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1.
Sci Rep ; 14(1): 10750, 2024 05 10.
Article En | MEDLINE | ID: mdl-38729988

Colorectal cancer (CRC) prevention requires early detection and removal of adenomas. We aimed to develop a computational model for real-time detection and classification of colorectal adenoma. Computationally constrained background based on real-time detection, we propose an improved adaptive lightweight ensemble model for real-time detection and classification of adenomas and other polyps. Firstly, we devised an adaptive lightweight network modification and effective training strategy to diminish the computational requirements for real-time detection. Secondly, by integrating the adaptive lightweight YOLOv4 with the single shot multibox detector network, we established the adaptive small object detection ensemble (ASODE) model, which enhances the precision of detecting target polyps without significantly increasing the model's memory footprint. We conducted simulated training using clinical colonoscopy images and videos to validate the method's performance, extracting features from 1148 polyps and employing a confidence threshold of 0.5 to filter out low-confidence sample predictions. Finally, compared to state-of-the-art models, our ASODE model demonstrated superior performance. In the test set, the sensitivity of images and videos reached 87.96% and 92.31%, respectively. Additionally, the ASODE model achieved an accuracy of 92.70% for adenoma detection with a false positive rate of 8.18%. Training results indicate the effectiveness of our method in classifying small polyps. Our model exhibits remarkable performance in real-time detection of colorectal adenomas, serving as a reliable tool for assisting endoscopists.


Adenoma , Artificial Intelligence , Colorectal Neoplasms , Humans , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/classification , Adenoma/diagnosis , Adenoma/classification , Colonoscopy/methods , Early Detection of Cancer/methods , Colonic Polyps/diagnosis , Colonic Polyps/classification , Colonic Polyps/pathology , Algorithms
2.
Biosens Bioelectron ; 259: 116384, 2024 May 15.
Article En | MEDLINE | ID: mdl-38768536

A novel ratiometric Molecularly Imprinted Electrochemical sensor for the specific marker of Glycyrrhiza glabra L. was developed in this work. To achieve simultaneous detection of two analytes on one sensor, we constructed a double template molecular imprinted electrochemical sensor with glabridin (GLA) and isoliquiritin (ISL) as templates. Further, Ferrocene/ZIF-8 (Fc/ZIF-8) composites were prepared via a one-pot solvothermal reaction and coated on the surface of a glassy carbon electrode (GCE), and the oxidation of Fc was presented as the internal reference signal. Nitrogen-doped carbon (NOC) with high conductivity was further loaded on the modified GCE. Based on theoretical exploration and computer directional simulation of density functional theory (DFT), the optimal functional monomer and the best ratio of double template molecules to functional monomer were screened. Under optimal conditions, the sensor produced electrochemical curves when exposed to a solution containing GLA and ISL. As the concentration of GLA and ISL increased, the peak current intensity of GLA and ISL (IGLA and IISL) also increased, while the peak current intensity of Fc (as a reference signal) remained relatively constant. The values of IGLA/IFc and IISL/IFc showed excellent linear relationships with GLA and ISL concentrations in the range of 0.1-160 µM and 0.5-150 µM, respectively. The detection limits were 0.052 µM and 0.27 µM (S/N = 3), respectively. Due to the imprinting effect of MIP and the existence of a reference signal, the sensor exhibited excellent selectivity and anti-interference ability and was successfully applied to the quality evaluation of Glycyrrhiza glabra L.

4.
Eco Environ Health ; 3(2): 192-201, 2024 Jun.
Article En | MEDLINE | ID: mdl-38646098

The association between the exposure of organochlorine pesticides (OCPs) and serum uric acid (UA) levels remained uncertain. In this study, to investigate the combined effects of OCP mixtures on hyperuricemia, we analyzed serum OCPs and UA levels in adults from the National Health and Nutrition Examination Survey (2005-2016). Four statistical models including weighted logistic regression, weighted quantile sum (WQS), quantile g-computation (QGC), and bayesian kernel machine regression (BKMR) were used to assess the relationship between mixed chemical exposures and hyperuricemia. Subgroup analyses were conducted to explore potential modifiers. Among 6,529 participants, the prevalence of hyperuricemia was 21.15%. Logistic regression revealed a significant association between both hexachlorobenzene (HCB) and trans-nonachlor and hyperuricemia in the fifth quintile (OR: 1.54, 95% CI: 1.08-2.19; OR: 1.58, 95% CI: 1.05-2.39, respectively), utilizing the first quintile as a reference. WQS and QGC analyses showed significant overall effects of OCPs on hyperuricemia, with an OR of 1.25 (95% CI: 1.09-1.44) and 1.20 (95% CI: 1.06-1.37), respectively. BKMR indicated a positive trend between mixed OCPs and hyperuricemia, with HCB having the largest weight in all three mixture analyses. Subgroup analyses revealed that females, individuals aged 50 years and above, and those with a low income were more vulnerable to mixed OCP exposure. These results highlight the urgent need to protect vulnerable populations from OCPs and to properly evaluate the health effects of multiple exposures on hyperuricemia using mutual validation approaches.

