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BACKGROUND: Ultrasound is valuable in tight control algorithms for Crohn's disease (CD). However, the correlation between ultrasonographic response and anti-tumor necrosis factor (TNF) drug levels remains unknown. Elucidating this correlation would be helpful in optimizing the use of anti-TNF drugs. Thus, the authors aimed to investigate this correlation. METHODS: Between June 2020 and June 2021, all patients with CD who completed anti-TNF induction therapy were retrospectively included. Ultrasound was performed at week 0 and week 14, and proactive therapeutic drug monitoring of anti-TNF drugs was performed at week 14. The receiver operating characteristic (ROC) curve was used in the correlation analysis. RESULTS: Ninety-two patients (60 treated with infliximab and 32 with adalimumab) were included. At week 14, an ultrasonographic response was detected in 43 patients. Patients with ultrasonographic response had significantly higher median drug levels (5.9 mcg/mL for infliximab; 18.2 mcg/mL for adalimumab) than those without (0.9 mcg/mL for infliximab, P < 0.001; 4.8 mcg/mL for adalimumab, P < 0.001). The ROC curve showed a significant correlation between ultrasonographic response and anti-TNF drug levels (area under the curve = 0.79 for infliximab, P < 0.001; area under the curve = 0.86 for adalimumab, P < 0.001). The optimal cut-off values for infliximab and adalimumab correlated with ultrasonographic response were 5.0 and 10.5 mcg/mL, respectively. An incremental increase was observed in ultrasonographic response with higher anti-TNF drug levels. CONCLUSIONS: Higher anti-TNF drug levels are associated with an increased likelihood of ultrasonographic response in patients with CD.
Assuntos
Doença de Crohn , Adalimumab/uso terapêutico , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/tratamento farmacológico , Humanos , Infliximab/uso terapêutico , Necrose/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfaRESUMO
AIM: To compare feasibility and safety after gastrointestinal checkup by standing-type magnetically controlled capsule endoscopy (SMCE) and conventional gastroscopy. METHODS: This was a prospective multicenter, blinded study that compared SMCE with gastroscopy in patients from April 2018 to July 2018. All patients first underwent SMCE and then subsequently had gastroscopy with i.v. anesthesia. We calculated the compliance rates of gastric lesion detection by SMCE using gastroscopy as the standard. Capsule retention rate, incidence of adverse events, and patient satisfaction were documented throughout the study. RESULTS: One hundred and sixty-one patients who completed SMCE and gastroscopy were included in the analysis. Positive compliance rate among SMCE and gastroscopy was 92.0% (95% CI: 80.77%-97.78%). Negative compliance rate was 95.5% (89.80%, 98.52%). Moreover, overall compliance rate was 94.41% (89.65%, 97.41%). Sixty-four pathological outcomes were identified. Of these 64 outcomes, 50 were detected by both procedures. The gastroscopy method neglected seven findings (such as five erosions, one polyp, and one ulcer). Furthermore, SMCE also overlooked seven lesions (i.e. one erosion, two polyps, one atrophy, and three submucosal tumors). Capsule retention or related adverse events were not reported. CONCLUSION: Standing-type magnetically controlled capsule endoscopy provides equivalent agreement with gastroscopy and may be useful for screening of gastric illnesses without any anesthesia.
