Volume 92  ·   Issue 36  ·  2012

In recent years, the number of patients with impaired immune function caused by various reasons is increasing day by day, concentrated in the field of organ transplantation, blood diseases, malignant tumor diseases, rheumatic immune system diseases, chronic liver and kidney diseases, chronic lung diseases, AIDS and diabetes. The author has discussed the diagnosis ideas of pulmonary complications in immunocompromised patients and mechanical ventilation treatment strategies for secondary respiratory failure in immunocompromised patients [1-2], but still feels that the understanding of this field is not deep enough. Now, the etiology of respiratory failure in immunocompromised patients is discussed as follows.

During the implementation of the "Clinical Research Development Strategy Research" project, which organized clinical research pre-research for the 12th Five-Year Plan of China, the Chinese Medical Association organized experts from clinical epidemiology, clinical medicine, epidemiology, statistics and medical research management to conduct extensive and in-depth discussions on the basic characteristics of "clinical research", and formed the following consensus: Clinical research is a scientific research activity organized and implemented by multi-disciplinary personnel with the main research content of diagnosis, treatment, prognosis and etiology of diseases, patients as the main research object, medical service institutions as the main research base, and multi-disciplinary personnel participating in the organization and implementation. This consensus has been written in the "Research Report on Clinical Research Development Strategy", which has become the basis for guiding and promoting the development of clinical research in China. The core of this consensus is to clarify the four basic characteristics of clinical research. An in-depth analysis of the basic characteristics will help us to understand the essence of clinical research, clarify what practical problems can be solved by clinical research, To clarify what problems should be paid attention to in the organization and implementation of clinical research.

Objective To explore the causes of postoperative anastomotic leakage of colorectal cancer.Methods A total of 1462 cases with colorectal cancer undergoing laparoscopic operation and intestinal anastomosis at our department over the last decade were analyzed retrospectively.Data analysis was performed with SPSS 13.0. The risk factors were analyzed by binary Logistic regression while the annual incidence of anastomotic leakage by trend X2 test. Results Thirty anastomotic leakage occurred in 1462cases with an incidence rate of 2.1％.There were significant correlations of anastomotic leakage with body built,tumor location,tumor size,operation time (X2 =6.117,50.167,36.693,4.481,P =0.013,0.000,0.000,0.034). However,there was no correction with gender,age or histological type ( P =0.871,0.775,1.000).Then the significance check of binary Logistic regression equation was performed. Tumor location was an independent risk factor of postoperative anastomotic leakage for colorectal cancer. The relative risk was 2.056.The annual incidence of anastomotic leakage was statistically insignificant (X2 =1.827,P =0.176). And the difference was. Conclusions The occurrence of anastomotic leakage after colorectal cancer surgery is significantly correlated with body built,tumor location,tumor size and operation time.And tumor location below peritoneal reversal is an independent risk factor of anastomotic leakage.

Objective To analyze the combination of hypertension and the use of antihypertensive drugs by different glucose tolerance status.Methods Matched case-control design was used to sample the subjects from the population for the prevalence of diabetes mellitus and metabolism syndrome from 2007 to 2008.There were 3 groups including normal glucose tolerance (NGT, n =2124), impaired glucose regulation (IGR,n =2162) and diabetes (DM,n =2470).The matched factors were location,age and gender.All subjects were interviewed to describe the hypertension and antihypertensive drugs of these conditions.Results After adjusting for age,gender and location,the combination of hypertension in IGR and DM groups was higher than NGT (28.3％,40.2％ and 19.9％ ) and OR was 1.29 ( 1.08 - 1.53) and 1.99 ( 1.67 - 2.37 ) respectively.The percent of treatment,prescription compliance and the surveillance of hypertension in total subjects were 48.6％,79.3％ and 62.5％. And no difference wasobserved among 3 groups.The proportion of calcium channel blocker of DM groups was higher than NGT group.The uses of angiotensin-converting enzyme inhibitors ( ACEI ) and angiotensin Ⅱ receptor blocker ( ARB ) showed no difference among 3 groups.Conclusions The combination of hypertension is higher in IGR and DM groups than that in NGT group. And the treatment rate of hypertension remains low. ACEI and ARB are underutilized in IGR and DM groups.

