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1.
Environ Sci Technol ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39255388

RESUMEN

Toxicity studies of water disinfection byproducts (DBPs) typically assume additive interactions. Coupling results from both the bottom-up cytotoxicity interaction approach by selecting six common DBPs and the top-down cytotoxicity fractionating the disinfected secondary effluent containing a much broader DBP selection, we demonstrated a novel effect of clear, nonadditive cytotoxicity at low chemical concentrations regardless of the number of DBP types involved. We revealed that the cytotoxicity interactions were influenced by the chemical's type, concentration factor, and mixing ratio. For the bottom-up approach, the average combination indices (CIs) were 1.61 (chloracetamide + chloroacetonitrile, antagonism), 1.03 (bromoacetamide+bromoacetonitrile, near additivity), and 0.69 (iodoacetamide + iodoacetonitrile, synergism) across the DBPs' concentration range of 10-4-10-7 M. These cytotoxicity interactions also varied with the components' mixing ratios. For the top-down approach, we obtained two fractions of DBP mixtures from the disinfected secondary effluent using solvents of different polarities. The effect of the concentration on CI values was significant, with a maximum 43.1% relative deviation in CI from LC5 to LC95. The average CI values across the sample concentration range of 1-50 × (concentration factor) varied from 1.68 (antagonism) to 0.89 (slight synergism) as the ratio of mixture A increased. These results call for further research in prioritizing the forcing DBPs in mixtures.

2.
Sci Total Environ ; 953: 175958, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39233077

RESUMEN

A burgeoning body of epidemiological and toxicological evidence suggests that thyroid health may be significantly impacted by exposure to both long- and short-chain perfluoroalkyl substances (PFAS) compounds. We conducted a meta-analysis to examine the association between 16 PFAS compounds and five thyroid hormones (TSH, TT3, TT4, FT3, and FT4) in the serum of a pregnant women, adolescents, and adults. The dose-response relationship between some PFAS and thyroid hormones in different population subpopulation was found and the model was fitted. We also amalgamated data from 18 animal experiments with previously published in vitro studies to elucidate the toxicological mechanisms underlying the impact of PFAS on the thyroid gland. The results of the study showed that (a) both conventional and emerging PFAS compounds were identified in human samples and exhibited associations with thyroid health outcomes; (b) in animal studies, PFAS have been found to impact thyroid gland health through two primary mechanisms: by influencing the hypothalamic-pituitary-thyroid axis and by binding to thyroid receptors. This study provides a systematic description of the health effects and risk assessment associated with PFAS exposure on the thyroid gland. Furthermore, dose-response relationships were established through the Hill model in python.

3.
Lancet ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39293462

RESUMEN

BACKGROUND: [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) prolongs radiographic progression-free survival and overall survival in patients with metastatic castration-resistant prostate cancer previously treated with androgen receptor pathway inhibitor (ARPI) and taxane therapy. We aimed to investigate the efficacy of 177Lu-PSMA-617 in patients with taxane-naive metastatic castration-resistant prostate cancer. METHODS: In this phase 3, randomised, controlled trial conducted at 74 sites across Europe and North America, taxane-naive patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer who had progressed once on a previous ARPI were randomly allocated (1:1) to open-label, intravenous 177Lu-PSMA-617 at a dosage of 7·4 GBq (200 mCi) ± 10% once every 6 weeks for six cycles, or a change of ARPI (to abiraterone or enzalutamide, administered orally on a continuous basis per product labelling). Crossover from ARPI change to 177Lu-PSMA-617 was allowed after centrally confirmed radiographic progression. The primary endpoint was radiographic progression-free survival, defined as the time from randomisation until radiographic progression or death, assessed in the intention-to-treat population. Safety was a secondary endpoint. This study is registered with ClinicalTrials.gov (NCT04689828) and is ongoing. In this primary report of the study, we present primary (first data cutoff) and updated (third data cutoff) analyses of radiographic progression-free survival; all other data are based on the third data cutoff. FINDINGS: Overall, of the 585 patients screened, 468 met all eligibility criteria and were randomly allocated between June 15, 2021 and Oct 7, 2022 to receive 177Lu-PSMA-617 (234 [50%] patients) or ARPI change (234 [50%]). Baseline characteristics were mostly similar between groups; median number of 177Lu-PSMA-617 cycles was 6·0 (IQR 4·0-6·0). Of patients assigned to ARPI change, 134 (57%) crossed over to receive 177Lu-PSMA-617. In the primary analysis (median time from randomisation to first data cutoff 7·26 months [IQR 3·38-10·55]), the median radiographic progression-free survival was 9·30 months (95% CI 6·77-not estimable) in the 177Lu-PSMA-617 group versus 5·55 months (4·04-5·95) in the ARPI change group (hazard ratio [HR] 0·41 [95% CI 0·29-0·56]; p<0·0001). In the updated analysis at time of the third data cutoff (median time from randomisation to third data cutoff 24·11 months [IQR 20·24-27·40]), median radiographic progression-free survival was 11·60 months (95% CI 9·30-14·19) in the 177Lu-PSMA-617 group versus 5·59 months (4·21-5·95) in the ARPI change group (HR 0·49 [95% CI 0·39-0·61]). The incidence of grade 3-5 adverse events was lower in the 177Lu-PSMA-617 group (at least one event in 81 [36%] of 227 patients; four [2%] grade 5 [none treatment related]) than the ARPI change group (112 [48%] of 232; five [2%] grade 5 [one treatment related]). INTERPRETATION: 177Lu-PSMA-617 prolonged radiographic progression-free survival relative to ARPI change, with a favourable safety profile. For patients with PSMA-positive metastatic castration-resistant prostate cancer who are being considered for a change of ARPI after progression on a previous ARPI, 177Lu-PSMA-617 may be an effective treatment alternative. FUNDING: Novartis.

