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2.
J Agric Food Chem ; 69(11): 3289-3297, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33710880

RESUMO

Oxathiapiprolin is a novel chiral piperidine thiazole isooxazoline fungicide that contains a pair of enantiomers. An effective analytical method was established for the enantioselective detection of oxathiapiprolin in fruit, vegetable, and soil samples using ultraperformance liquid chromatography-tandem triple quadrupole mass spectrometry. The optimal enantioseparation was achieved on a Chiralpak IG column at 35 °C using acetonitrile and 0.1% formic acid aqueous solution (90:10, v/v) as the mobile phase. The absolute configuration of the oxathiapiprolin enantiomers was identified with the elution order of R-(-)-oxathiapiprolin and S-(+)-oxathiapiprolin by electron circular dichroism spectra. The bioactivity of R-(-)-oxathiapiprolin was 2.49 to 13.30-fold higher than that of S-(+)-oxathiapiprolin against six kinds of oomycetes. The molecular docking result illuminated the mechanism of enantioselectivity in bioactivity. The glide score (-8.00 kcal/mol) for the R-enantiomer was better with the binding site in Phytophthora capsici than the S-enantiomer (-7.50 kcal/mol). Enantioselective degradation in tomato and pepper under the field condition was investigated and indicated that R-(-)-oxathiapiprolin was preferentially degraded. The present study determines the enantioselectivity of oxathiapiprolin about enantioselective detection, bioactivity, and degradation for the first time. The R-enantiomer will be a better choice than racemic oxathiapiprolin to enhance the bioactivity and reduce the pesticide residues at a lower application rate.

3.
iScience ; : 102264, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33688629

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with multiple direct and indirect cardiovascular complications. We sought to analyse the association of host co-morbidities (chronic respiratory illnesses, cardiovascular disease (CVD), hypertension or diabetes mellitus (DM)) with the acute cardiovascular complications associated with SARS-CoV-2 infection. Individual analyses of the majority of studies found median age was higher by ∼10 years in patients with cardiovascular complications. Pooled analyses showed development of SARS-CoV-2 cardiovascular complications was significantly increased in patients with chronic respiratory illness (odds ratio (OR) 1.67[1.48,1.88]), CVD (OR 3.37[2.57,4.43]), hypertension (OR 2.68[2.11,3.41]), DM (OR 1.60[1.31,1.95]) and male sex (OR 1.31[1.21,1.42]), findings that were mostly conserved during sub-analysis of studies stratified into global geographic regions. Age, chronic respiratory illness, CVD, hypertension, DM and male sex may represent prognostic factors for the development of cardiovascular complications in COVID-19 disease, highlighting the need for a multidisciplinary approach to chronic disease patient management.

4.
J Diabetes Complications ; : 107874, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33640265

RESUMO

AIMS: To investigate whether SUA is independently associated with NAFLD in non-obese type 2 diabetic patients in a Chinese population. METHODS: A cross-sectional study was carried out among 400 non-obese type 2 diabetic inpatients. Patients were stratified according to SUA levels and presence/absence of NAFLD. The clinical and laboratory features were collected retrospectively. Multivariate logistic regression analysis was conducted to estimate odds ratios of SUA for NAFLD. RESULTS: The levels of SUA were significantly higher in patients with NAFLD than those without NAFLD. SUA was positively associated with the risk factors of NAFLD such as BMI, serum insulin and lipids. The odds of NAFLD were increasingly higher from the second to the fourth quartile of SUA as compared to the lowest quartile. After adjustment for age, gender, BMI and other metabolic components, the odds of NAFLD remained significantly increased for quartile 4. CONCLUSIONS: SUA levels are strongly and independently associated with the prevalence of NAFLD. SUA may be used as a useful predictor to stratify the higher risks for NAFLD of non-obese type 2 diabetes patients.

