National Medical Journal of China
Volume 97 · Issue 34 · 2017
Natl Med J China
Liquid biopsy, coming to clinical practice
Malignant tumor is one of the major diseases that endanger human health[
The detection of circulating tumor cell in patients with liver cancer
Primary liver cancer is a malignant tumor with the fifth highest incidence among men, the third highest among women and the third highest fatality rate. It is highly prevalent in South Africa and East Asia. In recent years, the incidence rate has been increasing year by year in Europe and America[
Expert consensus on diagnosis and treatment of allergic bronchopulmonary aspergillosis
allergic bronchopulmonary aspergillosis (ABPA) is an allergic pulmonary disease caused by Aspergillus fumigatus sensitization, which manifests as chronic bronchial asthma (asthma for short) and recurrent pulmonary shadows, which may be accompanied by bronchiectasis. The disease is relatively rare and is often misdiagnosed or missed clinically[
Establishment of cut-off value of serum pro-gastrin-releasing peptide for diagnosis of small cell lung cancer and evaluation on the clinical diagnosis efficiency
To determine critical reference value (cut-off value) of serum pro-gastrin-releasing peptide (ProGRP) and neuron specific enolase(NSE) in the diagnosis of small cell lung cancer(SCLC). To evaluate the clinical significance of serum levels of ProGRP and NSE in diagnosis and differential diagnosis in SCLC.
Three hundred and fifty-two SCLC patients, 163 non small cell lung cancer(NSCLC)patients , 193 benign pulmonary disease patients and 140 healthy people visiting in National Cancer Hospital were analyzed retrospectively from January 2014 to July 2017.The levels of serum ProGRP and NSE of people were determined using electrochemiluminescent immunoassay respectively . Reference value ranges of the makers were determined by using the method of ROC curves.
In NSCLC group, benign lung disease group, healthy control group and mixed group (NSCLC+ lung benign diseases+ healthy control group) as a reference, the cut-off values were 58.3, 62.3, 57.8, 61.3 ng/L. In the diagnosis and differential diagnosis of SCLC and NSCLC, benign lung diseases, healthy controls and mixed group, AUC of ProGRP was 0.940 (0.919-0.961), 0.941 (0.921-0.960), 0.959 (0.944-0.975), 0.946 (0.928-0.963) respectively. The sensitivities of ProGRP were 86.4%, 84.9%, 86.4% and 84.7% respectively. The specificities of ProGRP were 95.7%, 96.9%, 99.3%, 98% respectively. In all groups the Youden′s index of ProGRP and NSE were 0.821 vs 0.612, 0.818 vs 0.674, 0.857 vs 0.810, 0.827 vs 0.674. In healthy controls, no statistically significant difference was found between ProGRP and NSE (P>0.05) in the diagnosis of AUC. However, in the remaining 3 groups, the ProGRP diagnosis of AUC was significantly greater than that of NSE (P<0.01). Compared with single marker detection, the sensitivity of combined detection of ProGRP and NSE in diagnosis of SCLC increased to 95.5%, 94%, 96.6% and 94% in each group. There was no significant difference between ProGRP and ProGRP+ NSE in the diagnosis of AUC when compared with the NSCLC group and the mixed group (P>0.05). However, when combined with a healthy control group and a benign lung disease group, the ProGRP+ NSE combination was the highest for AUC diagnosis, compared with ProGRP and NSE (P<0.01). In the SCLC ED group serum ProGRP and NSE levels[776.33(3 103.4)ng/L, 52.14(60.59)μg/L]were higher than those in the SCLC LD group[295.59(799.65)ng/L, 23.36(22.97)μg/L], respectively (all P<0.001). The serum ProGRP levels of N0, N1, N2 and N3 in TNM staging were 113.0(343.65), 167.04(724.56), 427.42(1 388.62), 735.99(1 709.95)ng/L respectively (all P<0.001). Serum ProGRP and NSE levels were not statistically different between the sex groups and the age groups (all P>0.05).
To establish the cut-off value of serum ProGRP is helpful for the diagnosis and differential diagnosis of SCLC.