5.
Expert Rev Anticancer Ther ; : 1-10, 2024 Apr 29.
Article En | MEDLINE | ID: mdl-38656796

BACKGROUND: Adjuvant therapy (AT) and neoadjuvant therapy (NAT) are standard treatments for pancreatic ductal adenocarcinoma (PDAC) depending on the status of the disease. However, whether AT improves survival after NAT and radical resection in all TNM stages remains unclear. RESEARCH DESIGN AND METHODS: We utilized the Surveillance, Epidemiology, and End Results (SEER) database (2010-2019) for PDAC patients who underwent radical surgery and applied Pearson's chi-square test, multivariate and univariate Cox regression, Kaplan-Meier plot, Log-rank tests, and propensity score matching (PSM) for analysis. RESULTS: Given PSM after enrolling 13,868 PDAC patients, significant differences in survival were identified between AT and neoadjuvant therapy plus adjuvant therapy (NATAT) (p = 0.023) as well as between NAT and NATAT (p < 0.001). According to the AJCC 8th TNM stage, a survival advantage associated with NATAT was exclusively observed in stage III and IV disease, except for T4N0M0. Some stage IV patients receiving NATAT exhibited comparable survival to their counterparts without metastasis. CONCLUSIONS: In this retrospective cohort study, we demonstrated that patients harboring tumors in late TNM stages, including N2 resectable PDAC, might have better survival from NATAT, and that certain patients with M1 disease might still benefit from comprehensive systemic therapy and radical resection.

6.
Cell Rep ; 43(3): 113942, 2024 Mar 26.
Article En | MEDLINE | ID: mdl-38489266

Tumor-associated macrophages (TAMs) shape tumor immunity and therapeutic efficacy. However, it is poorly understood whether and how post-translational modifications (PTMs) intrinsically affect the phenotype and function of TAMs. Here, we reveal that peptidylarginine deiminase 4 (PAD4) exhibits the highest expression among common PTM enzymes in TAMs and negatively correlates with the clinical response to immune checkpoint blockade. Genetic and pharmacological inhibition of PAD4 in macrophages prevents tumor progression in tumor-bearing mouse models, accompanied by an increase in macrophage major histocompatibility complex (MHC) class II expression and T cell effector function. Mechanistically, PAD4 citrullinates STAT1 at arginine 121, thereby promoting the interaction between STAT1 and protein inhibitor of activated STAT1 (PIAS1), and the loss of PAD4 abolishes this interaction, ablating the inhibitory role of PIAS1 in the expression of MHC class II machinery in macrophages and enhancing T cell activation. Thus, the PAD4-STAT1-PIAS1 axis is an immune restriction mechanism in macrophages and may serve as a cancer immunotherapy target.


Hydrolases , Protein Processing, Post-Translational , Mice , Animals , Protein-Arginine Deiminases/metabolism , Protein-Arginine Deiminase Type 4/genetics , Protein-Arginine Deiminase Type 4/metabolism , Hydrolases/metabolism , Histocompatibility Antigens Class II/metabolism , Macrophages/metabolism
7.
Network ; : 1-29, 2024 Mar 03.
Article En | MEDLINE | ID: mdl-38433470

As the number of patients increases, physicians are dealing with more and more cases of degenerative spine pathologies on a daily basis. To reduce the workload of healthcare professionals, we propose a modified Swin-UNet network model. Firstly, the Swin Transformer Blocks are improved using a residual post-normalization and scaling cosine attention mechanism, which makes the training process of the model more stable and improves the accuracy. Secondly, we use the log-space continuous position biasing method instead of the bicubic interpolation position biasing method. This method solves the problem of performance loss caused by the large difference between the resolution of the pretraining image and the resolution of the spine image. Finally, we introduce a segmentation smooth module (SSM) at the decoder stage. The SSM effectively reduces redundancy, and enhances the segmentation edge processing to improve the model's segmentation accuracy. To validate the proposed method, we conducted experiments on a real dataset provided by hospitals. The average segmentation accuracy is no less than 95%. The experimental results demonstrate the superiority of the proposed method over the original model and other models of the same type in segmenting the spinous processes of the vertebrae and the posterior arch of the spine.

