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OBJECTIVE: Alzheimer's disease (AD), a common degenerative disease of the central nervous system in the elderly, has become the third largest health killer after cardiovascular and cerebrovascular diseases and tumors. Based on the fact that Alzheimer's disease is a disease with multiple etiologies and complex pathology, a single target is bound to have a limited curative effect, and the synergy of multiple links and multiple targets is expected to achieve a better curative effect. The aim of this study is to investigate the brain targeting of a drug modified by chitosan, based on the new nanodrug delivery system for treating Alzheimer's disease developed by the research group. MATERIALS AND METHODS: Chitosan with good biocompatibility, biosorption, and degradation products that can protect and promote the regeneration of nerve cells was selected to combine with galantamine, a natural representative cholinesterase inhibitor, to develop a new nano drug delivery system for nasal delivery of anti-Alzheimer's disease with a multi-target synergistic effect. Synchronous analysis was conducted on the blood and brain tissue drug concentrations after intravenous and nasal administration of the original drug solution and system solution. The brain targeting index (DTI) is used to evaluate the brain targeting effect of the nano-drug delivery system after intranasal administration. RESULTS: The blood concentration of galantamine original drug solution and galantamine system solution after intravenous injection and nasal show that in the two administration methods of intravenous injection and nasal administration, under the same administration method, the time point of the system reaching the highest blood drug concentration is much higher than that of the original drug. The content of galantamine in plasma samples and tissue samples indicate that after intravenous administration and intranasal administration of the galantamine system, at the same time point, the drug concentration in brain tissue was far greater than that of the original drug of galantamine, and the duration was also longer. The concentration of drugs in brain tissue decreased gradually in the order of olfactory bulb, olfactory tract, brain, and cerebellum. In the brain tissues of the olfactory bulb, olfactory tract, cerebrum, and cerebellum, the drug concentration of the galantamine system after intravenous injection is lower than that after nasal administration. CONCLUSIONS: This study concludes that compared with the original drug solution, the nano drug delivery system has significant brain targeting for nasal administration, and intravenous injection also has brain targeting. In the olfactory bulb, olfactory tract, brain, and cerebellum, the brain targeting index at the olfactory bulb is the highest, and the targeting is the best.
Assuntos
Administração Intranasal , Doença de Alzheimer , Encéfalo , Quitosana , Inibidores da Colinesterase , Sistemas de Liberação de Medicamentos , Galantamina , Doença de Alzheimer/tratamento farmacológico , Quitosana/química , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Animais , Galantamina/administração & dosagem , Galantamina/farmacocinética , Inibidores da Colinesterase/administração & dosagem , Humanos , Ratos , Masculino , Sistemas de Liberação de Fármacos por Nanopartículas/químicaRESUMO
Biosafety of pathogenic microbiology laboratories generally highlights the use of protective equipment, procedures, and operating practices to protect personnel and the environment from potentially hazardous biological materials. Under the current complex situation where traditional and non-traditional biosafety issues coexist, laboratory-acquired infection (LAI) of pathogenic microorganisms may cause illness, disability and even death. Pathogenic microorganisms may also be carried to the surrounding environment, causing community infection, which should be taken seriously. Analysis of LAI cases helps to understand the causes of exposure and learn lessons from post-exposure prophylaxis to be prepared and even prevent problems before they happen. Human factors cause most LAIs, laboratory activities related to aerosolization, laboratory activities related to sharps materials, low ability of personnel performing the work, and deficiencies in laboratory facilities or management are the four main factors. This study focuses on the human factors that lead to LAI, combined with confirmed cases, discusses the biosafety risks of pathogenic microorganism laboratories, reviews the development and evolution of biosafety laboratories and the current protection measures for experimenters, and accordingly puts forward countermeasures and suggestions.