Objective To enhance the understandings of clinical,radiological and pathological features of hypersensitivity pneumonitis (HP).Methods Six HP cases with pathological data,clinical and radiological data were retrospectively analyzed during the period from February 2009 to September 2011 at Beijing Hospital of Ministry of Health. There were 2 males and 4 females with a mean age of 51.5 years (range:38-61 ). Clinically,the patients presented with chronic cough,shortness of breath and dyspnea (n =2 ). The disease course was 1 -8 months. Five cases had fed pigeons and other contact histories.Specimens obtained by transbronchial lung biopsy ( n =3 ) and open lung biopsy ( n =(3)) were paraffin embedded and stained by hematoxylin and eosin,special stains and immunohistochemistry.Results Four cases had subacute HP and 2 cases chronic HP.Three cases of subacute HP underwent transbronchial lung biopsy.One case of subacute HP and 2 cases of chronic HP were diagnosed by open lung biopsy. High-resolution computed tomography of lungs showed diffuse ground glass and patch shadow along the bronchial and centrilobular distributions. There was a predominance of upper half zone. Typical visible mosaic syndrome was present. There was poorly formed granuloma without cheesy necrosis. With an insidious medical history and complicated radiological features,chronic HP cases were characterized by pulmonary interstitial fibrosis.There were usual interstitial pneumonitis (UIP)-like fibrosis and fibrosis with an airwaycentered distribution type.The lesions were distributed around bronchioles.Continuous bridge fibrosis might be present. There were bronchiolar metaplasia of peribronchiolar alveoli,poorly formed granuloma and multinucleated giant cells in interstitium.Schaumann body was identified in 1 case.Conclusions Because of its diverse clinical, radiological and pathological features, HP may be easily confused with other interstitial lung diseases.Aggregate analyses yield a definite diagnosis.

Objective To compare the efficacies between transjugular intrahepatic portosystemic shunt (TIPS) and portoazygos devascularization (PAD) in the treatment of portal hypertension with variceal bleeding.Methods From December 1993 to December 2010,309 patients with portal hypertension and variceal bleeding were admitted. According to their general conditions and Child-Pugh grades,they were assigned to undergo TIPS ( group A,n =235 ) or PAD ( group B,n =74).Before operation,compared with the PAD group,the TIPS group possessed worse liver functions,more severe ascites and a greater frequency of bleeding. After operation,the therapeutic efficacies and changes of portal hemodynamics,recurrent variceal bleeding,post-operative encephalopathy and long-term survival were evaluated between two groups.Results The postoperative portal pressure in the TIPS group ( (42.6 ± 7.0) vs (26.3 ± 4.1 ) cm H2O )decreased much more than that in the PAD group( (38.7 ±5.2) vs (33.5 ±5.8) cm H2O,P ＜0.01 ).The rebleeding rates during early postoperation were 0.85％ (2/235) and 6.76％ (5/74) in TIPS and PAD groups respectively,the occurring rates of hepatic encephalopathy 4.68％ ( 11/235 ) and 4.05％ (3/74) and the rates of operative mortality 1.70％ (4/235) and 6.76％ (5/74) respectively.Survival rates of 1,3,5and 10 years were 98.30％ (231/235) vs 92.24％ ( 69/74 ),92.41％ ( 146/158 ) vs 88.06％ ( 59/67 ),80.77％ (84/104) vs 79.25％ (42/53),51.43％ (36/79) vs 51.85％ (14/27) in TIPS and PAD groups respectively.Conclusions As comparéd with PAD,TIPS offers the such advantages as less trauma,wider indication,faster hemostasis and satisfactory therapeutic efficacies.Especially for the emergency treatment of a patient with massive variceal bleeding and Child-Pugh C grade liver function,TIPS is a better option than PAD.

