Objective To observe the effect of different concentrations of glutamine(Gln)on the radiosensitivity of colorectal cancer HT-29 cells and explore the possible mechanism.Methods According to different Gln concentrations,HT-29 cells at logarithmical growth were divided into control group(2 mmol/L,as the basal medium concentration group)and experimental groups Ⅰ,Ⅱ and Ⅲ(4,6 and 8 mmol/L).After a 2-hour pre-treatment,all groups were exposed to 8 Gy irradiation of a Co-60 radiation source.CCK-8 assay and clonal formation assay were used respectively to explore the effects of different Gln concentrations on cell viability and cell radiosensitivity after irradiation.The level of reactive oxygen species(ROS)in each group was measured in 24 h after irradiation,and the apoptotic rate was detected with flow cytometry in 48 h after irradiation.The protein expression levels of Nrf2,HO-1,and cleaved-Caspase3 were determined by Western blotting.Results In 24 h after Gln intervention,the cell viability of experimental groups Ⅱ and Ⅲof non-irradiated HT-29 cells was significantly higher than that of the control group and of experimental group Ⅰ(P＜0.05).In 24 h after radiation,the cell viability of each experimental group was significantly higher than that of the control group(P＜0.05).In 14 d after radiation,there were more clone formation in each experimental group than the control group(P＜0.05).The ROS level was significantly lower in each experimental group than the control group in 24 h after radiation(P＜0.05).After 48 h of radiation,the apoptotic rate was notably lower in each experimental group than the control group(P＜0.05).The expression level of Nrf2 in the experimental group Ⅰ was higher than that of the control group(P＜0.05),those of Nrf2 and HO-1 in the experimental groups Ⅱ and Ⅲ were higher than those of the control group and experimental group Ⅰ(P＜0.05).While the expression of cleaved-Caspase3 in the experimental groups Ⅱ and Ⅲ was lower than the control group and experimental group Ⅰ(P＜0.05),and it in the experimental group Ⅲ was lower than that of experimental group Ⅱ(P＜0.05).Conclusion Gln can significantly reduce the radiosensitivity of HT-29 cells,which is associated with its reducing oxidative stress damage and reducing cell apoptosis.Our results suggest that Gln might be detrimental to radiation therapy in patients with colorectal cancer.