8.
Int J Surg ; 2024 Mar 18.
Article En | MEDLINE | ID: mdl-38498406

BACKGROUND: Surgical treatment of complex giant pituitary adenomas (GPAs) presents significant challenges. The efficacy and safety of combining transsphenoidal and transcranial approaches for these tumors remain controversial. In this largest cohort of patients with complex GPAs, we compared the surgical outcomes between those undergoing a combined regimen and a non-combined regimen. We also examined the differences in risks of complications, costs, and logistics between the two groups, which might offer valuable information for the appropriate management of these patients. MATERIALS AND METHODS: This was a multicenter retrospective cohort study conducted at 13 neurosurgical centers. Consecutive patients who received a combined or non-combined regimen for complex GPAs were enrolled. The primary outcome was gross total resection, while secondary outcomes included complications, surgical duration, and relapse. A propensity score-based weighting method was used to account for differences between the groups. RESULTS: Out of 647 patients (298 [46.1%] women, mean age: 48.5 ± 14.0 years) with complex GPAs, 91 were in the combined group and 556 were in the non-combined group. Compared with the non-combined regimen, the combined regimen was associated with a higher probability of gross total resection (50.5% vs. 40.6%, odds ratio [OR]: 2.18, 95% confidence interval [CI]: 1.30-3.63, P = 0.003). The proportion of patients with life-threatening complications was lower in the combined group than in the non-combined group (4.4% vs. 11.2%, OR: 0.25, 95% CI: 0.08-0.78, P = 0.017). No marked differences were found between the groups in terms of other surgical or endocrine-related complications. However, the combined regimen exhibited a longer average surgery duration of 1.3 h (P < 0.001) and higher surgical costs of 22,000 CNY (approximate 3,000 USD, P = 0.022) compared with the non-combined approach. CONCLUSIONS: The combined regimen offered increased rates of total resection and decreased incidence of life-threatening complications, which might be recommended as the first-line choice for these patients.

9.
J Fluoresc ; 2024 Mar 19.
Article En | MEDLINE | ID: mdl-38502406

Hydrogen sulfide (H2S) plays a key role in the physiology and pathology of organisms, and H2S in the environment is easily absorbed and harmful to health. It is of great significance to develop a probe with good selectivity, high sensitivity and good stability that can detect hydrogen sulfide inside and outside organisms. In this work, we designed a novel "turn-on" fluorescent probe CIM-SDB for the detection of H2S. The probe CIM-SDB used indene-carbazole as the fluorophore and 2,4-dinitrobenzenesulfonyl as the recognition site. The probe CIM-SDB exhibited high selectivity and sensitivity to H2S (detection limit as low as 123 nM). Moreover, the probe CIM-SDB was successfully applied to the detection of intracellular exogenous and endogenous H2S, and the test strips prepared by the probe CIM-SDB could realize the convenient and rapid detection of H2S.

10.
J Orthop Surg Res ; 19(1): 179, 2024 Mar 11.
Article En | MEDLINE | ID: mdl-38468352

BACKGROUND: Cholesterol (CHO) is an essential component of the body. However, high CHO levels in the body can damage bone mass and promote osteoporosis. CHO accumulation can cause osteoblast apoptosis, which has a negative effect on bone formation. The pathogenesis of osteoporosis is a complicate process that includes oxidative stress, endoplasmic reticulum (ER) stress, and inflammation. Geniposide (GEN) is a natural compound with anti-osteoporotic effect. However, the roles of GEN in osteopathogenesis are still unclear. Our previous studies demonstrated that GEN could reduce the accumulation of CHO in osteoblasts and the activation of ER stress in osteoblasts. However, the molecular mechanism of GEN in inhibiting CHO-induced apoptosis in osteoblasts needs to be further investigated. METHODS: MC3T3-E1 cells were treated with osteogenic induction medium (OIM). Ethanol-solubilized cholesterol (100 µM) was used as a stimulator, and 10 µM and 25 µM geniposide was added for treatment. The alterations of protein expression were detected by western blot, and the cell apoptosis was analyzed by a flow cytometer. RESULTS: CHO promoted osteoblast apoptosis by activating ER stress in osteoblasts, while GEN alleviated the activation of ER stress and reduced osteoblast apoptosis by activating the GLP-1R/ABCA1 pathway. Inhibition of ABCA1 or GLP-1R could eliminate the protective activity of GEN against CHO-induced ER stress and osteoblast apoptosis. CONCLUSION: GEN alleviated CHO-induced ER stress and apoptosis in osteoblasts by mediating the GLP-1R/ABCA1 pathway.


