RESUMO
Alzheimer's disease (Alzheimer's disease, AD) is a progressive neurological disorder characterized by memory loss and cognitive impairment. It is characterized by the formation of tau protein neurofibrillary tangles and ß-amyloid plaques. Recent studies have found that mitochondria in neuronal cells of AD patients exhibit various dysfunctions, including reduced numbers, ultrastructural changes, reduced enzyme activity, and abnormal kinetics. These abnormal mitochondria not only lead to the loss of normal neuronal cell function, but are also a major driver of AD progression. In this review, we will focus on the advances of mitochondria and their multi-omics in AD research, with particular emphasis on how mitochondrial dysfunction in AD drives disease progression. At the same time, we will focus on summarizing how mitochondrial genomics technologies have revealed specific details of these dysfunctions and how therapeutic strategies targeting mitochondria may provide new directions for future AD treatments. By delving into the key mechanisms of mitochondria in AD related to energy metabolism, altered kinetics, regulation of cell death, and dysregulation of calcium-ion homeostasis, and how mitochondrial multi-omics technologies can be utilized to provide us with a better understanding of these processes. In the future, mitochondria-centered therapeutic strategies will be a key idea in the treatment of AD.
Assuntos
Doença de Alzheimer , Mitocôndrias , Doença de Alzheimer/metabolismo , Doença de Alzheimer/terapia , Humanos , Mitocôndrias/metabolismo , Animais , Genômica/métodos , Metabolismo Energético , Proteômica/métodosRESUMO
Purpose: This study aimed to assess the effectiveness and safety of intravitreal injection of conbercept (IVC) in treating moderate to severe nonproliferative diabetic retinopathy (NPDR), with or without accompanying diabetic macular edema. Methods: In this longitudinal retrospective study, 35 patients (50 eyes) with moderate to severe NPDR and Diabetic Retinopathy Severity Scale (DRSS) scores between 43 and 53 were treated at the Department of Ophthalmology, First Affiliated Hospital of Kunming Medical University, from October 2018 to January 2023. Treatment protocol included three monthly IVC injections followed by a pro re nata (PRN) regimen over a two-year follow-up period. Outcome measures were best-corrected visual acuity (BCVA), intraocular pressure, central macular thickness (CMT), extent of hard exudate (HE), and changes in DRSS scores. DRSS scores before and after treatment were analyzed using the Wilcoxon rank-sum test. Both systemic and ocular adverse events were meticulously documented to ascertain safety. Results: From baseline to the final follow-up, the mean BCVA improved from 0.41 ± 0.39 to 0.23 ± 0.20 logMAR (p<0.05). The mean CMT decreased from 306.22 ± 77.40 to 297.97 ± 88.15 µm (p = 0.385). At 24 months, DRSS scores improved by ≥1 stage in 40 eyes (80%), ≥ 2 stages in 28 eyes (56%), ≥3 stages in 10 eyes (20%), and remained stable in 6 eyes (12%). The DRSS scores at each follow-up interval demonstrated statistically significant improvement from baseline (p<0.05). In 15 of 27 eyes (55.56%) with diabetic macular edema (DME), there was a significant reduction in the mean area of HE from baseline (p<0.05). No serious systemic adverse events were observed. Conclusion: IVC is an effective and safe treatment for moderate to severe NPDR, demonstrating significant improvements in DRSS scores.
RESUMO
Quantifying the source contributions of sediments in large fluvial systems with active wind erosion problems has crucial implications for understanding morphological evolution and ecological progression in the Earth system. Much effort have been focused on characterizing sediments of the Yellow River, but quantitation of the sediment source proportions at the basin-wide scale is lacking. To this end, the research aims to quantitatively elucidate the potential source contributions of sediments in the Yellow River based on geochemical characteristics and sediment fingerprinting technique, in order to identify sedimentary mixing effect and propose sustainable development strategies. In total, samples of four source groups (n = 107) and target floodplain sediments (n = 61) were collected and tested for elemental composition, grain size, magnetic susceptibility, and quartz grain microtextures. The results indicated that the optimal tracer combination was determined as P, Zn, and Ca. The average contributions of the "Tibetan Plateau", "Sandy deserts-Loess Plateau", "Loess Plateau", and "Loess Plateau-Qinling Mountains" source groups to the target sediments were 23.0 %, 21.5 %, 31.6 %, and 23.9 %, respectively. The accuracy of source apportionments was supported by the goodness of fit (GOF) and virtual mixtures tests. Meanwhile, large amounts of debris from surrounding mountains was transported to the Loess Plateau through fluvial processes and ultimately mixed with aeolian deposits, leading to sedimentary mixing effect. To maintain water balance and minimize erosion risk, the drought-resistant perennial planting and moderate grazing were recommended. The findings are instrumental in promoting soil and water conservation and disclosing fluvial and aeolian interaction on a global scale.