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Contenção de Riscos Biológicos , Laboratórios , Humanos , Profilaxia Pós-ExposiçãoRESUMO
Balling defect of the additively manufactured titanium lattice implants easily leads to muscle tissue rejection, which might cause failure of implantation. Electropolishing is widely used in surface polishing of complex components and has potential to deal with the balling defect. However, a clad layer could be formed on the surface of titanium alloy after electropolishing, which may affect the biocompatibility of the metal implants. To manufacture lattice structured ß-type Ti-Ni-Ta-Zr (TNTZ) for bio-medical applications, it is necessary to investigate the impact of electropolishing on material biocompatibility. In this study, animal experiments were conducted to investigate the in vivo biocompatibility of the as-printed TNTZ alloy with or without electropolishing; and proteomics technology was used to elaborate the results. The following conclusions were drawn: (a) a 30% oxalic acid electropolishing treatment was effective in solving balling defects, and ~21 nm amorphous clad layer would be formed on the surface of the material after polishing; (b) the electropolished TNTZ suggested decreased cell cytotoxicity and improved blood biocompatibility as compared to as-printed TNTZ; (c) the amorphous clad layer could make a barrier to prevent Ta and Zr ions from penetrating into the muscle tissue, and could form a good tissue regeneration at the implantation site during 4 weeks, indicating that the electropolished TNTZ has the potential as implants; and (d) the cells attached to the electropolished TNTZ showed higher antioxidant capacity but less proliferation than attached to as-printed TNTZ.
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Nióbio , Titânio , Animais , Próteses e Implantes , LigasRESUMO
Immune checkpoint blockade (ICB) targeting PD-1/PD-L1 has been used for the treatment of head and neck squamous cell carcinoma (HNSCC). However, the overall response rate to ICB therapy for HNSCC remains less than 20%. It has recently been reported that the appearance of tertiary lymphoid structures (TLSs) in tumor tissue is correlated with better prognosis and response to ICB treatment. Here, we demonstrated an immune classification for the tumor microenvironment (TME) of HNSCC by analyzing The Cancer Genome Atlas (TCGA)-HNSCC data set and found that immunotype D with TLS enrichment had a better prognosis and response to ICB treatment. Furthermore, we observed that TLSs were present in a part of tumor samples of human papillomavirus (HPV) infection negative HNSCC (HPV- HNSCC) and were associated with the densities of dendritic cell (DC)-LAMP+ DCs, CD4+ T cells, CD8+ T cells, and progenitor T cells in TME. We established an HPV- HNSCC mouse model with TLS-enriched TME by overexpressing LIGHT in a mouse HNSCC cell line. We found that the induction of TLS formation enhanced the response to PD-1 blockade treatment in the HPV- HNSCC mouse model, accompanied by increases in DCs and progenitor exhausted CD8+ T cells in the TME. Elimination of CD20+ B cells attenuated the therapeutic effect of PD-1 pathway blockade in TLS+ HPV- HNSCC mouse models. These results indicate that TLSs contribute to the favorable prognosis and antitumor immunity of HPV- HNSCC. Inducing TLS formation in HPV- HNSCC tumors is a potential therapeutic method for improving the ICB response rate in patients with HPV- HNSCC.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Estruturas Linfoides Terciárias , Humanos , Animais , Camundongos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Linfócitos T CD8-Positivos , Infecções por Papillomavirus/terapia , Receptor de Morte Celular Programada 1/uso terapêutico , Carcinoma de Células Escamosas/terapia , Prognóstico , Imunoterapia/métodos , Neoplasias de Cabeça e Pescoço/terapia , Microambiente TumoralRESUMO
OBJECTIVE: To explore the effect of polyethylene glycol loxenatide (long-acting GLP-1R agonist) on the lipid, glucose levels, and weight in type 2 diabetes mellitus patients with obesity. PATIENTS AND METHODS: A total of 40 obese patients with type 2 diabetes mellitus in our hospital from July 2019 to June 2020 were randomly divided into a control group and a study group. The study group was treated with metformin and polyethylene glycol loxenatide injection, while the control group was treated with metformin. RESULTS: Before treatment, there was no significant difference in FPG (Fasting Blood Glucose) and PPG (Post Prandial Glycaemia) levels between the study group and the control group (p>0.05). After a treatment period, the FPG and PPG levels in the study group were significantly lower than those in the control group (p<0.05). With the longer treatment time, the patient's weight and BMI were lower (p<0.05). The weight and BMI of patients changed the least after one month of treatment, and the weight and BMI changed the most after more than seven months of treatment. After a period of treatment, the levels of FPG and PPG in the blood of male patients in the study group were significantly lower than those of female patients (p<0.05). After treatment, the TG level of the study group was significantly lower than that of the control group (p<0.05). In comparison, the HDL-C level was significantly higher than that of the control group (p<0.05). CONCLUSIONS: Lipid and glucose levels of type 2 diabetes mellitus patients with obesity have decreased after 12 weeks of polyethylene glycol loxanatide use. The weight of type 2 diabetes mellitus patients with obesity has changed after using polyethylene glycol loxenatide for a period of treatment. Among them, there is a certain relationship between body weight and treatment time, gender, and original body weight, which is worthy of further research and promotion in clinical practice.
Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Humanos , Masculino , Feminino , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glicemia , Obesidade/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Metformina/uso terapêutico , LipídeosRESUMO
Objective: To analyze density of stromal tumor-infiltrating lymphocytes (sTIL) and expression of lymphocyte-activation gene-3 (LAG-3) protein in advanced gastric adenocarcinomas, and to investigate the correlation of sTIL and LAG-3 with the prognosis in patients with advanced gastric adenocarcinoma. Methods: The clinicopathological characteristics and follow-up data of 260 patients with advanced gastric adenocarcinoma were collected at Fujian Cancer Hospital, from January 2011 to December 2014. The percentage of sTILs was reported semi-quantitatively using histological section evaluation, the LAG-3 protein was detected using immunohistochemistry, and the expression was correlated with the clinicopathological features and patient outcomes. Results: Among the 260 cases, high density of sTIL was detected in 173 cases (66.5%) while LAG-3 high expression was observed in 160 cases (61.5%). These cases were divided into four groups. Group â : 48 cases (18.5%) were sTIL low/LAG-3 low; group â ¡: 52 cases (20.0%) were sTIL high/LAG-3 low; group â ¢: 39 cases (15.0%) were sTIL low/LAG-3 high; group â £: 121 cases (46.5%) were sTIL high/LAG-3 high. Kaplan-Meier survival analyses showed that patient prognoses were related to age, tumor size, tumor location, Lauren classification, perineural invasion, vascular invasion, TNM staging, postoperative adjuvant chemotherapy and molecular classification (P<0.05). Meanwhile, higher densities of sTIL and higher expression of LAG-3 were associated with better prognosis. Multivariate survival analysis showed age, tumor size, Lauren classification and postoperative adjuvant chemotherapy were independent prognostic factors for patient survival. The results showed a poor prognosis in low-sTIL/low-LAG-3 patients. Conclusions: Compared with low density of sTIL and low expression of LAG-3, high density of sTIL and high expression of LAG-3 are associated with better outcomes in patients with advanced gastric adenocarcinoma, respectively. Combined detecton of sTIL and LAG-3 may be more useful in gastric cancer than using either alone. Age, tumor size, Lauren classification and postoperative adjuvant chemotherapy are independent prognostic factors for patients with advanced gastric adenocarcinoma.
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Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/patologia , Humanos , Imuno-Histoquímica , Linfócitos do Interstício Tumoral/metabolismo , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologiaRESUMO
The aim of this study was to observe the effects of remifentanil on organ damage and energy metabolism in lipopolysaccharide (LPS)-induced septic rats. A total of 45 clean-grade male Wistar rats (weight 270-320 g) were randomly divided into three groups: a control group, an LPS group, and an LPS with remifentanil treatment (LPS+REM) group. After 6 hours of modeling, the levels of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in lung and kidney tissues of rats in each group were detected by ELISA. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in lung and kidney tissues were determined, and the content of lactic acid, pyruvate and epinephrine in heart and kidney tissues were detected. Reverse transcription polymerase chain reaction and the Western blot test were used to detect the expression of pyruvate dehydrogenase kinase 4 (PDK4) in the myocardial tissue. We found that remifentanil treatment inhibited the levels of IL-6, TNF-α, and MDA in the lung and kidneys 6 h after the administration of LPS and increased the level of SOD activity. Treatment with remifentanil reduced the expression of lactic acid, pyruvate, and epinephrine in the heart and kidney tissues and attenuated the expression of PDK4 messenger RNA and PDK4 protein in the myocardial tissue. We concluded that remifentanil might inhibit the release of tissue inflammatory factors, regulate the body's energy metabolism, and ultimately protect the sepsis tissue damage caused by LPS.
