chemically induced , Mice , Humans , Structure-Activity Relationship , 4-Hydroxycoumarins/pharmacology , 4-Hydroxycoumarins/chemistry , 4-Hydroxycoumarins/chemical synthesis , Molecular Structure , Dextran Sulfate , Male , Dose-Response Relationship, Drug , Rats , Lipopolysaccharides/pharmacology , Lipopolysaccharides/antagonists & inhibitors , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Interleukin-6/metabolism , Interleukin-6/antagonists & inhibitors , Interleukin-1 Receptor-Associated Kinases/antagonists & inhibitors , Interleukin-1 Receptor-Associated Kinases/metabolism , Molecular Docking Simulation , Mice, Inbred C57BL , Cell Line
18.
Surg Endosc ; 38(6): 3353-3360, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38698259

ABSTRACT

BACKGROUND AND AIMS: Many studies of gastric gastrointestinal stromal tumors (g-GISTs) following endoscopic resection (ER) have typically focused on tumor size, with most tumors at low risk of aggressiveness after risk stratification. There have been few systematic studies on the oncologic outcomes of intermediate- or high-risk g-GISTs after ER. METHODS: From January 2014 to January 2020, we retrospectively collected patients considered at intermediate- or high-risk of g-GISTs according to the modified NIH consensus classification system. The primary outcome was overall survival (OS). RESULTS: Six hundred and seventy nine (679) consecutive patients were diagnosed with g-GISTs and treated by ER between January 2014 and January 2020 in three hospitals in Shanghai, China. 43 patients (20 males and 23 females) were confirmed at intermediate-or high-risk. The mean size of tumors was 2.23 ± 1.01 cm. The median follow-up period was 62.02 ± 15.34 months, with a range of 28 to 105 months. There were no recurrences or metastases, even among patients having R1 resections. The 5-year OS rate was 97.4% (42/43). CONCLUSION: ER for intermediate- or high-risk gastric small GISTs is a feasible and safe method, which allows for a wait-and-see approach before determining the necessity for imatinib adjuvant or surgical treatment. This approach to g-GISTs does require that patients undergo close follow-up.


Subject(s)
Gastrointestinal Stromal Tumors , Stomach Neoplasms , Humans , Gastrointestinal Stromal Tumors/surgery , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/mortality , Male , Female , Retrospective Studies , Middle Aged , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Stomach Neoplasms/mortality , Aged , Adult , Treatment Outcome , Gastroscopy/methods , Survival Rate , China/epidemiology , Aged, 80 and over , Risk Assessment , Gastrectomy/methods
19.
BMC Musculoskelet Disord ; 25(1): 380, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38745214

ABSTRACT

BACKGROUND: Enlargement of the bone tunnel has become an unavoidable early complication after anterior cruciate ligament (ACL) reconstruction, whether it is a single or double-bundle ACL reconstruction. Preservation of the ACL stump in ACL reconstruction reduces enlargement of the bone tunnel. The purpose of this study was to investigate the question of whether single-bundle ACL reconstruction using the ACL femoral side retained stump technique reduces enlargement of the femoral tunnel. METHODS: Forty patients who underwent single-bundle reconstruction of the ACL were included in this study. The patients were categorized into a Remnant preservation group (Group R) and the Non-remnant preservation group (Group N). In the Remnant preservation group, a high-flexion femoral side retained stump technique was used intraoperatively for the establishment of the femoral side bone tunnel, and in the Non-remnant preservation group, the conventional femoral positioning method was used (we used a femoral positioning drill for localization and drilling of the femoral bone tunnel), and MRI of the operated knee joints was performed at 6 months postoperatively. We measured the internal diameter of the femoral bone tunnel at 5 mm from the intra-articular outlet of the femoral bone tunnel on an MRI scan image perpendicular to the femoral bone tunnel. The size of the tunnel was compared between the intraoperative drilling of the bone tunnel and the size of the bone tunnel at 6 months postoperatively. Postoperative clinical assessment was Lysholm score. RESULTS: After a 6-month follow-up of 40 patients, the diameter of the femoral tunnel at a distance of 5 mm from the inner opening of the femoral tunnel was 10.96 ± 0.67 mm and 10.11 ± 0.62 mm in patients of group N and group R, respectively, and the difference was statistically significant (P < 0.05).The diameter of the femoral tunnel at 6 months postoperatively in group N and group R compared to the intraoperative bone tunnel increased by 2.58 ± 0.24 mm and 1.94 ± 0.31 mm, and the difference was statistically significant (P < 0.05).The femoral tunnel enlargement rates of group N and group R were 30.94 ± 3.00% and 24.02 ± 5.10%, respectively, and the differences were significant (P < 0.05). CONCLUSION: ACL femoral side retained stump technique does not sacrifice the ideal location of the femoral tunnel and is able to preserve the possible benefits of the ACL stump: reduced femoral tunnel enlargement.