Assuntos
Cápsulas Endoscópicas , Endoscopia por Cápsula/instrumentação , Gastroscopia , Magnetismo , Gastropatias/diagnóstico , Adulto , Estudos de Viabilidade , Feminino , Humanos , Masculino , Preferência do Paciente , Método Simples-CegoRESUMO
Tobacco black shank is one of the most harmful soil-borne diseases infected by Phytophthora parasitica. In order to probe the control method to this disease, in this study, the mycelial growth rate method was employed to investigate the antifungal effects of extracts from stem-leaf and root, root exudates, and their combination of Scrophularia ningpoensis, Chuanmingshen violaceum and Pinellia ternata The results showed that: â Stem-leaf and root extracts of S. ningpoensis, C. violaceum and P. ternata exhibited different antifungal activities, and the inhibition increased with the increase of extract concentration. The antifungal effect of S. ningpoensis extracts at 0.5 gâ¢mL⻹ was the strongest than other medicinal plants, the inhibition rate of steam-leaf and root extracts reached 74.88%, 69.27%, respectively. The inhibitory effect of C. violaceum and P. ternata was relatively lower, however, there is a significant gain effect after combination of steam-leaf and root extracts of C. violaceum. â¡The root exudates of S. ningpoensis, C. violaceum and P. ternata showed fungistasis to Phytophthora nicotianae, and fungistasis was enhanced with the increase of root exudate concentration. The antifungal effect in the order of C. violaceum > S. ningpoensis > P. ternata. â¢The antifungal activity of combination of extract and root exudate from S. ningpoensis was similar with the effect of C. violaceum, they were both stronger than P. ternata, and the antifungal activity for three combination were located between the antifungal activity of their extracts and root exudates. S. ningpoensis and C. violaceum can be potentially applied to prevent and control the tobacco black shank.
Assuntos
Fungicidas Industriais/farmacologia , Compostos Fitoquímicos/farmacologia , Phytophthora/efeitos dos fármacos , Extratos Vegetais/farmacologia , Apiaceae/química , Pinellia/química , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Exsudatos de Plantas/farmacologia , Folhas de Planta/química , Raízes de Plantas/química , Scrophularia/químicaRESUMO
OBJECTIVE: We aimed to investigate the association between gastrointestinal ultrasound (GIUS) and capsule endoscopy (CE) in assessing disease activity in patients with small bowel Crohn's disease (CD). METHODS: Medical records of 74 patients with small bowel CD who were treated at our hospital between January 2020 and March 2022 were retrospectively reviewed, including 50 men and 24 women. All patients underwent both GIUS and CE within one week after their admissions. The Simple Ultrasound Scoring of Crohn's Disease (SUS-CD) and Lewis score were used to assess disease activity during GIUS and CE, respectively. P < 0.05 was considered as statistically significant. RESULTS: The area under the receiver operating characteristic curve (AUROC) of SUS-CD was 0.90 (95% confidence interval [CI] 0.81-0.99; P < 0.001). And the diagnostic accuracy of GIUS was 79.7%, with a sensitivity of 93.6%, a specificity of 81.8%, a positive predictive value of 96.7%, a negative predictive value of 69.2% in predicting active small bowel CD. Furthermore, the agreement between GIUS and CE was assessed using Spearman's correlation analysis and SUS-CD was correlated with Lewis score (r = 0.82, P < 0.001) CONCLUSION: Our findings demonstrate a strong correlation between GIUS and CE in assessing the disease activity in patients with CD affecting the small intestine.
Assuntos
Endoscopia por Cápsula , Doença de Crohn , Masculino , Humanos , Feminino , Doença de Crohn/diagnóstico por imagem , Estudos Retrospectivos , Índice de Gravidade de Doença , Intestino Delgado/diagnóstico por imagemRESUMO
OBJECTIVE: To identify key genes involved in occurrence and development of retinoblastoma. METHODS: The microarray dataset, GSE5222, was downloaded from the gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) between unilateral and bilateral retinoblastoma were identified and functional enrichment analysis performed. The protein-protein interaction (PPI) network was constructed and analysed by STRING and Cytoscape. RESULTS: DEGs were mainly associated with activation of cysteine-type endopeptidase activity involved in apoptotic process and small molecule catabolic process. Seven genes (WAS, GNB3, PTGER1, TACR1, GPR143, NPFF and CDKN2A) were identified as HUB genes. CONCLUSION: Our research provides more understanding of the mechanisms of the disease at a molecular level and may help in the identification of novel biomarkers for retinoblastoma.