The expression and association of CD14+ HLA-DRLow/- myeloid-derived suppressor cell-like cells and interleukin-1β in ovarian cancer
To analyze the percentage of CD14+ HLA-DRLow/- myeloid-derived suppressor cell-like cell subtypes(MDSCs) and interleukin-1β(IL-1β) concentration in peripheral blood and ascites of ovarian cancer patients, and to explore their association with clinicopathological characteristics.
Blood samples of 31 patients and ascites of 5 patients in Qilu Hospital of Shandong University from January 2016 to December 2016 were collected. Blood samples of 20 healthy volunteers with matched age were collected as control. The percentages of CD14+ HLA-DRLow/- cell subtypes in CD14+ monocytes were collected by flow cytometry and their phenotypes were analyzed. qRT-PCR was used to analyze the expression of immunosuppression factors in this subtype. ELISA was used to analyze IL-1β concentration in peripheral blood and ascites of ovarian cancer patients and healthy controls. The correlation between CD14+ HLA-DRLow/- cell percentage and IL-1β concentration was explored. The association between CD14+ HLA-DRLow/- cell percentage, IL-1β concentration and clinicopathological characteristics were analyzed.
The percentage of CD14+ HLA-DRLow/- cells in CD14+ monocytes of peripheral blood of healthy controls was (2.30±0.49)%, and the percentage in ovarian cancer patients was (3.74±0.95)%, with statistical significance (t=6.96, P<0.01). This cell subset showed similar phenotypes and factor expression with monocytic MDSCs. The percentage of CD14+ HLA-DRLow/- cells in peripheral blood ascites of ovarian cancer patients was (16.60±7.35)%, significantly higher than those in peripheral bloods (4.03±0.94)%(t=3.87, P<0.05). The concentration of IL-1β in peripheral blood of healthy controls was[3.88(0.41, 7.07)]ng/L, and the concentration in ovarian cancer patients was (12.77±3.52) ng/L, with statistical significance (Z=-4.93, P<0.01). IL-1β concentration in ascites of ovarian cancer patients was (62.17±23.05) ng/L, significantly higher than that in peripheral bloods (12.65±3.93) ng/L(t=5.20, P<0.01). IL-1β concentration was correlated with CD14+ HLA-DRLow/- cell percentage in ovarian cancer patients (R2=0.36 in peripheral blood, P<0.01; R2=0.68 in ascites, P<0.05), but not in healthy controls (R2=0.02, P>0.05). The percentage of CD14+ HLA-DRLow/- cells and IL-1β concentration were associated with metastasis and FIGO stage of ovarian cancer.
The elevated percentage of CD14+ HLA-DRLow/- cells and IL-1β concentration might involve in the development of ovarian cancer.
The value of serum human tumor protein P53 in colorectal cancer combined diagnosis and postoperative monitoring
The aim of this paper is to investigate the application value of serum human tumor protein P53 (TP53) in the diagnosis and postoperative monitoring of colorectal cancer.
One hundred and fifteen patients with colorectal cancer diagnosed without colorectal cancer and without surgery, radiotherapy and chemotherapy and total of 158 patients with colorectal benign disease and 182 healthy subjects were enrolled in this study. The levels of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) were detected by electrochemiluminescence assay. The expression of TP53 was analyzed by ELISA. Fourth-one patients with colorectal cancer were detected with one day before operation and the first seven days after operation. The expression of CEA, CA199 and TP53 was analyzed by ROC curve. The results were compared with those of CEA and CA199 diagnostic value.
The medians of the levels of TP53 in patients with colorectal cancer patients, colorectal benign, and healthy subjects are 316.0(24.6, 940.8 ) , 9.8(3.7, 30.1 ) and 1.9(1.4, 2.5 ) μg/L (H=260.161, P<0.01), respectively. The level of TP53 in patients with colorectal cancer was significantly higher than that in colorectal benign and healthy subjects. The levels of serum TP53 in patients with colorectal cancer show great discrepancies in different TNM stages, different tumor location, depth of invasion and lymph node metastasis (P<0.05) , but no difference in sex, age, and tumor growth type. The levels of TP53 in the same patient is 711.5(354.9, 1 068.0) μg/L in the first seven days after operation, significantly decreased when compared to it in the one day before the operation with the value of 952.6 (419.7, 1485.4) μg/L (Z=-1.989, P<0.05). The difference was statistically significant, and CEA, CA199 were not statistically significant. And the sensitivity (79.1%) and specificity (81.8%) of TP 53 were significantly higher than those of CEA (39.1%, 70.3%) and CA199 (47.8%, 69.1%). If TP53 was combined with CEA and CA199, sensitivity (86.1%) and specificity (87.9%) can be significantly improved, in which the area of Receiver Operating Characteristic (ROC) curve was 0.924.