Iridoids , Osteoblasts , Osteoporosis , Humans , Osteoblasts/metabolism , Osteoporosis/metabolism , Apoptosis , Endoplasmic Reticulum Stress , Cholesterol/metabolism , ATP Binding Cassette Transporter 1/metabolism , ATP Binding Cassette Transporter 1/pharmacology
11.
Chem Biol Interact ; 394: 110972, 2024 May 01.
Article En | MEDLINE | ID: mdl-38555047

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by complex clinical symptoms and multi-organ damage. One of the most prevalent complications of SLE is lupus nephritis (LN). Rutin, a natural flavonoid compound found in various plants used in traditional Chinese medicine, has shown promising anti-inflammatory, antioxidant, and renal protective effects. In our study, we treated MRL/lpr mice, a model known for spontaneously developing LN, with Rutin. Our findings reveal that Rutin markedly reduced serum cytokine and autoantibody levels and decreased inflammatory cell infiltration in renal tissues, thereby ameliorating kidney pathology. In vitro experiments indicated that Rutin's therapeutic effect on LN is linked to its significant reduction of oxidative stress in T cells. Further investigations suggest that Rutin enhances oxidative stress management through the modulation of Peroxisome proliferator-activated receptor gamma (PPARγ). We observed that Rutin modulates PPARγ activity, leading to reduced transcriptional activity of NF-κB and STAT3, which in turn inhibits the secretion of inflammatory cytokines such as IL-6, TNF-α, and IL-17. In summary, Rutin can exert an antioxidant effect by regulating PPARγ and shows therapeutic action against LN.


Lupus Nephritis , Mice, Inbred MRL lpr , NF-kappa B , Oxidative Stress , PPAR gamma , Rutin , T-Lymphocytes , Rutin/pharmacology , Rutin/therapeutic use , Animals , PPAR gamma/metabolism , Oxidative Stress/drug effects , Lupus Nephritis/drug therapy , Lupus Nephritis/metabolism , Lupus Nephritis/pathology , Mice , T-Lymphocytes/drug effects , T-Lymphocytes/metabolism , NF-kappa B/metabolism , Female , STAT3 Transcription Factor/metabolism , Cytokines/metabolism , Kidney/drug effects , Kidney/pathology , Kidney/metabolism , Antioxidants/pharmacology
12.
Medicine (Baltimore) ; 103(6): e37038, 2024 Feb 09.
Article En | MEDLINE | ID: mdl-38335431

Colorectal cancer (CRC) remains a significant global health concern, as characterized by its high mortality rate ranking second among all the leading causes of death. The liver serves as the primary site of CRC metastasis, and the occurrence of liver metastasis is a significant contributor to mortality among patients diagnosed with CRC. The survival rate of patients with colorectal liver metastasis has significantly increased with the advancement of comprehensive tumor therapy. However, radical surgery remains the key factor. Since there are frequently multiple liver metastases, which are prone to recurrence after surgery, it is crucial to preserve as much liver parenchyma as possible without affecting the prognosis. The issue of surgical margins plays a crucial role in this regard. In this review, we begin by examining the occurrence of positive surgical margins in liver metastases of patients diagnosed with CRC. We aim to define positive margins in hepatic surgery, examine the relationship between margins and prognosis and establish a foundation for future research in this field.