Objective To explore the feasibility of sentinel lymph node biopsy in peri-neoadjuvant chemotherapy for breast cancer patients.Methods A total of 252 breast cancer patients underwent sentinel lymph node biopsy and axillary lymph node dissection from January 2005 to November 2011,including 150patients in pre-neoadjuvant chemotherapy group and 102 in post-neoadjuvant chemotherapy group.The feasibility of sentinel lymph node biopsy under different clinical states of axillary lymph node was compared.Results No significant difference was found in the detection rate (98.5％ vs 92.8％ ),false negative rate (6.7％ vs 7.9％ ),accuracy (98.4％ vs 91.9％ ) and negative sensitivity (97.9％ vs 88.0％ ) of sentinel lymph node biopsy before neoadjuvant chemotherapy whether the axillary lymph node was negative or positive.However,the transfer rate of sentinel lymph node in the positive group was significantly higher than the negative group (28.8％ vs 67.5％,P =0.000).False negative rate of sentinel lymph node in biopsy was significantly higher in the post-neoadjuvant chemotherapy group than the pre-neoadjuvant chemotherapy group (7.5％ vs 23.9％,P =0.024) and the accuracy/negative sensitivity decreased significantly (95.1％ vs 83.5％,P =0.005/94.4％ vs 75.0％,P =0.003 ).No statistical difference existed in the detection rate,false negative rate,accuracy,negative sensitivity of sentinel lymph node in biopsy before and after neoadjuvant chemotherapy in patients with negative axillary lymph node for a preliminary diagnosis.The accuracy of sentinel lymph node decreased significantly in biopsy after neoadjuvant chemotherapy in patients with positive axillary lymph node confirmed pathologically for a preliminary diagnosis compared with before (98.4/83.7％,P =0.010),the transfer rate of sentinel lymph node increased significantly(28.8/53.7％,P =0.005 ) and negative sensitivity reduced significantly ( 97.9/68.0％,P =0.007 ) ; Compared with preneoadjuvant chemotherapy,the negative sensitivity decreased significantly in patients with axillary lymph node positive confirmed pathologically and then turned negative (94.4％ vs 57.1％,P =0.005 ) while the transfer rate of sentinel lymph node increased significantly ( 28.8％/65.0％,P =0.003 ).Conclusions Sentinel lymph node before neoadjuvant chemotherapy may accurately predict axillary lymph node metastasis.The detection rate,false negative rate,accuracy,negative sensitivity of sentinel lymph node in biopsy after neoadjuvant chemotherapy in patients with negative axillary lymph node for preliminary diagnosis are the same before neoadjuvant chemotherapy.Patients with positive axillary lymph node for a preliminary diagnosis are unsuitable for sentinel lymph node biopsy whether axillary lymph node turns negative or not after neoadjuvant chemotherapy.

Objective To compare Borrmann type Ⅳ gastric cancer with other types of cancer and explore their clinicopathological features and prognostic factors.Methods We retrospectively reviewed the medical records of 893 consecutive advanced gastric cancer patients. They were divided into 2 groups:Borrmann type Ⅳ ( n =139 ) and other macroscopic Borrmann types of cancer ( n =754 ).Their clinicopathologic characteristics and overall survival data were analyzed.Results Borrmann type Ⅳ gastric cancer was found to be associated with more advanced and unfavorable clinicopathological features. The incidence of preoperative biopsy-negative rate of Borrmann type Ⅳ gastric cancer was much higher ( 15.9％ )than other Borrmann types of gastric cancer.The 5-year survival rate of Borrmann type Ⅳ cancer patients was 9.9％ and it was significantly lower than that of other types.Moreover,the 5-year survival rate was higher in the patients with curative resection (18.7％) (P ＜ 0.05).Stratified analysis revealed that when the tumor TNM stages were of Ⅱ,Ⅲ,the survival data of Borrmann type Ⅳ cancer were worse than others.Multivariate analyses revealed distant metastasis and curability were independent prognostic factors for Borrmann type Ⅳ gastric cancer.Conclusions Borrmann type Ⅳ carcinoma has poor clinicopathological features and survival rate compared with other types. An early detection and curative resection may improve the prognosis for the patients with Borrmann type Ⅳ cancer.