RESUMO
Dry direct-seeded rice cultivation has gained popularity and expanded its cultivated area due to reduced labor requirements and water consumption. However, the impact of this cultivation method on cadmium (Cd) bioavailability in soil and the accumulation levels in grains remains uncertain. Field experiments were conducted in acidic soils at two locations in southern China to compare rice varieties and evaluate the dry direct-seeding method alongside the wet direct-seeding and traditional transplanting methods. Dry direct-seeded rice reached significantly higher Cd concentrations in its tissues starting from the heading stage than transplanted rice. Cd accumulation levels by the maturation stage in the brown rice of dry direct-seeded rice were 18.33 %-150.69 % higher than those of wet direct-seeded and transplanted rice, with a considerable ability to translocate Cd into brown rice. Furthermore, dry direct seeding decreased iron plaque formation, particularly in the amorphous Fe form; it resulted in high soil temperature and low moisture content during tillering, elevating Cd availability in the soil. Additionally, the proportion of ions and more labile forms of Cd in the soil solution was high. Moreover, the soil under dry direct seeding had high urease and acid phosphatase enzyme activities. However, low richness and diversity in the bacterial community were characterized by a significant increase in the relative abundance of Actinobacteria and Gammaproteobacteria at the class level, while exhibiting decreased relative abundances of Alphaproteobacteria, Bacilli, and KD4-96, along with fewer biomarkers. Nonetheless, these differences are gradually reduced during the maturation stage. Overall, although dry direct seeding offers several advantages, it is crucial to implement additional measures to mitigate the increased health risks linked to rice cultivation through this approach in Cd-contaminated areas.
Assuntos
Agricultura , Cádmio , Oryza , Poluentes do Solo , Solo , Oryza/metabolismo , Cádmio/metabolismo , Cádmio/análise , Poluentes do Solo/análise , Poluentes do Solo/metabolismo , China , Agricultura/métodos , Solo/química , Disponibilidade BiológicaRESUMO
Spontaneous abortion (SA) occurs in woman of childbearing age, jeopardizing their physical and mental health. Quercetin is a natural flavonoid, which exhibits a variety of pharmacological activities. However, the role and mechanisms of quercetin in SA still need to be further explored. Animal experiments were performed to examine the effect of quercetin in treating SA. Institute of Cancer Research mice were injected with lipopolysaccharide into the tail vein on the 7th day of gestation to establish a SA model. Gavage was performed during days 38 of gestation with high, medium and lowdose of quercetin. Then the effect of quercetin on embryos was evaluated. Animal experiment showed that quercetin could remarkably reduce the embryo loss rate and increase the mean weight of surviving embryos to some degree. Furthermore, network pharmacology was employed to explore the underlying mechanisms of quercetin in the treatment of SA. Several databases were used to collect the targets of SA and quercetin. Proteinprotein interaction network, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to elucidate the interactions between SA and quercetin. The relative mRNA expressions of several targets in uterine were detected by quantitative reverse transcriptase polymerase chain reaction (RTqPCR). Network pharmacology indicated that the effects of quercetin in treating SA were mainly related to hormone response and the modulation of defense response and inflammatory response, involving signaling pathways such as PI3KAkt, VEGF, MAPK and core targets such as AKT1, albumin, caspase3. RTqPCR showed that quercetin could upregulate AKT1, MAPK1, PGR, SGK1 and downregulate ESR1, MAPK3. The results showed that quercetin may modulate multiple signaling pathways by targeting core targets to prevent and treat SA.