4.
J Am Chem Soc ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39262277

RESUMEN

Detecting the ionic state at the solid-liquid interface is essential to reveal the various chemical and physical processes that occur at the interface. In this study, the adsorption states of the highly electronegative ions F- and OH- at the solid-liquid interface are detected by using the scanning tunneling microscopy break junction technique. With the active hydrogen atom of the amino group as a probe, the formed ionic hydrogen bonds are successfully detected, thereby enabling in situ monitoring of the ionic state at the solid-liquid interface. Through noise power spectral density analysis and theoretical simulations, we reveal the mechanism by which ionic hydrogen bonds at the interface affect the charge transport properties. In addition, we discover that the ionic state at the solid-liquid interface can be effectively manipulated by electric fields. Under high electric fields, the concentration of the anion near the electrode is higher, and the proportion of hydrogen bonds formed is greater than that under low electric fields. This study of the interfacial ionic state at the single-bond level provides guidance for the design of high-performance materials for energy conversion and environmental purification.

5.
Food Chem X ; 23: 101754, 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-39263339

RESUMEN

This study investigated the effects of incorporating different levels of Euglena gracilis microalgae powder (MP) on the dough properties, rheology, and quality attributes of Chinese steamed bread (CSB) for the first time. Moderate levels of MP (2%) reinforced the gluten network and improved protein structure, while higher levels (4-8%) adversely affected the gluten network and rheological properties. The addition of MP decreased the specific volume, pore number, and pore density of CSB, but increased pore size, hardness, and chewiness. It also imparted a yellow color to the CSB and slowed down moisture loss during storage. Notably, MP effectively increased the protein and lipid content of CSB, enhancing its nutritional value. The results suggest that optimizing the MP level is crucial to achieve nutritional enhancement while maintaining desirable texture and sensory attributes. An addition of 2% MP can strike a balance between nutrition and the overall quality of the final product.

6.
Front Oncol ; 14: 1382878, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39165684

RESUMEN

Background: Prolonged postoperative hospital stay following gastric cancer (GC) surgery is an important risk factor affecting patients' mood and increasing complications. We aimed to develop a nomogram to predict risk factors associated with prolonged postoperative length of stay (PLOS) in patients undergoing gastric cancer resection. Methods: Data were collected from 404 patients. The least absolute shrinkage and selection operator (LASSO) was used for variable screening, and a nomogram was designed. The nomogram performance was evaluated by the area under the receiver operating characteristic curve (AUC). The consistency between the predicted and actual values was evaluated via a calibration map, and the clinical application value was evaluated via decision curve analysis (DCA) and clinical impact curve analysis (CICA). Results: A total of 404 patients were included in this study. Among these patients, 287 were assigned to the training cohort, and 117 were assigned to the validation cohort. According to the PLOS quartile distance, 103 patients were defined as having prolonged PLOS. LASSO regression and logistic multivariate analysis revealed that 4 clinical characteristics, the neutrophil-lymphocyte ratio (NLR) on postoperative day one, the NLR on postoperative day three, the preoperative prognostic nutrition index and the first time anal exhaust was performed, were associated with the PLOS and were included in the construction of the nomogram. The AUC of the nomogram prediction model was 0.990 for the training set and 0.983 for the validation set. The calibration curve indicated good correlation between the predicted results and the actual results. The Hosmer-Lemeshow test revealed that the P values for the training and validation sets were 0.444 and 0.607, respectively, indicating that the model had good goodness of fit. The decision curve analysis and clinical impact curve of this model showed good clinical practicability for both cohorts. Conclusion: We explored the risk factors for prolonged PLOS in GC patients via the enhanced recovery after surgery (ERAS) program and developed a predictive model. The designed nomogram is expected to be an accurate and personalized tool for predicting the risk and prognosis of PLOS in GC patients via ERAS measures.

