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ObjectiveTo observe the clinical efficacy of the Modified Tongmai Anshen Formula （通脉安神方加减， MTAF） in the treatment of stable angina pectoris （SAP） with sleep disorders. MethodsA total of 148 patients suffering from SAP with sleep disorder were included and randomly divided into control group and treatment group， with 74 patients in each group. The control group received conventional western medicine， and the treatment group additionally received MTAF （1 dose per day）， both for 4 weeks. The changes in angina pectoris symptoms， traditional Chinese medicine （TCM） syndromes， sleep quality， quality of life， serological indicators including serum intercellular adhesion molecule-1 （ICAM-1） and vascular cell adhesion molecule-1 （VCAM-1）， brain-derived nerve growth factor （BDNF） and tyrosine kinase receptor B （TrkB） were compared between groups before and after treatment， and the safety was evaluated. ResultsIn the treatment group and the control group， the total effective rates of TCM syndromes（82.43% vs 52.70%）， angina pectoris （79.73% vs 64.86%） and sleep （89.19% vs 68.92%） showing significant difference （P＜0.001）. After treatment， the total TCM syndrome score， primary symptom score， secondary symptom score， and secondary symptoms sleeplessness， restlessness， tiredness and fatigue individual score， angina pectoris score， PSQI total score and each item score were all significantly reduced in both groups， while the SF-36 single item score significantly increased （P＜0.05）. The total TCM syndromes and primary symptom scores， secon-dary symptoms sleeplessness， restlessness， tiredness and fatigue individual score， angina pectoris score， time to fall asleep， sleep quality， hypnotic medication， sleep disturbance， daytime dysfunction score and PSQI total score were significantly lower in the treatment group than those in the control group after treatment （P＜0.05）， while the somatic pain， general health status， social functioning， emotional functioning， mental health， and health change were significantly higher in the treatment group （P＜0.05）. After treatment， ICAM-1 and VCAM-1 level significantly decreased （P＜0.05）， and BDNF and TrkB levels increased （P＜0.05） in the treatment group， while BDNF level significantly decreased in the control group （P＜0.05）. The TrkB level was significantly higher in the treatment group compared to the control group after treatment （P＜0.05）. A total of four adverse events occurred during the treatment， none of which were considered to be related to this study. ConclusionMTAF can significantly improve angina pectoris symptoms， TCM syndromes， sleep quality and quality of life in patients suffering from SAP with sleep disorders， the mechanism of which may be related to the protection of vascular endothelial function and central neurons.
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Objective To analyze the trend of disease burden of gastric cancer in Chinese residents from 1990 to 2019 and to provide reference for the prevention and control of gastric cancer in China. Methods The crude incidence and crude mortality rates of gastric cancer in Chinese residents of different genders from 1990 to 2019 were calculated from the Global Burden of Disease Study (GBD) database, and the standardized incidence and mortality rates were calculated to describe the trend of incidence and mortality of gastric cancer in Chinese residents. Disability Adjusted Life year (DALY) and years lived with Disability (DALY) were used. YLD, years of life lost (YLL) and other indicators were used to analyze the age and gender distribution of the disease burden of gastric cancer in Chinese residents. Joinpoint regression model was used to analyze the trend of the disease burden of gastric cancer. Results From 1990 to 2019, the incidence and crude incidence of gastric cancer increased, while the standard incidence decreased. The number of deaths was on the rise, the crude mortality rate and the standard mortality rate were both decreased, the morbidity and mortality index values of male were higher than that of female. The average annual average of the standardized DALY rate and the standardized YLL rate in China decreased by 2.30% (AAPC= -2.30%, P < 0.001), while the trend of the standardized YLD rate was not statistically significant (P=1.000). The average annual decrease rate of standardized DALY rate, standardized YLD rate and standardized YLL rate for males was smaller than that for females. In 2019, the peak rates of normalization of disease burden indicators were mainly distributed in the 55-74 age group. Conclusion From 1990 to 2019, the disease burden of gastric cancer in China showed a downward trend, and males and middle-aged and elderly people were the key prevention and treatment groups.