Assuntos
Aborto Espontâneo , Experimentação Animal , Medicamentos de Ervas Chinesas , Humanos , Feminino , Gravidez , Animais , Camundongos , Quercetina/farmacologia , Lipopolissacarídeos/efeitos adversos , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Simulação de Acoplamento MolecularRESUMO
OBJECTIVE: Organisms and cellular viability are of paramount importance to living creatures. Disruption of the balance between cell survival and apoptosis results in compromised viability and even carcinogenesis. One molecule involved in keeping this homeostasis is serum-glucocorticoid regulated kinase (SGK) 1. Emerging evidence points to a significant role of SGK1 in cell growth and survival, cell metabolism, reproduction, and life span, particularly in prenatal programming and reproductive senescence by the same token. Whether the hormone inducible SGK1 kinase is a major driver in the pathophysiological processes of prenatal programming and reproductive senescence? METHOD: The PubMed/Medline, Web of Science, Embase/Ovid, and Elsevier Science Direct literature databases were searched for articles in English focusing on SGK1 published up to July 2023 RESULT: Emerging evidence is accumulating pointing to a pathophysiological role of the ubiquitously expressed SGK1 in the cellular and organismal viability. Under the regulation of specific hormones, extracellular stimuli, and various signals, SGK1 is involved in several biological processes relevant to viability, including cell proliferation and survival, cell migration and differentiation. In line, SGK1 contributes to the development of germ cells, embryos, and fetuses, whereas SGK1 inhibition leads to abnormal gametogenesis, embryo loss, and truncated reproductive lifespan. CONCLUTION: SGK1 integrates a broad spectrum of effects to maintain the homeostasis of cell survival and apoptosis, conferring viability to multiple cell types as well as both simple and complex organisms, and thus ensuring appropriate prenatal development and reproductive lifespan.
Assuntos
Glucocorticoides , Proteínas Imediatamente Precoces , Gravidez , Feminino , Humanos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Imediatamente Precoces/genética , Proteínas Imediatamente Precoces/metabolismo , ReproduçãoRESUMO
Seborrheic keratosis(SK) is a very common skin tumor which is mostly frequently observed in the trunck, head, neck. SK in the auricle is rare and this condition should be excluded the possibility of malignancy by pathologic diagnosis. We report a case of 66-year-old man who presented with a brownish, papillomatous, verrucous mass in the auricle for the past seven years, which began to growing faster during the previous year. Dermoscopy and histopathological examination were performed and the patient was diagnosed with SK. He was treated with the carbon dioxide(CO2) laser and aminolevulinate photodynamic therapy (ALA-PDT). The CO2 laser was used for the removal of the thick hypertrophic lesions and to enhance the transdermal absorption efficiency of ALA. A 20% ALA cream(118 mg/cm2) was applied to his lesion and sealed for 3 h without light, followed by irradiation with 630-nm LED light (96 J/cm2, 80 mw/cm2). We use fluorescent diagnosis with aminolevulinic acid to define the tumor margins at the first session of ALA-PDT. After 4 sessions of ALA-PDT, the lesion was completely removed and did not recur. Therefore, we consider that ALA-PDT combined with CO2 laser is a safe and effective choice for the treatment of seborrheic keratosis in the auricle.
Assuntos
Ceratose Seborreica , Lasers de Gás , Fotoquimioterapia , Masculino , Humanos , Idoso , Fotoquimioterapia/métodos , Dióxido de Carbono , Fármacos Fotossensibilizantes/uso terapêutico , Ceratose Seborreica/tratamento farmacológico , Ceratose Seborreica/cirurgia , Lasers de Gás/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Ácido Aminolevulínico/uso terapêuticoRESUMO
Objective: Genomic profiles relating to H101 treatment-induced alterations are yet to be achieved. Here, we evaluated the impact of H101 via exome-sequencing approaches aiming to probe for potential biomarkers that are actionable in the treatment of persistent/recurrent/metastatic (P/R/M) cervical cancer. Methods: Whole exome sequencing (WES) was performd on paired pre- and post-H101 samples from 17 P/R/M cervical cancer patients who received serial intra-tumor injections of H101. Somatic mutations, including high-frequency mutations, microsatellite instability (MSI) status, tumor mutation burden (TMB), clonal evolution, and mutational signature were analyzed. Results: The median follow-up time after the H101 treatment was 14 months. Complete response was achieved in 9 patients, 3 patients achieved partial response, and 2 patients had stable disease, resulting in an objective response rate (ORR) of 70.6% (95% CI: 46.4%-96.7%). WES analysis showed no difference in treatment-related mutation characteristics, including non-synonymous-SNVs and TMB status. Patients with lower TMB were correlated with improved H101 response rates (P=0.044), whereas the same was not evident in high MSI (MSI-H) versus non-MSI-H patients (P=0.528). We observed a few high-frequency mutation genes (TTN, KMT2D, ALDOA, DNAH7, ADAP1, PTPN23, and THEMIS2) that probably carry functional importance in response to H101 treatment, among which KMT2D and ADAP1 mutations were associated with inferior progression-free survival (PFS) and/or overall survival (OS) (P<0.05). Notably, H101 treatment-induced accumulating subclones or clusters in primary tumors and some (Signature 2) were associated with shorter PFS. Conclusion: We conducted an unprecedented work via a WES-based approach and provided preliminary insights into H101 treatment-induced genetic aberrations in which some genes (TTN, KMT2D, ALDOA, DNAH7, ADAP1, PTPN23, and THEMIS2) could be considered potential therapeutic targets of H101-containing treatment in cervical carcinoma. Moreover, the therapy-associated characteristics such as clonal evolution and a mutational signature may warrant further evaluation of H101 in clinical settings for treating cervical carcinoma.
