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Cisplatin resistance is an important factor in the poor treatment effect of ovarian cancer patients. MicroRNA (miRNA) can regulate cellular structural molecules, DNA repair, cell cycle, apoptosis and Wnt/β-catenin signaling pathway, autophagy, methylation and cancer stem cell, which are involved in the regulation of cisplatin resistance in ovarian cancer. Further understanding the mechanism of miRNA regulation of cisplatin resistance in ovarian cancer will help find new treatment options to optimize existing treatment plans and improve efficacy.
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Objective To explore the diagnosis of clinically suspicious von Willebrand disease(vWD)in a family and its pathogene-sis.Methods The pedigree information and the biological specimen were collected from the clinically suspected VWD patient and her family members(4 persons in total)in Peking University First Hospital.The levels of platelet count(PLT),activated partial thrombo-plastin time(APTT),vWF antigen(vWF:Ag),vWF activity(vWF:Ac)and FⅧ activity(FⅧ:C)were detected,and vWF risto-cetin cofactor(vWF:RCo)assay,ristocetin-induced platelet aggregation assay(RIPA)and vWF collagen binding(vWF:CB)assay were performed for phenotype diagnosis.The peripheral blood genomic DNAs were extracted from the proband and her family members to perform whole-exome sequencing for identifying the mutation of vWF gene,The mutation site was analyzed by using bioinformation tools to explore the pathogenesis of the proband.Results The APTT of proband(m 1)was slightly prolonged and her vWF:Ag,vWF:Ac,vWF:RCo and vWF:CB were significantly decreased.There was no obvious aggregation in RIPA assay(1.0 mg/mL and 1.25 mg/mL).In her father(Ⅱ3),APTT,FⅧ:C,vWF:Ag,vWF:Ac and vWF:CB were normal,but vWF:RCo was slightly decreased.In her mother(Ⅱ4),APTT,FⅧ:C,vWF:Ag,vWF:RCo and vWF:CB were all normal,but vWF:Ac significantly decreased.In her brother(Ⅲ2),APTT and FⅧ:C were normal,but vWF:Ag,vWF:Ac,vWF:RCo and vWF:CB were reduced to varying degrees.In all the family members(father,mother and brpther),no apparent aggregation in RIPA(1.0 mg/mL)was shown.Genetic analysis showed that the proband(Ⅲ1)carried a compound heterozygous mutation of vWF gene c.7288-9T>G and c.1117C>T,her father(Ⅱ3)carried vWF gene c.7288-9T>G heterozygous mutation,and vWF gene c.1117C>T heterozygous mutation was presented in both mother(Ⅱ4)and brother(Ⅲ2).Conclusion According to the results of laboratory tests,the proband was diagnosed as type 2A vWD.The hetero-zygous mutation in vWF gene c.1117C>T and c.7288-9T>G may be the molecular mechanism leading to type 2A vWD in the proband.
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AIM: To investigate the effect of unilateral endoscopic dacryocystorhinostomy on binocular surface indexes.METHODS: Totally 45 cases with monocular primary acquired nasolacrimal duct obstruction(PANDO)who successfully underwent endoscopic dacryocystorhinostomy between 1 December 2022 and 31 July 2023 were enrolled in the study. Ocular surface indexes, including the non-invasive tear break-up time(NIBUT), Sjögren's International Collaborative Clinical Alliance ocular staining score(SICCA OSS), Korb score of lid wiper and Schirmer test scores, were collected preoperatively and at 0.5, 1 and 3 mo post-operatively. Subsequently, various indexes were compared at each time point between the operated and healthy eyes pre- and post-operatively.RESULTS: There was no significant differences between operated and healthy eyes in NIBUT, SICCA OSS, Korb scores and Schirmer test(all P>0.05). Furthermore, the Korb scores of operated eye at 0.5, 1 and 3 mo post-operatively were significantly lower than the preoperative value(P=0.034, 0.044, 0.027). Moreover, the Schirmer test score of the operated eye at 1 mo post-operatively was significantly lower than the preoperative value(P=0.0461).CONCLUSION:After a successful endoscopic dacryocystorhinostomy, tear drainage is restored, however, ocular surface damage worsens. These changes typically peak at 1 mo post-operatively before gradually improving.
