Purpose To investigate the relationship be-tween the level of tumor abnormal protein(TAP)and the molec-ular subtypes and clinicopathological features of breast cancer,and to analyze the value of TAP in breast cancer screening,di-agnosis and prognosis prediction.Methods The clinical data of 357 breast cancer patients were collected,and the elbow venous blood was collected to detect the TAP condensate area.Immuno-histochemical(IHC)EnVision two-step method was used to de-tect the expression of AR,ER,PR,HER2,p53 and Ki67,and FISH to detect HER2 gene.The relationship between TAP ex-pression and clinicopathological features,molecular subtypes and clinical stages of breast cancer was analyzed,and the rele-vant literature was reviewed.Results Among 357 breast cancer patients,9 cases(2.52％)were TAP negative,36 cases(10.08％)were weakly positive,312 cases(87.40％)were strongly positive,and the positive rate of TAP was 97.48％.AR was positive in 321 cases and negative in 36 cases,ER was pos-itive in 256 cases and negative in 101 cases,PR was positive in 214 cases and negative in 143 cases,HER2 was strongly posi-tive in 98 cases,weakly positive in 214 cases and negative in 45 cases,p53 was positive in 146 cases and negative in 211 cases,Ki67 index was ≥20％in 276 cases and＜20％in 81 case.A total of 155 cases of IHC HER2(2+)breast cancer were tested by FISH:140 cases were negative and 15 cases were positive.The expression level of TAP in patients of ≥50 years old expres-sionas significantly higher than that in patients of＜50 years old(P＜0.05).The expression level of TAP in patients with high Ki67 proliferation index was significantly higher than that in pa-tients with low Ki67 proliferation index(P＜0.05).There was a significant difference in TAP expression between patients with different molecular subtypes(P＜0.05).Tap expression was higher in triple-negative breast cancer patients than in non-tri-ple-negative breast cancer patients(P＜0.05),and it was high-er in Luminal B breast cancer patients than in non-Luminal B breast cancer patients(P＜0.05).There was a significant difference in TAP expression between patients with different clin-ical stages(P＜0.05),and TAP expression level was positively correlated with clinical stage in breast cancer.Conclusion TAP detection can improve the diagnostic accuracy of breast cancer,and has a certain correlation with the survival rate and prognosis of breast cancer patients.

Objective:To describe the characteristics, etiology and patterns of outpatients and inpatients patients with moderate or severe valvular heart disease (VHD).Methods:This is a cross-sectional study. Outpatients and inpatients with moderate or severe VHD who underwent transthoracic echocardiography for first examination from 1 st January 2001 to 1 st January 2020 in Southwest Hospital, Army Medical University were enrolled. Data were collected from medical records and big data platform of Southwest Hospital. Characteristics of age and gender, etiology and types of VHD were descriptively analysed. Results:A total of 68 354 patients with moderate or severe VHD were enrolled. The age was 63 (50, 72) years. And 35 706 (52.24%) patients were female. (1) Age characteristics: There was similar age trend between male and female patients with moderate or severe VHD. The number of patients increased firstly and then decreased and reached its peak in the age group of 65-69 years old. The peak age of mitral stenosis patients was 45-49 years, which was earlier than that of whole patients with moderate or severe VHD. The median age of patients with bicuspid aortic valve was 42 years. (2) Gender characteristics: The proportion of tricuspid regurgitation, pulmonary regurgitation, mitral regurgitation, mitral stenosis and valve surgery in female patients with moderate or severe VHD were higher than those in male patients. The proportion of aortic regurgitation, aortic stenosis and bicuspid aortic valve in male patients with moderate or severe VHD were significantly higher than those in female patients (all P<0.05). (3) Etiology: The proportion of rheumatic VHD was 13.07% (8 934/68 354), which was higher than that of degenerative VHD (0.67% (458/68 354)). (4) Types of VHD: Tricuspid regurgitation made contribution to the largest proportion with 60.72% (41 503/68 354), followed by mitral regurgitation, aortic regurgitation, mitral stenosis, pulmonary regurgitation and aortic stenosis. Conclusions:There are certain regional characteristics in the prevalence of moderate or severe VHD in southwest China, suggesting different attention should be paid on the whole process of refined management of moderate or severe VHD.