7.
J Integr Plant Biol ; 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39152659

RESUMEN

Coniferous forests are under severe threat of the rapid anthropogenic climate warming. Abies (firs), the fourth-largest conifer genus, is a keystone component of the boreal and temperate dark-coniferous forests and harbors a remarkably large number of relict taxa. However, the uncertainty of the phylogenetic and biogeographic history of Abies significantly impedes our prediction of future dynamics and efficient conservation of firs. In this study, using 1,533 nuclear genes generated from transcriptome sequencing and a complete sampling of all widely recognized species, we have successfully reconstructed a robust phylogeny of global firs, in which four clades are strongly supported and all intersectional relationships are resolved, although phylogenetic discordance caused mainly by incomplete lineage sorting and hybridization was detected. Molecular dating and ancestral area reconstruction suggest a Northern Hemisphere high-latitude origin of Abies during the Late Cretaceous, but all extant firs diversified during the Miocene to the Pleistocene, and multiple continental and intercontinental dispersals took place in response to the late Neogene climate cooling and orogenic movements. Notably, four critically endangered firs endemic to subtropical mountains of China, including A. beshanzuensis, A. ziyuanensis, A. fanjingshanensis and A. yuanbaoshanensis from east to west, have different origins and evolutionary histories. Moreover, three hotspots of species richness, including western North America, central Japan, and the Hengduan Mountains, were identified in Abies. Elevation and precipitation, particularly precipitation of the coldest quarter, are the most significant environmental factors driving the global distribution pattern of fir species diversity. Some morphological traits are evolutionarily constrained, and those linked to elevational variation (e.g., purple cone) and cold resistance (e.g., pubescent branch and resinous bud) may have contributed to the diversification of global firs. Our study sheds new light on the spatiotemporal evolution of global firs, which will be of great help to forest management and species conservation in a warming world.

8.
Heliyon ; 10(14): e34176, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39104480

RESUMEN

Objectives: This study aimed to summarize the existing literature on risk factors for arrhythmias after chemotherapy in cancer patients. To provide reliable evidence for treating arrhythmias after chemotherapy in oncology patients by assessing multiple biasing factors in the literature and quantifying the risk factors. Methods: The risk factors for arrhythmia following tumor chemotherapy were systematically collected from various reputable databases, including PubMed, Cochrane Library, MEDLINE, EMBASE, and multiple Chinese databases, covering the period from inception to May 2023. Two independent reviewers performed rigorous article screening, data extraction, and assessment of research quality. Data analysis was conducted using Review Manager 5.4 software, ensuring a standardized and robust approach to evaluate the gathered evidence. Results: The analysis of chemotherapy-induced arrhythmias included 16 articles, encompassing 14,785 cancer patients. Among the patients, 3295 belonged to the arrhythmia group, while 11,490 were in the non-arrhythmia group. These studies identified 12 significant risk factors associated with arrhythmias following chemotherapy in cancer patients. The findings of the analysis are as follows. General patient characteristics: The incidence of post-chemotherapy arrhythmias was 14.33 times higher in oncology patients aged ≥60 years compared to patients <60 years of age [OR = 14.33, 95%CI (8.51, 24.13), P<0.00001]. Patients with a smoking history exhibited a 1.67-fold higher risk of arrhythmia after chemotherapy [OR = 1.67, 95%CI (1.24, 2.25), P = 0.0007]. However, there was no significant correlation between gender and body mass index (BMI) with arrhythmia after chemotherapy in oncology patients (P = 0.52; P = 0.19). Disease-related factors: Patients with a history of hypertension, diabetes, and cardiovascular disease had a 1.93-fold, 1.30-fold, and 1.76-fold increased risk of arrhythmia after chemotherapy, respectively [OR = 1.93, 95%CI (1.66, 2.24), P<0.00001; OR = 1.30, 95%CI (1.10, 2.52), P = 0.002; OR = 1.76, 95%CI (1.51, 2.05), P<0.00001]. Additionally, the incidence of arrhythmia increased 1.97 times in patients with electrolyte and acid-base balance disorders following chemotherapy [OR = 1.97, 95%CI (1.41, 2.76), P<0.00001]. Chemotherapy-related factors: Seven articles examined the association between chemotherapy drugs and post-chemotherapy arrhythmias. The results indicated that oncology patients were 3.03 times more likely to develop arrhythmias with chemotherapy drugs compared to non-chemotherapy drugs [OR = 3.03, 95%CI (2.59, 3.54), P<0.00001]. Notably, anthracyclines and fluorouracil chemotherapy demonstrated a 2.98-fold and 3.35-fold increased risk of arrhythmia after chemotherapy, respectively [OR = 2.98, 95%CI (2.51, 3.03), P<0.00001; OR = 3.35, 95%CI (2.20, 5.10), P<0.00001]. The risk of arrhythmia after chemotherapy was 1.72 times higher in patients with chemotherapy cycles longer than 4 weeks than those with cycles shorter than 4 weeks [OR = 1.72, 95%CI (1.30, 2.28), P = 0.0001]. Conclusion: The occurrence of arrhythmia after chemotherapy in cancer patients was significantly associated with the patient's age, history of smoking, history of hypertension, history of diabetes, history of cardiovascular disease, chemotherapy drug use, and cycle. However, further high-quality evidence is needed to support these results.