Serum TP53 has a certain positive significance for the diagnosis, postoperative monitoring of colorectal cancer. Combined detection with CEA and CA199 can improve the sensitivity and specificity, implicating good clinical application value.
The localization diagnosis of patients with adrenocorticotropic hormone-dependent Cushing′s syndrome in adolescence
To elucidate the clinical characteristics and localization diagnosis of patients with adrenocorticotropic hormone (ACTH)-dependent Cushing′s syndrome (CS) in adolescence.
The clinical data, laboratory examination and localization diagnosis from 35 patients aged less than 18 years old with adolescent CS who were treated at Peking Union Medical College Hospital between January 1990 and March 2012 were analyzed.
There were 29 cases of Cushing′s disease (CD) and 6 cases of ectopic ACTH syndrome (EAS). Compared to patients with EAS, those with CD were older at diagnosis[(15.2±2.7) vs (12.8±4.4) years], and had longer disease course[(1.9±1.5) vs (0.7±0.3) years]and higher serum potassium[(3.8±0.6) vs (2.5±0.7) mmol/L], however the plasma ACTH level[(15.4±14.9) vs (42.5±22.7) pmol/L]was lower (all P<0.05). If the cut-off of the ratio of 24-hour urine free cortisol (24 h UFC) after low-dose dexamethasone suppression test (LDDST) to before LDDST was 0.65, the sensibility to diagnose CD was 70.8%, and the specificity was 100%. If the cut-off of the 24 h UFC ratio after high-dose dexamethasone suppression test (HDDST) to before HDDST was 0.54, the sensibility to diagnose CD was 91.7%, and the specificity was 100%. If the cut-off of the plasma ACTH ratio of inferior petrosal vein[bilateral inferior petrosal sinus sampling (BIPSS)]to peripheral vein was 2, only 6 CD patients (6/8) met it.
The study suggested that HDDST was more meaningful in the localization diagnosis of patients with ACTH-dependent CS in adolescence.
Modulation of umbilical cord blood mesenchymal stem cells on Treg cells in the patients with aplastic anemia
To research the modulation of Umbilical cord blood mesenchymal stem cells on the number and function of Treg cells in the patients with aplastic anemia, as well as the expression of LFA-1 on Treg cells.
A total of 20 newly diagnosed NSAA patients were collected from May 2015 to Jun 2016 in Department of Hematopathy, General Hospital of Jinan Military, and 10 healthy volunteers were recruited as controls. Separation of the patients and controls with peripheral blood mononuclear cells were divided into two groups, including PBMCs culture alone, PBMCs co-culture with UC-MSCs, application of flow cytometry detect respectively the proportion of the Treg cells and the expression of LFA-1 on Treg cells under different culture conditions. The Treg cells and CD4+ CD25-T lymphocyte were separated by magnetic cell sorting (MACS) system, CFSE label CD4+ CD25-T lymphocyte, comparing the inhibitive function of Treg cells on CD4+ CD25-T lymphocyte with or without co-culture with UC-MSCs.
The intensity of fluorescence expression of LFA-1 on T lymphocyte in aplastic anemia increased obviously((71.4±10.1)vs(52.5±8.7) , P=0.002), but the LFA-1 expressed on Treg cells had no significant difference(P=0.199). After co-cultured with UC-MSCs, the proportion of LFA-1 on Treg cells in aplastic anemia reduced greatly ((20.96±1.76)% vs(44.26±1.19)%, P=0.012), at the same time, UC-MSCs increased the proportion of Treg cells obviously ((5.33±1.14)%vs(1.94±0.65)%, P=0.003), but the effect of Treg cells on the mean frquency of dividing CD4+ CD25-T lymphocyte had no significant difference with or without co-culture with UC-MSCs(P=0.290).