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Histone lysine methyltransferases (HKMTs) deposit methyl groups onto lysine residues on histones and play important roles in regulating chromatin structure and gene expression. The structures and functions of HKMTs have been extensively investigated in recent decades, significantly advancing our understanding of the dynamic regulation of histone methylation. Here, we review the recent progress in structural studies of representative HKMTs in complex with nucleosomes (H3K4, H3K27, H3K36, H3K79, and H4K20 methyltransferases), with emphasis on the molecular mechanisms of nucleosome recognition and trans-histone crosstalk by these HKMTs. These structural studies inform HKMTs' roles in tumorigenesis and provide the foundations for developing new therapeutic approaches targeting HKMTs in cancers.
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Nucleosomes , Histones/metabolism , Histone-Lysine N-Methyltransferase/metabolism , Lysine/metabolism , Methyltransferases/metabolism , MethylationABSTRACT
OBJECTIVE@#To study the feasibility and potential benefits of beam angle optimization (BAO) to automated planning in liver cancer.@*METHODS@#An approach of beam angle sampling is proposed to implement BAO along with the module Auto-planning in treatment planning system (TPS) Pinnacle. An in-house developed plan quality metric (PQM) is taken as the preferred evaluating method during the sampling. The process is driven automatically by in-house made Pinnacle scripts both in sampling and scoring. In addition, dosimetry analysis and physician's opinion are also performed as the supplementary and compared with the result of PQM.@*RESULTS@#It is revealed by the numerical analysis of PQM scores that only 15% patients whose superior trials evaluated by PQM are also the initial trials. Gantry optimization can bring benefit to plan quality along with auto-planning in liver cancer. Similar results are provided by both dose comparison and physician's opinion.@*CONCLUSIONS@#It is possible to introduce a full automated approach of beam angle optimization to automated planning process. The advantages of this procedure can be observed both in numerical analysis and physician's opinion.
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Humans , Radiotherapy Planning, Computer-Assisted/methods , Feasibility Studies , Radiometry/methods , Liver Neoplasms/radiotherapy , Radiotherapy, Intensity-Modulated/methods , Radiotherapy DosageABSTRACT
Objective To establish a solvent desorption inductively coupled plasma-mass spectrometry (ICP-MS) method for determination of iodine in workplace air. Methods Iodine in workplace air was collected with alkaline activated carbon tube and desorbed with 10.0 mL pure water or 20 mmol/L sodium bicarbonate solution. Rhenium-185 was used as an internal standard for quantification. The sample was determined in standard mode and kinetic energy discrimination collision (KED) mode by ICP-MS. Results In standard mode, iodine showed a good linear range in the concentration of 9.0 to 1 100.0 μg/L, with a correlation coefficient of 0.999 3 and a detection limit of 2.7 μg/L. In KED mode, iodine showed a good linear range in the concentration of 24.3 to 800.0 μg/L, with a correlation coefficient of 0.999 1 and a detection limit of 7.3 μg/L. The average desorption efficiency using pure water ranged from 99.1% to 106.7%, with within-run relative standard deviation (RSD) of 3.1% to 8.0% and between-run RSD of 4.9% to 9.3%. The average desorption efficiency using sodium bicarbonate solution ranged from 96.5% to 105.3%, with within-run RSD of 4.9% to 8.6% and between-run RSD of 2.5% to 9.9%. There were no statistical significant differences in the main effects of desorption solution, ICP-MS detection mode, their interaction on average desorption efficiency and within-run RSD (all P>0.05). Samples could be stored at room temperature for at least 7 days. Conclusion This method is highly sensitive, accurate, and suitable for the determination of iodine in workplace air. The sample pretreatment is simple and rapid.
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Objective:To study the effect of cardiac rehabilitation program on recovery of patients after small incision aortic valve replacement.Methods:600 patients who underwent small incision aortic valve replacement in our hospital from January 2015 to January 2020 were retrospectively collected and divided into Cardiac rehabilitation group(CR) and control group by propensity matching analysis. Clinical data of CR group and control group were collected 6 months and 12 months after the beginning of Cardiac rehabilitation program. The primary outcome measures were the peak oxygen uptake(VO 2 Peak) of cardiopulmonary function test and the number of patients attending cardiovascular specialty in tertiary hospitals after the rehabilitation program began. The secondary outcome measures were 6-minute Walk test(6-MWT), psychological evaluation, and assessment of cardiovascular disease risk factors. Results:After 6 months and 12 months of cardiac rehabilitation program, the VO2 peak in CR group was statistically significant compared with the control group, and the 6-MWT index after 12 months was statistically significant.The cardiovascular specialist visits in tertiary hospitals in the two groups were statistically significant. The comparison of psychological self-rating scale and cardiovascular disease risk factors between the two groups was statistically significant after propensity matching analysis.Conclusion:Cardiac rehabilitation has a positive effect on postoperative recovery after small incision aortic valve replacement, and can improve patients’ motor ability.