Assuntos
Adenovírus Humanos , Carcinoma , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Resultado do Tratamento , Mutação , Instabilidade de Microssatélites , Genômica , Biomarcadores Tumorais/genéticaRESUMO
Subretinal fibrosis (SF) is an important cause of submacular neovascularization that leads to permanent vision loss, but has no effective clinical treatment. The present study examined the influence of metformin on SF, and investigated whether the mechanism involves the microRNA (miR)-140-3p/LIN28B/JNK/STAT3-mediated regulation of oxidative stress, angiogenesis and fibrosis-associated indicators. A mouse model of laser-induced SF was established. In addition, an ARPE-19 fibrotic cell model was established using TGF-ß1. A Cell Counting Kit-8 assay was used to examine cell viability. Flow cytometry was used to measure reactive oxygen species levels, and western blotting was used to detect the levels of proteins associated with epithelial-mesenchymal transition (EMT), signaling and fibrosis. The levels of superoxide dismutase, malondialdehyde, glutathione-peroxidase and catalase were measured using kits. Scratch assays and Transwell assays were used to assess cell migration and invasion, respectively, and reverse transcription-quantitative PCR was used to determine the levels of miR-140-3p and LIN28B. Dual-luciferase assays were used to verify the targeting relationship between miR-140-3p and LIN28B, and coimmunoprecipitation was used to confirm the interaction between LIN28B and JNK. Masson staining and hematoxylin and eosin staining were used to examine collagenous fibers and the histopathology of eye tissue. In ARPE-19 cells induced by TGF-ß1, metformin promoted miR-140-3p expression and inhibited LIN28B expression and JNK/STAT3 pathway activation, thereby inhibiting oxidative stress, EMT and fibrosis in ARPE-19 cells. The overexpression of LIN28B or treatment with the JNK/STAT3 agonist anisomycin partially reversed the inhibitory effect of metformin on oxidative stress and fibrosis in ARPE-19 cells. The dual-luciferase reporter assay and coimmunoprecipitation assay showed that miR-140-3p targeted the 3' untranslated region of LIN28B mRNA and inhibited LIN28B expression. LIN28B targeted and bound to JNK and regulated the JNK/STAT3 pathway. Therefore, it may be concluded that metformin can promote miR-140-3p expression, inhibit LIN28B and then inhibit the JNK/STAT3 pathway to alleviate SF.
RESUMO
N6-methyladenosine modifications (m6A) is one of the most abundant and prevalent post-transcriptional RNA modifications in plants, playing the crucial role in plant growth and development and stress adaptation. However, the m6A regulatory machinery in Aegilops_tauschii, the D genome progenitor of common wheat, is not well understood at present. Here, we systematically identified the m6A-related genes in Aegilops with a genome-wide search approach. In total, 25 putative m6A genes composed of 5 writers, 13 readers and 7 erasers were obtained. A phylogenetic analysis clearly grouped them into three subfamilies with the same subfamily showing similar gene structures and conserved domains. These m6A genes were found to contain a large number of cis-acting elements associating with plant hormones, regulation of growth and development as well as stress response, suggesting their widespread regulation function. Furthermore, the expression profiling of them was investigated using RNA-seq data to obtain stress-responsive candidates, of which 5 were further validated with a qPCR analysis. Finally, the genetic variation of m6A-related genes was investigated between Aegilops and D subgenome of wheat based on re-sequencing data, and an obvious genetic bottleneck occurred on them during the wheat domestication process. The promising haplotype association with domestication and agronomic traits was also detected. This study provided some insights on the genomic organization and evolutionary features of m6A-related genes in Aegilops, which will facilitate the further functional study and also contribute to broaden the genetic basis for genetic improvement in wheat and other crops.