9.
Zhongguo Gu Shang ; 37(8): 828-32, 2024 Aug 25.
Artículo en Chino | MEDLINE | ID: mdl-39183010

RESUMEN

OBJECTIVE: To investigate application of the Codamotion 2CX1 three-dimensional dynamic joint motion capture system to analyze the kinematic characteristics of patients with different degrees of meniscus injury. METHODS: From December 2020 to June 2022, 135 patients with meniscus injury and recruited normal people were collected, including 82 males and 53 females, aged 14 to 29 years old, with disease duration of 1 to 3 months. Combined with clinical symptoms and MRI examination, the diagnosis of meniscus injury was confirmed, and the patients were divided into stages, including 37 cases of grade 0(normal), 30 cases of gradeⅠ, 33 cases of gradeⅡ, 35 cases of grade Ⅲ according to Stoller grading standard. Subjects in each group were tested walking by using Codamotion 2CX1 three-dimensional dynamic joint motion capture system. Quantitative indexes of walking and kinematics were collected, including knee flexion and extension, internal and external rotation and internal and external turning, and their kinematics were analyzed. RESULTS: In the distribution of knee flexion/extension, there were significant differences in maximum knee flexion, minimum knee extension and knee flexion and extension range among 4 groups(P<0.05). In the distribution of internal/external rotation of knee joint, there were significant differences in the range of internal rotation and rotation of knee joint among 4 groups(P<0.05). In the distribution of internal/external turning of knee joint, there were significant differences in the range of internal and external turning of knee joint among 4 groups(P<0.05). The clinical stage progression was positively correlated with the range of motion of knee extension, external rotation, internal and external turning and turning range(P<0.05). It was negatively correlated with knee flexion, internal rotation, flexion extension and rotation range(P<0.05). The internal and external rotation angles of knee joint could be used as independent factors influencing the clinical stage of meniscus injury (P=0.006, 0.019<0.05). CONCLUSION: The knee movement of patients with meniscus injury has obvious changes, and the changes are different under different clinical stages. Gait analysis provides a reliable basis for the kinematic analysis of meniscus injury, helps to better understand the kinematic indexes of joints, and provides a reliable auxiliary diagnosis and treatment plan, which provides a new direction for the follow-up medical research.


Asunto(s)
Análisis de la Marcha , Humanos , Masculino , Femenino , Adulto , Fenómenos Biomecánicos , Adulto Joven , Adolescente , Análisis de la Marcha/métodos , Lesiones de Menisco Tibial/fisiopatología , Marcha , Articulación de la Rodilla/fisiopatología , Rango del Movimiento Articular
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(4): 1117-1120, 2024 Aug.
Artículo en Chino | MEDLINE | ID: mdl-39192407