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AIM: To observe the clinical efficacy of Yishen Yanggan Mingmu formula combined with anti-vascular endothelial growth factor(VEGF)in the treatment of wet age-related macular degeneration(wARMD).METHODS: A total of 58 patients(58 eyes)with wARMD who were treated in Ningbo Eye Hospital from September 2020 to November 2022 were collected. They were divided into two groups according to randomized digital table: 29 patients(29 eyes)for the combination group and the other 29 patients(29 eyes)for the injection group. The injection group was only given intravitreal injection of conbercept; the combination group was orally administrated with Yishen Yanggan Mingmu formula combined with intravitreal injection of conbercept. The best corrected visual acuity(BCVA), central macular thickness(CMT)and the improvement of traditional Chinese medicine(TCM)syndromes after 3mo of treatment were observed and the clinical efficacy was evaluated.RESULTS: After 3mo of treatment, the total improved effective rate of the combination group(76%)was higher than the rate of the injection group(66%). After the treatment, the BCVA of the two groups was both higher than that before treatment(P<0.05), the CMT in both groups was lower than that before the treatment(P<0.05), and the improvement of CMT of the combination group was better than the injection group(-155.93±143.79μm vs. -95.36±56.81μm, P<0.05). After 3mo of treatment, each kinds of TCM syndrome in the combination group were significantly improved compared with those syndromes before the treatment(P<0.001). In the injection group, only blurred vision was improved(P<0.05). After the treatment, the scores of dizziness and insomnia, soreness and weakness of waist and knees, paleness and cold limbs, dry eyes and fatigue in the combination group were significantly lower than the injection group(P<0.001).CONCLUSIONS: The Yishen Yanggan Mingmu formula combined with intravitreal anti-VEGF drug injection is effective in the treatment of wARMD.
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OBJECTIVE@#To detect the body surface temperature of the relevant back-shu points in patients with chronic persistent asthma by infrared thermal imaging technology, and observe the specific changes of the body surface temperature of the relevant back-shu points under the condition of lung disease.@*METHODS@#Forty-five patients with chronic persistent asthma (observation group) and 45 healthy subjects (control group) were selected. The body surface temperature of bilateral Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) were measured by BK-MT02A medical infrared thermography.@*RESULTS@#The body surface temperature of bilateral Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) in the observation group was higher than that in the control group (P<0.01, P<0.05). The body surface temperature of bilateral Feishu (BL 13) and Geshu (BL 17) was higher than that of ipsilateral Pishu (BL 20) and Shenshu (BL 23) in the two groups (P<0.01, P<0.05). There was no statistically significant difference in body surface temperature between ipsilateral Feishu (BL 13) and Geshu (BL 17), between ipsilateral Pishu (BL 20) and Shenshu (BL 23) (P>0.05).@*CONCLUSION@#The pathological increase of body surface temperature of Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) in patients with chronic persistent asthma indicates that above acupoints have specificity in reflecting lung diseases. The Feishu (BL 13) and Geshu (BL 17), which have significantly increased body surface temperature, not only provide objective basis for the pathological pathogenesis of "deficiency in origin and excess in symptom" in patients with chronic persistent asthma, but also reflect the different expressions of different acupoints on the same meridian for the lung diseases.