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In the electroencephalography (EEG) monitoring of patients with hypoxic-ischemic encephalopathy, generalized periodic discharges are often monitored abnormal waveforms. When there are some features of generalized periodic discharges (e.g., frequency≥1.5 Hz or plus), it indicates that the patient is at high risk for seizures or has a poor prognosis. Compared with conventional EEG, the time of continuous EEG monitoring is longer, so the detection rate of these waveforms is higher. At present, scholars at home and abroad have studied these waveforms, but there is controversy about the significance of these waveforms. In this paper, the definition and characteristics of these waveforms and their significance in determining prognosis and guiding treatment in patients with hypoxic-ischemic encephalopathy are reviewed.
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Objective:To determine the expression of glucose transporter 3 (GLUT3) in cutaneous squamous cell carcinoma (cSCC), and to evaluate its effect on the cSCC cell line A431.Methods:From June 2016 to December 2020, 22 paraffin-embedded tissue specimens were collected from patients with pathologically confirmed cSCC in the Department of Dermatology, Peking University Third Hospital, and 20 discarded normal skin tissues after dermatological surgeries served as controls. Immunohistochemical assay was performed to determine the GLUT3 expression in cSCC tissues and normal skin tissues. Cultured A431 cells were divided into two groups: GLUT3 overexpression group transfected with a lentiviral vector carrying the SLC2A3 gene, and negative control group transfected with an empty lentiviral vector. Real-time fluorescence-based quantitative PCR and Western blot analysis were conducted to determine the mRNA and protein expression of GLUT3 in A431 cells in different groups, the cell proliferation assay (MTS assay) was performed to estimate the cell proliferative activity, and the live-cell analysis system Incucyte S3 was used for real-time evaluation of the migratory and invasive abilities of A431 cells in different groups. The relative glucose consumption and lactic acid production in A431 cells at 48 hours were measured by using glucose and lactic acid assay kits, retrospectively. Two independent samples t-test was used for comparisons between two groups, and one-way analysis of variance was used for comparisons among multiple groups. Results:The GLUT3 expression was significantly higher in the cSCC tissues than in the normal skin tissues (immunohistochemical assay score: 9.39 ± 2.56 points vs. 2.30 ± 2.60 points; t = 8.91, P < 0.05). Compared with the negative control group, the mRNA and protein expression of GLUT3 markedly increased in the GLUT3 overexpression group. MTS assay showed significantly increased proliferative activity of A431 cells in the GLUT3 overexpression group compared with the negative control group after 24- and 96-hour treatment ( t = 2.49, 3.54, P = 0.048, 0.012, respectively); cell fusion rates in the scratched area were significantly higher in the GLUT3 overexpression group than in the negative control group in the cell migration assay at 6, 12 18, and 24 hours and cell invasion assay at 12, 18, and 24 hours (all P < 0.05). At 48 hours, the relative glucose consumption and lactic acid production in A431 cells were significantly higher in the GLUT3 overexpression group than in the negative control group ( t = 2.98, 2.20, P = 0.011, 0.038, respectively) . Conclusion:GLUT3 was highly expressed in the cSCC tissues, and may participate in the occurrence and development of cSCC by providing energy to cSCC cells via promoting glucose uptake in cells to enhance their proliferative, migratory and invasive abilities.
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Recently, great breakthroughs have been made in the treatment of melanoma with immune checkpoint inhibitors. However, only a small proportion of patients show a long-lasting response to immunotherapy, and risks of immune-related adverse events and drug resistance have been also increasing along with the emergence of combination treatment. This review summarizes biomarkers related to the efficacy of immune checkpoint inhibitors in the treatment of melanoma, aiming to predict and screen out patients who may benefit from immunotherapy, guide individualized clinical treatment, and reduce the occurrence of drug resistance and adverse reactions.
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A growing number of studies have shown that gut microbiota affects the development of melanoma through various mechanisms, and plays a vital role in the treatment of melanoma. This review summarizes the relationship between gut microbiota and the development of melanoma, the effect of gut microbiota on the checkpoint blockade immunotherapy of melanoma and related adverse effects.