Assuntos
Lipopolissacarídeos , Sepse , Animais , Metabolismo Energético , Epinefrina , Interleucina-6/metabolismo , Ácido Láctico , Lipopolissacarídeos/farmacologia , Masculino , Piruvatos , Ratos , Ratos Wistar , Remifentanil , Sepse/tratamento farmacológico , Sepse/metabolismo , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Gasdermin E (GSDME), as the major executive protein of pyroptosis, has been considered to be linked to antitumor immunity in recent years. However, the role of GSDME in oral squamous cell carcinoma (OSCC) remains to be elucidated. Here, by using a human OSCC tissue microarray, human OSCC tissue, and Tgfbr1/Pten conditional knockout mice, we found that GSDME was strongly expressed in OSCC and that GSDME expression in primary tumors was higher than that in metastatic lymph nodes. In addition, GSDME expression in OSCC was positively related to better prognosis. Moreover, GSDME-mediated pyroptosis occurred upon stimulation with chemotherapy drugs, and functional knockdown of GSDME attenuated the cisplatin-induced antitumor effect. Consistent with these results, bioinformatic analysis indicated that GSDME expression was positively correlated with the sensitivity of a number of antitumor drugs approved by the US Food and Drug Administration. Inhibition of GSDME expression by small interfering RNA in SCC7 cells significantly increased the expression of the cancer stem cell markers, CD44 and ALDH1. Furthermore, multiplexed immunohistochemistry and flow cytometry indicated that the expression of GSDME positively correlated with tumor-infiltrating CD8+ T cells, granzyme B, and M1 phenotype macrophages. Collectively, these findings demonstrated that GSDME is a potential positive prognostic factor of OSCC, and GSDME-mediated pyroptosis induced by chemotherapy plays a role in antitumor response.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Animais , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Carcinoma de Células Escamosas/metabolismo , Camundongos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
Objective: To investigate the clinicopathological features and differential diagnosis of NTRK3 gene rearrangement thyroid papillary carcinoma (PTC). Methods: The PTC cases without BRAF V600E mutation were collected at Fujian Provincial Hospital South Branch from January 2015 to January 2020. The cases of NTRK3 gene rearrangement PTC were examined using immunohistochemistry and fluorescence in situ hybridization (FISH). The clinical data, histopathological characteristics, immunohistochemical features and molecular pathological changes were retrospectively analyzed. Data from the TCGA PTC dataset and the literature were also studied. Results: A total of 3 PTC cases harboring NTRK3 gene rearrangement were confirmed. All the patients were female, aged from 26,49,34 years. Histologically, two of them demonstrated a multinodular growth pattern. Only one case showed prominent follicular growth pattern; the other two tumors showed a mixture of follicular, papillary and solid growth patterns. All tumors showed a typical PTC nuclear manifestation, with some nuclear pleomorphism, vacuolated foci and oncocytic features. The characteristic formation of glomeruloid follicular foci was present in two cases which also showed psammoma bodies, and tumoral capsular or angiolymphatic invasion. The background thyroid parenchyma showed chronic lymphocytic thyroiditis. Mitotic rates were low, and no cases had any tumor necrosis. The pan-TRK and TTF1 testing was both positive in 3 cases, while S-100 and mammaglobin were both negative in them. FISH studies confirmed the NTRK3 gene rearrangement in all 3 cases. Studies on the TCGA datasets and literature revealed similar findings. Conclusions: NTRK3 gene rearrangement PTC is rare. It may be easily misdiagnosed due to the lack of histological and clinicopathological characteristics. Molecular studies such as pan-TRK immunostaining, FISH and even next-generation sequencing are needed to confirm the diagnosis. Immunohistochemistry of pan-TRK performed in the PTC cases without BRAF V600E mutation can be used as a good rapid-screening tool. With the emergence of pan-cancer tyrosine receptor kinase inhibitors, proper diagnosis of these tumors can help determine appropriate treatments and improve their outcomes.