Objective: To investigate the representability and etiological diagnostic value of myocardium samples obtained from patients with hypertrophic cardiomyopathy (HCM) by transthoracic echocardiography-guided percutaneous intramyocardial septal biopsy (myocardial biopsy of Liwen procedure). Methods: This study was a retrospective case-series analysis. Patients with HCM, who underwent myocardial biopsy of Liwen procedure and radiofrequency ablation in Xijing Hospital, Air Force Military Medical University from July to December 2019, were included. Demographic data (age, sex), echocardiographic data and complications were collected through electronic medical record system. The histological and echocardiographic features, pathological characteristics of the biopsied myocardium of the patients were analyzed. Results: A total of 21 patients (aged (51.2±14.5) years and 13 males (61.9%)) were enrolled. The thickness of ventricular septum was (23.3±4.5)mm and the left ventricular outflow tract gradient was (78.8±42.6)mmHg (1 mmHg=0.133 kPa). Eight patients (38.1%) were complicated with hypertension, 1 patient (4.8%) had diabetes, and 2 patients (9.5%) had atrial fibrillation. Hematoxylin-eosin staining of myocardial samples of HCM patients before radiofrequency ablation evidenced myocytes hypertrophy, myocytes disarray, nuclear hyperchromatism, hypertrophy, atypia, coronary microvessel abnormalities, adipocyte infiltration, inflammatory cell infiltration, cytoplasmic vacuoles, lipofuscin deposition. Interstitial fibrosis and replacement fibrosis were detected in Masson stained biopsy samples. Hematoxylin-eosin staining of myocardial samples of HCM patients after radiofrequency ablation showed significantly reduced myocytes, cracked nuclear in myocytes, coagulative necrosis, border disappearance and nuclear fragmentation. Quantitative analysis of myocardial specimens of HCM patients before radiofrequency ablation showed that there were 9 cases (42.9%) with mild myocardial hypertrophy and 12 cases (57.1%) with severe myocardial hypertrophy. Mild, moderate and severe fibrosis were 5 (23.8%), 9 (42.9%) and 7 (33.3%), respectively. Six cases (28.6%) had myocytes disarray. There were 11 cases (52.4%) of coronary microvessel abnormalities, 4 cases (19.0%) of adipocyte infiltration, 2 cases (9.5%) of inflammatory cell infiltration,6 cases (28.5%) of cytoplasmic vacuole, 16 cases (76.2%) of lipofuscin deposition. The diameter of cardiac myocytes was (25.2±2.8)μm, and the percentage of collagen fiber area was 5.2%(3.0%, 14.6%). One patient had severe replacement fibrosis in the myocardium, with a fibrotic area of 67.0%. The rest of the patients had interstitial fibrosis. The myocardial specimens of 13 patients were examined by transmission electron microscopy. All showed increased myofibrils, and 9 cases had disorder of myofibrils. All patients had irregular shape of myocardial nucleus, partial depression, mild mitochondrial swelling, fracture and reduction of mitochondrial crest, and local aggregation of myofibrillary interfascicles. One patient had hypertrophy of cardiomyocytes, but the arrangement of muscle fibers was roughly normal. There were vacuoles in the cytoplasm, and Periodic acid-Schiff staining was positive. Transmission electron microscopy showed large range of glycogen deposition in the cytoplasm, with occasional double membrane surround, which was highly indicative of glycogen storage disease. No deposition of glycolipid substance in lysozyme was observed under transmission electron microscope in all myocardial specimens, which could basically eliminate Fabry disease. No apple green substance was found under polarized light after Congo red staining, which could basically exclude cardiac amyloidosis. Conclusion: Myocardium biopsied samples obtained by Liwen procedure of HCM patients are representative and helpful for the etiological diagnosis of HCM.
Biopsy/adverse effects* ; Cardiomegaly/pathology* ; Cardiomyopathy, Hypertrophic/diagnosis* ; Eosine Yellowish-(YS) ; Fibrosis ; Heart Defects, Congenital ; Hematoxylin ; Humans ; Lipofuscin ; Male ; Myocardium/pathology* ; Retrospective Studies

BACKGROUND: Prospective analyses have yet to identify a consistent relationship between sleep duration and the incidence of gastrointestinal (GI) cancers. The effect of changes in sleep duration on GI cancer incidence has scarcely been studied. Therefore, we aimed to examine the association between baseline sleep duration and annual changes in sleep duration and GI cancer risk in a large population-based cohort study. METHODS: A total of 123,495 participants with baseline information and 83,511 participants with annual changes in sleep duration information were prospectively observed from 2006 to 2015 for cancer incidence. Cox proportional-hazards models were used to calculate hazard ratios (HRs) and their confidence intervals (CIs) for GI cancers according to sleep duration and annual changes in sleep duration. RESULTS: In baseline sleep duration analyses, short sleep duration (≤5 h) was significantly associated with a lower risk of GI cancer in females (HR: 0.31, 95% CI: 0.10-0.90), and a linear relationship between baseline sleep duration and GI cancer was observed (P = 0.010), especially in males and in the >50-year-old group. In the annual changes in sleep duration analyses, with stable category (0 to -15 min/year) as the control group, decreased sleep duration (≤-15 min/year) was significantly associated with the development of GI cancer (HR: 1.29; 95% CI: 1.04-1.61), especially in the >50-year-old group (HR: 1.32; 95% CI: 1.01-1.71), and increased sleep duration (>0 min/year) was significantly associated with GI cancer in females (HR: 2.89; 95% CI: 1.14-7.30). CONCLUSIONS Both sleep duration and annual changes in sleep duration were associated with the incidence of GI cancer.
Cohort Studies ; Female ; Gastrointestinal Neoplasms/etiology* ; Humans ; Incidence ; Male ; Middle Aged ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Sleep