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Objective:To explore the relationship between metabolic score for insulin resistance (METS-IR) and chronic kidney disease (CKD) and albuminuria in the Chinese population.Methods:This cross-sectional study was conducted from January to December 2018 among residents aged 20 to 70 years in ten regions of eight provinces in China; all residents had lived in their region for more than 5 years. Various parameters were measured, included fasting blood glucose, 2-hour postprandial blood glucose, glycosylated hemoglobin (HbA 1c), blood lipids, renal function, urinary albumin/creatinine ratio (UACR), etc. Data of 5 060 subjects meeting the criteria were included in the study. CKD was defined as estimated glomerular filtration rate (eGFR)<60 ml·min -1·1.73 m -2 or UACR≥30 mg/g. Albuminuria was defined as UACR≥30 mg/g. METS-IR was calculated and categorized into quartiles: Q1, METS-IR≤32.19; Q2, METS-IR 32.20-37.10; Q3, METS-IR 37.11-42.58; and Q4, METS-IR>42.58. The correlation between METS-IR and CKD and albuminuria was analyzed by binary logistic regression, and subgroup analyses were performed. Results:There were 1 266, 1 266, 1 265, and 1 263 participants included in Q1-Q4 groups, respectively. With the increase of METS-IR quartile, various parameters increased, including age, fasting blood glucose, HbA 1c, triglycerides, serum uric acid, waist circumference, body mass index, and systolic and diastolic blood pressure, and the proportion of males also increased (all P<0.05). The proportion of patients with CKD and albuminuria increased significantly with the increase in interquartile range (Q) of METS-IR (all P<0.05). Logistic regression analysis showed that for every 1-unit increment of METS-IR, the risk of CKD and albuminuria were both increased by 2% [for both: odds ratio ( OR)=1.02, 95% confidence interval ( CI) 1.01-1.03]. Compared with the lowest METS-IR group (Q1), the ORs for CKD and albuminuria in the highest METS-IR group (Q4) were 1.57 (95% CI 1.17-2.10) and 1.46 (95% CI 1.09-1.96), respectively. In the subgroup analyses, increased METS-IR was significantly associated with CKD and albuminuria among women (CKD: OR=1.62, 95% CI 1.14-2.31; albuminuria: OR=1.53, 95% CI 1.07-2.18), individuals with HbA 1c<7% ( OR=1.64, 95% CI 1.21-2.23; OR=1.55, 95% CI 1.14-2.11), individuals with eGFR≥90 ml·min -1·1.73 m -2 ( OR=1.78, 95% CI 1.27-2.49; OR=1.80, 95% CI 1.28-2.53), and the Chinese Han population ( OR=1.56, 95% CI 1.13-2.17; OR=1.41, 95% CI 1.01-1.96). Conclusions:METS-IR is significantly associated with CKD and albuminuria in a Chinese population. Furthermore, the higher the METS-IR, the higher the risk of CKD and albuminuria.
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Objective:To explore the predictive value of transrectal multimodal ultrasound and prostate specific antigen (PSA) in clinically organ-confined prostate cancer.Methods:It was a cross-sectional study. The clinical data of patients with suspected prostate nodules treated in the First Hospital of Shanxi Medical University from May 2014 to April 2020 were analyzed retrospectively. Of the patients, 48 cases of clinically organ-confined prostate cancer and 51 cases of benign prostatic hyperplasia confirmed by clinical data and pathology were selected as research objects. The characteristics of transrectal multimodal ultrasound in the two groups were compared. Combined with PSA, logistic regression analysis was applied to screen the statistically significant features, and then the diagnosis model was established, and odds ratio of the variables were compared. The receiver operating characteristic (ROC) curve was constructed to analyze the predicting ability of the diagnosis model.Results:Four features were obtained with logistic regression analysis finally, including enhancement type, enhancement degree, elastography mode and PSA. The odds ratio of enhancement degree was higher than those of the other independent variables. The area under ROC curve of the diagnosis model was 0.868 ( P<0.01), the cut-off value was 0.514. The sensitivity and specificity of the diagnosis model in predicting clinically organ-confined prostate cancer was 79.2% and 80.4%, respectively. Conclusions:This combined diagnosis model of transrectal multimodal ultrasound and PSA has a certain clinical value in predicting clinically organ-confined prostate cancer.