Purpose To investigate the expression of fork-head box protein A1(FOXA1)in esophageal squamous cell car-cinoma(ESCC)and its association with clinicopathologic char-acteristics and prognosis.Methods Immunohistochemistry was used to detect FOXA1 protein expression in 532 cases of esopha-geal squamous cell carcinoma.The correlation between FOXA1 protein expression and clinicopathologic features and prognosis of patients was analyzed.Results In 532 cases of esophageal squamous cell carcinoma,183 cases overexpressed FOXA1 pro-tein(34.4％).FOXA1 overexpression was associated with ES-CC vascular infiltration(P=0.032),poorly differentiation(P=0.032),and tumor size(P＜0.001).The overall survival(OS)and disease free survival(DFS)of patients with stage Ⅰ+Ⅱ esophageal squamous cell carcinoma with high FOXA1 ex-pression tended to be poor(OS:P=0.094;DFS:P=0.107).In ESCC patients with survival longer than 24 months,the high FOXA1 expression group had significantly shorter OS and DFS(OS:P=0.048;DFS:P=0.047).Multivariate survival anal-ysis showed that the depth of tumor invasion was an independent prognostic factor affecting the prognosis of esophageal squamous cell carcinoma.Conclusion FOXA1 is overexpressed in e-sophageal squamous cell carcinoma,and its high expression is related to tumor size,vascular infiltration and poorly differentia-tion.Patients with high FOXA1 expression tended to have poor prognosis in OS and DFS.When OS and DFS≥24 months,high FOXA1 expression may be used as a reference indicator for poor prognosis in ESCC patients.

Objective:To explore the expression of peptidyl prolyl cis-trans isomerase (Pin1) activity in peripheral blood of patients with rheumatoid arthritis (RA) and the value and correlation of T helper cell 17/regulatory cells (Th17/Treg) cells, and to analyze the effect and influence of all-transretinoic acid (ATRA) on it.Methods:① Comparing the difference of Pin1 expression and absolute counts of Th17 and Treg between RA patients before and after treatment and healthy control group, Kruskal-Wallis rank sum test was used for analysis. ② To analyze the correlation between the expression of Pin1 and its general data, activity indicators [such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and disease activity score 28 joints (DAS28) scores], Th17, Treg and some cytokines in RA patients, and to use Pearson and Spearman correlation tests. ③ To analyze the difference of Pin1 expression and Th17/Treg in peripheral blood of RA patients treated with low-dose all-trans retinoic acid (10 mg twice a week) and traditional immunosuppressants such as hydroxychloroquine for 3 months respectively. Mann-Whitney U test was used for comparison between the two groups, and the difference was statistically significant with ( P<0.05). Results:① The activity of Pin1 in peripheral blood of the newly treated group of RA was [13.62(9.16, 19.42)] higher than that of the healthy control group [8.97(7.62, 11.45)]( Z=42.82 , P<0.05), and Th17 was [18.28(12.76, 24.08)] higher than that of the healthy control group [6.04(4.96, 4.96)]( Z=48.83 , P<0.05). Treg [11.06(5.31, 21.87). It was lower than that of healthy control group [40.41(24.33, 48.52)]( Z=42.21 , P<0.05). ② the activity of Pin1 in peripheral blood of RA patients was positively correlated with CRP, the number of involved joints, DAS28 score, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) ( r=0.396, P<0.05; r=0.683, P<0.05; r=0.466, P<0.05; r=0.315, P<0.05; r=0.416, P<0.05). ③ Compared with the newly treated RA group, the activity of Pin1 [6.94(5.96, 8.77), Z=42.82 , P<0.05] and Th17 7.38 decreased [7.38(3.85, 11.21), Z=48.83 , P<0.05], while Treg [40.41 (17.77, 33.47)] increased ( Z=42.21 , P<0.05). ④ Compared with the traditional medicine group, Treg [28.9(21.73, 37.36)] was higher in the retinoic acid group, and the difference was statistically significant ( Z=-2.683 , P<0.05). The activity of Pin1 was [6.23(5.58, 8.75)], but there was no statistical significance ( Z=-1.622 , P=0.104). Conclusion:Pin1 in peripheral blood of RA patients is over-expressed. Th17 is increased and Treg is decreased. ATRA combined with other traditional drugs can reduce Pin1 activity, promote Treg growth and improve disease activity of RApatients to a certain extent.