The intensity of fluorescence expression of LFA-1 on lymphocyte in aplastic anemia increases obviously, indicating the possible pathogenesis of AA. UC-MSCs inhibit the expression of LFA-1 on Treg cells and enhance the proportion of Treg cells, but UC-MSCs doesn′t directly improve the immunosuppression of single Treg cells.
Effects of cell cycle regulatory genes on breast cancer neo-adjuvant chemotherapy by M-FISH
The dysregulation of cell cycle could influence cell proliferation, differentiation and response to medicine. The purpose of this study is to explore the correlation between cell cycle regulatory genes and breast cancer neo-adjuvant chemotherapy (NAC) in patients with local advanced breast cancer, and thus to find some predictors of NAC to provide guidance for clinical treatment.
Ninety five cases of local advanced breast cancer were collected, which were treated with NAC of TAC (Taxanes/Anthracycline/Cyclophosphamide) regimen. Multi-gene fluorescence in situ hybridization (M-FISH) was used to study the correlation between copy number variations of cell cycle regulatory genes (c-myc, Mdm2, CCND1, CHEK2, Rb1, p53, p16, p21) and clinical effect of NAC.
In the effective group, there were 18 cases of c-Myc amplification and 52 cases of no amplification. There were 11 cases of CCND1 amplification and 59 cases of no amplification; 12 cases of p53 deletion and 58 cases without deletion; 11 cases of p16 deletion and 59 cases without deletion. In the ineffective group, there were 12 cases of c-Myc amplification and 13 cases of no amplification; CCND1 amplification in 9 cases, no amplification in 16 cases; p53 deletion in 10 cases, no deletion in 15 cases; p16 deletion in 10 cases and no deletion in 15 cases. The copy number of the above four genes was statistically different between the two groups. C-Myc gene amplification (P=0.040), CCND1 gene amplification (P=0.033), p53 gene deletion (P=0.020) and p16 gene deletion (P=0.012) were significant correlation with poor effect of NAC. Among them, the effect of NAC in patients with two or more genes copy number variations of c-Myc, CCND1, p53, p16 were poorer than that in patients with one or not gene copy number variations (P=0.000). In addition, the copy number variations of CCND1 (P=0.049), c-Myc (P=0.049), and p16 (P=0.008) were correlated with neo-adjuvant chemotherapeutic effect respectively in Luminal breast cancer, Her-2 positive breast cancer, and triple-negative breast cancer.
These results indicated that the copy number variations of c-Myc, CCND1, p53, and p16 in patients were significant correlation with poor effect of NAC.
Therapeutic effect of AngioJet mechanical thrombus aspiration system combined with catheter directed thrombolysis on acute deep vein thrombosis
To analyze the curative effect of AngioJet mechanical thrombus aspiration combined with catheter directed thrombolysis (CDT) on acute lower extremity deep vein thrombosis (LEDVT).
The clinical data of 20 cases of acute LEDVT treated by AngioJet combined with CDT were analyzed. The inferior vena cava filter was implanted preoperatively, and then the thrombolysis was performed by using AngioJet. The thrombolytic catheter was placed for CDT treatment, and the thrombolysis was evaluated by review angiography.
All cases were successfully punctured and catheterized. The suction time was (235±75) seconds. The usage of urokinase was (180±90)*104 U. The differences before and after thrombolysis of ipsilateral and contralateral thigh circumference were (8.3±1.5) cm and (2.5±1.0) cm, respectively. The differences before and after thrombolysis of the ipsilateral and contralateral calf circumference were (2.4±1.0)cm and (1.5±0.7) cm, respectively. All of which had statistical significant (P<0.01).
AngioJet mechanical thrombus aspiration system is a novel and safe method for the treatment of acute LEDVT. When used in conjunction with CDT, its advantages was more significant.