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Objective:To investigate the risk factors of long-term mortality in patients with acute pulmonary embolism (APE) and to explore the predictive value of echocardiography.Methods:A total of 109 APE patients admitted in First Hospital of Shanxi Medical University between December 2010 and November 2014 were enrolled in this study. APE was diagnosed by computed tomography pulmonary angiography (CTPA) or ventilation-perfusion pulmonary scintigraphy. Transthoracic echocardiography (TTE) parameters and clinical parameters within 48 h of onset were collected. All the patients were treated with standard anticoagulation, thrombolysis, or thrombectomy. Regular follow-up was carried out, with the average follow-up period of (7.20±1.04) years. The patients were divided into survival group and fatal group according to their follow-up results. The echocardiographic parameters and primary biochemical laboratory parameters within 48 h after onset were compared between the survival group and the fatal group by t test or χ 2 test. Cox regression analysis was conducted to analyze the influencing factors of long-term prognosis of patients with APE. Survival analysis was performed in patients with echocardiographic assessment of right ventricular (RV) enlargement and/or dysfunction and without RV enlargement and/or dysfunction by Kaplan-Meier method, and the survival curves were plotted. The comparison between the two groups was performed by log-rank test. Results:The average follow-up period was (7.20±1.04) years. Fourteen patients were lost in the follow-up, and 95 patients were included in the final analysis, among whom 58 survived and 37 died with a fatality rate of 39.0%. Cox regression analysis showed that age ( HR=2.32, 95% CI:1.31-4.13, P=0.004), malignancy ( HR=6.49, 95% CI:2.32-18.14, P<0.001), right atrial (RA)/left atrial (LA) area ratio ( HR=2.01, 95% CI:1.16-3.48, P=0.013), RV enlargement and/or dysfunction ( HR=5.90, 95% CI: 1.45-23.94, P=0.013), Charlson comorbidity index (CCI) score ( HR=1.75, 95% CI: 1.04-2.96, P=0.035), low oxygen saturation ( HR=1.70, 95% CI:1.14-2.53, P=0.009) were independent risk factors associated with long-term mortality in patients with APE. Kaplan Meier survival curve analysis showed that the cumulative survival rates of patients with RV enlargement and/or dysfunction at 1, 3, 5 and 7 years were 92.8%, 66.7%, 59.4% and 52.2% respectively, and those without RV enlargement and/or dysfunction were 96.2%, 92.3%, 84.6% and 84.6%,respectively (log rank test, P=0.006). Conclusions:Patients with APE have high long-term mortality. Early echocardiographic RV enlargement and/or dysfunction, RA/LA area ratio, age, malignant tumor, CCI score and low oxygen saturation are independent risk factors related to long-term mortality in patients with APE. Ultrasound evaluation of patients with RV enlargement and/or dysfunction has a certain value in predicting long-term mortality in patients with pulmonary embolism.
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Objective:To investigate associations between clinicopathological characteristics and mutations in susceptibility genes in cutaneous melanoma (CMM) .Methods:A total of 94 patients with confirmed CMM were collected from People′s Hospital of Xinjiang Uygur Autonomous Region from January to December in 2019, and their clinical and histopathological characteristics were retrospectively analyzed. In 48 paraffin-embedded melanoma tissue specimens, Sanger sequencing was performed to detect mutations in the BRAF, NRAS, c-KIT genes and the promoter region of human telomerase reverse transcriptase (hTERT) gene, and the association between gene mutations and clinicopathological characteristics was analyzed. Measurement data were compared using t test, and enumeration data were compared using chi-square test or Fisher′s exact test. Results:Among the 94 patients with CMM, there were 46 (48.9%) males and 48 (51.1%) females, with the age being 58.5 ± 16.0 years; 41 (43.6%) patients were of Han nationality, and 53 (56.4%) were of ethnic minorities. Skin lesions were located at the acral sites in 50 (53.2%) patients, including 27 (28.7%) of Han nationality; non-acral skin lesions occurred in 44 (46.8%) , including 14 (31.8%) of Han nationality; there was a significant difference in the nationality distribution between the acral CMM group and non-acral CMM group ( χ2 = 5.25, P = 0.022) . Histopathological examination showed CMM of Clark grades Ⅳ or Ⅴ in 41 (43.6%) cases, ulcers in 52 (55.3%) cases, and lymph node metastasis in 32 (34.04%) cases at the first clinic visit. Gene sequencing revealed BRAF gene mutations in 11 (22.9%) of 48 cases, including c.1799 T>A (p.V600E) , c.1790 T>A (p.L597Q) and c.1394 C>T (p.S465F) ; NRAS gene mutation c.182 A>G (p.Q61R) was identified in 5 (10.4%) cases; c-KIT gene mutations were