RESUMEN

OBJECTIVE: To investigate the clinical characteristics and prognosis of primary bone marrow lymphoma. METHODS: The clinical data of 6 patients with primary bone marrow lymphoma admitted to Gansu Provincial People's Hospital from February 2011 to March 2023 were collected, and their clinical characteristics and prognosis were retrospectively analyzed and summarized. RESULTS: The median age of 6 patients was 61(52-74) years old. There were 2 males and 4 females. All patients had fever and abnormal blood routine examination. Physical examination and imaging examination showed no lymphadenopathy, no extranodal lesions in lung, gastrointestinal, liver and spleen, skin, etc. After strict exclusion of systemic lymphoma involvement in the bone marrow, the diagnosis was confirmed by bone marrow examination, 5 cases were primary myeloid diffuse large B-cell lymphoma and 1 case was primary myeloid peripheral T-cell lymphoma (NOS). 1 case abandoned treatment, 5 cases received CHOP-like or combined R regimen, including 1 case of autologous stem cell transplantation. 4 cases died and 2 case survived. The median OS was 5.5 (1-36) months. CONCLUSION: The prognosis of primary marrow lymphoma is poor, and bone marrow-related examination is an important means of diagnosis. Diffuse large B-cell lymphoma is the most common histomorphologic and immune subtype, and autologous hematopoietic stem cell transplantation may improve the prognosis.


Asunto(s)
Linfoma de Células B Grandes Difuso , Humanos , Masculino , Femenino , Pronóstico , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/terapia , Neoplasias de la Médula Ósea/terapia , Neoplasias de la Médula Ósea/diagnóstico , Médula Ósea/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(4): 1165-1172, 2024 Aug.
Artículo en Chino | MEDLINE | ID: mdl-39192414

RESUMEN

OBJECTIVE: To analyze the clinical characteristics and occurrence of thrombotic/bleeding events of patients with myeloproliferative neoplasm (MPN), and explore the main influencing factors, and create a risk prediction. METHODS: The clinical data of 126 MPN patients with BCR-ABL fusion gene negative in the Department of Hematology of Gansu Provincial Hospital from January 2016 to September 2021 were collected, and their clinical characteristics, occurrence of thrombotic/bleeding events and main influencing factors were analyzed and summarized retrospectively. Then, a risk prediction model for thrombotic/bleeding events in MPN patients was constructed. RESULTS: Among 126 MPN patients, 50 patients (39.7%) had experienced thrombotic/bleeding events, including 44 patients (34.9%) with thrombotic events and 6 patients (4.8%) with bleeding events. Among thrombotic diseases, cerebral thrombosis was the most common (23/44, 52.3%), followed by 9 cases of limb artery thrombosis mainly characterized by finger and toe tip artery ischemia, occlusion and gangrene (9/44, 20.5%). Bleeding events included intracerebral hemorrhage and gastrointestinal hemorrhage. Univariate analysis showed that hypertension, hyperhomocysteinemia, white blood cell (WBC) ≥10×109/L, hematocrit (HCT) ≥49%, platelet (PLT) ≥600×109/L and JAK2V617F gene mutation were risk factors for thrombotic/bleeding events in MPN patients, while CALR gene mutation was a protective factor. Multivariate analysis showed that hypertension and PLT≥600×109/L were independent risk factors for thrombotic/bleeding events in MPN patients. The goodness of fit of the constructed risk prediction model was 0.872, and the area under the ROC curve was 0.838. The model was validated with clinical data, the sensitivity, specificity and accuracy was 78.85%, 87.83% and 84.13%, respectively . CONCLUSION: The risk of thrombotic/bleeding events in MPN patients with high WBC count, hypertension and hyperhomocysteinemia is higher. Controlling hypertension and hyperhomocysteinemia and reducing WBC and PLT counts are helpful to prevent thrombotic/bleeding events and improve the life quality of patients.


Asunto(s)
Trastornos Mieloproliferativos , Trombosis , Humanos , Factores de Riesgo , Estudios Retrospectivos , Trombosis/etiología , Trastornos Mieloproliferativos/complicaciones , Hemorragia/etiología , Hipertensión/complicaciones , Hiperhomocisteinemia/complicaciones , Janus Quinasa 2/genética , Recuento de Leucocitos , Femenino , Masculino , Calreticulina/genética , Recuento de Plaquetas
12.
J Phys Chem Lett ; 15(34): 8910-8916, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39172035

RESUMEN

According to the classic superatom model, metal nanoclusters with a "magic number" of free valence electrons display high stability, manifesting as the closed-shell-dependent electronic robustness. The icosahedral nanobuilding blocks containing eight free electrons were the most common in constructing metal nanoclusters; however, the structure defect-dependent variations of the free electron count in icosahedral configurations are still far from thorough research. Here, we reported a hydride-containing [Pt2Ag15(SAdm)4(DPPOE)4H]2+ nanocluster with two largely defective Pt1Ag8 icosahedral cores. Together with previously reported complete or slightly defective icosahedra in metal nanoclusters, the largely defective Pt1Ag8 core provided important clues to reveal the evolutionary mode of structural defects and free electrons in icosahedral nanoclusters; the free electron count of icosahedron was reduced two-by-two (i.e., from 8e to 6e and then to 4e) accompanied by the structure defection. Overall, the work presented a novel Pt2Ag15 nanocluster with a largely defective core structure that enables an atomic-level understanding of the relationship between structural defects and free electrons in icosahedral nanoclusters.