5.
Biomed Res Int ; 2021: 4721812, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33564676

RESUMO

Background: Elderly patients receiving nasal feeding have weaker physiological function, and placement of a nasogastric tube weakens the natural barrier of the cardia-esophageal sphincter; therefore, the risk of gastroesophageal reflux (GER) is higher. Many studies have shown that pepsin is extremely sensitive in predicting GERD, so this study intends to investigate the level of pepsin in saliva of elderly patients with nasal feeding and analyze its influencing factors. Methods: This was a cross-sectional study. Patients admitted to the Chinese PLA General Hospital from April 2018 to October 2018 who received nasal feeding were included. One ml of saliva was collected from each patient in while sitting during fasting in the morning and 1 hour after lunch for 3 consecutive days. Pepsin was quantified by enzyme-linked immunosorbent assay (ELISA). The patients were predivided into two groups (≥7.75µg/ml or <7.75µg/ml) based on the median pepsin. Baseline and clinical factors were compared. Results: The mean age of the patients was 91.09 ± 4.91 years. There were statistical differences in diabetes and feeding methods between the two groups. There was a positive correlation between the morning and postprandial pepsin levels (r = 0.442, P < 0.001), and has no statistical difference (P = 0.175). Multivariate analysis showed that the risk factors for higher pepsin levels were diabetes (odds ratio (OR): 2.67; 95% CI: 1.225-5.819, P = 0.013) and nasal feeding methods (OR: 2.475; 95% CI: 1.183-5.180, P=0.016). Conclusions: For patients undergoing nasal feeding who are older than 80 years, the fasting and 1-hour postprandial pepsin concentration were consistent. Diabetes and feeding methods are risk factors for high pepsin levels. For the elderly over 80 years old, age has no influence on pepsin concentration.

6.
Stem Cell Res Ther ; 12(1): 80, 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33494833

RESUMO

BACKGROUND: Patients with peripheral nerve injury (PNI) often suffer from hypoxic ischemic impairments, in particular when combined with vascular damage, causing neuronal dysfunction and death. Increasing attention has been paid on skin precursor-derived Schwann cells (SKP-SCs), and previous study has shown that SKP-SCs could promote sensory recovery after cell therapy for PNI, resembling the effect of naive SCs, and SKP-SC-derived extracellular vesicles (SKP-SC-EVs) are putatively supposed to be promising therapeutic agents for neural regeneration. METHODS: SKPs were induced to differentiate towards SCs with cocktail factors (N2, neuregulin-1ß, and forskolin) in vitro. SKP-SC-EVs were isolated by exoEasy Maxi Kit and characterized by morphology and phenotypic markers of EVs. Rat sensory neurons from dorsal root ganglions (DRGs) were primarily cultured in regular condition or exposed to oxygen-glucose-deprivation (OGD) condition. SKP-SC-EVs were applied to DRGs or sensory neurons, with LY294002 (a PI3K inhibitor) added; the effect on neurite outgrowth and cell survival was observed. Moreover, microRNA (miR) candidate contained in SKP-SC-EVs was screened out, and miR-mimics were transfected into DRG neurons; meanwhile, the negative regulation of PTEN/PI3K/Akt axis and downstream signaling molecules were determined. RESULTS: It was shown that SKP-SC-EVs could improve the neurite outgrowth of DRGs and sensory neurons. Furthermore, SKP-SC-EVs enhanced the survival of sensory neurons after OGD exposure by alleviating neuronal apoptosis and strengthening cell viability, and the expression of GAP43 (a neuron functional protein) in neurons was upregulated. Moreover, the neuro-reparative role of SKP-SC-EVs was implicated in the activation of PI3K/Akt, mTOR, and p70S6k, as well as the reduction of Bax/Bcl-2 ratio, that was compromised by LY294002 to some extent. In addition, transferring miR-21-5p mimics into sensory neurons could partly protect them from OGD-induced impairment. CONCLUSIONS: Sum up, SKP-SC-EVs could improve neurite outgrowth of DRG sensory neurons in physiological and pathological condition. Moreover, the in vitro therapeutic potential of SKP-SC-EVs on the survival and restoration of OGD-injured sensory neurons was evidenced to be associated with miR-21-5p contained in the small EVs and miR-21-5p/PTEN/PI3K/Akt axis.