identified in 6 (12.5%) cases, including c.1727 T>C (p.L576P) and c.1669 T>C (p.W557R) ; mutations in the promoter region of hTERT gene were identified in 7 (14.6%) cases, including 4 cases with a mutation at 124 bp upstream of the ATG start codon (C228T) and 3 cases with a mutation at 146 bp upstream of the ATG start codon (C250T) . Among 26 patients aged < 60 years, BRAF gene mutations were found in 9, and the incidence of BRAF gene mutations was significantly higher in the patients aged < 60 years than in those aged ≥ 60 years (2/22, P < 0.05) , but significantly lower in the patients with acral CMM (3/27) than in those with non-acral CMM (8/21, P < 0.05) ; the incidences of the NRAS, c-KIT and hTERT gene mutations were all significantly higher in the patients with lymph node metastases (3/10, 4/10, 4/10, respectively) than in those without (2/38, 2/38, 3/38, respectively, all P < 0.05) . Conclusion:CMM lesion locations significantly differed among different ethnic groups; the BRAF gene mutation was associated with the age of patients and lesion locations of CMM; NRAS, c-KIT gene mutations and hTERT promoter mutations were closely related to lymph node metastasis.
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Objective:To evaluate the efficacy and safety of apatinib in combination with chemoradiotherapy for head and neck squamous cell carcinoma (HNSCC).Methods:37 patients orally received apatinib at 250 mg/d during concurrent chemoradiotherapy until completion of radiotherapy, complete remission assessed by imaging examination, the onset of unacceptable toxicity or death. Baseline characteristics, objective response rates (ORR) and adverse events were assessed in all enrolled patients with complete baseline and safety data. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. Prognostic factors were statistically identified using Cox regression models.Results:The ORR was 85%(95% CI: 72%-98%). The median PFS was 17.9 months and the 2-year OS rate was 62%(95% CI: 48%-80%). Ineffective short-term efficacy ( HR=0.035, 995% CI: 0.02-0.652, P=0.025) was an independent risk factor for poor OS. In addition, ineffective short-term efficacy ( HR=0.104, 95% CI: 0.017-0.633, P=0.014) and lymphocytopenia ( HR=17.539, 95% CI: 2.040-150.779, P=0.009) were independent risk factors for poor PFS. Common adverse events (>60%) included lymphocytopenia (76%), leukopenia (68%) and irradiation-induced mucosal injury (65%). The most common treatment-associated grade 3 adverse event was lymphopenia (49%). Conclusions:Apatinib combined with chemoradiotherapy yield significant anti-tumor activity for HNSCC with controllable toxicity. For patients with advanced HNSCC, short-term efficacy and lymphocytopenia may be potential predictors for clinical efficacy of apatinib combined with chemoradiotherapy.
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Objective:To investigate the risk factors of postoperative acute respiratory distress syndrome (ARDS) in patients with esophageal cancer.Methods:The clinical data of patients with esophageal cancer who underwent surgery in the Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University from January 2020 to April 2021 were retrospectively analyzed, 223 patients were enrolled. The patients were divided into ARDS group (28 cases) and non-ARDS group (195 cases) according to whether ARDS occurred after surgery. The clinicopathological features of the two groups were compared, and the risk factors of postoperative ARDS were analyzed by univariate and multivariate logistic regression.Results:The age of patients in the ARDS group was higher than that in the non-ARDS group [(70±4) years old vs. (66±7) years old, P = 0.024]. The proportion of patients with history of chronic obstructive pulmonary disease (COPD) in the ARDS group was higher than that in the non-ARDS group [25.0% (7/28) vs. 4.6% (9/195), P < 0.001]. There were no statistical differences in gender, systolic pressure, body mass index, left ventricular ejection fraction, laboratory related examinations, history of smoking, history of diabetes, history of hypertension, history of cardiovascular disease, history of cerebrovascular disease, pathological type, tumor location, tumor stage and postoperative complications between the two groups (all P > 0.05). After further adjusting for gender, multivariate logistic regression analysis showed that the old age (≥65 years old) ( OR = 4.581, 95% CI 1.299-16.154, P = 0.018) and the history of COPD ( OR= 5.493, 95% CI 1.644-18.358, P = 0.006) were independent risk factors for postoperative ARDS in patients with esophageal cancer. Conclusions:Esophageal cancer patients with an age of ≥65 years old or history of COPD have a high risk of postoperative ARDS. Age and history of COPD may have certain significances in judging the occurrence of postoperative ARDS in patients with esophageal cancer.