Colorectal Neoplasms , Liver Neoplasms , Humans , Margins of Excision , Hepatectomy , Colorectal Neoplasms/pathology , Liver Neoplasms/pathology , Prognosis
13.
Ecotoxicol Environ Saf ; 272: 116091, 2024 Mar 01.
Article En | MEDLINE | ID: mdl-38340600

BACKGROUND: Whether and to what extent the impact of exposure to various polychlorinated biphenyls (PCBs) congeners on diabetes, as well as the important contributors, have remained unclear. OBJECTIVE: We aimed to investigate the association patterns between PCBs mixture and diabetes, identify the critical congeners, and explore the potential modifiers. METHODS: The present study included 5900 U.S. adults from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2016. Weighted logistic regression, restricted cubic spline regression, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were applied to estimate the linear and non-linear associations of single and mixed PCB exposure with diabetes. Subgroup analyses were also conducted to explore potential sex differences. RESULTS: In the weighted logistic regression model, total PCBs were positively associated with diabetes (OR = 1.33, P < 0.025), and significant non-linear associations were observed using RCS analyses. The non-linear positive association between PCBs mixed exposure and diabetes was likewise found in the WQS and BKMR results. PCB180, PCB194, PCB196, and PCB167 were with the highest weights in the WQS, and PCB209 and PCB66 were with the highest posterior inclusion probabilities in the BKMR. Additionally, exposure to total PCBs and most of individual PCB congeners were significantly associated with elevated risk of in females (OR = 1.74; P for trend < 0.001), while fewer significant associations were observed in males. CONCLUSION: The present study highlighted the importance of the long-term surveillance of PCBs and the need to enhance protective measures against them. Notably, these associations were non-linear, congener-specific, and significantly stronger in females than males, especially at relatively high levels of PCBs exposure. Further prospective and mechanistic studies were warranted to ascertain the causal effects between PCBs mixture and diabetes.


Diabetes Mellitus , Environmental Pollutants , Polychlorinated Biphenyls , Adult , Female , Humans , Male , Polychlorinated Biphenyls/toxicity , Polychlorinated Biphenyls/analysis , Environmental Pollutants/toxicity , Environmental Pollutants/analysis , Environmental Exposure/analysis , Nutrition Surveys , Bayes Theorem , Diabetes Mellitus/epidemiology
14.
Micromachines (Basel) ; 15(2)2024 Feb 02.
Article En | MEDLINE | ID: mdl-38398964

This paper presents a two-axis AlScN-based water-immersible MEMS mirror fabricated in an 8-inch MEMS process. Compared with other studies, this device has a larger optical aperture 10 mm in diameter. The resonant frequencies of the device are 1011 Hz in air and 342 Hz in water. The scanning angle reaches ±5° and ±2° at resonant frequencies in air and water, respectively. The cavitation phenomenon is observed when the device is operating in water, which leads the device to electrical failure. To address this issue, a device with reduced resonant frequencies-246 Hz and 152 Hz in air and water-is characterized, through which the bubbles can be effectively prohibited. This MEMS mirror could potentially be used in ultrasound and photoacoustic microscopy applications.

15.
Sci Rep ; 14(1): 55, 2024 01 02.
Article En | MEDLINE | ID: mdl-38167475

Airborne surface and underwater human pose recognition are crucial for various safety and surveillance applications, including the detection of individuals in distress or drowning situations. However, airborne optical cameras struggle to achieve simultaneous imaging of the surface and underwater because of limitations imposed by visible-light wavelengths. To address this problem, this study proposes the use of light detection and ranging (LiDAR) to simultaneously detect humans on the surface and underwater, whereby human poses are recognized using a neural network designed for irregular data. First, a temporal point-cloud dataset was constructed for surface and underwater human pose recognition to enhance the recognition of comparable movements. Subsequently, radius outlier removal (ROR) and statistical outlier removal (SOR) were employed to alleviate the impact of noise and outliers in the constructed dataset. Finally, different combinations of secondary sampling methods and sample sizes were tested to improve recognition accuracy using PointNet++. The experimental results show that the highest recognition accuracy reached 97.5012%, demonstrating the effectiveness of the proposed human pose detection and recognition method.


