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A series of chemotherapeutic drugs that induce DNA damage, such as cisplatin (DDP), are standard clinical treatments for ovarian cancer, testicular cancer, and other diseases that lack effective targeted drug therapy. Drug resistance is one of the main factors limiting their application. Sensitizers can overcome the drug resistance of tumor cells, thereby enhancing the antitumor activity of chemotherapeutic drugs. In this study, we aimed to identify marketable drugs that could be potential chemotherapy sensitizers and explore the underlying mechanisms. We found that the alcohol withdrawal drug disulfiram (DSF) could significantly enhance the antitumor activity of DDP. JC-1 staining, propidium iodide (PI) staining, and western blotting confirmed that the combination of DSF and DDP could enhance the apoptosis of tumor cells. Subsequent RNA sequencing combined with Gene Set Enrichment Analysis (GSEA) pathway enrichment analysis and cell biology studies such as immunofluorescence suggested an underlying mechanism: DSF makes cells more vulnerable to DNA damage by inhibiting the Fanconi anemia (FA) repair pathway, exerting a sensitizing effect to DNA damaging agents including platinum chemotherapy drugs. Thus, our study illustrated the potential mechanism of action of DSF in enhancing the antitumor effect of DDP. This might provide an effective and safe solution for combating DDP resistance in clinical treatment.
Subject(s)
Female , Male , Humans , Cisplatin/pharmacology , Disulfiram/pharmacology , Testicular Neoplasms/drug therapy , Fanconi Anemia/drug therapy , Alcoholism/drug therapy , Drug Resistance, Neoplasm , Cell Line, Tumor , Substance Withdrawal Syndrome/drug therapy , Apoptosis , Antineoplastic Agents/therapeutic use , Cell ProliferationABSTRACT
@#Objective To compare the clinical outcomes of transcatheter aortic valve implantation (TAVI) in oncology and non-oncology patients with severe aortic stenosis (AS). Methods A computer-based search in PubMed, The Cochrane Library, EMbase, CBM, CNKI and Wanfang databases from their date of inception to December 2021 was performed, together with reference screening, to identify eligible clinical trials. Two investigators screened the articles, extracted data, and evaluated quality independently. RevMan 5.3 and Stata 12.0 softwares were used for meta-analysis. Results The selected 8 cohort studies contained 57 988 patients, including 12 335 cancer patients and 45 653 non-cancer patients. The results of meta-analysis showed that in patients with cancer, the 30-day mortality [OR=0.74, 95%CI (0.65, 0.84), I2=0%, P<0.000 01], stroke [OR=0.87, 95%CI (0.76, 0.99), I2=0%, P=0.04] and acute kidney injury [OR=0.81, 95%CI (0.76, 0.85), I2=49%, P<0.000 01] were lower than those in patients without cancer. The 1-year mortality [OR=1.46, 95%CI (1.15, 1.86), I2=62%, P=0.002] and late mortality [OR=1.51, 95%CI (1.24, 1.85), I2=61%, P<0.000 1] were higher in patients with cancer. Conclusion It is effective and safe in cancer patients with severe AS undergoing TAVI. However, compared with patients without cancer, it is still high in long-term mortality, and further study of the role of TAVI in cancer patients with AS is necessary.
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With the rapid development of artificial intelligence technology, researchers have applied it to the diagnosis of various tumors in the urinary system in recent years, and have obtained many valuable research results. The article sorted the research status of artificial intelligence technology in the fields of renal tumors, bladder tumors and prostate tumors from three aspects: the number of papers, image data, and clinical tasks. The purpose is to summarize and analyze the research status and find new valuable research ideas in the future. The results show that the artificial intelligence model based on medical data such as digital imaging and pathological images is effective in completing basic diagnosis of urinary system tumors, image segmentation of tumor infiltration areas or specific organs, gene mutation prediction and prognostic effect prediction, but most of the models for the requirement of clinical application still need to be improved. On the one hand, it is necessary to further improve the detection, classification, segmentation and other performance of the core algorithm. On the other hand, it is necessary to integrate more standardized medical databases to effectively improve the diagnostic accuracy of artificial intelligence models and make it play greater clinical value.