RESUMO
Salinization of groundwater is a major challenge for groundwater management in long-term irrigation areas, decoupling its complex influencing factors can provide insights for the sustainable development of irrigation areas. In this study, the natural-human driving factors of groundwater salinization in the Yinchuan Plain, a typical irrigated area, were identified using isotope analysis, information entropy, and self-organizing map. Results show that groundwater in the study area is seriously salinized with obvious spatial heterogeneity. Multiple natural conditions and frequent human activities complicate the salinization characteristics of groundwater. On this basis, four typical natural influence units of groundwater were identified, namely, an evaporation and upward leakage zone, a runoff zone, an evaporation zone, and a runoff and upward leakage zone. Information entropy was proposed to quantify the complexity of groundwater resulting from human activities: The complexity difference between densely populated areas and natural dominant areas is mainly reflected in Na+, SO42-, and Cl-. Multiple human-made drivers of complex water environment were further separated into three patterns by the SOM model: blockage-evaporation type, leakage-evaporation type, and irrigation type. The blockage of drainage ditches and obstruction of salt discharge has the highest impact on the salinization of groundwater, followed by irrigation activities and transportation losses. Water excessive stagnation caused by blockage or irrigation is the root cause of groundwater salinization in the irrigated area, and its impact is greater than that of the traditional understanding of groundwater level rise. Based on the evaluation of irrigation water quality, management initiatives for irrigated areas should prioritize dredging and maintaining a healthy soil and groundwater environment in tandem.
Assuntos
Água Subterrânea , Poluentes Químicos da Água , Humanos , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Água Subterrânea/análise , Solo , Meio Ambiente , Irrigação Agrícola/métodosRESUMO
BACKGROUND: Adjuvant chemoradiotherapy (CRT) has been shown to reduce the risk of recurrence for patients with risk factors after radical hysterectomy (RH). Early initiated CRT could result in superior oncological outcomes. Here, we aimed to compare the survival outcome of intermediate- or high-risk cervical cancer (CC) patients who, received adjuvant CRT between minimally invasive surgery (MIS) and open surgery. METHODS: Data on stage IB1-IIA2 patients who underwent RH and postoperative CRT in our institution, from 2014 to 2017, were retrospectively collected. Patients with high or intermediate-risk factors who met the Sedlis criteria received sequential chemoradiation (SCRT). According to the surgical approaches, the enrolled patients were divided into MIS and open surgery groups. Then, the disease-free survival (DFS), overall survival (OS), and prognostic factors were analyzed. RESULTS: Among 129 enrolled CC patients, 68 received open surgery and 61 received MIS. The median time interval from surgery to chemotherapy and to radiotherapy was shorter in the MIS group (7 days vs. 8 days, P=0.014; 28 days vs. 35, P<0.001). Three-year DFS and OS were similar in both groups (85.2% vs. 89.7%, P=0.274; 89.9% vs. 98.5%, P=0.499). Further, sub-analysis indicated that the DFS and OS in intermediate/high-risk groups had no significant difference. Cox-multivariate analyses found that tumor size >4 cm and time interval from surgery to radiotherapy beyond 7 weeks were adverse independent prognostic factors for DFS. CONCLUSION: Based on the population we studied, for early-stage (IB1-IIA2) CC patients with intermediate- or high-risk factors who received postoperative SCRT, although the difference was not significant, the DFS and OS in the MIS group were slightly lower than the ORH group, and tumor size >4 cm and delayed adjuvant radiotherapy beyond 7 weeks were risk factors for recurrence.
Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias do Colo do Útero/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Quimiorradioterapia AdjuvanteRESUMO
Deregulation of NEK2(NIMA-related serine/threonine 2) confers chemotherapeutic resistance to apoptosis and is closely correlated with poor prognosis in hepatocellular carcinoma (HCC). Here, we find that nanoparticles are prepared through hemisynthesis from natural nitidine chloride (NC) with enhanced antitumor activity. Nitidine chloride nanoparticle (TPGS-FA/NC) treatment show good therapy effect in Li-7 hepatocellular carcinoma cells. Additionally, molecular docking technologies are aimed at NEK2 protein (PDB ID: 6SGD) to analyze the detailed binding interactions with the potent target. NC participates in interactions with Asp159 residue. These studies advance the understanding of the modification of nitidine chloride substituent and provide useful drug design information for liver cancer treatment.