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Objective:To investigate the effect of the methyltransferase inhibitor azacitidine (5-azaC) on the expression of homeobox A9 (HOXA9) gene in, as well as proliferation, invasion and migration of A375 cells.Methods:In vitro cultured A375 cells were treated with 5-azaC at various concentrations of 1, 5, 10 and 20 μmol/L, while routinely cultured A375 cells receiving no drug intervention served as control group. Methylation-specific PCR was performed to analyze methylation status of the HOXA9 gene promoter region after the treatment with different concentrations of 5-azaC, in order to screen the optimal concentration of 5-azaC for following experiments. Cell counting kit-8 (CCK8) assay was conducted to evaluate the proliferation of A375 cells, Transwell and wound healing assays were performed to estimate the invasion and migration of A375 cells, and real-time fluorescence-based quantitative PCR (qRT-PCR) and Western blot analysis were conducted to determine the mRNA and protein expression of HOXA9 in A375 cells after 5-azaC treatment. Two-independent-sample t test was used for comparisons between two groups. Results:Methylation was observed in the HOXA9 gene promoter region in A375 cells in the control group. After 5-azaC treatment, methylated and unmethylated states coexisted in the HOXA9 gene promoter region in A375 cells, and the higher the concentration of 5-azaC, the higher the degree of demethylation of the HOXA9 gene. Therefore, 20 μmol/L 5-azaC was selected to treat A375 cells for 72 hours, which served as 5-azaC treatment group in subsequent experiments. Compared with the control group, the 5-azaC treatment group showed significantly decreased cellular proliferative ability (72.46% ± 2.19% vs. 100%, t = 28.09, P < 0.001) , significantly decreased number of invasive cells (242.70 ± 29.19 vs. 466.00 ± 22.65, t = 10.47, P < 0.001) , significantly decreased migratory ability (27.56% ± 2.74% vs. 35.69% ± 2.50%, t = 3.79, P = 0.019) , significantly increased HOXA9 mRNA expression (1.73 ± 0.28 vs. 1.01 ± 0.15, t = 3.93, P = 0.017) , and significantly increased HOXA9 protein expression (0.62 ± 0.03 vs. 0.50 ± 0.01, t = 3.82, P = 0.019) . Conclusion:5-azaC can inhibit the proliferative, invasive and migratory ability of A375 melanoma cells, and one of the possible mechanisms underlying this process may be that 5-azaC reverses the methylation in the HOXA9 gene promoter region, activates HOXA9 gene expression, and participates in the regulation of biological behaviors of melanoma cells.
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Objective:To evaluate the relationship between thalamocortical glutamate and neuronal activity in mice with neuropathic pain-induced sleep disorders.Methods:SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 15-25 g, were divided into 2 groups ( n=14 each) using a random number table method: sham operation group (Sham group) and neuropathic pain group (CCI group). Neuropathic pain was induced by chronic constrictive injury (CCI). The animals were anesthetized with intraperitoneal 10% chloral hydrate 3 ml/kg.The right sciatic nerve was exposed and 4 ligatures were placed on the sciatic nerve at 1 mm intervals.The mechanical paw withdrawal threshold and thermal paw withdrawal latency on the operated side were measured at 1 day before CCI (T 0) and 3, 5, 7, 14 and 21 days after CCI (T 1-5). Electroencephalogram recording electrodes were stereotaxically implanted in visual cortex at T 3, and electroencephalogram were monitored for 6 h, the percentages of non-rapid eye movement, rapid eye movement and wakefulness in the total time were calculated.Microwire electrodes were implanted epidurally over the ventral posterior (VP) nucleus of the thalamus and primary somatosensory cortex (S1) using a brain stereotaxic apparatus at T 3, and the data acquisition system was used to record field potentials at T 4, the percentage of power of each wave was calculated, and the coherence of the field potentials of VP and S1 was simultaneously evaluated.The mice were sacrificed at T 4, brain tissues were collected, and proton nuclear magnetic resonance spectroscopy was used to determine the level of neurotransmitter in the thalamus and cortex. Results:Compared with group Sham, the mechanical paw withdrawal threshold was significantly decreased and thermal paw withdrawal latency was shortened at T 1-5, the percentage of non-rapid eye movement time was decreased, the percentage of wakefulness time was increased, the percentage of δ wave power in the VP area was decreased, the percentage of δ wave power in the VP and S1 areas was increased, and the coherence of the field potentials of VP-S1 was increased in the frequency range of δ wave (1-4 Hz) and α wave (8-14 Hz), and the levels of glutamate, glutamine and glutamate-glutamine in the thalamus and cortex were increased in group CCI ( P<0.05). Conclusions:Neuropathic pain-induced sleep disturbance is related to increased thalamocortical glutamate levels, resulting in changes in the electrical activity of thalamocortical neurons of mice.