As water-soluble, natural pigments, anthocyanins are responsible for the red, purple and blue colors of many flowers, which attract pollinators to spread pollen. The colors of flowers are also essential for plants to survive in the nature and become one of the most significant characteristics of ornamental plants. In the booming floriculture industry, to produce various flower colors could increase the richness of natural colors, but it is still difficult to breed flowers with coveted blue color. The diversity of flower color is mainly determined by the types and contents of anthocyanins and their derivatives. The synthesis of delphinidin pigments is the key factor for breeding blue flowers. However, there are no structural genes in many plants to biosynthesize delphinidin pigments. Blue flowers are successfully created by genetic engineering in recent years. In this paper, using common ornamental plants as examples, we review the mechanism of plant flower coloration from the aspects of the key factors affecting the synthesis of delphinidin pigment and the production strategies of blue flowers based on the regulation of anthocyanin metabolism. Different strategies of molecular breeding could provide opportunities to improve colors of other floriculture plants and to develop anthocyanin-rich economic crops, such as colored cotton with blue fibers.
Anthocyanins ; metabolism ; Flowers ; Gene Expression Regulation, Plant ; Genetic Engineering ; Pigmentation ; genetics

Objective To investigate the clinical value of fetal echocardiography in prenatal diagnosis , classification and outcome of abnormal origin of pulmonary artery from ascending aorta ( AOPA) . Methods From January 2014 to June 2018 ,18 cases of AOPA diagnosed by echocardiography in 43966 fetuses from Shaanxi Fetal Congenital Heart Disease Diagnostic Center were retrospectively analyzed . The echocardiographic features ,pathological and anatomical classification ,genetic characteristics and outcome of postnatal echocardiography were summarized . Results Abnormal origin of pulmonary artery branches could be demonstrated by color Doppler imaging system in 18 cases . Ten cases ( 55 .6％ ) of right pulmonary artery abnormalities originated from ascending aorta ( AORPA ) ,in which 6 cases ( 60％ ) were distal pulmonary artery abnormalities ,4 cases ( 40％ ) were proximal pulmonary artery abnormalities . Eight cases( 44 .4％ ) of left pulmonary artery abnormalities originated from ascending aorta ( AOLPA ) ,including 7 cases ( 87 .5％ ) of distal pulmonary artery abnormalities and 1 case ( 12 .5％ ) of proximal pulmonary artery abnormalities . Twelve AOPAs were associated with other intracardiac malformations with 6 right ventricular double outlet (DORV) accompanying with pulmonary stenosis ,3 tetralogy of fallots( TOF) ,2 atrioventricular septal defects( AVSD) ,1 single ventricle with single atrium ,and 1 Berry syndrome ,and no casese were associated with extracardiac malformations .Amniocentesis karyotype analysis and gene chip detection in 5 cases showed normal results . Four of 18 cases were born ,in which 3 cases died and 1 case was progressively suffered with right pulmonary artery atresia ,10 cases were inducted of labor ( 4 autopsy) and following-up was lost in 4 cases . Conclusions Incidence of AOLPA and distal type in fetal AOPA is higher than that in child and adult from references ,DORV is abnormal type mostly associated with intracardiac malformation . AOPA has no obvious genetic result for less cases . The main risk after AOPA birth is pulmonary infection . Echocardiography is of great value for AOPA in prenatal diagnosis , outcome observation and surgical planning after birth .

