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1.
J Ethnopharmacol ; 282: 114582, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34492322

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Due to the modernization of traditional Chinese medicine (TCM) and the influence of traditional medication habits (TCM has no toxicity or side effects), arsenic poisoning incidents caused by the abuse of realgar and realgar-containing Chinese patent medicines have occurred occasionally. However, the potential mechanism of central nervous system toxicity of realgar remains unclear. AIM OF THE STUDY: This study aimed to clarify the specific mechanism of realgar-induced neurotoxicity. MATERIALS AND METHODS: In this study, the roles of ERK1/2 and p38 MAPK in realgar-induced neuronal autophagy and overactivation of the nuclear factor erythroid-derived factor 2-related factor (Nrf2) signalling pathways was investigated in vivo and in vitro. RESULTS: The arsenic in realgar passed through the blood-brain barrier and accumulated in the brain, resulting in damage to neurons, synapses and myelin sheaths in the cerebral cortex and a decrease in the total antioxidant capacity. The specific mechanism is that the excessive activation of Nrf2 is regulated by the upstream signalling molecules ERK1/2 and p38MAPK. At the same time, p38 MAPK and ERK1/2 interfere with autophagy, thereby promoting autophagy initiation but causing subsequent dysfunctional autophagic degradation and inducing the p62-Keap1-Nrf2 feedback loop to promote Nrf2 signalling pathway activation and nerve cell apoptosis. CONCLUSIONS: This study confirmed the role of the signalling molecules p38 MAPK and ERK1/2 in perturbing autophagy and inducing the p62-Keap1-Nrf2 feedback loop to activate the Nrf2 signalling pathway in realgar-induced neurotoxicity.

2.
Cell Death Dis ; 12(10): 911, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34615856

RESUMO

Sphingolipid metabolic dysregulation has increasingly been considered to be a drug-resistance mechanism for a variety of tumors. In this study, through an LC-MS assay, LIM and SH3 protein 1 (LASP1) was identified as a sphingolipid-metabolism-involved protein, and short-chain enoyl-CoA hydratase (ECHS1) was identified as a new LASP1-interacting protein through a protein assay in colorectal cancer (CRC). Gain- and loss-of-function analyses demonstrated the stimulatory role played by ECHS1 in CRC cell proliferation, migration, and invasion in vitro and in vivo. Mechanistic studies of the underlying tumor-supportive oncometabolism indicate that ECHS1 enables altering ceramide (Cer) metabolism that increases glycosphingolipid synthesis (HexCer) by promoting UDP-glucose ceramide glycosyltransferase (UGCG). Further analysis showed that ECHS1 promotes CRC progression and drug resistance by releasing reactive oxygen species (ROS) and interfering mitochondrial membrane potential via the PI3K/Akt/mTOR-dependent signaling pathway. Meanwhile, the phenomenon of promoting the survival and drug resistance of CRC cells caused by ECHS1 could be reversed by Eliglustat, a specific inhibitor of UCCG, in vitro and in vivo. IHC assay showed that ECHS1 was overexpressed in CRC tissues, which was related to the differentiation and poor prognosis of CRC patients. This study provides new insight into the mechanism by which phospholipids promote drug resistance in CRC and identifies potential targets for future therapies.

3.
Chemosphere ; 287(Pt 1): 132075, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34474378

RESUMO

Influence of land use type and urbanization level on the distribution of pharmaceuticals and personal care products (PPCPs) from the developed regions of Beijing-Tianjin-Hebei in the northern China was evaluated. The seasonal and spatial variations of the 22 target PPCPs were analyzed in the 63 sampling sites along the whole Beiyun River Basin. Results showed that the total PPCPs concentration had a wide variation range, from 132 ng L-1 to 25474 ng L-1. Spatial interpolation analysis showed that agricultural land presented higher PPCPs contamination level than build-up land (p < 0.05) and the concentration was negatively correlated with urbanization level. Source apportionment showed the untreated sewage source contributed to 34%-53% of the PPCPs burden in the Beiyun River. Risk assessment indicated that diethyltoluamide, carbamazepine, octocrylene, gemfibrozil and triclocarban had high risks (RQ > 1), and small tributaries had the highest mixed risk (MRQ = 34). Species sensitivity distribution combined with the safety threshold method showed that PPCPs would have potential risk on aquatic organisms even at very low concentrations and triclocarban posed the highest risk in the Beiyun River.