OBJECTIVE: To compare the registration accuracy of three-dimensional (3D) facial scans for the design of full-arch implant supported restoration by five methods and to explore the suitable registration method. METHODS: According to the criteria, ten patients with maxillary edentulous jaw or end-stage dentition requiring implant supported restorations were enrolled in this study. A special rim with individual feature marks reflected appropriate occlusal relationship and esthetic characteristics was made for each patient. Both 3D facial scan data of natural laughter and with opener traction to expose the teeth or occlusal rim of each patient were acquired by facial scan and input to the digital analysis software Geomagic Qualify 2012. The dataset was superimposed by five different methods: seven facial anatomical landmark points alignment, facial immobile area alignment (forehead and nasal area), facial anatomical landmark points and immobile area combining alignment, facial feature points alignment, facial and intraoral feature points alignment with the same local coordinate system. The three-dimensional deviation of the same selected area was calculated, the smaller the deviation, the higher the registration accuracy. The 3D deviation was compared among the three registration methods of facial anatomical landmark points, facial immobile area alignment and the combination of the above two methods. Friedman test was performed to analyze the difference among the three methods (α=0.05). The effect of the aid of the facial and intraoral feature points were evaluated. Paired t test were performed to analyze the difference (P<0.05). RESULTS: The average three-dimensional deviation of the selected area after alignment with the facial anatomical landmarks was (1.501 2±0.406 1) mm, significantly larger than that of the facial immobile area best-fit alignment [(0.629 1±0.150 6) mm] and the combination of the two methods[(0.629 1±0.150 6) mm] (P < 0.001). The aid of the facial feature points could significantly reduce the deviation (t=1.001 3, P < 0.001). There was no significant statistical difference in the remaining groups. CONCLUSION The forehead area of the 3D facial scan can be exposed as much as possible. The establishment of facial characteristic landmark points and the use of the invariant area alignment can improve the accuracy of registration. It should be clinically feasible to apply three-dimensional facial scan to the design of full-arch implant supported restoration with the registration of the immobile area on the face especially the forehead area.
Computer-Aided Design ; Humans ; Imaging, Three-Dimensional ; Jaw, Edentulous/diagnostic imaging* ; Maxilla/diagnostic imaging* ; Radionuclide Imaging

Objective To investigate whether elevated baseline levels of high sensitivity C-Reactive Protein (hsCRP) and neutrophil (NE) are associated with an increased risk of breast cancer in Kailuan female cohort. Methods Females from Kailuan cohort (2006-2007) were included in this study. Information on check-up, hsCRP and NE were collected at baseline for all subjects. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (95%CI) of association between baseline hsCRP and NE values and breast cancer risk. Results By December 31, 2015, a total of 18 866 participants were enrolled in this study. During the follow-up, 183 new cases of breast cancer were observed. All participants were divided into three groups according to the level of hsCRP (<1 mg/L, 1-3 mg/L and >3 mg/L). The cumulative incidence of breast cancer were 829/105, 1 211/105 and 1 495/105 in these 3 groups, respectively ( 2=12.08， P=0.002). Compared with participants with lower hsCRP levels (<1 mg/L), individuals with the highest hsCRP (>3 mg/L) levels had significantly increased risk of breast cancer (HR=1.71,95%CI: 1.18-2.47, P=0.005), howerver, we didn’t find the statistically significant association between NE level (<3.70×109/Lvs. ≥3.70×109/L) and the risk of brease cancer (P>0.05). Conclusions Elevated levels of hsCRP at baseline might increase the risk of breast cancer in females.