Ischemia/reperfusion injury study in isolated mouse hearts using a pressure-volume curve
To establish and assess the feasibility and sensitivity of left ventricular elasticity, compliance and stiffness for study of ischemia/reperfusion injury in an isolated mouse heart model utilizing the pressure-volume curve framework.
An isolated, balloon-in-ventricle, isovolumically contracting, crystalloid-perfused Langendorff heart preparation was set up from 15 male C57/6BL mice aged 12-14 weeks. End-systolic pressure-volume relationship (ESPVR) and end-diastolic pressure-volume relationship (EDPVR) were obtained by measuring left ventricular (LV) systolic pressure (LVSP) and diastolic pressure under different balloon volumes. End-systolic elasticity (Ees), end-diastolic stiffness (Sed) and compliance (Ced) were calculated from the slope of ESPVR and EDPVR. Measurements of LVSP, developed pressure (LVDP), end of diastolic pressure (EDP), the rate of pressure development dp/dtmax and dp/dtmin were monitored during 30 min stabilization, 20 min global ischemia and 40 min reperfusion. The reliability and coefficient of variation (CV) of these parameters were compared with Ees and Ced.
During stabilization, the heart rate was (395±40) bpm, LVDP was (126±25) mmHg, + dp/dtmax was (5 590±625) mmHg/s, -dp/dtmin was (-4 128±625) mmHg/s, Ees was 5.7±0.3, Ced was 0.7±0.2, Sed was 1.4±0.1. Ischemia/reperfusion injury resulted in significant decrease in contractile function parameters. The recovery level of LVSP, LVDP, dp/dtmax and dp/dtmin were (57±19)%, (23±6)%, (23±7)% and (21±5)% (all P<0.001), respectively. The EDP increased to (5.4±2.0) times than the baseline after ischemia/reperfusion injury. The Ees and Ced was deceased to (42±2)% and (33±2)%, compared with baseline. The stiffness was increased up to (3.1±0.2) times higher than the baseline. The CV of Ees,Sed and Ced were lower than LVSP, LVDP, EDP, dp/dtmax,dp/dtmin,while the reliability of Ees, Sed and Ced were higher than the classic contractile function parameters.
Pressure-volume curves are feasible during ischemia/reperfusion injury in the isolated mouse heart model with acceptable reliability and sensitivity.
Effects of human mesenchymal stem cells on airway inflammation in allergic asthma mice and the underlying mechanism
To investigate the effects of human umbilical cord mesenchymal stem cells (hUC-MSCs) on airway inflammation in an ovalbumin (OVA) induced asthma mouse model and the underlying mechanism.
Twenty-four BALB/c mice were randomly divided into four equal groups: normal control group, OVA-induced asthmatic model group, hUC-MSCs treated group (50 μl of hUC-MSCs was transplanted into the trachea of asthmatic mice ) and hUC-MSCs control group (50 μl of hUC-MSCs was transplanted into the trachea of control mice). Human umbilical cord mesenchymal stem cells from umbilical cord of healthy new born babies were used as the source of hUC-MSCs for this study. The asthmatic conditions of the airways and the lungs were assessed by examining: (1) histopathological changes of the airways and the lungs; (2) expression of cytokines IL-6 and TGF-β mRNA by real-time PCR; (3) total leukocytes and mast cell count in bronchoalveolar lavage fluid (BALF) and number of IL-17-expressing CD4+ cells (Th17 cells) in the lung tissue using flow cytometry.
Typical histopathological changes of asthma were confirmed in the asthmatic model group. These changes included intensive inflammatory cell infiltration around the airways and patchy airway occlusion by hyperviscous mucus. The number of total leukocytes and mast cells in BALF were significantly increased in the asthmatic mice when compared with the control group (P<0.05). Mice in the asthmatic model group had significantly higher percentage of Th17 cells in lung tissues when compared with the control group (2.90% vs 0.76%, P<0.05). In contrast, in the asthmatic mice treated with hUC-MSCs, the inflammatory cell infiltration was significantly reduced compared with asthmatic mice, as observed by significantly lower leukocytes and mast cells in BALF (P<0.05) and significant reduction in the percentage of Th17 cells in the lung of OVA-challenged mice following hUC-MSCs treatment (percentage of Th17 cells: 0.24% vs 2.90%, P<0.05). The expression of mRNA for IL-6 and TGF-β was significantly suppressed in the hUC-MSCs treatment group (0.23 vs 2.30 and 0.56 vs 6.60, both P<0.01). No asthmatic pathological changes in both normal and hUC-MSCs control groups were observed.
hUC-MSCs significantly inhibit the airway inflammation in OVA-induced asthmatic mice. This inhibition is associated with the suppression of Th17 cells and the down-regulation of inflammatory factors such as IL-6 and TGF-β in the lungs.