4.
Sci Total Environ ; 802: 149891, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34474296

RESUMO

Animals exposure to polychlorinated biphenyls (PCBs) may result in retention of hydroxylated PCBs (OH-PCBs). OH-PCBs can be accumulated in animals, including humans, through the transmission of food chain. However, there are few studies on the accumulation and metabolism of OH-PCBs exposed to the body through daily diet. Therefore, this study was conducted to investigate the fate of OH-PCBs after being ingested through dietary intake. By adding 3-OH-PCB101 and 4-OH-PCB101 to the edible tissue of crucian carp, which were used as raw materials to prepare mouse feed, with an exposure concentration of 2.5 µg/kg ww. The exposure experiment lasted for a total of 80 days. The blood, feces and 11 tissues of mice at different times were analyzed qualitatively and quantitatively. It was found that major OH-PCB101 were accumulated in intestine or excreted with feces. A small part was accumulated in heart, lung and spleen. For the first time that the conversion from OH-PCB101 to PCB101 in mice was discovered, which shows from another perspective that persistent organic pollutants are difficult to be completely degraded in the environment. 4-MeO-PCB101, 3-MeSO2-PCB101, and 4-MeSO2-PCB101 were also found in various tissues. The results of this study show that after OH-PCBs accumulated in animals re-enter the organism through the food chain, they can be metabolized again and may be reversely transformed into the parent compounds. The present research shed new light on simulating the metabolic transformation process of OH-PCBs exposed to mammals through ingestion of fish. Available data show that second-generation persistent organic pollutants in the environment still need to be continuously concerned.

5.
Curr Med Sci ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34515914

RESUMO

OBJECTIVE: To study data about SARS-CoV-2 virus shedding and clarify the risk factors for prolonged virus shedding. METHODS: Data were retrospectively collected from adults hospitalized with laboratory-confirmed coronavirus disease-19 (COVID-19) in Wuhan Union Hospital. We compared clinical features among patients with prolonged (a positive SARS-CoV-2 RNA on day 23 after illness onset) and short virus shedding and evaluated risk factors associated with prolonged virus shedding by multivariate regression analysis. RESULTS: Among 238 patients, the median age was 55.5 years, 57.1% were female, 92.9% (221/238) were administered with arbidol, 58.4% (139/238) were given arbidol in combination with interferon. The median duration of SARS-CoV-2 virus shedding was 23 days (IQR, 17.8-30 days) with a longest one of 51 days. The patients with prolonged virus shedding had higher value of D-dimer (P=0.002), IL-6 (P<0.001), CRP (P=0.005) and more lobes lung lesion (P=0.014) on admission, as well as older age (P=0.017) and more patients with hypertension (P=0.044) than in those the virus shedding less than 23 days. Multivariate regression analysis revealed that prolonged viral shedding was significantly associated with initiation arbidol >8 days after symptom onset [OR: 2.447, 95% CI (1.351-4.431)], ≥3 days from onset of symptoms to first medical visitation [OR: 1.880, 95% CI (1.035-3.416)], illness onset before Jan. 31, 2020 [OR: 3.289, 95% CI (1.474-7.337)]. Arbidol in combination with interferon was also significantly associated with shorter virus shedding [OR: 0.363, 95% CI (0.191-0.690)]. CONCLUSION: Duration of SARS-CoV-2 virus shedding was long. Early initiation of arbidol and arbidol in combination with interferon as well as consulting doctor timely after illness onset were helpful for SARS-CoV-2 clearance.