Objective:To investigate the count of circulating tumor cells(CTC)as well as the mutation of TP53 and PI3K gene in patients with early breast cancer, and to analyze the relationship between the gene mutation and clinicopathological features.Methods:A total of 30 patients diagnosed with breast cancer and benign breast masses were collected during January to February 2015.CellSearch method was used to detect CTCs in blood.The mutations of TP53 (p.R248Q,p.R273H,p.R175H)and PI3K(p.E545K,p.H1047R)in patients' blood,CTC,and urine were detected by droplet digital PCR techniques(ddPCR).Meanwhile,the clinical data of all patients were collected including age of onset, tumor size,histological grade,molecular typing,axillary lymph node status,and Ki-67.The relationship between the mutations and clinicopathological features was analyzed.Results:A total of 82(18.9%)were found positive mutations in 435 samples from 29 patients with blood,CTC,and urine samples.The mutation rate of each gene was different,the highest was TP53(p.R175H)with 29 samples(6.7%),the lowest was PI3K(p.E545K)having only 1 sample(0.2%).The mutation rates of five genes were statistically different(χ2 = 50.133,P< 0.001).There were significant differences in the mutation rates among five genes of CTC,blood,and urine(likelihood ratio = 14.204,P= 0.007;χ2 = 25.172,P< 0.001;χ2 =16.681,P=0.002).The highest mutation rate was TP53(p.R175H)in the three types of specimens.There was a correlation between TP53 gene mutation and the clinicopathological features of some patients with breast cancer.The molecular type of breast cancer and the degree of Ki-67 were correlated with the mutation of TP53(p.R248Q)in CTC specimen(Fisher's Exact Test = 10.839,P=0.003;P=0.028).The axillary lymph node metastasis was related to the mutation of TP 53(p.R175H) gene in CTC specimens(P=0.058).Conclusions:The molecular classification of breast cancer and the degree of tumor marker Ki-67 are associated with TP53(p.R248Q)mutation in CTC specimens from patients with early breast cancer.Axillary lymph node metastasis may also be associated with TP53(p.R175H)mutation in CTC specimens.It is suggested that the mutation of TP53 gene in CTC specimens may be a potential indicator for the selection of treatment regimen and prognosis of early breast cancer.

The objective of this prospective study of the risks of treatment failure in patients with drug-susceptible pulmonary tuberculosis (PTB) was to provide reference data to help develop a disease control strategy. Participants were recruited in eight provinces of China from October 2008 to December 2010. A total of 1447 patients with drug-susceptible PTB and older than 15 years of age were enrolled. Demographic characteristics, bacteriological test results, and patient outcome, i.e., cure or treatment failure were recorded and compared using the chi-square or Fisher's exact tests. Multivariate logistic regression was used to identify factors associated with risk of treatment failure. Of the 1447 patients who were enrolled, 1349 patients (93.2%) were successfully treated and 98 (6.8%) failed treatment. Failure was significantly associated with age 365 years [odds ratio (OR)=2.522, 95% confidence interval (CI): (1.097-5.801)], retreatment [OR=2.365, 95% CI: (1.276-4.381)], missed medicine [OR=1.836, 95% CI: (1.020-3.306)], treatment not observed [OR=1.879 95% CI: (1.105-3.195)], and positive culture result after the first [OR=1.971, 95% CI: (1.080-3.597)] and second month [OR=4.659, 95% CI: (2.590-8.382)]. The risk factors associated with treatment failure were age 365 years, retreatment, missed medication, treatment not observed, and positive culture at the end of month 1 or month 2. These risk factors should be monitored during treatment and interventions carried out to reduce or prevent treatment failure and optimize treatment success.
Adolescent ; Adult ; Aged ; Antitubercular Agents ; therapeutic use ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Mycobacterium tuberculosis ; drug effects ; physiology ; Prospective Studies ; Retreatment ; Risk Factors ; Treatment Failure ; Tuberculosis, Multidrug-Resistant ; drug therapy ; epidemiology ; microbiology ; Tuberculosis, Pulmonary ; drug therapy ; epidemiology ; microbiology ; Young Adult

OBJECTIVETo explore the mechanisms of Chinese herbal medicine Sanqi Oral Liquid, composed of Astragalus membranaceus and Panpax notoginseng, in alleviating renal injury by observing its effect on the expressions of CD4(+), CD8(+) and CD68(+) cells in 5/6 nephrectomized rats with chronic renal failure.