Objective To observe the telomerase activity (TA) in bone marrow mononuclear cell (BMMNC) at pre-therapy and post-therapy in patients with immune related hematocytopenia and immune related pancytopenia (IRH/IRP) so as to explore the relationship between TA and disease process.Methods TA in BMMNC of 108 IRH/IRP patients was detected with telomeric repeat amplification protocol (TRAP)-PCR-ELISA.The expressions of anti-human immunoglobulin IgG,Fcγ Ⅱ receptor (FcγⅡ R),mannose receptor (MR) and interleukin 17A (IL-17A) located on membrane surface were observed by immunofluorescence(IF). A total of 30 iron deficiency anemia patients were selected as case control.Results The TA of 108 IRH/IRP patients were 0.251 ± 0.021. And it increased as compared with the control group of 0.062 ± 0.031 at pre-therapy (P ＜ 0.01 ).The HLA-B27+ patients among them was 0.270 ± 0.020 while HLA-B27 - patients 0.181 ± 0.013 (P ＜ 0.05).And HLA-B27 + IgG elevated IRP was 0.341 ±0.016 and HLA-B27-IgG elevated 0.183 ±0.010,the difference of TA was significant between two groups ( P ＜ 0.01 ). IgG antibody positive immature hemocyte could be observed in marrow of IRH/IRP patients,and FcγⅡ R was expressed highly on those activated macrophage ( M(ψ) ) in bone marrow. Both IL-17A and MR were expressed on activated dendritic cells and M(ψ) in marrow of HLA-B27 + patients.After the therapy of glucocorticoids associated with cyclosporine A and other drugs,the patient' s hemogram recovered and the telomerase in BMMNC were re-devitalized. Conclusions The TA of the BMMNC in marrow of IRH/IRP patients is increased, and it shows a close relation between apoptotic degree of hematopoietic cell and the activation of immunocytes. In IRH/IRP,synchronism and equilibrium exist between BMMNC apoptosis and TA.

Objective To examine the prevalence of metabolic syndrome (MS) and microalbuminuria (MAU) in subjects with different levels of glucose tolerance and probe the risk factors for the development of MAU.Methods A total of 951 subjects were divided into 3 groups according to the results of oral glucose tolerance test (OGTT).Among them,there were 674 subjects with normal glucose tolerance (NGT),195 with impaired glucose regulation (IGR) and 82 newly-diagnosed cases of type 2 diabetes mellitus (T2DM). MAU was diagnosed if urine albumin-to-creatinine ratio (UACR) was 30 - 300 mg/g.Results ( 1 ) Compared to the NGT subjects,both the IGR and newly-diagnosed T2DM subjects had the significantly higher levels of age,body mass index (BMI),waist circumference,fasting plasma glucose,2-hour post OGTT glucose (2 hPG),glycated hemoglobin,glycated albumin,fasting insulin,homeostasis model of assessment-insulin resistance (HOMA-IR),triglyceride,systolic blood pressure (SBP) and UACR but a lower level of high density lipoprotein-cholesterol (HDL-C) ; (2) The incident rate of MS and MAU in the IGR and newly-diagnosed T2DM subjects was 54.4％ ( 106/195 ),12.3％ (24/195) and 61.0％ (50/82),12.2％ (10/82) respectively versus 9.1％ (61/674) and 4.9％ (33/674) in the NGT subjects.The incident rate of abdominal obesity,hypertension,hypertriglyceridemia,low HDL-C,MS and MAU in the IGR and newly-diagnosed T2DM subjects was significantly higher than that of the NGT subjects ( all P ＜ 0.05 ) ; (3) Multiple regression analysis showed that BMI,SBP and 2 hPG were independently associated with UACR.Logistic regression analysis indicated that BMI,SBP and 2 hPG were independent risk factors of MAU.Conclusions The prevalence of MS and MAU is significantly higher in the IGR and newly-diagnosed T2DM subjects.BMI,SBP and 2 hPG are independent risk factors of MAU.