13.
Chem Sci ; 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39170720

RESUMEN

The identification of targets for candidate molecules is a pivotal stride in the drug development journey, encompassing lead discovery, drug repurposing, and the scrutiny of potential off-target or side effects. Consequently, enhancing the precision of target prediction has significant implications. Moreover, current target prediction methods primarily rely on the principle of ligand-based chemical similarity, lacking the capture of novel compound-target relationships based on ligand high-level characterization similarity. Therefore, in this context, we introduce a pioneering algorithm known as the Fused Multiple Biological Signatures (FMBS) strategy. This approach leverages a Bayesian framework to amalgamate 25 predictable biological space characterizations of molecules to predict novel targets through scaffold hopping, thereby improving target prediction accuracy and providing a versatile tool for a wide range of small-molecule target prediction. When juxtaposed with alternative target prediction methods, FMBS showcases notable efficacy, outperforming traditional descriptors. Through an analysis of scaffold hopping cases, we elucidate how FMBS attains heightened accuracy by assimilating comprehensive and complementary high-dimensional signatures, thereby underscoring its potential in unearthing novel compound-target relationships. The findings underscore that our approach adeptly pinpoints promising candidate targets, thereby expediting drug mechanism exploration through the integration of multiple high-level characterizations.

14.
J Pain ; : 104645, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39089662

RESUMEN

Chronic neuropathic pain has been one of the prominent causes of disability, and acupuncture has shown promise in treatment. The present study aimed to characterize acupuncture modulation of chronic neuropathic pain and explore the related functional brain changes. Sixty chronic sciatica patients were divided into acupuncture- or sham acupuncture groups and received 10 sessions of treatment during 4 weeks. The visual analog scale for leg pain, oswestry disability index (ODI), and resting-state functional magnetic resonance images were assessed at baseline and after treatment. Then, fractional amplitudes of low-frequency fluctuations (fALFF) and support vector regression analyses were performed. Compared with sham acupuncture, acupuncture significantly improved symptoms, including visual analog scale for leg pain and ODI. In addition, acupuncture exhibited increased fALFF of the right superior parietal lobule (SPL) and right postcentral gyrus. Furthermore, the actual 4-week ODI values were positively correlated with the support vector regression-predicted values based on the right SPL fALFF and baseline clinical measurements. These results indicate that the spontaneous neural activity of the right SPL and right postcentral gyrus may be involved in the modulation of acupuncture in chronic neuropathic pain. In addition, the spontaneous neural activity of the right SPL might be used as the predictor of response to acupuncture therapy. PERSPECTIVE: This clinical neuroimaging study elucidated the neural basis of acupuncture in chronic sciatica. Neurological indicators and clinical measurements could be used as potential predictors of acupuncture response. This study combines neuroimaging and artificial intelligence techniques to highlight the potential of acupuncture for the treatment of chronic neuropathic pain. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR2100044585, http://www.chictr.org.cn.

15.
Pest Manag Sci ; 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39096082

RESUMEN

BACKGROUND: Peach brown rot caused by Monilinia fructicola severely affects the quality and yield of peach, resulting in large economic losses worldwide. Methyl benzimidazole carbamate (MBC) fungicides and sterol demethylation inhibitor (DMI) fungicides are among the most applied chemical classes used to control the disease but resistance in the target pathogen has made them risky choices. Timely monitoring of resistance to these fungicides in orchards could prevent control failure in practice. RESULTS: In the current study, we developed methods based on recombinase polymerase amplification (RPA) and CRISPR/Cas12a systems to detect MBC and DMI resistance based on the E198A mutation in the ß-tubulin (MfTub2) gene and the presence of the Mona element in the upstream region of the MfCYP51, respectively. For MBC resistance, RPA primers were designed that artificially incorporated PAM sites to facilitate the CRISPR/Cas12a reaction. Subsequently, specific tcrRNAs were designed based on the E198A mutation site. For the detection of the Mona element, we designed RPA primers M-DMI-F2/M-DMI-R1 that in combination with crRNA1 detected 'Mona' and distinguished resistant from sensitive strains. CONCLUSION: Both methods exhibited high sensitivity and specificity, requiring only a simple isothermal device to obtain results within 1 h at 37 °C. The FQ-reporter enabled visualization with a handheld UV or white light flashlight. This method was successfully used with purified DNA from lab cultures and crude DNA from symptomatic fruit tissue, highlighting its potential for on-site detection of resistant strains in orchards. © 2024 Society of Chemical Industry.