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Objective:To retrospectively analyze the relationship between patterns of local recurrence and radiotherapy target dose after adjuvant radiotherapy for the pancreatic ductal adenocarcinoma(PDAC), aiming to provide reference for exploring reasonable target and dosage.Methods:Clinical data of 138 patients with T 1-4N 0-2M 0 PDAC who underwent adjuvant radiotherapy after radical resection from April 2012 to December 2020 were analyzed retrospectively. The influencing factors of local recurrence and the correlation between local recurrence site and radiotherapy target dose were analyzed. Results:The median follow-up time was 37.2 months. The median overall survival (mOS) was 29.9 months. The 5-year OS rate was 27.4%. And the median progression-free survival (mPFS) was 13.9 months. There were 24 cases of local recurrence (17.4%), and 10 cases of local recurrence complicated with distant metastasis (7.2%). The correlation between local recurrence site and radiotherapy target dose could be evaluated in 19 patients with complete clinical data. The first local recurrence occurred near the para-aortic (Ao), the celiac axis (CA) and the superior mesenteric artery (SMA) were 8, 5 and 4 cases, respectively. The radiotherapy doses of 8 patients with local recurrence only in the PTV field were above 45 Gy. There were 8 cases of local recurrence both in and out of the PTV field, including 3 cases with dose line between 40 and 52 Gy, 2 cases with dose line between 20 and 47.5 Gy, and 3 cases with dose line between 0.5 and 52.5 Gy. There were 3 cases of local recurrence out of the PTV field, and the dose line ranged from 0 to 20 Gy.Conclusions:The local recurrence rate of PDAC after radical surgery combined with postoperative radiotherapy is low, but a small number of patients have recurrence in the high-dose range of radiation field and regional recurrence out of the field. For these patients, it may be necessary to explore a more appropriate target dose and range for adjuvant radiotherapy.
ABSTRACT
Objective:To investigate the effects of piperine on experimental colon carcinogenesis induced by 1, 2-dimethylhydrazine (DMH)/sodium dextran sulfate (DSS) and its mechanism.Methods:36 mice were divided into control group, model group and piperine group, 12 mice in each group. The control group was given normal saline by gavage; The model group and piperine group were given 3.6 mg/(kg·d) of normal saline and piperine respectively after establishing the experimental colon cancer model induced by DMH/DSS. Tumor load and volume were observed. Hematoxylin and eosin (HE) staining was used to observe the histological change of colon in mice. RAS/PI3K/AKT related pathway protein expression was detected by Western blot.Results:The body weight gain, protein expression levels of cleaved poly-ADP ribose polymerase (PARP), cleaved caspase-3 in model group were significantly lower than those in the control group (all P<0.05). The protein expression levels of Bcl-2, Bax, pan-Ras, p-MEK, p-ERK, PI3K, p-AKT, NF-κBP65, c-Myc and cyclin D1 in model group were significantly higher than those in the control group (all P<0.05). The body weight gain, protein expression levels of cleaved PARP and cleaved caspase-3 in piperine group were significantly higher than those in model group (all P<0.05). The protein expression levels of Bcl-2, Bax, pan-Ras, p-MEK, p-ERK, PI3K, p-AKT, NF-κBP65, c-Myc and cyclin D1 in piperine group were significantly lower than those in model group (all P<0.05). Conclusions:Piperine can inhibit the occurrence of experimental colon cancer induced by DMH/DSS, which may involve multiple components of RAS/PI3K/AKT signal axis.