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Humans , Temperature , Asthma/diagnostic imaging , Meridians , Acupuncture Points , Acupuncture Therapy/methodsABSTRACT
BACKGROUND@#Colorectal cancer (CRC) screening is effective in reducing CRC incidence and mortality. The aim of this study was to retrospectively determine and compare the detection rate of adenomas, advanced adenomas (AAs) and CRCs, and the number needed to screen (NNS) of individuals in an average-risk Chinese population of different ages and genders.@*METHODS@#This was a retrospective study performed at the Institute of Health Management, Chinese People's Liberation Army General Hospital. Colonoscopy results were analyzed for 53,152 individuals finally enrolled from January 2013 to December 2019. The detection rate of adenomas, AAs, or CRCs was computed and the characteristics between men and women were compared using chi-squared test.@*RESULTS@#The average age was 48.8 years (standard deviation [SD], 8.5 years) for men and 50.0 years (SD, 9.0 years) for women, and the gender rate was 66.27% (35,226) vs . 33.73% (17,926). The detection rates of adenomas, AAs, serrated adenomas, and CRCs were 14.58% (7750), 3.09% (1641), 1.23% (653), and 0.59% (313), respectively. Men were statistically significantly associated with higher detection rates than women in adenomas (17.20% [6058/35,226], 95% confidence interval [CI] 16.74-17.53% vs . 9.44% [1692/17,926], 95% CI 8.94-9.79%, P < 0.001), AAs (3.72% [1309], 95% CI 3.47-3.87% vs . 1.85% [332], 95% CI 1.61-2.00%, P < 0.001), and serrated adenomas (1.56% [548], 95% CI 1.43-1.69% vs . 0.59% [105], 95% CI 0.47-0.70%, P < 0.001). The detection rate of AAs in individuals aged 45 to 49 years was 3.17% (270/8510, 95% CI 2.80-3.55%) in men and 1.69% (69/4091, 95% CI 1.12-1.86%) in women, and their NNS was 31.55 (95% CI 28.17-35.71) in men and 67.11 (95% CI 53.76-89.29) in women. The NNS for AAs in men aged 45 to 49 years was close to that in women aged 65 to 69 years (29.07 [95% CI 21.05-46.73]).@*CONCLUSIONS@#The detection rates of adenomas, AAs, and serrated adenomas are high in the asymptomatic population undergoing a physical examination and are associated with gender and age. Our findings will provide important references for effective population-based CRC screening strategies in the future.
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Humans , Male , Female , Middle Aged , Retrospective Studies , Early Detection of Cancer , Colonoscopy/methods , Adenoma/epidemiology , Colorectal Neoplasms/epidemiologyABSTRACT
Objectives To learn the echocardiography skills of intensivists after receiving a basic critical care echocardiography training course, and investigate factors that may influence their performance. Methods We completed a web-based questionnaire that assessed the skills in ultrasound scanning techniques of intensivists who took a training course on basic critical care echocardiography held in 2019 and 2020. Mann-Whitney test was used to analyze the factors which might affect their performance on image acquisition, recognizing clinical syndrome, and measuring the diameter of inferior vena cava, left ventricular ejection fraction and left ventricular outflow tract velocity-time integral.Results We enrolled 554 physicians from 412 intensive care units across China. Among them, 185 (33.4%) reported that they had 10%-30% chance of being misled by critical care echocardiography when making therapeutic decision, and 34 (6.1%) reported that the chance was greater than 30%. Intensivists who performed echocardiography under the guidance of a mentor and finished ultrasound scanning more than 10 times per week reported significant higher scores in image acquisition, clinical syndrome recognition, and quantitative measurement of inferior vena cava diameter, left ventricular ejection fraction and left ventricular outflow tract velocity-time integral than those without mentor and performing echocardiography 10 times or less per week respectively (all P < 0.05).Conclusion The skills in diagnostic medical echocardiography of Chinese intensivists after a basic echocardiographic training course remain low, and further quality assurance training program is clearly warranted.