7.
Chemosphere ; 272: 129577, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33465616

RESUMO

Dicarboximide fungicides mainly including procymidone, iprodione, vinclozolin, and dimethachlon are often applied as protective fungicides, 3,5-dichloroaniline (3,5-DCA) is their common metabolite in plant and environment. In this study, the acute toxicity of procymidone, iprodione and their metabolite of 3,5-DCA toward zebrafish was evaluated by semi-static method. The enrichment and metabolism of procymidone and iprodione in zebrafish were also clarified. The results indicated that procymidone and iprodione exhibited moderately toxic to adult zebrafish with the LC50 of 2.00 mg/L, 5.70 mg/L at 96 h. Both procymidone and iprodione could be metabolized to 3,5-DCA in zebrafish, which showed higher toxic to adult zebrafish with the LC50 of 1.64 mg/L at 96 h. From the perspective of histomorphology, for all treatment groups, the brain of the zebrafish was significantly damaged, while the damage to gut and gills was lighter. For procymidone, the biological concentration factor (BCF8d) were 236 and 246 at the exposure concentration of 0.2 mg/L and 0.04 mg/L, and the BCF8d were 3.2 and 2.4 for iprodione at the exposure concentration of 0.5 mg/L and 0.1 mg/L. Therefore, the procymidone and iprodione were moderate-enriched and low-enriched in zebrafish, respectively.


Assuntos
Fungicidas Industriais , Hidantoínas , Aminoimidazol Carboxamida/análogos & derivados , Compostos de Anilina , Animais , Compostos Bicíclicos com Pontes , Fungicidas Industriais/toxicidade , Peixe-Zebra
8.
Cancer Cell Int ; 21(1): 71, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33482821

RESUMO

BACKGROUND: Recent studies have established the roles of microRNAs (miRNAs) in cancer progression. The aberrant expression of miR-335-5p has been reported in many cancers, including gastric cancer (GC). In this study, the precise roles of miR-335-5p in GC as well as the molecular mechanisms underlying its effects, including the role of its target MAPK10, were evaluated. METHODS: Quantitative real-time PCR was used to evaluate miR-335-5p levels in GC cell lines and tissues. MTT and colony formation assays were used to detect cell proliferation, and Transwell and wound-healing assays were used to evaluate the invasion and migration of GC cells. The correlation between levels of miR-335-5p and the cell cycle-related target gene mitogen-activated protein kinase 10 (MAPK10) in GC was analyzed. In addition, the candidate target was evaluated by a luciferase reporter assay, qRT-PCR, and western blotting. RESULTS: The levels of miR-335-5p were downregulated in GC tissues and cell lines. Furthermore, miR-335-5p inhibited the proliferation and migration of GC cells and induced apoptosis. Additionally, miR-335-5p arrested the cell cycle at the G1/S phase in GC cells in vitro. Levels of miR-335-5p and the cell cycle-related target gene MAPK10 in GC were correlated, and MAPK10 was directly targeted by miR-335-5p. CONCLUSIONS: These data suggest that miR-335-5p is a tumor suppressor and acts via MAPK10 to inhibit GC progression.

9.
Environ Res ; 194: 110696, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33385383

RESUMO

The stereoselective fates of chiral pesticides in the environment has been reported in many studies. However, there is little data focused on the fate of chiral fosthiazate in the soil and aquatic ecosystems at chiral view. This study investigated the stereoselective fate of fosthiazate in the soil and aquatic ecosystems using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) and liquid chromatography tandem time-of-flight mass spectrometry (LC-TOF/MS/MS). Significant stereoselective degradation among four fosthiazate stereoisomers were found in both greenhouse soil and water-sediment microcosms. In greenhouse soil, (1R,3S)-fosthiazate degraded faster than other three stereoisomers with the half-life of 2.7 d. The fosthiazate stereisomers in the seawater-sediment microcosm degraded more rapidly than in the river water-sediment microcosm. However, (1S,3R)-fosthiazate and (1S,3S)-fosthiazate possessed shorter degradation half-lives than their enantiomers in both microcosms, with the half-lives ranging from 3.4 d to 15.8 d. Ten degradation products were identified in the water-sediment microcosms, and, six of them were reported for the first time. Oxidation and hydrolysis were confirmed as the main degradation pathways of fosthiazate in the water-sediment microcosms. Our results revealed that the (1R,3S)-fosthiazate and (1R,3R)-fosthiazate may cause more serious ecotoxicity due to the longer half-lives than the other two stereoisomers in environment.