Deep Learning , Drowning , Humans , Light , Movement , Neural Networks, Computer
16.
Sci Rep ; 14(1): 1502, 2024 01 17.
Article En | MEDLINE | ID: mdl-38233602

HBV-miR-3 is encoded by HBV and takes part in pathogenesis of HBV-related liver disease. Whether HBV-miR-3 has a relationship with HBV replication and is predictive of PegIFN-α treatment response is still unknown. HBV-miR-3 quantification is based on qRT-PCR. The relationship of HBV-miR-3 and HBV replication, and predictive value of HBV-miR-3 were evaluated in a cohort of 650 HBeAg positive patients from a multi-center, randomized phase III clinical trial for the study of PegIFN-a2b. HBV-miR-3 is significantly positively related to HBVDNA, HBVpgRNA, HBeAg and HBsAg at baseline and at all the different time points during PegIFN-α treatment. Both univariate regression analyses and multivariate logistic regression analyses showed HBV-miR-3 is a predictor of HBeAg seroconversion in the patients treated with PegIFN-α at weeks of 0, 12, and 24. 70.0% of patients with HBV-miR-3 < 3log at week 12 achieved HBeAg seroconversion, otherwise, with HBV-miR-3 > 6log at week 12 no patient obtained HBeAg seroconversion. Conbination of HBV-miR-3 and HBeAg is more strongly predictive of HBeAg seroconversion (83.64%) at week 12. HBV-miR-3 is new biomarker for HBV replication and positively correlated to HBV replication. HBV-miR-3 is also an early predictor of HBeAg seroconversion in the patients treated with PegIFN-α.


Antiviral Agents , MicroRNAs , Humans , Antiviral Agents/therapeutic use , Hepatitis B virus/genetics , Interferon-alpha/therapeutic use , Hepatitis B e Antigens , Seroconversion , Polyethylene Glycols/therapeutic use , Treatment Outcome , DNA, Viral , Recombinant Proteins/therapeutic use
17.
Aging (Albany NY) ; 16(1): 43-65, 2024 Jan 10.
Article En | MEDLINE | ID: mdl-38206293

Prostate cancer (PRAD) is one of the common malignant tumors of the urinary system. In order to predict the treatment results for PRAD patients, this study proposes to develop a risk profile based on endoplasmic reticulum stress (ERS). Based on the Memorial Sloan-Kettering Cancer Center (MSKCC) cohort and the Gene Expression Omnibus database (GSE70769), we verified the predictive signature. Using a random survival forest analysis, prognostically significant ERS-related genes were found. An ERS-related risk score (ERscore) was created using multivariable Cox analysis. In addition, the biological functions, genetic mutations and immune landscape related to ERscore are also studied to reveal the underlying mechanisms related to ERS in PRAD. We further explored the ERscore-related mechanisms by profiling a single-cell RNA sequencing (scRNA-seq) dataset (GSE137829) and explored the oncogenic role of ASNS in PRAD through in vitro experiments. The risk signature composed of eight ERS-related genes constructed in this study is an independent prognostic factor and validated in the MSKCC and GSE70769 data sets. The scRNA-seq data additionally revealed that several carcinogenic pathways were noticeably overactivated in the group with high ERS scores. As one of the prognostic genes, ASNS will significantly inhibit the proliferation, migration and invasion abilities of PRAD cells after its expression is interfered with. In conclusion, this study developed a novel risk-specific ERS-based clinical treatment strategy for patients with PRAD.


Prostatic Neoplasms , Humans , Male , Carcinogenesis , Carcinogens , Endoplasmic Reticulum Stress/genetics , Prognosis , Prostatic Neoplasms/genetics
18.
Ther Drug Monit ; 46(1): 89-94, 2024 02 01.
Article En | MEDLINE | ID: mdl-38192036

BACKGROUND: This study aimed to identify the factors that influence voriconazole (VCZ) plasma concentrations and optimize the doses of VCZ in patients with end-stage liver disease (ESLD). METHODS: Patients with ESLD who received a VCZ maintenance dose of 100 mg twice daily (group A, n = 57) or the VCZ maintenance dose of 50 mg twice daily (group B, n = 37), orally or intravenously, were enrolled in this study. Trough plasma concentrations (Cmin) of VCZ between 1 and 5 mg/L were considered within the therapeutic target range. RESULTS: The VCZ Cmin was determined in 94 patients with ESLD. The VCZ Cmin of patients in group A was remarkably higher than those in group B (4.85 ± 2.53 mg/L vs 2.75 ± 1.40 mg/L; P < 0.001). Compared with group A, fewer patients in group B had VCZ Cmin outside the therapeutic target (23/57 vs. 6/37, P = 0.021). Univariate and multivariate analyses suggested that both body weight and Model for End-Stage Liver Disease scores were closely associated with the VCZ Cmin in group B. CONCLUSIONS: These data indicate that dose optimization based on body weight and Model for End-Stage Liver Disease scores is required to strike an efficacy-safety balance during VCZ treatment in patients with ESLD.