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Humans , Clinical Competence , East Asian People , Echocardiography/standards , Stroke Volume , Ventricular Function, Left , Self-Assessment , Physicians/standards , Internal Medicine/standardsABSTRACT
We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
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Humans , Consensus , Critical Care/methods , Intensive Care Units , Pain/drug therapy , Analgesics/therapeutic use , Delirium/therapy , Critical IllnessABSTRACT
OBJECTIVE@#To elucidate the renoprotective effect of resveratrol (RSV) on sphingosine kinase 1 (SphK1) signaling pathway and expression of its downstream molecules including activator protein 1 (AP-1) and transformation growth factor-β1 (TGF-β1) in lipopolysaccharide (LPS)-induced glomerular mesangial cells (GMCs).@*METHODS@#The rat GMCs line (HBZY-1) were cultured and randomly divided into 5 groups, including control, LPS (100 ng/mL), and 5, 10, 20 µmol/L RSV-treated groups. In addition, SphK1 inhibitor (SK-II) was used as positive control. GMCs were pretreated with RSV for 2 h and treated with LPS for another 24 h. GMCs proliferation was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The proteins expression of SphK1, p-c-Jun and TGF-β1 in GMCs were detected by Western blot, and DNA-binding activity of AP-1 was performed by electrophoretic mobility shift assay (EMSA). The binding activity between RSV and SphK1 protein was detected by AutoDock Vina and visualized by Discovery Studio 2016.@*RESULTS@#LPS could obviously stimulate GMCs proliferation, elevate SphK1, p-c-Jun and TGF-β1 expression levels and increase the DNA-binding activity of AP-1 (P<0.05 or P<0.01), whereas these effects were significantly blocked by RSV pretreatment. It was also suggested that the effect of RSV was similar to SK-II (P>0.05). Moreover, RSV exhibited good binding affinity towards SphK1, with docking scores of -8.1 kcal/moL and formed hydrogen bonds with ASP-178 and LEU-268 in SphK1.@*CONCLUSION@#RSV inhibited LPS-induced GMCs proliferation and TGF-β1 expression, which may be independent of its hypoglycemic effect on preventing the development of mesangial cell fibrosis and closely related to the direct inhibition of SphK1 pathway.
Subject(s)
Animals , Rats , Lipopolysaccharides/pharmacology , Mesangial Cells , Resveratrol/pharmacology , Transcription Factor AP-1 , Transforming Growth Factor beta1 , Intercellular Signaling Peptides and Proteins , Cell Proliferation , DNA , Cells, CulturedABSTRACT
Objective:To explore the correlation between SAM domain and HD domain-containing protein 1 (SAMHD1) and programmed death-ligand 1 (PD-L1) expression in lung adenocarcinoma.Methods:The expression of SAMHD1 in lung adenocarcinoma and its effect on prognosis were analyzed by online database GEPIA and Kaplan-Meier Plotter. The expression of SAMHD1 in lung adenocarcinoma cell lines was detected by quantitative real-time PCR (qPCR) and Western blotting. SAMHD1 gene was silenced in H1975, H1299 and LLC cells by small interfering RNA transfection and lentivirus infection, respectively. The mRNA and protein expression levels of PD-L1 in lung adenocarcinoma cells of control group, siSAMHD1-1 group and siSAMHD1-2 group were detected by qPCR and Western blotting. The membrane PD-L1 level was detected by flow cytometry. A mouse lung adenocarcinoma xenograft model was constructed. The PD-L1 levels in the tumor tissues of control group and shSAMHD1 group were detected by immunohistochemistry. Cell proliferation activities of the control, siSAMHD1-1 and siSAMHD1-2 groups were detected by CCK-8 assays.Results:The GEPIA database results showed that the mRNA expression of SAMHD1 in lung adenocarcinoma was lower than that in normal lung tissue (4.81±0.90 vs. 5.99±0.76, t=20.67, P<0.001) . The median overall survival time of patients with high SAMHD1 expression was significantly longer than that of patients with low SAMHD1 expression (109.0 months vs. 87.7 months, χ2=26.83, P=0.002) . The relative mRNA expression levels of SAMHD1 in A549, PC9, H1299 and H1975 cells were 1.00±0.02, 0.75±0.05, 3.49±0.19 and 7.25±0.38 ( F=589.00, P<0.001) , and the relative protein expression levels were 1.00±0.06, 0.34±0.07, 1.67±0.22 and 2.11±0.63 ( F=15.79, P=0.001) . In H1975 cells, the relative mRNA levels of PD-L1 in the control, siSAMHD1-1 and siSAMHD1-2 groups were 1.00±0.00, 1.54±0.26 and 2.89±0.13 ( F=102.30, P<0.001) , and the relative protein expression levels were 1.00±0.01, 1.50±0.10 and 1.52±0.33 ( F=6.65, P=0.030) . In H1299 cells, the relative mRNA levels of PD-L1 in the three groups were 