7.
J Hazard Mater ; 423(Pt B): 127048, 2021 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-34537642

RESUMO

Bifunctional oxygen-doped graphitic carbon nitride (OCN) was fabricated to activate peroxymonosulfate (PMS) for degrading imidacloprid (IMD). The modulated electronic structure of OCN promoted the adsorption, electron transfer, and formation of the redox site of PMS. The light absorption capacity, and the separation and migration speed of photogenerated carriers of OCN were increased. Consequently, 94.5% of IMD (3.0 mg/L) was removed by OCN-10/PMS process in 2.0 h. Compared with g-C3N4/PMS (0.048 h-1), the IMD degradation rate constant of OCN-10/Vis/PMS system (1.501 h-1) was increased by 30.3 times. The PMS oxidation on electron-deficient C atoms and holes, the PMS reduction around electron-rich O atoms and photogenerated electrons, and the multiple reactions of superoxide radical were the sources of the main active species singlet oxygen. Moreover, even under different pH conditions, coexisting anions, humic acid, and other neonicotinoid pesticides, the OCN-10/Vis/PMS system still showed acceptable applicability. Finally, mass spectrometry identified that hydroxylation and N-dealkylation of amines were the primary degradation pathways of IMD. This paper demonstrates an environmental-friendly combined activation strategy of PMS that can be operated day and night with low energy consumption, aiming to pave the way for developing metal-free photocatalysts for high-efficient environmental purification based on advanced oxidation coupling technology.

8.
J Hematol Oncol ; 14(1): 149, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34530888

RESUMO

CD19 chimeric antigen receptor (CAR)-T cells have been used to treat patients with refractory chronic lymphocytic leukemia (CLL). However, approximately 50% of patients do not respond to this therapy. To improve the clinical outcome of these patients, it is necessary to develop strategies with other optimal targets to enable secondary or combinational CAR-T cell therapy. By screening a panel of surface antigens, we found that CD32b (FcγRIIb) was homogeneously expressed at high site density on tumor cells from CLL patients. We then developed a second-generation CAR construct targeting CD32b, and T cells transduced with the CD32 CAR efficiently eliminated the CD32b+ Raji leukemic cell line in vitro and in a mouse xenograft model. Furthermore, CD32b CAR-T cells showed cytotoxicity against primary human CLL cells that were cultured in vitro or transplanted into immunodeficient mice. The efficacy of CD32b CAR T cells correlated with the CD32b density on CLL cells. CD32b is not significantly expressed by non-B hematopoietic cells. Our study thus identifies CD32b as a potential target of CAR-T cell therapy for CLL, although further modification of the CAR construct with a safety mechanism may be required to minimize off-target toxicity.

9.
Huan Jing Ke Xue ; 42(10): 4698-4707, 2021 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-34581112

RESUMO

Land use is an important factor affecting non-point nutrient loading. Here, the Wuxi River basin was selected to analyze the influence of sub-basin land use on nutrient concentrations using remotely sensed land use data and monthly river water quality variables from October 2019 to September 2020. The results showed that the water quality of the river was closely related to land-use type. Specifically, dryland farmland, villages, and building land have a strong promoting influence on nitrogen, phosphorus, organic carbon, and phytoplankton chlorophyll a. The proportion of orchard land was also positively correlated with river nutrient concentrations. A negative correlation was observed between the proportion of forest land and nutrient concentrations. Moreover, the proportion of the water area in rivers and reservoirs was negatively correlated with the total dissolved nitrogen and nitrate concentrations in the river, and the proportion of the water area in natural pits and fishponds was negatively correlated with river nitrate and ammonia concentrations. Furthermore, the proportion of river and fishpond areas was positively correlated with the concentration of dissolved total phosphorus, dissolved organic carbon, and the permanganate index, while the proportion of the natural pond area was positively correlated with the concentration of particulate phosphorus and phytoplankton chlorophyll a. The influence of land-use types on water quality was also affected by distance from the river. This research indicates that the appropriate utilization of land and wetlands is key to controlling non-point nutrient loading in the river network, including Lake Taihu. Specifically, the self-purification capacity of wetland waters should be incorporated into nutrient control schemes, and special attention should be paid to the reduction of non-point source pollution in the drylands along the downstream riverbanks and urbanized areas.