OBJECTIVETo investigate the protective effect of LR-90 on articular cartilage in rabbit model of osteoarthritis.

METHODSThe cultured rabbits chondrocytes were assigned to be treated with IL-1β (10ng/ml) or IL-1β (10ng/ml)+LR-90 (50 mg/L). The mRNA expression of MMP-13, ADAMTS-5, aggrecan and collagen II in chondrocytes were assessed by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). Twenty male New Zealand white rabbits underwent bilateral anterior cruciate ligament transection (ACLT) to establish a animal model of osteoarthritis. Four weeks after model established, on the basis of randomization one knee of each rabbit was treated with 50 mg/L LR-90 in normal saline (NS) (experimental group) and the other knee was treated with same volume of NS (control group), 1/week × 5. Nine weeks after ACLT all rabbits were sacrificed and the knee joints were evaluated by gross morphology and histology. The mRNA expression of IL-1β, MMP-13, ADAMTS-5, aggrecan and collagen Ⅱ in articular cartilage was analyzed by RT-PCR.

RESULTSGross morphology and Mankin histological evaluation showed that the extent and grade of cartilage damage in the experimental group were less severe than those in the control group.Compared to IL-1β group, LR-90 treatment suppressed the mRNA expression of MMP-13 and ADAMTS-5, and enhanced aggrecan and collagen Ⅱ mRNA expression. Consistent with the in vitro results, the intraarticular LR-90 administration suppressed the mRNA expression of IL-1β,MMP-13 and ADAMTS-5 (all P<0.01), while enhanced mRNA expression of aggrecan and collagen Ⅱ in cartilage (all P<0.01).

CONCLUSIONLR-90 protects against cartilage degradation and inhibits the progression of osteoarthritis in rabbit mode1 of osteoarthritis, which is associated with the suppressing IL-1β, MMP-13, ADAMTS-5 and promoting aggrecan and collagen Ⅱ mRNA expression in cartilage.

ADAM Proteins ; metabolism ; Aggrecans ; metabolism ; Animals ; Anterior Cruciate Ligament ; surgery ; Butyrates ; pharmacology ; Cartilage, Articular ; metabolism ; pathology ; Cells, Cultured ; Chondrocytes ; metabolism ; Collagen Type II ; metabolism ; Disease Models, Animal ; Injections, Intra-Articular ; Interleukin-1beta ; pharmacology ; Male ; Matrix Metalloproteinase 13 ; metabolism ; Osteoarthritis ; drug therapy ; Rabbits

Objective To investigate the effects of stress intensity and the expected duration of stress on the inhibition ability of individual responses to stress. Methods A total of 60 cases of hospitalized patients in respiratory department were selected in the study,including 31 male cases and 29 female cases. Incorporated patients were divided into the high-stress group and the low-stress group ( 30 cases in each group) according to whether the patient accepted a invasive examination or not. Then,within each group,pa-tients were further randomly sub-divided into the acute expectation group and the chronic expectation group ( 15 cases in each group) in the form of a lottery. Detection risk disclosure was conducted at 2 hours and at 24 hours before the examination. Visual analogue scale ( VAS) and stop-signal task were used to detect the level of psychological fear and the inhibition ability of individual responses to stress of each group following informing of the detection risk,and the comparative analysis was conducted afterwards. Results ( 1) The score of psychological fear in the high-stress group was significantly increased when compared to the low-stress group ((3.90±2.71) vs (0.80±1.24)),showing statistical difference (F(1,58)=30.16, P<0.01);addi-tionally,there was no statistical difference in the score of psychological fear in subjects between the acute and chronic expectation group ((2.60±2.90) vs (2.10±2.41);F(1,58)=0.785, P>0.05);meanwhile,no statisti-cal difference of the interaction between stress intensity and the expected duration of stress on the level of psychological fear (F(1,58)=0.031, P>0.05). (2) As for stop-signal task,the signal execution error rate of the high-stress group was significantly increased than that in the low-stress group ((9.40±5.80)%vs (8.30± 12.60)%),and the statistical difference was significant (P<0.01).Signal execution responses duration was obviously prolonged in the acute expectation group than that in the chronic expectation group ((677.25±201. 26)ms vs (588.24±127.10)ms),and the difference was statistically significant (P<0.05); meanwhile,stop-signal error rate at 400 ms was significantly decreased ((57.00±26.00)% vs (70.00±23.80)%),and the difference was statistically significant (P<0.05). There was no statistical significance in the interaction be-tween stress intensity and the expected duration of stress (P>0.05) . Conclusion There is no interaction be-tween the effect of the stress intensity and the expected duration of stress on the inhibition ability of individu-al responses to stress. The stress intensity is more important than the expected duration of stress to exert more important influence in the inhibition ability of individual responses to stress.