RESUMO
BACKGROUND: Stemness of CD133+EPCAM+ hepatocellular carcinoma cells ensures cancer resistance to apoptosis,which is a challenge to current liver cancer treatments. In this study, we evaluated the tumorcidal activity of a novel nanoparticle of nitidine chloride (TPGS-FA/NC, TPGS-FA: folic acid modified D-α-tocopheryl polyethylene glycol 1000 succinate, NC: nitidine chloride), against human hepatocellular carcinoma (HCC) cell line Huh7 growth in vitro and in vivo. METHODS: Huh7 cells were treated with TPGS-FA/NC. Cell proliferation was assessed using MTT and colony assays. The expression of cell markers and signaling proteins was detected using western blot analyses. A sphere culture technique was used to enrich cancer stem cells (CSC) in Huh7 cells. TPGS-FA/NC (7.5, 15, 30, 60, 120 µg/mL) dose-dependently inhibited the proliferation of HCC cells, which associated with a reduction in AQP3 and STAT3 expression. Importantly,TPGS-FA/NC (10, 20, and 40 µg/mL) significantly reduced the EpCAM+/CD133+cell numbers, suppressed the sphere formation. The in vivo antitumor efficacy of TPGS-FA/NC was proved in Huh7 cell xenograft model in BALB/c nude mice, which were administered TPGS-FA/NC(4 mg· kg - 1· d - 1, ig) for 2 weeks. RESULTS: TPGS-FA/NC dose-dependently suppressed the AQP3/STAT3/CD133 axis in Huh7 cells. In Huh7 xenograft bearing nude mice, TPGS-FA/NC administration markedly inhibited Huh7 xenograft tumor growth . CONCLUSIONS: TPGS-FA/NC inhibit HCC tumor growth through multiple mechanisms, and it may be a promising candidate drug for the clinical therapy of hepatocellular carcinoma.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Células-Tronco Neoplásicas , Antígeno AC133/metabolismo , Animais , Benzofenantridinas , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Molécula de Adesão da Célula Epitelial , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Nus , Nanopartículas/administração & dosagem , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologiaRESUMO
Background: To assess the efficacy and safety of recombinant human adenovirus type 5 (H101) in patients with persistent, recurrent, or metastatic gynecologic malignancies. Methods: The study retrospectively enrolled patients with persistent/recurrent/metastatic gynecologic malignancies who received H101-containing treatment at The First Affiliated Hospital of Xi'an Jiaotong University from September 1, 2019 to September 30, 2021. H101 was injected intratumorally into target lesions and dosage was calculated based on tumor diameter once a day for five consecutive days. The primary endpoint was local control (LC) rate. Secondary endpoints included objective response rate (ORR), duration of response (DOR) and progression-free survival (PFS). Safety was the exploratory endpoint. Depending on prior treatment, patients received H101 either as monotherapy or as a combination therapy. Results: Totally, 29 patients were enrolled in the study. Median follow-up was 6.3 months (range: 3.2-27.9) from data analysis cut-off on December 31, 2021. The LC rate at 3 months was 44.8%, while ORR was 72.4%. Median DOR and PFS rates were not determined. The DOR rate, PFS rate at 6 and 12 months were 88.1%, 74.6% and 70.5%, 62.2%, respectively. Responses were observed in all four cancer types. Most treatment-related adverse events (90.5%) were grade 1 or 2, with the most common being fever (70%). Clinically significant adverse events were uncommon (7.9% in grade 3 and 1.6% in grade 4). No treatment-related deaths occurred. Conclusion: Our study showed that H101 (either monotherapy or combination therapy) has promising efficacy and favorable safety in patients with persistent, recurrent, metastatic gynecologic malignancies.