Assuntos
Receptor trkC , Neoplasias da Glândula Tireoide , Biomarcadores Tumorais , Feminino , Rearranjo Gênico , Humanos , Hibridização in Situ Fluorescente , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genéticaRESUMO
OBJECTIVE: Diabetes mellitus is a chronic metabolic disease which has an adverse impact on the quality of patient's life, so patients often need to receive treatment for a long time. Selection of medications with high therapeutics effects and low cost is very important for patients to take medicine for a longer period of time. Sitagliptin is a drug which is widely used in clinics and can effectively control blood glucose level. This article explores the pharmacoeconomic value of Sitagliptin in the treatment of diabetes mellitus. PATIENTS AND METHODS: A total of 100 patients with diabetes mellitus treated were recruited in this study. The patients were randomly divided into 4 groups with 25 cases in each group. Patients in group A were treated with pioglitazone, group B with Sitagliptin, group C with metformin and group D with glimepiride. The cost of the drugs, the treatment results and adverse effects were compared. RESULTS: Compared with group A, C and D, the cost-effectiveness ratio of group B was low (p<0.05), and the therapeutic effect was high (p<0.05). In addition, the incidence of adverse reactions in group B was lower than that in group A, C and D (p<0.05). There was no significant difference in the levels of FPG, 2hPG and HbAlc in patients among the four groups before treatment (p>0.05). After treatment, the levels of FPG, 2hPG and HbAlc in group B were significantly lower than those in groups A, C and D (p<0.05). Finally, there was no significant difference in waist circumference and BMI among the four groups before treatment (p>0.05). After treatment, the waist circumference and BMI in group B were lower than those in groups A, C and D (p<0.05). CONCLUSIONS: The application of Sitagliptin in the treatment of diabetic patients can effectively enhance the therapeutic effect. The cost effectiveness is satisfactory, and the blood glucose level can be maintained at a stable state.
Assuntos
Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Fosfato de Sitagliptina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Custo-Benefício , Diabetes Mellitus/economia , Farmacoeconomia , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/economia , Masculino , Metformina/economia , Metformina/uso terapêutico , Pessoa de Meia-Idade , Pioglitazona/economia , Pioglitazona/uso terapêutico , Fosfato de Sitagliptina/efeitos adversos , Fosfato de Sitagliptina/economia , Compostos de Sulfonilureia/economia , Compostos de Sulfonilureia/uso terapêuticoRESUMO
Based on Yichang health big data platform, 850 608 patients from September 2018 to September 2019 were included in this study. According to the date of birth, the participants were divided into early childhood famine exposure group, fetal famine exposure group and non-famine exposure group. The incidence of adult herpes zoster (HZ) in Yichang city was analyzed, and the correlation between early life famine exposure and adult HZ was analyzed. In 2019, the crude incidence rate of adult HZ in Yichang was 6.83. The crude incidence rate of adult HZ in females (7.26) was higher than that in males (6.40). Compared with the non-famine exposure group, fetal famine exposure was associated with the incidence of adult HZ (OR=1.21; 95%CI: 1.01-1.45, P=0.041). After stratification by sex, fetal famine exposure was only found to be associated with the onset of adult HZ in females (OR=1.28, 95%CI:1.02-1.61, P=0.034).