Objective To improve the understanding of cutaneous Mycobacterium haemophilum infection.Methods Clinical and laboratory data were collected from two patients with cutaneous Mycobacterium haemophilum infection.The clinical and histopathologic manifestations, etiology and treatment of cutaneous Mycobacterium haemophilum infection were analyzed.Results The two patients were both immunocompromised.Lesions, which occurred after trauma in both the patients, began as well-marginated subcutaneous nodules, and then gradually progressed into ulceration with crusting and abscess formation.Histopathological examination revealed epithelial cell granuloma or histiocytic infiltrate in the dermis, as well as focal necrosis and neutrophil abscesses.Acid-fast staining showed abundant bacilli in tissues.These bacilli only grew in iron-containing medium, and were finally identified as Mycobacterium haemophilum by PCR and sequencing.According to the result of antimicrobial sensitivity testing, both the patients were treated with rifampicin, clarithromycin and moxifloxacin.Three months later, the condition was improved in both of them.Conclusions Mycobacterium haemophilum infection occurs most frequently in immunocompromised populations after trauma, manifests as subcutaneous nodules and abscesses with histopathological changes consistent with infectious granuloma.Molecular biological approaches are reliable for the identification of Mycobacterium haemophilum.

Objective To investigate the expression of protein interacting with Cα kinase 1 (PICK1) and its significance in colorectal adenocarcinoma.Methods The expression of PICK1 were detected by immunohistochemistry and Western blot methods in tissues of colorectal adenocarcinoma,colorectal adenoma,colorectal polyp and adjacent tissues.The correlation between PICK1 and clinical pathological data was explored.Results Immunohistochemical assay showed that the positive ratio of PICK1 protein was 72.5 ％ (74/102),and overexpressed in 31 cases (30.4 ％,31/102) with colorectal adenocarcinoma.The ratio of high expression level of PICK1 in colorectal adenoma tissues (22.2 ％,8/36) was significantly higher than that in the adjacent tissues (0,0/40) (P ＜ 0.05).The ratio of high expression level of PICK1 in colorectal polyp tissues (5.6 ％,2/36) was no statistically difference compared with that of the adjacent tissues (P ＞ 0.05).Western blot analysis revealed that the expression of PICK1 in colorectal adenocarcinoma (1.10±0.04) was significantly higher than that in the adjacent tissues (0.75±0.07) (P ＜ 0.05).The result showed significant correlation with the tumor location,the degree of differentiation,depth of invasion,TNM stages and lymph metastasis (all P ＜ 0.05).However,there is no correlation was revealed between PICK1 expression and the patients age,gender (both P ＞ 0.05).Conclusion The expression of PICK1 may be associated with the tumorgenesis,progression,invasion and metastasis of colorectal adenocarcinoma,which contributes to the prognosis of patients.