Objective To establish a model of cigarette smoke exposure to asthmatic rats and glucocorticoid resistance induced by nicotine in alveolar epithelioid cells A549 and study the mechanism for the change of glucocorticoid sensitivity induced by p38 mitogen-activated protein kinase (p38 MAPK )inhibitor SB203580. Methods Sixty Wistar rats were randomly divided into 4 groups:normal group,asthmatic group,cigarette smoke exposure to asthmatic group and SB203580 group.The mRNA expressions of glucocorticoid receptor (GR),heat shock protein 90 (HSP90) and p38 MAPK were detected by real time-polymerase chain reaction (RT-PCR) while their protein expressions detected by Western blot in vivo.A549 cells were divided averagely into 4 groups:group A:normal; group B:1 μmol/L dexamethasone (DEX) ; group C:1 μmol/L DEX + 1 μ mol/L nicotine; group D:1 μmol/L DEX + 1 μmol/L nicotine +1 μ mol/L SB203580. Immunofluorescence staining was used to study the in vitro colocalization ofglucocorticoid receptor (GR) in A549 cells.Results The mRNA expression of GR was 0.671 ± 0.002 in cigarette smoke exposure to asthmatic group and 0.595 ± 0.061 in SB203580 group ( P =0.065 ). The protein expression of GR was 0.700 ± 0.033 in cigarette smoke exposure to asthmatic group and 0.628 ±0.091 in SB203580 group (P =0.148).The mRNA expression of HSP90 was 0.558 ± 0.009 in cigarette smoke exposure to asthmatic group and 0.377 ± 0.046 in SB203580 group (P =0.000 ). The protein expression of HSP90 was 0.507 ± 0.030 in cigarette smoke exposure to asthmatic group and 0.402 ± 0.050in SB203580 group ( P =0.005 ). The mRNA expression of p38 MAPK was 0.971 ± 0.012 in cigarette smoke exposure to asthmatic group and 0.278 ± 0.049 in SB203580 group (P =0.000). The proteinexpression of p38 MAPK was 0.982 ± 0.038 in cigarette smoke exposure to asthmatic group and 0.338 ±0.042 in SB203580 group ( P =0.000 ).The ratio of GR amount within A549 nucleus versus that in cytoplasm was 0.077 ± 0.047 in group C and 0.592 ± 0.249 in group D ( P =0.000 ).Conclusion The mechanism of SB203580 enhancing the corticosteroid sensitivity may be improving nuclear translocation of GR to elevate corticosteroid sensitivity.

Objective To explore the expression and significance of neutrophil gelatina(s)e-associated lipocalin(NGAL)in renal interstitial fibrosis (RIF) in rats.Methods A total of 60 male Sprague-Dawley rats were randomly divided into 3 groups of sham operation (SOR),unilateral ureteral obstruction (UUO)and angiotensin-converting enzyme inhibitor (ACEI).The serum concentrations of NGAL and tumor necrosis factor-alpha (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA).And the expressions of NGAL,matrix metalloproteinase-9 (MMP-9) and transforming growth factor-β1 (TGF-β1) were observed by immunohistochemistry.Results ( 1 ) The levels of serum NGAL and TNF-α in UUO group obviously increased as compared to those in ACEI and SOR groups ( NGAL:(69.2 ± 5.6)vs (41.0 ± 10.4 ),( 10.8 ±3.8)pg/ml; TNF-α:(116.2±9.2) vs(99.8 ±14.0),(29.2±5.7)ng/ml; all P＜0.05).(2) The expressions of NGAL,TGF-β1 and MMP-9 in renal tubular epithelial cells of UUO group increased as compared to those in SOR group.The expression of TGF-β1 in ACEI group was apparently less than that in UUO group.The protein levels of NGAL and MMP-9 in ACEI group were obviously lower than those in UUO group within Day 14 post-operation and significantly higher than those in UUO group at Days 21 and 28.(3)In UUO group,the level of NGAL was positively correlated with the serum levels of TNF-α and serum creatinine(r =0.910,0.673,P ＜ 0.01 ).The expression of NGAL had a highly positive correlation with MMP-9( r =0.913,P ＜ 0.01 )and the index of interstitial damage and the degrees of TGF-β1 at Days 3 -7 post-operation(r =0.937,0.847,P ＜ 0.01 ).And the expression of NGAL was negatively correlated with the index of interstitial damage and the degrees of TGF-β1 at Days 14 - 28 post-operation ( r =- 0.945,-0.944,P ＜ 0.01 ).Conclusion The expression of NGAL significantly increases in UUO modal of rats.And it is closely correlated with MMP-9,TNF-α and TGF-β1.ACEI may influence the biological effects of NGAL by suppressing inflammatory responses,down-regulating the expression of TGF-β1 and regulating the expression and the activity of MMP-9.