Assuntos
Lagos , Poluentes Químicos da Água , China , Clorofila A , Monitoramento Ambiental , Nitrogênio/análise , Nutrientes , Fósforo/análise , Poluentes Químicos da Água/análise
10.
Huan Jing Ke Xue ; 42(10): 4739-4752, 2021 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-34581116

RESUMO

Monthly datasets of ecological indicators from 2010 to 2020 in Shahe Reservoir, Tianmuhu, China, were examined to reveal the long-term variations in water ecological security and its driving factors. The results of Secchi disk depth(SD) measurements revealed significantly spatial variation(P<0.05) within the reservoir. The highest SD was recorded in the downstream-linked reservoir, and the lowest SD was recorded in the upstream tributaries. In contrast, the values of other water ecological indicators were higher in the upstream tributaries than in the transition region and the downstream-linked reservoir area. In summer and autumn, the SD was low, while the concentrations of total phosphorous(TP), chlorophyll a(Chl-a), the permanganate index, and cyanobacterial biomass(BMc) were high. During the thermal stratification period from May to September, the concentrations of 2-methylisoborneol(MIB) and Chl-a were highest at a depth of 4 m, while diatom biomass(BMb) and BMc reached their maximum at depths of 2 m and 0.5 m, respectively. Therefore, spatial and temporal variations should be fully considered when evaluating aquatic ecological security. Focusing on spring and summer, when the risk of water ecological security was high, Chl-a combined with SD and MIB along with their correlation with other water quality indexes, was used to evaluate and optimize the ecological security of Shahe Reservoir. The evaluation results showed that the aquatic ecological security of the reservoir was excellent over the last 10 years; however, annual fluctuations have been large and the evaluation scores were spatially variable. While seasonal sampling strategies focusing on three layers depths are economical and reliable for lake regions with thermal stratification, our results indicate that tailored monitoring may be required to determine the aquatic ecological security of lakes and reservoirs. In Shahe Reservoir, the decrease in the SD and the increase in MIB caused by high TP and algal blooms were the most important drivers of ecological service function in the reservoir. Furthermore, hydrometeorological factors may also play important roles in the aquatic ecological security of reservoirs.


Assuntos
Monitoramento Ambiental , Nitrogênio , China , Clorofila/análise , Clorofila A , Eutrofização , Lagos , Nitrogênio/análise , Fósforo/análise , Estações do Ano
11.
Plant J ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34587334

RESUMO

Malvids is one of the largest clades of rosids and include 58 families and exhibit remarkable morphological and ecological diversity. Here, we report a high-quality chromosome-level genome assembly for Euscaphis japonica, an early-diverging species within malvids. Genome-based phylogenetic analysis suggests that the unstable phylogenetic position of E. japonica may result from ILS and hybridization event during the diversification of the ancestral population of malvids. E. japonica experienced two polyploidisation events: the ancient whole genome triplication event (WGT) shared with most eudicots (commonly known as the γ event) and a more recent whole genome duplication event (WGD), unique to E. japonica. By resequencing 101 samples from 11 populations, we speculate that the temperature has led to the differentiation of the evergreen and deciduous of E. japonica and the completely different population histories of these two groups. A total of 1,012 candidate positively selected genes (PSGs) in the evergreen were detected, some of which are involved in flower and fruit development. We found that reddening and dehiscence of the E. japonica pericarp and long fruit-hanging time promoted the reproduction of E. japonica populations, and revealed the expression patterns of genes related to fruit reddening, dehiscence, and abscission. The key genes involved in pentacyclic triterpene synthesis in E. japonica were identified, and different expression patterns of these genes may contribute to pentacyclic triterpene diversification. Our work sheds light on the evolution of E. japonica and malvids, particularly on the diversification of E. japonica and the genetic basis for their fruit dehiscence and abscission.