10.
Br J Clin Pharmacol ; 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33506975

RESUMO

AIMS: This open-label, phase I study evaluated the pharmacokinetics and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for the treatment of chemotherapy-induced neutropenia in children with acute leukaemia. METHODS: PEG-rhG-CSF was administered as a single 100 mcg/kg (3 mg maximum dose) subcutaneous injection at the end of each chemotherapy period when neutropenia occurred. Blood samples were obtained from patients treated with PEG-rhG-CSF. PEG-rhG-CSF serum concentrations were determined by an enzyme-linked immunosorbent assay. Population pharmacokinetic (PPK) analysis was implemented using the nonlinear mixed-effects model. Short-term safety was evaluated through adverse events collection (registered at clinicaltrials.gov identifier: 03844360). RESULTS: A total of 16 acute leukaemia patients (1.8-13.6 years) were included, of whom two (12.5%) had grade 3 neutropenia, six (37.5%) had grade 4 neutropenia, and eight (50.0%) had severe neutropenia. For PPK modelling, 64 PEG-rhG-CSF serum concentrations were obtainable. A one-compartment model with first-order elimination was used for pharmacokinetic data modelling. The current weight was a significant covariate. The median (range) of clearance (CL) and area under the serum concentration-time curve (AUC) were 5.65 (1.49-14.45) mL/h/kg and 16514.75 (6632.45-54423.30) ng·h/mL, respectively. Bone pain, pyrexia, anaphylaxis and nephrotoxicity were not observed. One patient died 13 days after administration, and the objective assessment of causality was that an association with PEG-rhG-CSF was "possible". CONCLUSIONS: The AUC of PEG-rhG-CSF (100 mcg/kg, 3 mg maximum dose) in paediatric patients with acute leukaemia were similar to those of PEG-rhG-CSF (100 mcg/kg) in children with sarcoma. PEG-rhG-CSF is safe, representing an important therapeutic option for chemotherapy-induced neutropenia in paediatric patients with acute leukaemia.

11.
Int J Med Sci ; 18(1): 29-41, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390771

RESUMO

Rationale: Previous studies of coronavirus disease 2019 (COVID-19) were mainly focused on cross-sectional analysis. In this study, we sought to evaluate the dynamic changes of immunological and radiographic features, and the association with the outcome of pulmonary lesions in COVID-19 patients. Methods: Peripheral blood samples and radiographic data were collected longitudinally for up to 8 weeks from 158 laboratory-confirmed COVID-19 patients. The chest computed tomography (CT) scans were scored based on a semi-quantification assessment according to the extent of pulmonary abnormalities; the temporal change of the immunological and radiographic features was analyzed. Results: Compared with mild and moderate patients, severe patients had significantly decreased counts of lymphocytes, CD4+ T cells, CD8+ T cells, and CD19+ B cells but dramatically elevated counts of neutrophils and levels of interleukin (IL)-6. Sequential monitoring showed a sustained increase in lymphocytes counts and significantly decreased levels of IL-6 in severe patients during the disease course. Notably, patients with persistent pulmonary lesions (CT score ≥ 5 in week 8) showed high levels of IL-6 during the follow-up period, compared with those with recovery lesions (CT score < 5 in week 8). More importantly, the peak expression of IL-6 prior to the aggravated lung injury was mainly found in patients with persistent lesions, and multivariate analysis showed that IL-6 level upon admission was an independent factor associated with the persistent pulmonary injury. Conclusion: Prolonged elevation of IL-6 is associated with persistent pulmonary lesions in COVID-19 patients. Sequential monitoring and timely intervention of IL-6 may favor the clinical management of COVID-19.


Assuntos
/imunologia , Interleucina-6/sangue , Lesão Pulmonar/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , /complicações , Feminino , Humanos , Estudos Longitudinais , Lesão Pulmonar/diagnóstico por imagem , Lesão Pulmonar/virologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Radiografia Torácica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
12.
Ecotoxicol Environ Saf ; 207: 111221, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32911181