Case 412 goiter-atrial fibrillation-normal TSH-FT3FT4elevated
A 47-year-old male was admitted to the Department of Endocrinology and Metabolism of Weihai Municipal Hospital on June 28, 2016 due to "neck thickening and palpitations for 7 years". The patient self-complained that 7 years ago, he found that his neck was thickened, often palpitations, fatigue and excessive sweating. The symptoms were sometimes severe and sometimes mild, which could be relieved by itself and aggravated after activity and drinking. And have had paroxysmal atrial fibrillation and persistent atrial fibrillation. Coronary stenosis was confirmed by coronary angiography in a local hospital, and coronary stenting was performed after atrial fibrillation was controlled. The atrial fibrillation was in remission for several months but did not completely disappear. Later, he was diagnosed with "hyperthyroidism" (hyperthyroidism) in a hospital in Beijing. He was given methimazole 10 mg, 3 times/d orally, and propranolol 10 mg, 3 times/d orally for 2 months. Except for palpitations, other symptoms were not significantly improved. Since the onset of the disease, there was no hand trembling, no increase in the frequency of stool, no feeling of cold and constipation, and no obvious change in weight. The patient complained that every time after taking methimazole, free triiodothyronine (FT3) and free thyroxine (FT4) did not decrease to normal, but thyroid stimulating hormone (TSH) increased, and the goiter was obviously enlarged, but the goiter shrank after stopping the drug. After taking the medication for more than 1 year, FT was reexamined multiple times3FT4All elevated, TSH normal or elevated. Later, he was suspected to be "pituitary TSH tumor", and pituitary magnetic resonance imaging (MRI) was performed, but no space-occupying lesions were found. He had a somatostatin radionuclide scan in Peking Union Medical College Hospital, and no abnormalities were found. He returned to the local area and continued to take propranolol treatment and intermittently took methimazole treatment until now. Past history: The patient had poor concentration since childhood, poor computational power and mathematics scores. Family history: His father is 155 cm tall and weighs 60 kg. He complained of being easily sleepy, relatively slow in reaction and poor in mathematics when he went to school. At home visit, the heart rate was 84 beats/min, the rhythm was homogeneous, and there was no murmur.
Effect of oral HIF stabilizer in the treatment of renal anemia
Renal anemia is one of the most common complications in patients with chronic kidney disease (CKD), and it is also the main factor that increases all-cause mortality in patients with CKD[
Research progress of early tubulointerstitial lesions in diabetes mellitus
Recent studies have found that tubulointerstitial lesions in diabetes mellitus are probably the early lesions of diabetic nephropathy (DN), and the severity of the lesions is closely related to the progression and prognosis of DN[
New progress in diagnosis and treatment of distal deep vein thrombosis
Distal deep vein thrombosis (DVT) is also known as calf DVT, subpopliteal DVT. This type of disease is relatively common, accounting for more than 30% to 50% of lower limb DVT diagnosed by ultrasound[
New progress of prognosis and early warning system for chronic and acute liver failure
acute on chronic liver failure (ACLF) is the most common type of liver failure. It was first proposed at the 2009 Asia-Pacific Annual Conference on liver Diseases and updated in 2014: ACLF refers to the onset of chronic liver disease (existing or undiagnosed) due to acute inducing effects, with clinical manifestations of jaundice [serum bilirubin ≥5 mg/dl (85 mmol/L)] and coagulation dysfunction [international standard ratio (INR) ≥1.5 or prothrombin activity (PTA)<40%], complicated with ascites and/or hepatic encephalopathy within 4 weeks[
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