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Herpes Zoster , Efeitos Tardios da Exposição Pré-Natal , Adulto , Pré-Escolar , Fome Epidêmica , Feminino , Herpes Zoster/epidemiologia , Humanos , Incidência , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologiaRESUMO
Chromium may regulate dairy cow metabolism; a chelated formation of chromium methionine (Cr-Met) is available to the feed industry. The objective of this study was to investigate the effect of Cr-Met supplementation on lactation performance, hepatic respiratory rate and anti-oxidative capacity in early-lactating Holstein dairy cows. 64 multiparous cows were assigned to 16 blocks based on parity and milk yield and then the four cows in a block were randomly allocated to four treatment groups with 0, 4, 8 or 16 g/d of Cr-Met per cow supplemented to a basal diet. Cows were moved from an open dry lot to a naturally ventilated tie stall barn 2 weeks before treatment to adapt to this facility, fed and milked at 0630, 1400, and 1930 h every day. The experiment lasted for 12 weeks. Milk yield and composition were recorded weekly. Dry matter intake was measured every 2 weeks for a total of six times throughout the trial. The plasma variables were measured in weeks 4, 8 and 12 of the experiment. Supplementation of Cr-Met did not affect DM intake of cows. As the supplementation of Cr-Met increased, yields of milk, fat, energy corrected milk (P < 0.01) and lactose (P = 0.01) increased in a linear manner. In terms of plasma variables, insulin concentration decreased in a linear manner with Cr-Met supplementation. As for variables relating to hepatic respiration rate, concentrations of pyruvate and NAD in the plasma were increased in quadratic manners, and lactic dehydrogenase activity was linearly increased as Cr-Met feeding levels increased. Moreover, plasma glutathione peroxidase and superoxide dismutase activity were increased in a linear manner. In conclusion, our study suggested that Cr-Met supplementation improved lactation performance of early-lactating dairy cows through enhancing antioxidant capacity and hepatic cellular respiration.
Assuntos
Lactação , Metionina , Animais , Bovinos , Cromo , Dieta/veterinária , Suplementos Nutricionais , Feminino , Leite , Gravidez , Taxa RespiratóriaRESUMO
To evaluate the impacts of guanidinoacetic acid (GAA) and coated folic acid (CFA) on growth performance, nutrient digestion and hepatic gene expression, fifty-two Angus bulls were assigned to four groups in a 2 × 2 factor experimental design. The CFA of 0 or 6 mg/kg dietary DM folic acid was supplemented in diets with GAA of 0 (GAA-) or 0·6 g/kg DM (GAA+), respectively. Average daily gain (ADG), feed efficiency and hepatic creatine concentration increased with GAA or CFA addition, and the increased magnitude of these parameters was greater for addition of CFA in GAA- diets than in GAA+ diets. Blood creatine concentration increased with GAA or CFA addition, and greater increase was observed when CFA was supplemented in GAA+ diets than in GAA- diets. DM intake was unchanged, but rumen total SCFA concentration and digestibilities of DM, crude protein, neutral-detergent fibre and acid-detergent fibre increased with the addition of GAA or CFA. Acetate:propionate ratio was unaffected by GAA, but increased for CFA addition. Increase in blood concentrations of albumin, total protein and insulin-like growth factor-1 (IGF-1) was observed for GAA or CFA addition. Blood folate concentration was decreased by GAA, but increased with CFA addition. Hepatic expressions of IGF-1, phosphoinositide 3-kinase, protein kinase B, mammalian target of rapamycin and ribosomal protein S6 kinase increased with GAA or CFA addition. Results indicated that the combined supplementation of GAA and CFA could not cause ADG increase more when compared with GAA or CFA addition alone.