RESUMO

Pydiflumetofen is a novel and efficient broad-spectrum chiral fungicide consisting of a pair of enantiomers. A simple and sensitive chiral analytical method was established to determine the enantiomers of this chiral fungicide in food and environmental samples by ultra-high-performance liquid chromatography tandem triple quadrupole mass spectrometry (UHPLC-MS/MS) using QuEChERS method coupled with octadecylsilane-dispersive solid-phase extraction (C18-dSPE) as extraction procedure. The specific optical rotation and the absolute configuration of the enantiomers were identified by polarimetry and electronic circular dichroism (ECD). The elution order of the pydiflumetofen enantiomers on Lux Cellulose-2 was S-(-)-pydiflumetofen and R-(+)-pydiflumetofen. The average recoveries of eleven matrices ranged from 71.3% to 107.4%. The intraday relative standard deviations (RSDs) were less than 11.8%, and the interday RSDs were less than 12.6% for the two enantiomers. Stereoselective dissipation in pakchoi and soil were observed: S-(-)-pydiflumetofen was degraded faster than R-(+)-pydiflumetofen in pakchoi, causing the enantiomer fraction (EF) of the enantiomers to change from 0.50 to 0.42 in 7 days. However, R-(+)-pydiflumetofen was degraded faster than S-(-)-pydiflumetofen in soil, causing the EF of the enantiomers to change from 0.49 to 0.52 in 21 days. This study provides a method for monitoring pydiflumetofen enantiomer residues, which is crucial for improving risk assessments and the development of chiral pesticides.


Assuntos
Fungicidas Industriais/análise , Pirazóis/análise , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida , Praguicidas/análise , Solo/química , Poluentes do Solo/análise , Extração em Fase Sólida/métodos , Estereoisomerismo , Espectrometria de Massas em Tandem/métodos
13.
Eur J Cancer Care (Engl) ; : e13382, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33277772

RESUMO

OBJECTIVE: To quantitatively examine the relationship between social support and suicidal ideation (SI) among patients with cancer and identify the moderators that influence the magnitude of this association. METHODS: Publications were searched in PubMed, PsycINFO, EMBASE, Cochrane Library and Chinese National Knowledge Infrastructure from database inception to May, 2020. Correlation coefficients (r) were chosen as the effect size with a random model to evaluate the overall effect size between social support and SI in patients with cancer. To assess statistical heterogeneity, we examined potential moderator variables on the social support and SI. RESULTS: A total of 881 studies were identified in initial search, and twelve studies were eligible. A negative, small but significant correlation (r = -0.22, 95% CIs: -0.30,-0.14, p < 0.001) was observed between social support and SI in patients with cancer, with a significant heterogeneity (I2  = 95.24%, Q = 231.27, p < 0.001). Moderator analyses indicated that race/ethnicity (Q(1) = 8.4, p < 0.05) and measurements of social support (Q(3) = 9.78, p < 0.05) and SI (Q(3) = 9.69, p < 0.05) significantly moderate the effect size between social support and SI. CONCLUSION: Taken together, we found a negative yet significant association between social support and SI in patients with cancer, which supported the importance of social support for the prevention of SI in patients with cancer.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33188385

RESUMO

OBJECTIVES: Nowadays, real-world data can be used to improve currently available dosing guidelines and to support regulatory approval of drugs for use in neonates by overcoming practical and ethical hurdles. This proof-of-concept study aimed to assess the population pharmacokinetics of azlocillin in neonates using real-world data, to make subsequent dose recommendations and to test these in neonates with early-onset sepsis (EOS). METHODS: This prospective, open-label, investigator-initiated study of azlocillin in neonates with EOS was conducted using an adaptive two-step design. First, a maturational pharmacokinetic-pharmacodynamic model of azlocillin was developed, using an empirical dosing regimen combined with opportunistic samples resulting from waste material. Second, a Phase II clinical trial (ClinicalTrials.gov: NCT03932123) of this newly developed model-based dosing regimen of azlocillin was conducted to assure optimized target attainment [free drug concentration above MIC during 70% of the dosing interval ('70% fT>MIC')] and to investigate the tolerance and safety in neonates. RESULTS: A one-compartment model with first-order elimination, using 167 azlocillin concentrations from 95 neonates (31.7-41.6 weeks postmenstrual age), incorporating current weight and renal maturation, fitted the data best. For the second step, 45 neonates (30.3-41.3 weeks postmenstrual age) were subsequently included to investigate target attainment, tolerance and safety of the pharmacokinetic-pharmacodynamic model-based dose regimen (100 mg/kg q8h). Forty-three (95.6%) neonates reached their pharmacokinetic target and only two neonates experienced adverse events (feeding intolerance and abnormal liver function), possibly related to azlocillin. CONCLUSIONS: Target attainment, tolerance and safety of azlocillin was shown in neonates with EOS using a pharmacokinetic-pharmacodynamic model developed with real-world data.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33020163