Assuntos
Neoplasias da Retina , Retinoblastoma , Biomarcadores Tumorais/genética , Biologia Computacional , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias da Retina/diagnóstico , Neoplasias da Retina/genética , Retinoblastoma/diagnóstico , Retinoblastoma/genéticaRESUMO
The present study assessed human hepatocellular adenoma (HCA) as a potential source of biological material for bioartificial liver (BAL) systems. The histological characteristics of HCA tissues from 8 patients were examined using hematoxylin and eosin staining. The glycogen synthesis capacity of HCA cells was assessed using Periodic Acid-Schiff (PAS) staining and the expression of genes involved in liver function were examined using immunohistochemical staining (IHC) and reverse transcription-quantitative PCR analysis. Primary cells from HCA tissues were subsequently isolated and cultured in vitro. Cells within HCA tissues from 8 patients exhibited a polygonal shape, similar to that of cells in adjacent normal liver tissues. PAS staining of HCA tissues indicated the capacity of these cells to synthesize and store glycogen. Furthermore, IHC and PCR analyses revealed that the expression of liver function genes in HCA tissues were similar to those observed within normal adjacent liver tissues. Primary cells isolated from HCA tissues exhibited an irregular polygonal shape and positive in vitro growth. The current study demonstrated that HCA tissues exhibit histological and functional characteristics matching those of normal human liver tissue and may therefore be a promising alternative to hepatocytes as a source of biological material for BAL systems.
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The expression of tumor protein 53-inducible nuclear protein 1 (TP53INP1) is upregulated in certain cancers and downregulated in others. However, its expression in hepatocellular carcinoma (HCC) is not clear. The present study aimed to investigate the expression and prognostic value of TP53INP1 and its association with clinicopathological parameters in HCC. TP53INP1 expression in HCC tissue samples was examined via immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction. Expression was categorized as high or low. The correlations of TP53INP1 expression with clinical characteristics and patients' prognoses were determined. TP53INP1 was frequently decreased in HCC tissues compared with adjacent non-tumorous liver tissues. This decreased expression was significantly associated with American Joint Committee on Cancer stage (P=0.014) and vascular invasion (P=0.024). Kaplan-Meier analysis further revealed that recurrence-free survival (RFS) (P=0.001) and overall survival (OS) (P=0.002) were significantly worse among patients with low TP53INP1 expression than among those with high TP53INP1 expression. In addition, multivariate analyses revealed that TP53INP1 was an independent predictor of OS [hazard ratio (HR)=2.680, 95% confidence interval (CI)=1.087-6.608, P=0.032) and RFS (HR=2.284, 95% CI=1.157-4.511, P=0.017). In conclusion, the expression of TP53INP1 was decreased in HCC, and TP53INP1 downregulation was an independent predictor of poor prognosis in patients with HCC.
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Ileal Crohn's disease (CD) arising from the alteration of intestinal homeostasis is characterized by two features, namely a decrease in Paneth cell-produced antimicrobial peptides that play a key role in maintaining this balance and an increase in NOD2, an intracellular sensor. Although mutations in NOD2 are highly correlated with the incidence of CD, the physiological role of NOD2 in intestinal immunity remains elusive. Here, we show that NOD2 can down-regulate the expression of human enteric antimicrobial peptides during differentiation of the Paneth cell lineage. This finding, which links the decrease of human enteric antimicrobial peptides to increased NOD2 in ileal CD patients, provides a new view into the pathogenesis of ileal CD.
Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Diferenciação Celular , Proteína Adaptadora de Sinalização NOD2/metabolismo , Celulas de Paneth/citologia , Celulas de Paneth/metabolismo , Peptídeos Catiônicos Antimicrobianos/genética , Diferenciação Celular/genética , Linhagem Celular Tumoral , Linhagem da Célula/genética , Doença de Crohn/genética , Doença de Crohn/metabolismo , Regulação para Baixo , Fator 9 de Crescimento de Fibroblastos/metabolismo , Regulação da Expressão Gênica , Humanos , Íleo/metabolismo , Íleo/patologia , Mucosa Intestinal/metabolismo , Proteína Adaptadora de Sinalização NOD2/genética , Interferência de RNA , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismoRESUMO
Huperzine A (HupA) is a plant alkaloid that is of great interest as a therapeutic candidate for the treatment of Alzheimer's disease. However, the current production of HupA from plants in large quantity is unsustainable because the plant resource is scarce and the content of HupA in plants is extremely low. Surprisingly, this compound was recently found to be produced by various endophytic fungi, which are much more controllable than the plants due to simpler genetics and ease of manipulation. However, it might be due to the innate properties of endophytic symbiosis, that production of this chemical in large quantity from endophytes has not yet been put into practice. Endophytic Colletotrichum gloeosporioides ES026 was previously isolated from a HupA producing plant and the fungi also proved to produce HupA. In this study, various fermentation conditions were tried to optimize the production of HupA from C. gloeosporioides ES026. Optimization of these parameters resulted in a 25.58% increase in HupA yield. Potato extracts supplemented with glucose or sucrose but not maltose facilitated HupA producing from the fungi. A final concentration of 0.5-2% ethanol stimulated the growth of fungi while methanol with the same treatment slightly inhibited the growth. However, both methanol and ethanol greatly increased the HupA production with the highest yield of HupA (51.89% increment) coming from ethanol treatment. Further analysis showed that both ethanol and methanol were strong inducers of HupA production, while ethanol was partially used as a carbon source during fermentation. It was noticed that the color of that ethanol treated mycelia gradually became dark while methanol treated ones stayed grey during fermentation. The present study sheds light on the importance of optimizing the fermentation process, which, combined with effective inducers, maximizes production of chemicals of important economic interest from endophytic fungi.
Assuntos
Alcaloides/biossíntese , Colletotrichum/metabolismo , Endófitos/metabolismo , Etanol/farmacologia , Metanol/farmacologia , Alcaloides/química , Biomassa , Carbono/farmacologia , Inibidores da Colinesterase/farmacologia , Colletotrichum/efeitos dos fármacos , Colletotrichum/crescimento & desenvolvimento , Endófitos/efeitos dos fármacos , Endófitos/crescimento & desenvolvimento , Fermentação/efeitos dos fármacos , Viabilidade Microbiana/efeitos dos fármacos , Micélio/efeitos dos fármacos , Micélio/metabolismo , Sesquiterpenos/química , Temperatura , Fatores de TempoRESUMO
The aim of this study was to explore the clinical efficiency and side effects of GHA-priming therapy on patients with acute monocytic leukemia, and to analyze its mechanism. 37 patients with refractory, relapse, hypocellular acute monocytic leukemia and elderly patients with AML-M(5) were treated with GHA-priming therapy (G-CSF, homoharringtonine and low dosage of cytarabine). Clinical efficiency, side effects, and therapy-relevant mortality were observed. By using U937 cell line as in vitro model, effect of G-CSF on cell cycle was determined by propidium iodide staining method. The inhibition rate, apoptosis rate of U937 cell line treated with various combination of G-CSF, homoharringtonine and cytarabine were detected by flow cytometry. The expression of MLAA34 on U937 before or after treating with chemotherapy was analyzed by immunohistochemical method. The results showed that in all the 37 patients, the total remission rate was 62.2% [complete remission rate was 45.95% (17/37) and partial remission rate was 16.2% (6/37)]. The incidence of granulocyte deficiency was 18.92% (2/37) with median time of 4 days. The severe infection occurred in 2 cases. No severe bleeding, no mild digestive effect occurred. Other non-hematological toxicities were low in vitro when incubated with G-CSF for 24 hours, the S-phase cells obviously increased. The inhibition rate, apoptosis rate and expression of MLAA34 of U937 cells treated by GHA significantly decreased as compared with cells treated with HA. It is concluded that the GHA priming therapy can be used to treat patients with refractory, relapse, senile and hypocellular acute monocytic leukemia with satisfied response rate and low hematological and non-hematological toxicities. G-CSF can enhance cytotoxicity of drugs such as Ara-C and HHT by promoting G(0) phase cells into the reproductive cycle. GHA and HA therapy can inhibit cell proliferation, induce apoptosis, and the former has a more significant function. GHA priming therapy can down regulate the expression of MLAA 34. MLAA-34 is a novel anti-apoptotic factor of acute monocytic leukemia.