End Stage Liver Disease , Humans , End Stage Liver Disease/drug therapy , Drug Monitoring , Voriconazole/therapeutic use , Severity of Illness Index , Body Weight
19.
Sci Total Environ ; 912: 169145, 2024 Feb 20.
Article En | MEDLINE | ID: mdl-38061653

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of legal blindness. It remains unclear whether and to what extent the ambient ozone pollution could increase the risk of AMD. METHODS: A nationwide cross-sectional survey was conducted in 129 major cities in 27 of 31 provincial regions across China from 2018 to 2021. Data in relation to demographics, residential address, and medical histories were collected. The exposure-response relationship between ozone exposure and AMD was explored using the restricted cubic splines. A piecewise logistic regression model was used to examine the magnitudes of the association, after adjusting demographic, social-economic and co-pollutants. Residential ozone exposures were estimated using a satellite-based model. RESULTS: A total of 624,167 middle-aged and older participants were included in the final analyses, the overall prevalence of AMD was 16.76 %. The risk of AMD was consistently increasing with higher warm-season ozone concentration, and the risk became much larger after the cut-off of 110 µg/m3 (approximately 50 ppb). Every 10 µg/m3 increment in warm-season ozone concentration, the adjusted odds ratio (OR) for AMD were 1.15 (1.13, 1.16) and 1.66 (1.63, 1.69) when the warm-season ozone concentration was below or above 110 µg/m3, respectively. CONCLUSION: This large-scale nationwide study provides the first epidemiological evidence demonstrating significant associations between long-term residential ozone exposure and AMD prevalence. Based on our findings, in conjunction with WHO global air quality guidelines, we suggest that a warm-season ozone of 110 µg/m3 should be adopted for middle-aged and older populations to reduce the risk of AMD. Ongoing efforts to reduce ozone exposure in communities through improved air quality regulations and public education are essential for the improvement of public health.


Air Pollutants , Air Pollution , Ozone , Middle Aged , Humans , Aged , Ozone/analysis , Air Pollutants/analysis , Cross-Sectional Studies , Particulate Matter/analysis , Environmental Exposure/analysis , China/epidemiology
20.
Br J Pharmacol ; 181(3): 393-412, 2024 02.
Article En | MEDLINE | ID: mdl-37580308

BACKGROUND AND PURPOSE: Damage to the testis following exposure to ionizing radiation has become an urgent problem to be solved. Here we have investigated if inhibition of p38 mitogen-activated protein kinase (p38MAPK) signalling could alleviate radiation-induced testicular damage. EXPERIMENTAL APPROACH: In mice exposed to whole body radiation (2-6 Gy), morphological changes of the epididymis and testis was measured by histochemical staining. immunohistochemical and immunofluorescence procedures and western blotting were used to monitor expression and cellular location of proteins. Expression of genes was assessed by qPCR and RNA-Seq was used to profile gene expression. KEY RESULTS: Exposure to ionizing radiation induced dose-dependent damage to mouse testis. The sperm quality decreased at 6 and 8 weeks after 6 Gy X-ray radiation. Radiation decreased PLZF+ cells and increased SOX9+ cells, and affected the expression of 969 genes, compared with data from non-irradiated mice. Expression of genes related to p38MAPK were enriched by GO analysis and were increased in the irradiated testis, and confirmed by qPCR. Levels of phospho-p38MAPK protein increased at 28 days after irradiation. In irradiated mice, SB203580 treatment increased spermatozoa, SOX9+ cells, the area and diameter of seminiferous tubules, sperm movement rate and density. Furthermore, SB203580 treatment increased SCP3+ cells, accelerating the process of spermatogenesis. CONCLUSION AND IMPLICATIONS: Exposure to ionizing radiation clearly changed gene expression in mouse testis, involving activation of p38MAPK signalling pathways. Inhibition of p38MAPK by SB203580 partly alleviated the testicular damage caused by radiation and accelerated the recovery of sperms through promoting spermatogenesis.


Semen , Testis , Male , Mice , Animals , Testis/anatomy & histology , Testis/metabolism , Spermatogenesis/radiation effects , Spermatozoa/metabolism , Signal Transduction
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