RESUMO

Background: The pharmacological activity of ceftriaxone depends on unbound concentration. However, direct measurement of unbound concentration is obstructive, and high individual variability of the unbound fraction of ceftriaxone was shown in children. We aim to evaluate and validate a method to predict unbound ceftriaxone in pediatric patients.Methods: Ninety-five pairs of concentration (total and unbound) from 92 patients were measured by the bioanalysis method we developed. The predictive performance of the three equations (empirical in vivo equation, disease adapted equation and multiple linear regression equation) was assessed by mean absolute prediction error (MAPE), mean prediction error (MAE), the proportion of the prediction error within ± 30% (P30) and ± 50% (P50) and linear regression of predicted versus actual unbound levels (R2).Results: The average total and unbound ceftriaxone concentrations were 126.18 ± 81.46 µg/mL and 18.82 ± 21.75 µg/mL, and the unbound fraction varied greatly from 4.75% to 39.97%. The MPE, MAPE, P30, P50 and R2 of empirical in vivo equation, disease equation and multiple linear equation were -.0.17 vs 0.00 vs 0.06, 0.24 vs 0.15 vs 0.27, 63.2% vs 89.5% vs 74.7% and 96.8% vs 97.9% vs 86.3% and 0.8730 vs 0.9342 vs 0.9315. The disease adapted equation showed the best predictive performance.Conclusion: We have developed and validated a bioanalysis method with one-step extraction pre-treatment for the determination of total ceftriaxone, and a prediction equation of unbound concentration was recommended. The proposed method can facilitate the clinical practice and research of unbound ceftriaxone in children.

16.
Front Pharmacol ; 11: 566060, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33041807

RESUMO

Carbapenem-resistant enterobacteriaceae (CRE) bloodstream infections have been rapidly spreading worldwide with a high mortality and pose a challenge to therapeutic decision-making, especially in premature neonates because insufficient empirical antimicrobial therapy is independently associated with high mortality. This case reported that a premature infant with CRE bloodstream infection was treated successfully with high-dose meropenem treatment with model-based therapeutic drug monitoring (TDM). In clinical settings, treatment target attainment of meropenem can be improved by increasing the frequency of administration, prolonging the infusion time, and using a high dose. This case report shows a successful regimen for CRE infection in a premature neonate and emphasizes the utility of model-based TDM of high-dose meropenem treatment. The adequate antimicrobial benefit provided by innovative techniques could ensure the efficacy and safety of high-dose meropenem therapy for CRE infection.

17.
Ann Palliat Med ; 9(5): 3373-3378, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33065788

RESUMO

BACKGROUND: The coronavirus disease (COVID-19) poses an unprecedented challenge to health and epidemic prevention system, especially the healthcare of patients with cancer. We sought to study the impact of COVID-19 on lung cancer patients in our center. METHODS: We initiated a retrospectively study to analyze the impact of COVID-19 on lung cancer patients in our center, who were accepted for routine anticancer treatment before the epidemic and planned to return to hospital in January and February of 2020. RESULTS: A total of 161 cases of lung cancer were included in the final analysis. As of April 15, 95 patients had delayed their return visit, and 47 cases were finally designated as having delayed admission during the epidemic and having to discontinue or delay their regular anticancer treatments. Of these 47 delayed patients, 33 were evaluated for tumor status using a computed tomography scan, 6 of these 33 cases (18.18%) were diagnosed as progressive disease (PD), and 5 cases did not return for visit. CONCLUSIONS: This is the first study investigating impact of COVID-19 on non-COVID-19 lung cancer patients during the pandemic. The study demonstrates the significant impact of the COVID-19 crisis on oncological care, indicating the need for appropriate change of treatment decisions and continued follow-up and psycho-oncological support during this pandemic.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Infecções por Coronavirus , Imunoterapia , Neoplasias Pulmonares/terapia , Pandemias , Pneumonia Viral , Radioterapia , Carcinoma de Pequenas Células do Pulmão/terapia , Tempo para o Tratamento/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Quimiorradioterapia , China , Assistência à Saúde , Progressão da Doença , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem
18.
J Pathol Clin Res ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33089969