16.
Cardiovasc Toxicol ; 24(10): 1028-1036, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39136863

RESUMEN

Previous studies have found a possible association between nickel and metabolic syndrome (MetS), but with conflicting results. No studies have determined whether nickel exposure increases the prevalence of MetS in the general U.S. population. Therefore, we used data from the National Health and Nutrition Examination Survey (NHANES) to assess the association between urinary nickel and MetS. Since urinary nickel levels were presented as a skewed distribution, they were normalized using a logarithmic transformation. Weighted multivariate logistic models, restricted cubic spline, threshold effect analysis, and subgroup analyses were used to examine the association between urinary nickel concentration and the risk of MetS and its components. Based on data from 1577 participants, individuals in the second, third, and fourth quartiles of urinary nickel had an adjusted OR for MetS of 1.42 (95% CI: 0.88, 2.28), 2.00 (95% CI: 1.22, 3.28), and 1.68 (95% CI: 1.05, 2.70), respectively, representing an inverted "L"-shaped nonlinear dose-response relationship with an inflection point at 0.2141 ng/L. Patients over the age of 40, males, less educated, and smokers are more susceptible to nickel exposure. In addition, there were significant associations between nickel and most components of the MetS, with the strongest to weakest correlations being high fasting glucose, reduced high-density lipoprotein, abdominal obesity, and elevated blood pressure; however, there was no significant correlation between nickel and hyperlipidemia. In conclusion, environmental nickel exposure increases the prevalence of MetS in U.S. adults, particularly in males over 40 years of age, those with less education, and smokers.


Asunto(s)
Síndrome Metabólico , Níquel , Encuestas Nutricionales , Humanos , Síndrome Metabólico/epidemiología , Síndrome Metabólico/inducido químicamente , Síndrome Metabólico/diagnóstico , Níquel/orina , Níquel/efectos adversos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Estados Unidos/epidemiología , Prevalencia , Medición de Riesgo , Estudios Transversales , Adulto Joven , Anciano , Factores de Riesgo Cardiometabólico , Factores de Riesgo , Factores Sexuales , Factores de Edad
17.
Clin Oral Investig ; 28(9): 487, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39145865

RESUMEN

OBJECTIVE: To assess the influence of unilateral open disc repositioning surgery (ODRS) of the temporomandibular joint (TMJ) on the internal derangement (ID) of the contralateral joint. METHODS: Patients with bilateral ID of TMJ who underwent unilateral ODRS were enrolled and followed-up for one year. They were divided into two groups based on the contralateral disease: the anterior disc displacement with reduction (ADDWR) and without reduction (ADDWoR). Postoperative evaluation included clinical and MRI evaluation. Indices measured were unilateral intermaxillary distance (UID), visual analogue scale (VAS), disc length (DL), condylar height (CH), and disc-condyle angle (DCA). Paired t tests were used to compare the clinical and MRI indices between different time points. RESULTS: Ninety-six patients were enrolled, including 47 in the ADDWR group and 49 in the ADDWoR group. One-year post-surgery, ODRS led to significant increases in MMO, DL, and CH, and decrease in VAS and DCA on the operated side (P < 0.05). In ADDWR group, UID, DL, and CH increased significantly, and VAS decreased (P < 0.05), with no significant change in DCA (P > 0.05). In ADDWoR group, clinical and MRI variables worsened slightly, except for UID, which remained unchanged (P > 0.05). CONCLUSIONS: ODRS is a promising method for correcting TMJ ID and may improve condition of ADDWR and decrease progress of ADDWoR at the contralateral joint. Preoperative bilateral TMJ evaluation is essential for better outcomes. CLINICAL RELEVANCE: ODRS can effectively treat TMJ ID and produce adaptive changes in the contralateral ID, for which continuous monitoring of the contralateral joint is essential.