Objective To explore the effects of icotinib on the proliferation and apoptosis of various lung cancer cell lines.Methods Human lung cancer cell lines HCC827,H1650,H1975,A549 and human epidermal cancer cell line A431 were treated in vitro with icotinib or gefitinib at a concentration gradient of 0 -40 μmol/L.Their proliferation effects were analyzed by the thiazolyl blue (MTT) assay and the apoptotic effects detected by flow cytometer.The downstream signaling proteins were detected by Western blot.Results The median inhibitory concentrations ( IC50 ) of icotinib for A431 and HCC827 cell lines were (0.04 ± 0.02 ) and ( 0.15 ± 0.06 ) μmol/L respectively.No significant differences exi(r)ted between the inhibitions of gefitinib and icotinib on A431,HCC827,H1650,H1975 and A549 cell lines ( all P ＞0.05).Compared with H1650,H1975 and A549 cell lines,icotinib significantly inhibited A431 (P =0.009,0.005 and 0.000) and HCC827 (P =0.001,0.001 and 0.000) cell lines.And it lowered the expressions of p-AKT,p-ERK and survivin protein expression through the inhibited activity of p-EGFR protein.Conclusion Icotinib can arrest the proliferation of lung adenocarcinoma cells with EGFR mutation or overexpression by inhibiting the signal pathways of AKT-ERK and survivin.

Objective To investigate the inhibitory effect of siRNA targeting Akt on the biological behavior of esophagus squamous cell carcinoma cell line in vitro and to explore the relationship between Akt and vasculogenic mimicry (VM)-related genes in esophageal squamous cell carcinoma.Methods The plasmid-harboring small interfering RNA targeting Akt was introduced into Ecal09 cells by liposomemediated transfection. The proliferation of Eca109 cell was determined by colony formation assay. The cellular migration was evaluated by Transwell migration assay. And three dimensional cell culture was employed to observe and count the number of capillary structure for each cell group.Flow cytometry ( FCM )was used to detect the apoptotic rate of Eca109,Eca109/Neo and Eca109/siRNA Akt cells under normoxia exposure.The apoptotic rate was assessed by Annexin V/7-AAD double labeling. And the expressions of Akt and matrix metalloproteinase-2 ( MMP-2 ) protein were detected by Western blotting. Results The results of Western blotting showed that the expression of Akt in stably transfected group were significantly lower than empty carrier and untransfected groups (0.03 ±0.01 vs 1.49 ±0.39 and 1.47 ±0.41,both P ＜0.05). Transwell migration assay showed that fewer Ecal09/8 cells could move through the artificial basement membrane as compared with untransfected and empty carrier groups (48 ± 9 vs 128 ± 10 and 122 ±11,both P ＜0.05 ).Clone formation number of stably transfected group was significantly lower than empty carrier and untransfected groups (63 ± 7 vs 148 ± 11 and 163 ± 15,both P ＜ 0.05).Annexin V/7-AADdouble standard method demonstrated that the apoptotic rate of stably transfected group was much more than those of untransfected and empty carrier groups ( 12.2％ ± 1.6％ vs 4.8％ ± 0.8％ and 4.2％ ± 0.8％,both P ＜0.05 ).Eca109 and Eca109/Neo cells were capable of forming the in vitro structures of VM.And the number of tube-shaped structure in stably transfected group was markedly less than those of untransfected and empty carrier groups ( 14.0 ± 1.2 vs 30.0 ± 1.2 and 27.7 ± 1.5,both P ＜ 0.05 ). MMP-2 protein expression in stably transfected group was less than those of untransfected and empty carrier groups (both P ＜0.05). Conclusions The PI3K/Akt pathway is involved in the regulation of VM formation in esophageal squamous cell carcinoma through the action of MMP-2.Blockade of this pathway may provide a new therapeutic approach to human esophagus squamous cell carcinoma.