RESUMO

Few studies have explored HER2 status in cervical adenocarcinoma, particularly in the gastric-type adenocarcinoma (GAC), a nonhuman-papillomavirus-related subtype with poor clinical outcomes. In this study, we investigated HER2 expression and amplification by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in 209 well annotated cervical adenocarcinomas diagnosed using the International Endocervical Adenocarcinoma Criteria and Classification. IHC identified HER2 protein expression in 57.4% (123/209) of adenocarcinomas, of which 62 were IHC 1+ (negative), 38 2+ (equivocal) and 23 3+ (positive). HER2 amplification was found in 13 cases (6.2%) including 10 with IHC 3+ and 3 with IHC 2+. Among all the major histotypes of cervical adenocarcinoma, HER2 amplification was most common in GAC cases with a frequency of 14.7% (5/34). Moreover, HER2 amplification was more frequently associated with 2018 International Federation of Gynecology & Obstetrics (FIGO) stage III/IV, perineural involvement and ovarian spread (p < 0.05) while IHC 3+ was more common in patients with lymphovascular invasion and ovarian involvement (p < 0.05). Survival analysis indicated that FIGO stage III/IV, GAC, and p53 overexpression were associated with poor disease-specific survival and tumor recurrence (p < 0.05). In conclusion, HER2 amplification was present in a subset of adenocarcinomas, and more common in GAC, pointing to a potential benefit from trastuzumab treatment. HER2 overexpression does not identify gene amplification status in cervical adenocarcinoma; therefore, FISH is suggested for both IHC positive and equivocal cases. Further investigation on more cases with longer follow-up times is required to consolidate these findings.

19.
Biomed Res Int ; 2020: 7838924, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908912

RESUMO

We aim to investigate the role of THAP11 (thanatos-associated protein11) in gastric cancer and its regulation mechanisms. THAP11 expression was analyzed in 51 pairs of GC tissues and the corresponding paracancerous tissues by qRT-PCR and Western blot. After THAP11 was overexpressed or knocked-down, cell proliferation, cell cycle, and apoptosis were detected in MKN-45 cells. We found that THAP11 was significantly downregulated in GC tissues and GC cell lines. Functionally, THAP11 overexpression markedly inhibited cell growth, induced G1/G0 cell-cycle arrest, and promoted cell apoptosis of MKN-45 cells, while silencing of THAP11 led to increased cell growth, increased DNA synthesis, and inhibited apoptosis. In addition, THAP11 negatively regulated the expression of c-Myc, decreased cyclinD1 protein, and increased p27 and p21 protein levels. We also found cell growth suppression induced by THAP11 was rescued by c-Myc overexpression, further confirming that THAP11 suppresses gastric cancer cell growth via the c-Myc pathway. THAP11 acts as a cell growth suppressor and exerts its role possibly through negatively regulating c-Myc pathway in gastric cancer.

20.
Antimicrob Agents Chemother ; 64(11)2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-32816735

RESUMO

Ceftriaxone is a third-generation cephalosporin used to treat infants with community-acquired pneumonia. Currently, there is a large variability in the amount of ceftriaxone used for this purpose in this particular age group, and an evidence-based optimal dose is still unavailable. Therefore, we investigated the population pharmacokinetics of ceftriaxone in infants and performed a developmental pharmacokinetic-pharmacodynamic analysis to determine the optimal dose of ceftriaxone for the treatment of infants with community-acquired pneumonia. A prospective, open-label pharmacokinetic study of ceftriaxone was conducted in infants (between 1 month and 2 years of age), adopting an opportunistic sampling strategy to collect blood samples and applying high-performance liquid chromatography to quantify ceftriaxone concentrations. Developmental population pharmacokinetic-pharmacodynamic analysis was conducted using nonlinear mixed effects modeling (NONMEM) software. Sixty-six infants were included, and 169 samples were available for pharmacokinetic analysis. A one-compartment model with first-order elimination matched the data best. Covariate analysis elucidated that age and weight significantly affected ceftriaxone pharmacokinetics. According to the results of a Monte Carlo simulation, with a pharmacokinetic-pharmacodynamic target of a free drug concentration above the MIC during 70% of the dosing interval (70% fT >MIC), regimens of 20 mg/kg of body weight twice daily for infants under 1 year of age and 30 mg/kg twice daily for those older than 1 year of age were suggested. The population pharmacokinetics of ceftriaxone were established in infants, and evidence-based dosing regimens for community-acquired pneumonia were suggested based on developmental pharmacokinetics-pharmacodynamics.

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