1.00±0.08, 1.63±0.03 and 2.14±0.03 ( F=368.80, P<0.001) , and the relative protein levels of PD-L1 were 1.00±0.07, 1.88±0.35 and 2.05±0.38 ( F=10.66, P=0.011) . The expression level of PD-L1 in the siSAMHD1-1 and siSAMHD1-2 groups was higher than that in the control group (all P<0.05) . Flow cytometry results showed that in H1975 cells, the fluorescence intensity of membrane PD-L1 in the control, siSAMHD1-1 and siSAMHD1-2 groups were 246.83±27.59, 325.60±8.00 and 308.93±7.60 ( F=17.56, P=0.003) , and in H1299 cells, the fluorescence intensity of membrane PD-L1 in the three groups were 959.00±6.25, 1 084.33±7.64 and 1 085.33±21.22 ( F=86.74, P<0.001) . The fluorescence intensity of PD-L1 in the siSAMHD1-1 group and siSAMHD1-2 group was higher than that in the control group (all P<0.05) . In xenograft mouse model, the H-SCORE of PD-L1 in the shSAMHD1 group was higher than that in the control group (7.99±1.10 vs. 4.49±0.43, t=5.13, P=0.007) . The proliferative activities of H1975 cells in the control group, siSAMHD1-1 group and siSAMHD1-2 group at 72 h were 0.50±0.02, 0.75±0.05 and 0.73±0.06 ( F=25.01, P=0.001) . The proliferative activities of H1299 cells in the three groups at 72 h were 0.80±0.01, 1.00±0.04 and 0.93±0.07 ( F=13.90, P=0.006) . The cell proliferation activity in the siSAMHD1-1 group and siSAMHD1-2 group was higher than that in the control group (all P<0.05) . Conclusion:SAMHD1 silencing induces PD-L1 expression in lung adenocarcinoma.
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Objective:To explore the effect of dynamic changes of cerebral oxygen saturation before and after treatment on the progression of infarction in patients with acute ischemic stroke (AIS).Methods:Totally 39 patients with first onset AIS within 24 hours in Tianjin First Central Hospital and Shanghai Fourth People′s Hospital Affiliated to Tongji University from May 2018 to July 2020 were enrolled retrospectively. All patients underwent multi-modal MR at admission (baseline) and within 2 weeks after standardized treatment, including diffusion weighted imaging (DWI), susceptibility weighted imaging (SWI), and dynamic magnetic sensitive contrast-enhanced magnetic resonance perfusion imaging (DSC-PWI). The degree of asymmetrically prominent cortical vein (APCV) at admission was observed on SWI, and the venous oxygen saturation (SvO 2) of APCV on the infarcted cerebral hemisphere was calculated in all patients before and after treatment. The original DWI and DSC-PWI images obtained from two MR scans were imported into the software to obtain the delayed perfusion volume [peak time (T max)>6 s] and the infarct core volume (apparent diffusion coeffivient value<620×10 -6 mm 2/s). According to the comparison of baseline infarct core (DWI-ASPECT) score and follow-up (FUP-ASPECT) score, all patients were divided into infarct progression group (27 cases) and non-infarct progression group (12 cases). Two independent sample t-test or Mann Whitney U-test were used to compare the differences of baseline infarct core volume, baseline SvO 2, SvO 2 change, baseline hypoperfusion volume and hypoperfusion volume change between the two groups. Univariate analysis and multivariate logistic regression analysis were used to obtain independent predictors of infarct progression. Pearson correlation analysis was used to evaluate the correlation between SvO 2 change, hypoperfusion volume change and infarct change score respectively. Results:Difference in baseline infarct core volume, baseline SvO 2, hypoperfusion volume and hypoperfusion volume change between infarct progression group and non-progression group had no statistical significance ( P>0.05). There was significant difference in the change of SvO 2 between the infarct progression group and non-infarct progression group after treatment [(27±11)%, (35±6)% respectively, t=-2.56, P=0.015]. Univariate logistic regression analysis showed that the change value of SvO 2 was the influencing factor of infarction progression of AIS (OR=0.872, 95%CI 0.773-0.984, P=0.026). Multivariate logistic regression analysis showed that the baseline NIHSS score (OR=1.248, 95%CI 1.042-1.494, P=0.016) was an independent predictor of infarction progression in AIS, and the change value of SvO 2 (OR=0.814, 95%CI 0.688-0.964, P=0.017) was an independent protective factor. The change of SvO 2 was positively correlated with the score of infarct change ( r=0.425, P=0.007). Conclusions:The change of SvO 2 after AIS treatment can independently predict the progress of acute infarction. Improvement of SvO 2 after treatment is conducive to delay the progress of infarction.