Objective To validate a novel method of expanding late endothelial progenitor cells (EPC) in vitro.Methods We cultured mononuclear cells (MNC) from human peripheral blood on the plate with the feeder layer cells,i.e.irradiated late EPC or human umbilical vein endothelial cells.After 21days,the numbers of late EPC colonies were counted separately. And the surface antigen of late EPC was detected by fluorescence-activated cell sorter (FACS) and their in vitro ability of forming vascular structure examined by matrigel.Results Both colony numbers of late EPC with feeder layer cell culturing were over 20 times than those without (40.0 ±3.9,39.3 ±3.1 vs 2.0 ± 1.3,both P ＜0.05).And the former's late EPC colony appeared earlier.The late EPC expressed CD31,CD34,eNOS,Flt-1,P1H12,Sendo,VE cadherin and CD117. And vascular structures were discerned.Conclusions The method of feeder layer cells may vastly expand the quantity of late EPC. And microenvironment plays an important role in its expansion.

The patient was an 82-year-old female who was admitted to the Affiliated Hospital of Ningbo University on August 28, 2011 because of the right breast sarcoma 2 years after surgery, and the left breast mass was found for half a year. In February 2009, the patient accidentally found an egg-sized and painless mass in the right breast, which gradually increased (about 9 cm ×7 cm in size) with pain after more than 2 months. She underwent "right mastectomy + right axillary lymph node dissection" in the Affiliated Hospital of Ningbo University on April 29, 2009 as "malignant tumor in the inner and lower quadrants of the right breast". The postoperative pathological report was "undifferentiated sarcoma with coagulative necrosis and right axillary lymph node metastasis (1/8)". No radiotherapy or chemotherapy was performed after surgery. In December 2010, a prominent mass in the right abdominal wall was found, about 5 cm in diameter and with poor mobility. After surgical resection, the pathological report was "inflammatory pleomorphic undifferentiated tumor". In February 2011, a mass in the left breast (about the size of a ping-pong ball) was found, which gradually increased.

Medical Record Abstract A 45-year-old male was admitted to Peking Union Medical College Hospital on December 28, 2011 due to "episodic asthma for 20 years, aggravated for 3 days". The patient had repeated asthma since 1991, and was diagnosed as "bronchial asthma" in other hospitals. He was intermittently treated with salbutamol and dexamethasone, without regular diagnosis and treatment. In the past 3 years, he had symptoms almost every day, and his life was in a semi-self-care state. On December 25, 2011, his asthma aggravated significantly, and he also wheezed when sitting and resting. On December 27, he was given methylprednisolone (40 mg intravenous infusion) and theophylline locally, but the effect was not good. The next day, he came to our hospital for emergency treatment due to aggravation of his condition. Physical examination: wheezing appearance, wheezing sounds in both lungs, finger oxygen saturation 79%, heart rate 168 beats/min, breathing 45 beats/min, blood gas analysis (nasal tube 10 L/min): pH 7.24, PCO2 62 mm Hg (1mm Hg =0.133 kPa), PO2102 mm Hg, HCO3-26.6 mmol/L, Tracheal intubation, mechanical ventilation, sedative pumping and admission to intensive care unit.

Multiple myeloma (MM) is a heterogeneous lymphatic tumor with survival time ranging from several months to several decades. It is very important to establish an accurate prognostic judgment system for individualized treatment of patients. In recent years, abnormalities in cellular and molecular genetics have become the most important factor affecting the prognosis of MM. The rapid development of cellular and molecular genetics and the widespread use of targeted drugs have made great changes in the prognostic influence index and survival time of MM patients, and the traditional prognostic model can no longer accurately judge the prognosis. The top international MM research groups have formulated new prognostic stratification models and treatment strategies based on cellular and molecular genetics. The following is an introduction to the research and progress in this field in recent years.