12.
Asian J Psychiatr ; 65: 102824, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34479025

RESUMO

PURPOSE: Not all young people who have experienced childhood abuse and neglect will become depressed or have the same degree of depression. Psychological resilience may probably lead to part of the difference according to previous studies. To observe the association between childhood abuse and neglect and depression and analyze whether psychological resilience has mediating and moderating effects on this association. METHODS: A cross-sectional sampling with a self-report questionnaire used to measure childhood abuse and neglect, psychological resilience, and depression of college students was conducted in four universities in Hefei City, in October 2018. SPSS PROCESS was used to test the hypotheses of mediating and moderating effects. RESULTS: Among 4034 students, 58.1% were boys and 41.9% were girls, the average age was 20.4 years (SD = 1.4). A positive association between childhood abuse and neglect and depression was found in the population, whereas negative relationships between psychological resilience and depression, and childhood abuse and neglect were observed (r = 0.251, -0.477, and -0.196, respectively, p < 0.001). For the mediating effect of psychological resilience, the 1000-sample bootstrap demonstrated that the indirect effect was statistically significant (ß = 0.073, 95% CI: 0.057-0.092). For the moderating effect, R-square increased because the interaction effect was statistically significant (ΔR2 = 0.008, p < 0.001). CONCLUSIONS: Our study supported the conclusion of previous studies that psychological resilience mediates and moderates the process of depression. Future research can further reveal the role of psychological resilience by examining different types of childhood abuse and neglect.

13.
Reproduction ; 162(5): 353-365, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34486978

RESUMO

There are around 300 million adolescent pregnancies worldwide, accounting for 11% of all births worldwide. Accumulating evidence demonstrates that many adverse perinatal outcomes are associated with adolescent pregnancies. However, how and why these abnormalities occur remain to be defined. In this study, pregnancy at different stages was compared between 25- and 30- day-old and mature female mice. We found that the litter size of adolescent pregnancy is significantly decreased from F1 to F3 generations compared to mature pregnancy. On days 8 and 12 of pregnancy, multiple abnormalities in decidual and placental development appear in F3 adolescent pregnancy. On days 5 and 8, uterine endoplasmic reticulum stress is dysregulated in F3 adolescent pregnancy. Embryo implantation and decidualization are also compromised in adolescent pregnancy. Many genes are abnormally expressed in adolescent estrous uteri. The abnormal endocrine environment and abnormal implantation from uterine immaturity may result in multiple pregnancy failures in adolescent pregnancy. The aim of this study is to shed light on human adolescent pregnancy.

14.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-462420

RESUMO

SARS-CoV-2 Beta variant of concern (VOC) resists neutralization by major classes of antibodies from non-VOC COVID-19 patients and vaccinated individuals. Here, serum of Beta variant infected patients revealed reduced cross-neutralization of non-VOC virus. From these patients, we isolated Beta-specific and cross-reactive receptor-binding domain (RBD) antibodies. The Beta-specificity results from recruitment of novel VOC-specific clonotypes and accommodation of VOC-defining amino acids into a major non-VOC antibody class that is normally sensitive to these mutations. The Beta-elicited cross-reactive antibodies share genetic and structural features with non-VOC-elicited antibodies, including a public VH1-58 clonotype targeting the RBD ridge independent of VOC mutations. These findings advance our understanding of the antibody response to SARS-CoV-2 shaped by antigenic drift with implications for design of next-generation vaccines and therapeutics. One sentence summarySARS-CoV-2 Beta variant elicits lineage-specific antibodies and antibodies with neutralizing breadth against wild-type virus and VOCs.

15.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-459480

RESUMO

The emergence of current SARS-CoV-2 variants of concern (VOCs) and potential future spillovers of SARS-like coronaviruses into humans pose a major threat to human health and the global economy 1-7. Development of broadly effective coronavirus vaccines that can mitigate these threats is needed 8,9. Notably, several recent studies have revealed that vaccination of recovered COVID-19 donors results in enhanced nAb responses compared to SARS-CoV-2 infection or vaccination alone 10-13. Here, we utilized a targeted donor selection strategy to isolate a large panel of broadly neutralizing antibodies (bnAbs) to sarbecoviruses from two such donors. Many of the bnAbs are remarkably effective in neutralization against sarbecoviruses that use ACE2 for viral entry and also show strong binding to non-ACE2-using sarbecoviruses. The bnAbs are equally effective against SARS-CoV-2 VOCs compared to the original virus. Neutralization breadth is achieved by bnAb binding to epitopes on a relatively conserved face of the receptor binding domain (RBD) as opposed to strain-specific nAbs to the receptor binding site that are commonly elicited in SARS-CoV-2 infection and vaccination 14-18. The generation of a large panel of potent bnAbs provides new opportunities and choices for next-generation antibody prophylactic and therapeutic applications and, importantly, provides a basis for effective design of pan-sarbecovirus vaccines.