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Chansu has demonstrated adverse reactions in clinical settings, which is associated with its toxicity and limits its clinical applications. But there are methodological limitations for drug safety evaluation. In the current study, ultra-high performance liquid chromatography, lipidomic profiling, and molecular docking were used to systemically assess Chansu-induced acute inflammatory irritation and further identify the underlying drug targets. Compared with the EtOAc extract, Chansu water fraction containing indolealkylamines caused acute inflammatory irritation in rats, including acute pain (spontaneous raising foot reaction), and inflammation (paw edema). At the molecular level, lipids analysis revealed significantly higher levels of pro-inflammatory mediators of the COX and LOX pathways. However, anti-inflammatory mediators from the CYP 450, ALA, and DHA pathways markedly decreased after exposure to Chansu water fraction. Moreover, four indolealkylamines from Chansu showed a high theoretical affinity to a known irritation target, 5-HT
Subject(s)
Animals , Rats , Bufanolides , Edema/drug therapy , Inflammation , Lipidomics , Molecular Docking Simulation , WaterABSTRACT
Objective Focused cardiac ultrasound (FCU) and lung ultrasound (LU) are increasingly being used in critically ill patients. This study aimed to investigate the effect of FCU in combination with LU on these patients and to determine if the timing of ultrasound examination was associated with treatment change. Methods This is a multicenter cross-sectional observational study. Consecutive patients admitted to the intensive care unit (ICU) were screened for enrollment. FCU and LU were performed within the first 24 h, and treatment change was proposed by the performer based on the ultrasound results and other clinical conditions. Results Among the 992 patients included, 502 were examined within 6 h of ICU admission (early phase group), and 490 were examined after 6 h of admission (later phase group). The early phase group and the later phase group had similar proportions of treatment change (48.8%
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Humans , Critical Illness , Cross-Sectional Studies , Echocardiography , Intensive Care Units , Lung/diagnostic imaging , Retrospective StudiesABSTRACT
Objective:To summarize clinical features, diagnosis, treatment, and follow-up of children with pseudohypoaldosteronism type 1 (PHA1) and review relevant literatures to improve the understanding of the disease and reduce misdiagnosis.Methods:Six children with the main performance of salt losing treated in the Shanghai Children′s Hospital from January 2015 to December 2018, who were diagnosed as PHA1 after relevant auxiliary examinations and genetic tests.They were classified and analyzed for their treatment courses and follow-up prognosis.Results:Six children with PHA1 had varying degrees of salt losing, dehydration and infection.After the examination, 3 cases with urinary system malformations were diagnosed as secondary PHA1.Genetic testing of 2 cases revealed 2 hete-rozygous mutations c. 1439+ 1G>C and c. 875+ 1G>A in the intron region of the SCNN1A gene, and they were diagnosed as multiple target organ defect/systemic PHA1 according to American College of Medical Genetics and Genomics(ACMG) guidelines.The other case failed to be examined by genetic testing due to the refusal of parents, and was finally diagnosed as renal PHA1 according to clinical diagnosis and treatment.Conclusions:PHA1 is a rare cause of infant salt-losing syndrome, renal and secondary PHA1 children can recover quickly after sodium supplementation and the secondary factors are removed; while multiple target organ defect/systemic PHA1 has severe clinical manifestations, electrolyte imbalance is not easy to correct, and fatal arrhythmia is prone to occur, the mortality rate is high.It is easy to be misdiagnosed in clinical practice.Auxiliary examination and genetic testing can help to diagnose and classify PHA1, as well as individualized treatment.