RESUMO
Salinization of irrigation areas is a global environmental challenge. The uncertainty in the distribution of salinization is increased by the complexity of the natural environment. This study adopted Yinchuan Plain as a typical irrigation area to study the relationship between soil salinity and the environment from the perspective of macro-environmental elements and micro-ion composition. A Geographic Weighted Regression model (GWR) was used to predict the risk of salinization in the Yinchuan Plain. The results showed obvious spatial variation in soil salinization in the Yinchuan Plain. Farmland accounted for the largest proportion of salinized land area, followed by woodland and "other" land use categories. The main characteristic ions in the salinized area of the Yinchuan Plain were SO42-, K++Na+and Cl-. The rank of ions in terms of change rate with increasing soil salinity was: SO42- > K+ + Na+ > Cl- > Ca2+ > HCO3- > Mg2+ > CO32-. However, the rank of ions in terms of their sensitivity to salinization was: HCO3- > Ca2+ > Mg2+ > SO42- > Cl- > K+ + Na+. On this basis, the geographical indicators of DEM and NDVI, groundwater indicators of groundwater depth and TDS, climate indicators of SPEI, as well as soil indicators of PH and organic matter were taken as the representative ecological drivers of salinization in irrigation areas. These environmental factors were found to control the distribution of salinization, whereas human activity affected the degree of change in salinization. The enrichment of SO42- in the Yinchuan Plain was mainly related to agricultural activities (such as pesticides application and irrigation evaporation), and followed by phreatic evaporation. The salt ions carried by irrigation and rainfall further polluted phreatic water. In the end, the measures of optimizing drainage, combined irrigation, and improving planting layout were recommended for the effectively and economically controlling of salinization.
Assuntos
Água Subterrânea , Poluentes Químicos da Água , Irrigação Agrícola/métodos , China , Monitoramento Ambiental/métodos , Água Subterrânea/química , Humanos , Salinidade , Solo , Poluentes Químicos da Água/análiseRESUMO
OBJECTIVE: The aim of this study was to assess the efficacy and safety of intrapleural perfusion with hyperthermic chemotherapy (IPHC) in treating malignant pleural effusion (MPE) compared to normothermic chemoperfusion of the pleural cavity (NCPC), and to investigate the better treatment to control MPE. METHODS: Malignant pleural effusion patients were enrolled in the study and treated with NCPC or IPHC under video-assisted thoracoscopic surgery (VATS). The chest drainage duration, clinical characteristics, and recurrence time of pleural effusion of patients were collected for statistical analysis. The chi-squared test and the Fisher's exact test were applied to compare the distribution differences in categorical variables. Progression-free survival (PFS) was estimated by the Kaplan-Meier method and was compared by the log-rank test. The survival analysis was performed using the Cox proportional hazards method. RESULTS: A total of 37 MPE patients were enrolled in this study. Twenty-seven patients received NCPC and 10 patients received IPHC under VATS. Significant differences were found in pathological types (p = 0.011), chest drainage duration (p = 0.005), and remission rate (p = 0.009) between two different treatment groups. The chest drainage duration of IPHC under VATS was shorter than the NCPC group (t = 2.969, p = 0.005). The remission rate of MPE in IPHC group was better than the NCPC one (OR = 0.031, 95% CI: 0.002-0.507, p = 0.015). The result of the Kaplan-Meier method showed that IPHC group could significantly prolong the PFS of patients with MPE compared to NCPC group (log-rank p = 0.002). Univariate cox regression analysis showed that patients with MPE in the IPHC group presented significant longer PFS than the NCPC group (HR = 0.264, 95% CI: 0.098-0.713, p = 0.009). Multivariate cox regression analysis further verified this conclusion (HR = 0.268, 95% CI: 0.096-0.753, p = 0.012). CONCLUSION: Compared to the NCPC, the IPHC under VATS presents a better control effect on MPE, shorter tube placement time, and longer complete remission time. For this reason, we recommend IPHC under VATS as the first-line treatment for patients with MPE those who can tolerate minimally invasive surgery.