Notch signaling pathway is an information exchange platform between neighboring cells, and plays an important role in cell determination, development, differentiation, proliferation, apoptosis, adhesion and epithelial-mesenchymal cell transformation. Notch was first discovered in Drosophila, and there are four homologs (Notch1~4) in mammals. After binding to the ligand Jagged/Delta, Notch conformation changes, and is cleaved by tumor necrosis factor α-converting enzyme (TACE) and γ-secretase, and the Notch intracellular domain (NICD) is released into the nucleus, and the Recombination signal binding protein for immunoglobulin J κ (RBP-J κ) During the cardiac embryonic development, Notch signal participates in the regulation of myocardial differentiation, regulating the formation of atrioventricular sulcus, valve, outflow tract and trabeculae, and its key molecular mutations can lead to a series of congenital heart diseases [2]. Recently, it has been found that Notch signal has multiple functions such as inducing neovascularization, promoting stem cell differentiation into myocardium, inhibiting cardiac fibroblast-myofibroblast transformation (CMT), protecting ischemic myocardium, and mediating the repair of myocardial injury and improving cardiac function [3-6]. The role of Notch signal pathway in the repair of myocardial injury is summarized as follows.

The patient was a 55-year-old female. Physical examination and ultrasound revealed a left kidney tumor, accompanied by fever and severe anemia, without macroscopic hematuria. A palpable mass in the left upper abdomen was hard in texture. Abdominal enhanced CT showed that the left kidney tumor was about 14 cm ×10 cm ×8 cm in size. The enhanced scan showed obviously uneven enhancement, and tumor thrombi were found in the left renal vein and inferior vena cava. MRI abdominal macrovascular imaging showed that the inferior vena cava tumor thrombi was about 6.9 cm long and the left renal vein tumor thrombi was about 9 cm long. The laboratory examination of hemoglobin was 67 g/L, and there were no obvious abnormalities in liver function, kidney function and blood coagulation. No metastasis was found on lung CT and whole body bone scan. The diagnosis was left kidney cancer with inferior vena cava grade II tumor thrombi.

The patient was a 47-year-old female. On December 5, 2011, she came to Henan Cancer Hospital for surgical treatment due to "gastric fundus-cardia cancer". Intraoperative exploration found that there was no ascites, no metastatic nodules in the liver, peritoneum and pelvis, and the tumor was located in the gastric fundus-cardia area, about 4 cm ×5 cm ×1 cm in size. Total gastrectomy + D2 lymph node dissection was performed, and double 25 mm tubular stapler Roux-en-Y anastomosis was performed. The operation was smooth, with about 200 ml of intraoperative bleeding without blood transfusion. One week after the operation, CT reexamination confirmed that there was no peritoneal effusion, and 76% diapramide upper gastrointestinal angiography confirmed that the anastomosis healed well. Two weeks after the operation, the suture was removed and the patient was discharged from the hospital. On December 25, the patient suddenly vomited bright red blood, about 500 ml, without special treatment. At 5:00 on the 27th, the patient suddenly vomited bright red blood, about 500 ml, and the blood could quickly coagulate; Physical examination after emergency admission at 8:00: blood pressure 100/72 mm Hg (1 mm Hg =0.133 kPa), heart rate 85 beats/min, anemic appearance, flat and soft abdomen, no tenderness, rebound pain and muscle tension in the whole abdomen, negative moving voiced sound, intestinal sound 6 beats/min, slightly higher pitch.

The patient was a 51-year-old male. During physical examination in October 2011, B-ultrasound found that the right lobe of the liver occupied hypoechoic space, with clear boundary, and the size was about 51 mm ×41 mm. He was considered a malignant tumor. He was admitted to hospital on November 1, 2011. On November 3, 2011, abdominal enhanced MRI showed that lobulated mass-shaped long T1 and T2 signal shadows were seen in the V and VIII segments of the liver, with a size of about 56 mm ×46 mm, and high signal shadows were found on diffusion-weighted imaging. After enhancement, the mass shadows were significantly enhanced in the arterial phase, reduced in the venous phase, and multiple enlarged lymph nodes were seen in the retroperitoneum, which was considered a malignant tumor. Asking for medical history, it was found that the patient had undergone right liver tumor resection 3 years ago, and the postoperative pathological diagnosis was "inflammatory pseudotumor".