METHODSA total of 102 SD rats were randomly divided into six groups: three treatment groups were administrated with high, medium and low dosage of Sanqi Oral Liquid respectively by gavage; a normal group, a 5/6 nephrectomized model group, and a group treated with coated aldehyde oxygenstarch were used as controls. Following oral administration of Sanqi Oral Liquid for 12 weeks, the general condition and renal pathological changes were observed, and the renal function, platelet count (PLT) and the expressions of CD4(+), CD8(+) and CD68(+) cells were determined for each group.

RESULTSThere were proliferation of mesangial matrix, renaltubularnecrosis and obvious tubulointerstitial fibrosis in the model group, and they were much milder in the treatment groups. Compared with the model group, the amounts of blood urea nitrogen (BUN), serum creatinine (Scr) and PLT in the treatment groups decreased (P<0.05 for all); and in the group administrated of medium dosage of Sanqi Oral Liquid, the expression of CD4(+) cells was up-regulated and those of CD8(+) and CD68(+) cells were down-regulated (P<0.05 for all), leading to an increased ratio of CD4(+)/CD8(+)(P<0.01).

CONCLUSIONSanqi Oral Liquid has a significant effect on regulating lymphocyte subsets, reducing the infiltration of macrophages in renal tissues and alleviating tubulointerstitial fibrosis, and this may be one of mechanisms of Sanqi Oral Liquid in delaying the progression of chronic kidney diseases.

Administration, Oral ; Animals ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Astragalus membranaceus ; chemistry ; CD4-Positive T-Lymphocytes ; drug effects ; pathology ; physiology ; CD8-Positive T-Lymphocytes ; drug effects ; pathology ; physiology ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Kidney Failure, Chronic ; drug therapy ; immunology ; pathology ; surgery ; Lymphocyte Count ; Male ; Nephrectomy ; Panax notoginseng ; chemistry ; Rats ; Rats, Sprague-Dawley ; Solutions

Objective To estimate the incidence and mortality rates of cancers in China in 2008.Methods Data from 36 cancer registry sites in China and from the Third National Death Survey in China (2004-2005) were used to estimate the incidence and mortality of cancer in China in 2008 by using mathematical models.Prediction on cancer incidence and mortality in the next 20 years was carried out.Results According to the age-standardized incidence rates,the top cancer sites were lung,stomach,liver,breast,oesophageal,colorectal,corpus uterine,cervical,leukemia and brain tumor.According to the age-standardized mortality rates,the top cancers in China were lung cancer,liver cancer,stomach cancer,oesophageal cancer,colorectal cancer,breast cancer,cervical cancer,leukemia,brain tumor and corpus uterine cancer.Cancer happened more frequently among people older than 40 years,particularly among males.Data related to prediction showed that the incidence and mortality of cancer in China would gradually increase in the next 20 years.Conclusion Both incidence and mortality of cancers in China had been increasing,with the most common cancers appeared to be lung,breast and digestive tract cancers,in China.People older than 40 years should be under specific care to receive prevention and care on cancer,with males in particular.

In the canonical version of evolution by gene duplication,one copy is kept unaltered while the other is free to evolve.This process of evolutionary experimentation can persist for millions of years.Since it is so short lived in comparison to the lifetime of the core genes that make up the majority of most genomes,a substantial fraction of the genome and the transcriptome may-in principle-be attributable to what we will refer to as "evolutionarytransients",referring here to both the process and the genes that have gone or are undergoing this process.Using the rice gene set as a test case,we argue that this phenomenon goes a long way towards explaining why there are so many more rice genes than Arabidopsis genes,and why most excess rice genes show low similarity to eudicots.