Subject(s)
Humans , Male , Algorithms , Artificial Intelligence , Prognosis , Prostatic Neoplasms/diagnosis , TechnologyABSTRACT
, a widely used Chinese herbal medicine, was considered as central nervous system (CNS) drug for years. Both ethanol extracts (EES) and water extracts (WES) of it were applied clinically. Unfortunately, the difference of their efficacy and even effective material foundation of remains obscure. In this study, to explore the active constituents of , we compared pharmacodynamics and chemical profiles / of EES/WES for the first time using multiple chemical analysis, pharmacological and data processing approaches. It was proved that there was no significant difference in the anti-depressive effects between WES and EES. However, the contents of most components and in plasma were higher in EES than those in WES, which was unconvincing for their similar efficacy. Therefore, we further explored components of targeted onto brain and the results showed that 5 lignans were identified with definite absorptivity respectively both in EES and WES caused by the limitation of blood-brain barrier. Moreover, bioinformatic analysis predicted their anti-depressive action. Above all, the systematic strategy screened 5 brain-targeted effective substances of and it was suggested that exploring the components into nidi would promote the studies on herbs effective material basis.
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OBJECTIVE@#To investigate the effect of interleukin (IL) -13 combined with cold stimulation on synthesis and secretion of mucin (MUC) 5AC in human bronchial epithelial cell line 16HBE and explore the role of transient receptor potential 8 (TRPM8) and anti-apoptotic factor B-cell lymphoblast-2 (Bcl-2) in this process.@*METHODS@#16HBE cells were stimulated with 10 ng/mL IL-13, 1 mmol/L menthol, or both (1 mmol/L menthol was added after 6 days of IL-13 stimulation), and the changes in the expression of MUC5AC, intracellular Ca@*RESULTS@#The mRNA and protein expressions of MUC5AC increased significantly in 16HBE cells following stimulation with IL-13, menthol, and both (@*CONCLUSIONS@#Menthol combined with IL-13 produces a synergistic effect to promote the synthesis and secretion of MUC5AC in 16HBE cells possibly by activating TRPM8 receptor to upregulate the expression of Bcl-2.
Subject(s)
Humans , Bronchi , Epithelial Cells/drug effects , Interleukin-13 , Menthol/pharmacology , Mucin 5ACABSTRACT
Objective T o observe the changes of cystathionine β-synthase (C B S ) expression in the cere-bral cortex after brain contusion at different tim es. Methods A n experim ental m odel of traum atic brain injury (T B I) in m ice w as established by an im proved w eight-drop device. T hen W estern blotting and im m unohistochem ical exam ination w ere used to detect the C B S expression in cerebral cortex around in-jury at different tim e points (1 h, 6 h, 12 h, 1 d, 2 d, 3 d, 7 d). Results T he results of W estern blotting revealed that the expression level of C B S w as dow n-regulated and reached its low est level at the 3rd days after injury, and then restored to norm al level after 7 days. T he results of im m unohistochem istry show ed that C B S w as present in the norm al brain cortex. C B S expression gradually decreased at the 3rd days after injury, and then restored to norm al level after 7 days. Conclusion C B S has the potential to be a reference index for tim e estim ation after brain contusion in forensic practice.
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Objective To observe the time-course expression of calcium-calmodulin dependent protein ki-naseⅡδ (CaMKⅡδ) in cerebral cortex after traumatic brain injury (TBI). Methods The TBI rat model was established. The expression of CaMKⅡδ in cerebral cortex around injured area was tested by Western blotting and immunohistochemical staining . Results Western blotting revealed expression of CaMKⅡδ in normal rat brain cortex. It gradually increased after TBI, peaked after 3 days, and then returned to normal level. The result of immunohistochemical staining was consistent with that of West-ern blotting. Conclusion The expression of CaMKⅡδ around injured area after TBI increased initially and then decreased. It could be used as a new indicator for wound age determination following TBI.