Assuntos
Hipertermia Induzida , Perfusão/métodos , Cavidade Pleural/efeitos dos fármacos , Derrame Pleural Maligno/terapia , Cirurgia Torácica Vídeoassistida , Idoso , Antineoplásicos/administração & dosagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Perfusão/efeitos adversos , Modelos de Riscos Proporcionais , Resultado do TratamentoRESUMO
Groundwater is an important water resource in arid and semi-arid regions. The impact of human activities on groundwater is increasing. After 60 years running, the groundwater quality and its formation mechanism are imperative questions needed to be answered in Jiaokou Irrigation District, Guanzhong Basin, China. In this study, the quality of groundwater in Jiaokou Irrigation District was assessed by a new integrated-weight water quality index (IWQI), and the groundwater chemistry is studied through integrated statistical, geostatistical and hydrogeochemical approaches. The patterns for the average anion and cation concentrations were HCO3- > SO42- > Cl- > NO3- > CO32- > NO2-, and Na+ > Mg2+ > Ca2+ > K+ > NH4+, respectively. Statistics showed that the major water chemistry types were HCO3-Na, SO4·Cl-Na, and Cl·SO4-Na. A new integrated-weight water quality index (IWQI) was proposed based on the entropy-weighted method and CRITIC method and showed excellent performance for explaining and evaluating the groundwater quality. The IWQI results show 65.33% of groundwater, mainly distributed in the central and western parts of this study area, was unsuitable for drinking. Furthermore, SO42ï¼, HCO3ï¼, Clï¼, NO3ï¼, and Na+ had more important effects on groundwater quality. The weathering process affecting groundwater quality in the study area is carbonate dissolution, followed by silicate weathering and evaporite dissolution, whereas the major geochemical processes include the dissolution and precipitation of calcite, as well as the dissolution of dolomite and gypsum (anhydrite). Cation exchange also plays an important role in the hydrogeochemical evolution of groundwater with a long residence time. Anthropogenic activities affecting groundwater quality included long-term irrigation infiltration and excessive use of fertilizers. The findings and the results of the study can improve understanding of the processes driving groundwater chemistry in Jiaokou Irrigation District, and can be used for reference to other similar regions in the world.
Assuntos
Monitoramento Ambiental , Poluentes Químicos da Água/análise , Ânions , Carbonato de Cálcio , Carbonatos/análise , China , Fertilizantes/análise , Água Subterrânea/análise , Água Subterrânea/química , Humanos , Magnésio , Qualidade da Água , Tempo (Meteorologia)RESUMO
The study proposes a new set pair analysis - variable fuzzy improved model (SPA-VFIM) by integrating the set pair analysis (SPA), variable fuzzy sets (VFS) theory, and binary semantic (BS). The SPA-VFIM method gets over the shortcomings of the existing SPA and VFS methods. The use of BS solves the problem of the weighted average principle (WAP) not being conducive to the timeliness of assessment. The existing and newly proposed methods were used to evaluate the groundwater quality in the Jiaokou Irrigation District, China, to show the advantages of the SPA-VFIM method. The results of SPA-VFIM method show that more than 80% of the groundwater, mainly distributed in the central and western parts of the study region, is assessed as level IV and level V, according to the Chinese Groundwater Quality Standards (GB/T 14848-2017). The assessment results are consistent with ground-based measurements of water quality, and NO3-, Na+, SO42-, Total Hardness (TH), and Cl- are the main pollutants. The SPA-VFIM and existing methods were compared. The results indicate that 57.69% and 76.92% of the assessment results by the SPA-VFIM method agree well with that of the SPA and VFS methods, respectively, indicating that the new SPA-VFIM method is reasonable and effective in groundwater quality. The results of groundwater quality assessment show that local authorities should pay more attention to areas with poor and very poor groundwater quality. These findings are beneficial to the future groundwater management plans dealing with drinking and irrigation and the sustainable development of water resources in this irrigation district.
RESUMO
Clear cell adenocarcinoma (CCAC) of the uterine cervix is a rare histological subtype of cervical cancer. The optimal treatment paradigm for this tumor has not yet been established. In recent years, oncolytic viruses have become a promising strategy for cancer treatment. However, the role of oncolytic viruses in treating CCAC of the uterine cervix is unclear. We report a case study of a 19-year-old woman with locally advanced CCAC of the uterine cervix. The patient was first treated with external beam radiation therapy (50 Gy/25 f) and chemotherapy (cisplatin, 40 mg/m2/week, 5 weeks) with only slight reduction of the cervical tumor (45 mm × 34 mm × 51 mm). After receiving one cycle of intratumor injection therapy of Oncorine (5.0×1011 virus particles daily, from day 1 to day 5), her cervical tumor was dramatically reduced (29 mm × 26 mm × 24 mm). Subsequently, the patient received two cycles of intratumor injection therapy of Oncorine combined with brachytherapy (7 fractions) and chemotherapy (cisplatin and paclitaxel). No serious adverse events occurred during treatment. The results at the 7-month follow-up showed that the patient achieved complete response. Our case was a successful exploration of Oncorine in the treatment of locally advanced CCAC of the uterine cervix, which supports the use of oncolytic viruses as a promising treatment option for young women with this tumor.