16.
Theranostics ; 11(17): 8464-8479, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34373753

RESUMO

As glutamine plays a central role in cancer metabolism, inhibition of glutaminolysis has become an ideal anticancer therapeutic target. However, glutaminolysis inhibition leads to activation of autophagy, which compromises its antitumor effect. Hence, we investigated the mechanism underlying glutaminolysis inhibition-induced pro-survival autophagy. Methods: High-throughput sequencing was performed on colorectal cancer (CRC) cells before and after glutaminolysis inhibition to identify differentially expressed genes. Activating transcription factor 4 (ATF4) pathway enrichment in glutaminolysis inhibited cells was identified through gene set enrichment analysis. ATF4 expression was assessed by quantitative real-time PCR (qRT-PCR) and western blotting. The function of ATF4 on mechanistic target of rapamycin (mTOR) regulation was assessed by western blotting. Luciferase reporter assays and chromatin immunoprecipitation were used to confirm the regulation of DNA damage inducible transcript 4 (DDIT4) by ATF4. mRNA half-life assays, RNA immunoprecipitation, qRT-PCR and western blotting were performed to determine the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 regulation of pro-survival autophagy was measured by tandem monomeric red fluorescent protein-green fluorescent protein fluorescence microscopy. Finally, the synergistic effect of autophagy and glutaminolysis inhibition was analyzed in an azoxymethane/dextran sodium sulfate mouse model. Results: The ATF4 pathway was activated in CRC cells upon glutaminolysis inhibition. Functionally, ATF4 transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition. Interestingly, glutaminolysis inhibition promoted ATF4 mRNA expression by abrogating N6-methyladenosine (m6A) modification and YTHDF2-mediated RNA decay. Finally, inhibition of ATF4-induced autophagy enhanced the antitumor efficacy of glutaminolysis inhibition. Conclusion: Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Targeting ATF4-induced autophagy is a new strategy to synergize glutaminolysis-targeting therapies for cancer treatment.

17.
Pediatr Neonatol ; 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34389261

RESUMO

BACKGROUND: Anti-epileptic drugs have different effects on neonatal seizures, and new agents have been widely used in recent years. Meanwhile, significant differences still exist in the treatment for neonatal seizures, whether in choice of drug or in duration of treatment. And with the increase in options for treatment, the best choice of second-line treatment has not been recommended. METHODS: The MEDLINE, the Cochrane Library, Web of Science, Embase and clinicaltrials.gov databases were searched (January 1, 1960 to October 20, 2020). Randomized controlled trials (RCTs) or observational investigations studying anti-epileptic drugs for neonatal seizures were selected. And then we conducted a network meta-analysis and examined comparative efficacy of the first-line and second-line anti-epileptic drugs for neonatal seizures. RESULTS: Data were extracted from 11 included studies by 2 independent investigators. Random effects models were used to estimate odds ratios (ORs). We performed direct meta-analyses with a random effects model and network meta-analyses for first-line and second-line drugs. Five published RCTs and 6 observational investigations with 1333 patients and 6 interventions contributed to the analysis. CONCLUSION: We recommend phenobarbital as the first-line drug for neonatal seizures. In addition, there is a tendency for levetiracetam to be an effective second-line treatment for neonatal seizures after failure of first-line drugs.