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Objective To investigate the relationshipbetween glucose fluctuation and the degree of nervous dysfunction of the acute cerebral infarction in patients with type 2 diabetes mellitus.Methods 30 patients with ACI and T2DM were chosen as observation group and 30 patients with T2DM without ACI as the control group.Glucose fluctuation in all patients were monitored for 72h with the continuous glucose monitoring system(CGMS).High frequency ultrasound was used to detect the carotid intima-media thickness (IMT).The levels of blood lipids,glycosylated hemoglobin (HbA1c),homocysteinemia(Hcy) and C-reactive protein(C-RP) were detected in all the patients.The national institute of health stroke scale(NIHSS) was performed.The correlation between NIHSS and other observed factors were analyzed.Results (1)The mean amplitude of glycemic excursions (MAGE),blood glucose standard deviation(SDBG),absolute means of daily differences(MODD),the largest amplitude of glycemic excursions(LAGE),blood lipids,HbA1c,Hcy,C-RP and IMT were statistically significant different between the two groups (all P＜0.05); (2)The MAGE,SDBG,IMT,Hey,C-RP,low-density lipoprotein cholesterol-C (LDL-C),and systolic blood pressure(SBP) were correlated with the NIHSS score (all P＜0.05) ;(3)With NIHSS score as the dependent variable and the indicators above as the independent variables,the multiple stepwise regression analysis showed that the MAGE,IMT,Hcy came into the final equation.Conclusions The blood glucose fluctuation is probably the influential factor on the development of acute cerebral infarction in T2DM patients.Therapy for lowering blood glucose smoothly should be established as soon as possible to recover the nerve function after cerebral infarction and reduce the incidence of stroke recurrence.
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Objective To assess the factors that influence the accuracy of real-time continuous glucose monitoring system (RT-CGM).Methods A total of 79 diabetic patients wore RT-CGM for three days continuously while calibrating by interphalangeal glucose values 4-8 times a day.We counted matching rate of interphalangeal glucose values and RT-CGM probe value,and analyzed correlation of the matching rate with MAGE,SDBG,MBG,AUC10,AUC3.9,and NGE by Pearson correlation analysis and multiple linear regression analysis.Then we grouped corresponding match rate by MAGE and MBG,compared the difference among groups.Furthermore,we analyzed correlation of RT-CGM probe values of all-day,fasting-postprandial,and nighttime and the corresponding interphalangeal glucose values by Pearson correlation analysis.Results Pearson correlation analysis showed that the matching rate was negatively correlated with the MAGE,SDBG,MBG,and AUC10.MAGE,MBG,and NGE were in the regression equation.MAGE ＜3.9 mmol/L,matching rate was 81％,3.9 ≤ MAGE＜7 mmol/L,matching rate was 67％,MAGE≥7 mmol/L,the matching rate was 52％,the difference among 3 groups was statistically significant (P＜0.01).MBG＜7.8 mmol/L,matching rate was 78％,7.8 ≤ MBG＜ 10 mmol/L,matching rate was 68％,MBG ≥10 mmol/L,the matching rate was 57％,the difference among 3 groups was statistically significant (P ＜ 0.01).When Youden index was 0.409 and MAGE was less than 3.745 mmol/L,the match rate was more than 75％.When Youden index was 0.369 and MBG was less than 8.38 mmol/L,the matching rate was more than 75％.The correlation coefficients of all day,fasting,postprandial and nighttime probe values and the corresponding interphalangeal glucose values were 0.958,0.963,0.944,and 0.965 (all P＜0.01).Conclusions The probe values show good consistency with the interphalangeal glucose values,are able to be used for blood glucose assessment.Blood glucose fluctuations influences accuracy of RT-CGM,the smaller the blood glucose fluctuations,the smaller the mean glucose concentration,the smaller the effective blood glucose fluctuations in frequency,the higher would be the accuracy.It seems to be more effective to do calibration during fasting and nighttime.