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Novel cancer immunotherapy can treat tumors through regulating innate immunity and adaptive immune system. cGMP-AMP synthase (cGAS) is a key regulator of innate immune response to both exogenous and endogenous DNA. After recognizing the cytoplasmic DNA, cGAS produces the second messenger cyclic GMP-AMP (cGAMP), which subsequently combines with the adaptor STING (also known as MITA, MPYS and ERIS) to mediate innate immunity by inducing the production of type I interferons and inflammatory cytokines. Recent studies have revealed that the cGAS/STING signaling pathway can be activated by tumor-derived DNA and by-products of genomic instability and affect the incidence and development of tumors, which plays a critical role in the natural antitumor immunity across cancer types and immune checkpoint blockade therapy. In this article, current understanding of cGAS/STING signaling pathway in tumors was summarized, the pivotal role in tumor immunity and radiotherapy was highlighted, and the potential targeted or alternative therapy of this signaling pathway was reviewed.
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For local treatment of ulcerative colitis, a new azoreductase driven prodrug CDDO-AZO from bardoxolone methyl (CDDO-Me) and 5-aminosalicylate (5-ASA) was designed, synthesized and biologically evaluated. It is proposed that orally administrated CDDO-AZO is stable before reaching the colon, while it can also be triggered by the presence of azoreductase in the colon to fragment into CDDO-Me and 5-ASA, generating potent anti-colitis effects. Superior to olsalazine (OLS, a clinically used drug for ulcerative colitis) and CDDO-Me plus 5-ASA, CDDO-AZO significantly attenuated inflammatory colitis symptoms in DSS-induced chronic colitis mice, which suggested that CDDO-AZO may be a promising anti-ulcerative colitis agent.
Subject(s)
Animals , Mice , Colitis/drug therapy , Mesalamine/pharmacology , Nitroreductases , Oleanolic Acid/pharmacology , ProdrugsABSTRACT
Objective:To investigate the feasibility of predicting lateral cervical lymph node metastasis (LLNM) in patients with papillary thyroid carcinoma (PTC) based on the nomogram constructed by dual-energy CT data.Methods:In total 417 patients with PTC confirmed by pathology in Tianjin First Central Hospital from January 2015 to December 2018 were retrospectively analyzed as a training group. Internal validation was conducted, including 139 patients in the LLNM group and 278 patients in the non-LLNM group. A total of 169 PTC patients from January 2019 to June 2020 were included as an external validation group, including 58 patients in the LLNM group and 111 patients in the non-LLNM group. The morphological characteristics of the primary thyroid lesions on dual-energy CT iodine maps were analyzed, including tumor location, maximum diameter, calcification, and extrathyroidal extension (ETE). Iodine concentration (IC) of the PTC parenchyma and the internal carotid artery on the same level in the arterial and venous phases were measured, and normalized iodine concentration (NIC) was calculated. The independent risk factors for LLNM were obtained by univariate and multivariate logistic regression analysis. Base on the results, a prediction model was constructed and expressed in the form of a nomogram. The internal and external validation of the model was carried out using ROC curve.Results:Multivariate binary logistic regression analysis showed that the lesion location in the upper polar of the thyroid, the presence of ETE, IC in arterial phase>2.9 mg/ml, IC in the venous phase>3.2 mg/ml, and NIC in the arterial phase>0.21 were independent risk factors for LLNM prediction. The nomogram based on the above factors was constructed with an area under the ROC curve (AUC) of 0.895 (95%CI 0.862-0.923). With a cut-off value of 0.79, the sensitivity and specificity were 86.3% and 75.2%, respectively. As for the external validation group, the AUC of the model was 0.887 (95%CI 0.830-0.931), with the sensitivity of 82.8%, and the specificity of 81.1%.Conclusion:The application values of the nomogram model based on dual-energy CT data in preoperative evaluation of the possibility of LLNM of PTC patients has been verified. The model constructed in this study might be helpful with the individualized treatment in a certain degree.