18.
Huan Jing Ke Xue ; 42(9): 4222-4233, 2021 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-34414720

RESUMO

Because Jiangsu is an important economic province of China, it is necessary to examine the pollution characteristics and assess the ecological risk of environmentally persistent pharmaceutical pollutants (EPPPs) in this region. In this study, surface water samples were obtained from grade 1-4 rivers and lakes (with an area of 50 km2 or more) in Jiangsu Province, and then analyzed to determine the pollution level of EPPPs. In total, 35 EPPPs were detected in the surface water of Jiangsu Province, with total concentrations in the samples ranging from 66.74 to 2189.83 ng·L-1. The 17 EPPPs with a detection rate of more than 25% are discussed in this study. The total concentrations of 35 EPPPs were 72.48-1142.79 ng·L-1, and the mean concentration was 345.20 ng·L-1. The total concentration of EPPPs was higher in the north and south than in the central part of Jiangsu. Yangzhou city had the highest concentration of EPPPs in the whole province, and the main sources of this pollution were domestic sewage, shipping sewage discharge, and drug use in fishery breeding. The total concentration of EPPPs decreased on both sides of the region, with the Beijing-Hangzhou Canal and waste from the Yellow River forming the middle line. An ecological risk assessment of 17 EPPPs showed that single target drugs posed a low risk to water ecology in Jiangsu Province. The combined risk quotient of 17 EPPPs in water of Jiangsu Province was 0.03-0.52, indicating that EPPPs posed a low to moderate risk.


Assuntos
Poluentes Ambientais , Preparações Farmacêuticas , Monitoramento Ambiental , Medição de Risco , Água
19.
Inorg Chem ; 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34351141

RESUMO

Despite the numerous titanium-oxo clusters (TOCs) which have been reported, the nature of small clusters (nuclearity < 10) as model compounds showed large deviation from that of nanoscale TiO materials. Therefore, theoretical and experimental studies for large TOCs merit more attention. We recently prepared and crystallographically characterized a series of large TOCs: Ti11O15(OiPr)16(Cophen) (1), Ti11O15(OiPr)16(Mnphen) (2), Ti10O14(OEt)16(Mnphen)2 (3), and Ti10O14(OEt)16(Mnphphen)2 (4) (phen = 1,10-phenanthroline, phphen = 4,7-biphenyl-phen). These compounds are derivatives of a Ti12 parent cluster by replacing one or two of the five-coordinated titanium atoms of the Ti12 cluster with a transition metal M, Co(II) and Mn(II), that is chelated by a phen group. The effects of mono- and bis-substituted Mphen on the charge and structure of the clusters are discussed. Theoretical evaluation of the frontier orbitals of the clusters is carried out on the basis of the precisely defined crystal structures. Different from the dye molecule to TiO core charge transfer for the dye-modified TOCs, charge transfer in these clusters is from TiO/TiOM to phen/Mphen. The effects of different metal ions and the number of substituted Mphen moieties on the photocurrent properties are evaluated. The results will be of interest to research on cluster chemistry, especially on the TOC chemistry.

20.
Cancer Biol Med ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34378879

RESUMO

OBJECTIVE: Distinguishing immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) from the AEs caused by chemotherapy, targeted therapy, or infection is highly difficult. This study offers new insights into evaluating the diagnosis, differential diagnostic, and prognostic value of ferritin for irAEs induced by ICIs. METHODS: From December 1, 2018, to April 1, 2019, we examined 318 patients with malignant tumors who received serum ferritin monitoring. The cohort comprised 231 patients treated with PD-1 inhibitor or combination with chemotherapy, and 87 patients treated with chemotherapy. Of the 231 patients, 90 had irAEs (irAE group), 70 had non-irAEs (non-irAE group), 67 had no AEs (no irAE-non irAE group), and 4 had unclassified AEs. In the 87 patients, 60 had AEs (AE group), and 27 had no AEs (no AE group). Statistical analyses were conducted with nonparametric Mann-Whitney tests. RESULTS: At the onset of AEs in the irAE group, ferritin (normal range, 35-150 µg/L) rose to a median of 927 µg/L (range, 117-17,825 µg/L) from 86 µg/L at baseline (range, 29-421 µg/L) (P < 0.001). Ferritin levels at the onset of AEs in the irAE group were significantly higher than those in the non-irAE group (median, 81 µg/L; range, 32-478 µg/L) (P < 0.001) and the AE group (median, 103 µg/L; range, 23-712 µg/L) (P < 0.001). After treatment in the irAE group, ferritin continuously decreased to a normal range in recovered patients, showed no significant changes in stable patients, and continued to rise in patients who died. CONCLUSIONS: Ferritin can be used as a diagnostic, differential diagnostic, and prognostic marker for irAEs in patients treated with ICIs.

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