Subject(s)
Anterior Cruciate Ligament Reconstruction , Femur , Humans , Anterior Cruciate Ligament Reconstruction/methods , Anterior Cruciate Ligament Reconstruction/adverse effects , Femur/surgery , Femur/diagnostic imaging , Adult , Female , Male , Young Adult , Anterior Cruciate Ligament/surgery , Anterior Cruciate Ligament/diagnostic imaging , Adolescent , Anterior Cruciate Ligament Injuries/surgery , Magnetic Resonance Imaging , Treatment Outcome , Postoperative Complications/prevention & control , Postoperative Complications/etiology , Knee Joint/surgery , Knee Joint/diagnostic imaging , Middle Aged
20.
Technol Cancer Res Treat ; 23: 15330338241256814, 2024.
Article in English | MEDLINE | ID: mdl-38773777

ABSTRACT

Objective: This prospective study aims to evaluate acute irradiation-induced xerostomia during radiotherapy by utilizing the normalized iodine concentration (NIC) derived from energy spectrum computed tomography (CT) iodine maps. Methods: In this prospective study, we evaluated 28 patients diagnosed with nasopharyngeal carcinoma. At 4 distinct stages of radiotherapy (0, 10, 20, and 30 fractions), each patient underwent CT scans to generate iodine maps. The NIC of both the left and right parotid glands was obtained, with the NIC at the 0-fraction stage serving as the baseline measurement. After statistically comparing the NIC obtained in the arterial phase, early venous phase, late venous phase, and delayed phase, we chose the late venous iodine concentration as the NIC and proceeded to analyze the variations in NIC at each radiotherapy interval. Using the series of NIC values, we conducted hypothesis tests to evaluate the extent of change in NIC within the parotid gland across different stages. Furthermore, we identified the specific time point at which the NIC decay exhibited the most statistically significant results. In addition, we evaluated the xerostomia grades of the patients at these 4 stages, following the radiation therapy oncology group (RTOG) xerostomia evaluation standard, to draw comparisons with the changes observed in NIC. Results: The NIC in the late venous phase exhibited the highest level of statistical significance (P < .001). There was a noticeable attenuation in NIC as the RTOG dry mouth grade increased. Particularly, at the 20 fraction, the NIC experienced the most substantial attenuation (P < .001), a significant negative correlation was observed between the NIC of the left, right, and both parotid glands, and the RTOG evaluation grade of acute irradiation-induced xerostomia (P < .001, r = -0.46; P < .001, r = -0.45; P < .001, r = -0.47). The critical NIC values for the left, right, and both parotid glands when acute xerostomia occurred were 0.175, 0.185, and 0.345 mg/ml, respectively, with AUC = 0.73, AUC = 0.75, and AUC = 0.75. Conclusion: The NIC may be used to evaluate changes in parotid gland function during radiotherapy and acute irradiation-induced xerostomia.


Subject(s)
Iodine , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Parotid Gland , Tomography, X-Ray Computed , Xerostomia , Humans , Xerostomia/etiology , Male , Parotid Gland/radiation effects , Female , Nasopharyngeal Carcinoma/radiotherapy , Middle Aged , Adult , Aged , Nasopharyngeal Neoplasms/radiotherapy , Prospective Studies , Radiation Injuries/etiology , Radiation Injuries/diagnosis , Radiotherapy Dosage
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