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Objective To explore the effect of concave and convex interface on in vitro culture of mouse embryonic stem cells. Methods Mouse embryonic stem cells were cultured on substrate with concave and convex interface. The biological morphology of cell colony was observed. The pluripotency of embryonic stem cells was detected by immunofluorescence and alkaline phosphatase (ALP) staining. Results Embryonic stem cells on concave substrates and convex substrates had higher stereo degree and circularity than those on flat substrates, but it was more obvious on concave substrates. Besides, the expression level of Oct4-GFP and the staining intensity of ALP in embryonic stem cells which were cultured on concave substrates and convex substrates were significantly higher than those on flat basement, especially on concave substrates. Conclusion sCompared with flat substrates, concave substrates and convex substrates had positive effects on the pluripotency maintenance of embryonic stem cells, which could help to maintain pluripotency, but concave substrates had better effects. Changing the substrate curvature could help to maintain pluripotency of embryonic stem cells cultured in vitro. The research findings are of great significance to the study and clinical application of embryonic stem cells.
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Objective:To establish a method for rapid determination of iodine in whole blood by direct alkali dilution inductively coupled plasma mass spectrometry (ICP-MS).Methods:Totally 0.50 ml whole blood sample was collected, and 2% ammonia and 0.01% Triton X-100 solution were added to constitute a total volume of 10.0 ml. After shaking to uniformity, 1.0 μg/ml rhodium and 20% isopropanol were used as on-line internal standard solution. The flow ratio of internal standard solution to the solution to be measured was 1∶16. The sample was quantitatively determined by ICP-MS. The linear range, limit of detection (LOD), accuracy and precision of the method were evaluated.Results:Iodine in whole blood could be determined and had a good linear relationship within the range of 0-200 μg/L, with correlation coefficient ( r) > 0.999. The LOD of the method was 0.1 μg/L, the limit of quantitation (LOQ) was 0.3 μg/L, the recovery rate of iodine in whole blood was 88.5%-106.1%, and the relative standard deviation was 2.2%-4.7% ( n=7). Conclusions:A method for rapid determination of iodine in whole blood by direct alkali dilution ICP-MS is successfully established. This method is accurate, simple, rapid, and highly automatic, and it can be widely applied in determination of iodine in whole blood.
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Objective:To explore the appropriate radiotherapy time and method in the treatment of patients with brain metastases (BM) due to from non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation.Methods:Totally 69 EGFR-mutant NSCLC patients with BM treated in Zhongnan Hospital of Wuhan University from January 2014 to September 2018 were retrospectively reviewed. The patients were divided into two groups according to the time of brain radiotherapy, including the upfront radiotherapy group ( n=45) who received concurrent brain radiotherapy and EGFR-tyrosine kinase inhibitors(TKI)treatments and deferred radiotherapy group ( n=24) who received brain radiotherapy after intracranial progression during EGFR-TKI treatment. The upfront radiotherapy group was further divided into two groups, the group treated with WBRT concurrent with EGFR-TKI ( n=20) and the group treated with SRS concurrent with EGFR-TKI ( n=25). Overall survival (OS), progression-free survival (PFS) and intracranial progression-free survival (iPFS) time were evaluated. Results:The median OS of 69 patients was 31.2 months. For the upfront and deferred radiotherapy groups, the 1-, 2- year OS were 95%, 64% and 80%, 35%, the difference between the two groups was statistically significant. On subgroup analysis, the upfront WBRT, upfront SRS and deferred radiotherapy groups 1-, 2- year OS were 95%, 96%, 80% and 42%, 88%, 35%. Moreover, the upfront SRS group was associated with improved OS relative to the deferred radiotherapy group ( HR: 0.10, 95% CI: 0.23-0.46, P=0.003), but the upfront WBRT and deferred radiotherapy groups shared similar OS ( HR: 0.54, 95% CI: 0.21-1.32, P=0.180). There were no significant difference in iPFS and PFS between the upfront and deferred radiotherapy groups( P>0.05). Conclusions:Upfront brain radiotherapy prolonged the survival of BM patients metastasized from EGFR-mutant NSCLC. SRS concurrent with EGFR-TKI may be superior to WBRT concurrent with EGFR-TKI in the treatment of BM metastasized from EGFR-mutant NSCLC.