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Ração Animal , Bovinos/crescimento & desenvolvimento , Ácido Fólico/administração & dosagem , Glicina/análogos & derivados , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Creatina , Detergentes , Dieta/veterinária , Suplementos Nutricionais , Digestão , Expressão Gênica , Glicina/administração & dosagem , Fator de Crescimento Insulin-Like I , Fígado , Masculino , Nutrientes , Fosfatidilinositol 3-Quinases , RúmenRESUMO
AIM: To investigate the performance of a deep-learning approach termed lesion-aware convolutional neural network (LACNN) to identify 14 different thoracic diseases on chest X-rays (CXRs). MATERIALS AND METHODS: In total, 10,738 CXRs of 3,526 patients were collected retrospectively. Of these, 1,937 CXRs of 598 patients were selected for training and optimising the lesion-detection network (LDN) of LACNN. The remaining 8,801 CXRs from 2,928 patients were used to train and test the classification network of LACNN. The discriminative performance of the deep-learning approach was compared with that obtained by the radiologists. In addition, its generalisation was validated on the independent public dataset, ChestX-ray14. The decision-making process of the model was visualised by occlusion testing, and the effect of the integration of CXRs and non-image data on model performance was also investigated. In a systematic evaluation, F1 score, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) metrics were calculated. RESULTS: The model generated statistically significantly higher AUC performance compared with radiologists on atelectasis, mass, and nodule, with AUC values of 0.831 (95% confidence interval [CI]: 0.807-0.855), 0.959 (95% CI: 0.944-0.974), and 0.928 (95% CI: 0.906-0.950), respectively. For the other 11 pathologies, there were no statistically significant differences. The average time to complete each CXR classification in the testing dataset was substantially longer for the radiologists (â¼35 seconds) than for the LACNN (â¼0.197 seconds). In the ChestX-ray14 dataset, the present model also showed competitive performance in comparison with other state-of-the-art deep-learning approaches. Model performance was slightly improved when introducing non-image data. CONCLUSION: The proposed LACNN achieved radiologist-level performance in identifying thoracic diseases on CXRs, and could potentially expand patient access to CXR diagnostics.
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Redes Neurais de Computação , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Radiografia Torácica/métodos , Doenças Torácicas/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
Coated copper sulphate (CCS) could be used as a Cu supplement in cows. To investigate the influences of copper sulphate (CS) and CCS on milk performance, nutrient digestion and rumen fermentation, fifty Holstein dairy cows were arranged in a randomised block design to five groups: control, CS addition (7·5 mg Cu/kg DM from CS) or CCS addition (5, 7·5 and 10 mg Cu/kg DM from CCS, respectively). When comparing Cu source at equal inclusion rates (7·5 mg/kg DM), cows receiving CCS addition had higher yields of fat-corrected milk, milk fat and protein; digestibility of DM, organic matter (OM) and neutral-detergent fibre (NDF); ruminal total volatile fatty acid (VFA) concentration; activities of carboxymethyl cellulase, cellobiase, pectinase and α-amylase; populations of Ruminococcus albus, Ruminococcus flavefaciens and Fibrobacter succinogenes; and liver Cu content than cows receiving CS addition. Increasing CCS addition, DM intake was unchanged, yields of milk, milk fat and protein; feed efficiency; digestibility of DM, OM, NDF and acid-detergent fibre; ruminal total VFA concentration; acetate:propionate ratio; activity of cellulolytic enzyme; populations of total bacteria, protozoa and dominant cellulolytic bacteria; and concentrations of Cu in serum and liver increased linearly, but ruminal propionate percentage, ammonia-N concentration, α-amylase activity and populations of Prevotella ruminicola and Ruminobacter amylophilus decreased linearly. The results indicated that supplement of CS could be substituted with CCS and addition of CCS improved milk performance and nutrient digestion in dairy cows.