Asunto(s)
Imagen por Resonancia Magnética , Disco de la Articulación Temporomandibular , Trastornos de la Articulación Temporomandibular , Humanos , Femenino , Masculino , Estudios Prospectivos , Trastornos de la Articulación Temporomandibular/cirugía , Trastornos de la Articulación Temporomandibular/diagnóstico por imagen , Adulto , Disco de la Articulación Temporomandibular/cirugía , Disco de la Articulación Temporomandibular/diagnóstico por imagen , Resultado del Tratamiento , Luxaciones Articulares/cirugía , Luxaciones Articulares/diagnóstico por imagen , Persona de Mediana Edad , Dimensión del Dolor , Adolescente
18.
Kidney Dis (Basel) ; 10(4): 284-294, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39131882

RESUMEN

Introduction: Patients undergoing maintenance hemodialysis are vulnerable to coronavirus disease 2019 (COVID-19), exhibiting a high risk of hospitalization and mortality. Thus, early identification and intervention are important to prevent disease progression in these patients. Methods: This was a two-center retrospective observational study of patients on hemodialysis diagnosed with COVID-19 at the Lingang and Xuhui campuses of Shanghai Sixth People's Hospital. Patients were randomized into the training (130) and validation cohorts (54), while 59 additional patients served as an independent external validation cohort. Artificial intelligence-based parameters of chest computed tomography (CT) were quantified, and a nomogram for patient outcomes at 14 and 28 days was created by screening quantitative CT measures, clinical data, and laboratory examination items, using univariate and multivariate Cox regression models. Results: The median dialysis duration was 48 (interquartile range, 24-96) months. Age, diabetes mellitus, serum phosphorus level, lymphocyte count, and chest CT score were identified as independent prognostic indicators and included in the nomogram. The concordance index values were 0.865, 0.914, and 0.885 in the training, internal validation, and external validation cohorts, respectively. Calibration plots showed good agreement between the expected and actual outcomes. Conclusion: This is the first study in which a reliable nomogram was developed to predict short-term outcomes and survival probabilities in patients with COVID-19 on hemodialysis. This model may be helpful to clinicians in treating COVID-19, managing serum phosphorus, and adjusting the dialysis strategies for these vulnerable patients to prevent disease progression in the context of COVID-19 and continuous emergence of novel viruses.

19.
Onco Targets Ther ; 17: 629-642, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39131903

RESUMEN

Background: Anlotinib and apatinib, both vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs), are clinically established in the treatment of advanced non-small cell lung cancer (NSCLC) in China, with anlotinib emerging as a standard treatment strategy. This study was conducted to evaluate the efficacy and safety of apatinib and anlotinib, and to compare their differences in treating patients with advanced NSCLC. Patients and Methods: We retrospectively analyzed the data of patients with advanced NSCLC treated with apatinib or anlotinib at a hospital in Eastern China from January 2017 to December 2021. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profile. Results: A total of 145 patients were included in this study. Median PFS (mPFS) was 3.53 months for the apatinib group and 5.3 months for the anlotinib group (HR = 0.59, 95% CI: 0.41-0.84; P = 0.004), and median OS (mOS) was 7.6 months versus 15.6 months (HR = 0.68, 95% CI: 0.46-1.00; P = 0.048), which all showed significant differences after adjusting for confounders (P < 0.05). Subgroup analysis revealed that the presence or absence of bone metastases significantly influenced PFS in both treatment groups. The ORR was 3.03% in the anlotinib group versus 10.13% in the apatinib group (P = 0.12), the DCR was 72.73% versus 51.90% (P = 0.21). No unanticipated adverse events (AEs) were observed. The incidence of grade 3-4 AEs was significantly higher in the apatinib group (31.65% vs 13.64%, P < 0.05). Conclusion: Anlotinib demonstrated greater efficacy and safety compared to apatinib in the treatment of advanced NSCLC, particularly in patients with bone metastases and EGFR(-).

20.
Front Pediatr ; 12: 1440383, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39132306

RESUMEN

Background: Congenital absence of the gallbladder (CAGB) is an exceedingly rare embryological anomaly of the biliary system, with a complex etiology involving the failure of gallbladder formation during embryogenesis. Clinical manifestations are diverse; most patients are asymptomatic, while some present with symptoms such as biliary colic. The complexity of its clinical presentation and radiological features renders diagnosis challenging. Case presentation: Fetal ultrasound at 22 weeks of gestation revealed an absent gallbladder. At 9 years and 11 months of age, the child exhibited significant weight gain and abnormalities. Abdominal ultrasound and magnetic resonance images demonstrated fatty liver and gallbladder agenesis. Liver function tests indicated mild abnormalities, with aspartate aminotransferase at 67 IU/L and alanine aminotransferase at 44 IU/L. Following 6 months of hepatoprotective and lipid-lowering therapy, a satisfactory treatment response was achieved, with normalization of liver function and improvement in fatty liver. Conclusions: CAGB may be associated with other congenital abnormalities, although isolated cases are uncommon. Clinically, it may manifest as nonspecific biliary, gastrointestinal, or urinary symptoms, mimicking various digestive disorders and leading to misdiagnosis. Genetic sequencing and in-depth embryological research may elucidate the etiology and enhance diagnostic accuracy.

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