[Analysis of surgical approaches and mandibular treatment strategies for different types of tumors involving parapharyngeal space].

In view of the surgical complexity of parapharyngeal space tumors involved, this paper summarized the disease data of patients with parapharyngeal space tumors involved in the Department of Oral and Maxillofacial Surgery, the First Hospital of Shanxi Medical University from January 2015 to January 2021. It also summarized the surgical approach and mandibular management, so as to explore surgical strategies for different characteristics of parapharyngeal space tumors involved. A total of 49 patients, including 28 males and 21 females, median age 52 years (range 24-72 years). They were treated with four surgical approaches for tumor resection, 25 cervical approach, 5 cheek and neck approach, 3 transoral approach, and 16 cervical-maxillary approach. Among the patients treated with cervical-maxillary approach, 3 patients were treated with mandible square resection, and 6 patients were treated with temporary mandible dissection. Seven cases were treated with tumor resection and partial mandibular resection. There are various surgical approaches and mandibular management methods involving tumors in the parapharyngeal space, and clinical decisions should be made based on tumor diameter, location, boundary, blood supply and pathological types.

[Significance of IgA isotype of anti-v-raf murine sarcoma viral oncogene homologue B1 antibody in rheumatoid arthritis].

OBJECTIVE: To detect serum IgA isotype of anti-v-raf murine sarcoma viral oncogene homologue B1 (BRAF) antibody levels in the rheumatoid arthritis (RA) patients in order to investigate their clinical significance in RA. METHODS: Serum samples were obtained from 61 RA patients, 21 osteoarthritis (OA) patients, 16 systemic lupus erythematosus (SLE) patients, 16 gout patients, 16 Sjögren's syndrome (SS) patients and 22 healthy controls. IgA isotype of anti-BRAF antibody levels in the sera were examined by enzyme-linked immunosorbent assay (ELISA). The associations between IgA isotype of anti-BRAF antibody levels and the clinical features including age, disease duration and laboratory parameters including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), disease activity score in 28 joints (DAS28), anti-cyclic citrullinated peptide (anti-CCP) antibody, immunoglobulin and BRAF protein levels in the RA patients were evaluated. Data analyses were performed by using SPSS 19.0 program. RESULTS: The serum IgA isotype of anti-BRAF antibody levels in the RA patients were significantly higher than in the SLE, gout, OA patients and healthy controls, the P value was 0.011, < 0.001, < 0.001 and < 0.001, respectively. The serum IgA isotype of anti-BRAF antibody levels in the SS patients were also significantly higher than in the SLE, gout, OA patients and healthy controls, the P value was 0.029, 0.004, 0.001 and < 0.001, respectively. However, there was no difference between the RA and SS patients (P=0.762). IgA isotype of anti-BRAF antibody was measurable in the RA patients without RF, anti-CCP antibody or anti-keratin antibody (AKA) antibodies. The levels of IgA isotype of anti-BRAF antibody in the RA patients did not show any correlation with clinical features such as age and disease duration or laboratory parameters including ESR, CRP, RF, DAS28, anti-CCP antibody, immunoglobulin and BRAF protein levels. Compared with the clinical features and laboratory indexes of normal and elevated levels of IgA isotype of anti-BRAF antibody groups in the RA patients, there was no significant differences between the two groups in age, disease duration, ESR, CRP, RF, DAS28, anti-CCP antibody, immunoglobulin or BRAF protein levels. CONCLUSION: The elevated level of IgA isotype of anti-BRAF antibody in the RA patients showed that IgA isotype of anti-BRAF antibody might play a role in the pathogenesis of RA. Furthermore, detection of IgA isotype of anti-BRAF antibody in the serum negative RA patients showed that it might be helpful for the diagnosis of the serum negative RA patients.

MiR-155-5p affects Wilms' tumor cell proliferation and apoptosis via targeting CREB1.

The article "MiR-155-5p affects Wilms' tumor cell proliferation and apoptosis via targeting CREB1", by X.-S. Zhao, B. Han, J.-X. Zhao, N. Tao, C.-Y. Dong, published in Eur Rev Med Pharmacol Sci 2019; 23 (3): 1030-1037-DOI: 10.26355/eurrev_201902_16990-PMID: 30779069, has been retracted by the authors due to a slight deviation in the data. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/16990.

[A novel attention fusion network-based multiple instance learning framework to automate diagnosis of chronic gastritis with multiple indicators].

Objective: To explore the performance of the attention-multiple instance learning (MIL) framework, an attention fusion network-based MIL, in the automated diagnosis of chronic gastritis with multiple indicators. Methods: A total of 1 015 biopsy cases of gastritis diagnosed in Fudan University Cancer Hospital, Shanghai, China and 115 biopsy cases of gastritis diagnosed in Shanghai Pudong Hospital, Shanghai, China were collected from January 1st to December 31st in 2018. All pathological sections were digitally converted into whole slide imaging (WSI). The WSI label was based on the corresponding pathological report, including "activity" "atrophy" and "intestinal metaplasia". The WSI were divided into a training set, a single test set, a mixed test set and an independent test set. The accuracy of automated diagnosis for the Attention-MIL model was validated in three test sets. Results: The area under receive-operator curve (AUC) values of Attention-MIL model in single test sets of 240 WSI were: activity 0.98, atrophy 0.89, and intestinal metaplasia 0.98; the average accuracy of the three indicators was 94.2%. The AUC values in mixed test sets of 117 WSI were: activity 0.95, atrophy 0.86, and intestinal metaplasia 0.94; the average accuracy of the three indicators was 88.3%. The AUC values in independent test sets of 115 WSI were: activity 0.93, atrophy 0.84, and intestinal metaplasia 0.90; the average accuracy of the three indicators was 85.5%. Conclusions: To assist in pathological diagnosis of chronic gastritis, the diagnostic accuracy of Attention-MIL model is very close to that of pathologists. Thus, it is suitable for practical application of artificial intelligence technology.