Assuntos
Ração Animal , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Sulfato de Cobre/administração & dosagem , Suplementos Nutricionais , Animais , Bovinos , Digestão/efeitos dos fármacos , Enzimas/efeitos dos fármacos , Feminino , Fermentação/efeitos dos fármacos , Lactação/efeitos dos fármacos , Fígado/metabolismo , Microbiota/efeitos dos fármacos , Nutrientes/metabolismo , Rúmen/metabolismoRESUMO
OBJECTIVE: To investigate the effects of orthokeratology on biological parameters and visual quality of adolescents with low-grade corneal astigmatism myopia. PATIENTS AND METHODS: In this study, a total of 41 myopic adolescents were prescribed with orthokeratology glasses in our hospital from February 2018 to March 2019 and voluntarily cooperated with relevant examinations before and after wearing orthokeratology lenses. Patients' uncorrected distant visual acuity (UCVA-D), uncorrected near visual acuity (UCVA-N) and naked eye near stereoacuity before wearing glasses, 1 month, and 3 months after wearing glasses were observed. The corneal astigmatism of patients was observed. The corneal endothelial cell density was observed. The dynamic adjustment function (NP, AF, NRA, PRA) values of patients were observed. The comparison of biological indexes in different time periods was observed. The changes of corneal curvature before wearing orthokeratology lens, 1 month and 3 months after wearing orthokeratology lens were observed. RESULTS: There were significant changes of patients 1 month after wearing orthokeratology lenses (p < 0.05), while there was no significant difference between 3 months after wearing the orthokeratology lenses and 1 month after wearing the orthokeratology lenses (p < 0.05). Patients' NCAV-D and UCVA-N were recorded by a conversion method of 5 points. There were differences in the NCVA-D, NCVA-N, naked eye near stereoacuity before, 1 month, and 3 months after wearing glasses (p < 0.05). By observing patients' biological indicators and dynamic adjustment, it was found that there were statistically significant differences in NP, AF, BRA and PRA before wearing the glasses, 1 month and 3 months after wearing the glasses (p < 0.05). CONCLUSIONS: The use of orthokeratology can greatly correct myopia patients' vision, improve their stereoscopic vision, control the progression of myopia, and improve their eye regulation, which is of high safety and great short-term effect.
Assuntos
Astigmatismo/terapia , Córnea/patologia , Miopia/terapia , Procedimentos Ortoceratológicos , Adolescente , Astigmatismo/patologia , Criança , Feminino , Humanos , Masculino , Miopia/patologia , Acuidade VisualRESUMO
Objective: To compare the efficacy and safety of olaparib in combination with pembrolizumab with pembrolizumab alone in second-line treatment for patients with extensive stage-small cell lung cancer (ES-SCLC) whose ages ranged from 40 to 80 years. Methods: From March 2017 to October 2019, 21 patients with progressed or relapsed small cell lung cancer after standard first line treatment were enrolled in this study. The olaparib/pembrolizumab group (n=11) was treated by olaparib 300mg twice per day combined with pembrolizumab 200mg once every 3 weeks, while pembrolizumab group was treated by pembrolizumab alone. Results: The objective response rate (ORR) of olaparib/pembrolizumab group and pembrolizumab group were 45.5% and 10.0%, respectively (P=0.149), and the disease control rate (DCR) were 81.8% and 70.0% (P=0.635). The median progression-free survival (PFS) were 5.93 months and 3.53 months (P=0.036), the median overall survival (OS) were 10.43 months and 8.43 months (P=0.063). The adverse reaction incidences of all grades were 90.9% and 70.0% (P=0.311), and the incidences of grade â ¢-â ¤ including myelosuppression were 36.4% and 10.0% (P=0.311), gastrointestinal reaction were 9.1% and 10.0%, (P=1.000) and other immune-related adverse events were 18.2% and 30.0% (P=1.000). Further analysis showed the metastatic number (P=0.006), platinum sensitivity (P=0.036) and LDH level (P=0.022) significantly affected the ORR of olaparib/pembrolizumab therapy. Conclusion: Our preliminary study indicates that olaparib combined with pembrolizumab is an efficient and safe second-line treatment therapy for patients with ES-SCLC.
Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Ftalazinas/uso terapêutico , Piperazinas/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológicoRESUMO
Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "LncRNA SNHG16 functions as an oncogene by sponging miR-200a-3p in pancreatic cancer, by J.-Q. Guo, Z.-J. Yang, S. Wang, Z.-Z. Wu, L.-L. Yin, D.-C. Wang, published in Eur Rev Med Pharmacol Sci 2020; 24 (4): 1718-1724-DOI: 10.26355/eurrev_202002_20347-PMID: 32141539" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20347.