[Clinical characteristics of elderly and younger onset rheumatoid arthritis].

Objective: To compare the clinical and laboratory characteristics and therapy methods of elderly onset rheumatoid arthritis (EORA) and younger onset rheumatoid arthritis (YORA). Methods: The clinical, laboratory and therapeutic data of 481 RA patients in the Department of Rheumatology and Immunology in Peking University Third Hospital from January 2013 to December 2018 were collected and used to analyze the difference of characteristics between EORA group and YORA group, which might be useful for better diagnosis and treatment of EORA patients. Quantitative data of normal distribution were compared with t test between the two groups. Results: There were 481 patients in this cohort, of which 137(28.5%) were EORA, 344(71.5%) were YORA, with a mean age of (59±14) years (19-87 years). There were 358 females (74.4%) and 123 males (25.6%). The percentage of male patients was obviously higher in EORA group (36.5% vs 21.2%, χ(2)=12.012, P<0.01), and the average disease course was obviously shorter (Z=-7.985, P<0.01). Disease Activity Score 28 (DAS28) score was higher in EORA group (5.6±1.3 vs 5.2±1.6, t=2.549, P<0.05), meanwhile the incidences of pleural effusion and interstitial lung disease (ILD) were higher (6.6% vs 1.7%, 29.9% vs 18.3%, respectively; χ(2)=7.550, 7.797, both P<0.05). The incidences of venous thrombosis, primary hypertension, diabetes mellitus, cerebrovascular disease, coronary heart disease (CHD), peripheral atherosclerosis and cataract in EORA group were all significantly higher than those in YORA group (all P<0.05). Erythrocyte sedimentation rate (ESR) and D-Dimer in EORA group were all remarkably higher (both P<0.05). The rate of using glucocorticoid in EORA group was higher but the rate of using methotrexate and anti-tumor necrosis factor-α agents were lower (χ(2)=5.271, 8.407, 9.356, all P<0.05). Conclusion: Compared to YORA group, the percentage of male patients and disease activity of EORA group are higher. The occurrence of pleural effusion, ILD, venous thrombosis, primary hypertension, diabetes mellitus, cerebrovascular disease, CHD, peripheral atherosclerosis and cataract in EORA group are higher than those in YORA group.

MiR-193 promotes cell proliferation and invasion by ING5/PI3K/AKT pathway of triple-negative breast cancer.

OBJECTIVE: Triple-negative breast cancers (TNBC) are a subtype of breast cancer lacking of estrogen receptor (ER), progesterone receptor (PR), and human EGF-like receptor 2 (HER2). MiR-193 always acted as an oncogene and promoted toxic aldehyde accumulation and tyrosine hydroxylase dysfunction. The purpose of this study is to explore the function of miR-193 in triple-negative breast cancer. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the mRNA level of miR-193 expression in 50 cases of TNBC tissues and para-cancerous specimens. Also, the relation between miR-193 level and the overall survival of TNBC patient was analyzed. MiR-193 mimic and miR-193 inhibitor oligos, as well as the corresponding negative control, were synthesized from RiboBio (Guangzhou, China). RESULTS: MiR-193 expression was higher in triple-negative breast cancer tissues and cell lines than the corresponding adjacent non-tumor tissues and normal cell lines. Upregulation of miR-193 predicted poor prognosis of TNBC patients. Overexpression of miR-193 promoted cell proliferation and invasion, while that was suppressed by the knockdown of miR-193. MiR-193 binds to the 3'-UTR of an inhibitor of growth family member 5 (ING5) mRNA to mediate the expression of ING5 in TNBC cells. The knockdown of miR-193 inhibited cell invasion-mediated epithelial-mesenchymal transition (EMT). Furthermore, the knockdown of miR-193 suppressed cell proliferation through the ING5/phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/AKT) signal pathway. CONCLUSIONS: MiR-193 enhanced cell invasion-mediated EMT and improved cell proliferation through the ING5/PI3K/AKT signal pathway in triple-negative breast cancer. The newly identified miR-193/ING5/PI3K/AKT axis provides novel insight into the pathogenesis of triple-negative breast cancer.

[Clinical characteristics of psoriatic arthritis with positive rheumatoid factor or anti-cyclic citrullinated peptide antibody].

OBJECTIVE: To analyze the clinical and laboratory features of psoriatic arthritis (PsA) patients with positive rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP) antibody. METHODS: In the study, 77 PsA patients who were hospitalized in the Department of Rheumatology and Immunology of Peking University Third Hospital from January 2007 to June 2019 were enrolled. All the patients met Classification Criteria for Psoriatic Arthritis or Moll or Wright Criteria. Rheumatoid factor (RF) and anti-cyclic-citrullinated peptide (CCP) antibody were tested in these patients. According to whether anti-CCP antibody or RF was detected in serum, all the patients were divided into anti-CCP antibody or RF positive group (15 cases), anti-CCP antibody or RF negative group (62 cases). According to the detection of anti-CCP antibody in serum, all the patients were divided into anti-CCP antibody positive group (7 cases) and anti-CCP antibody negative group (70 cases). Clinical and laboratory data were collected. The differences of clinical and laboratory indicators between the RF or anti-CCP antibody positive and negative PsA patients were compared. Clinical and laboratory indicators between the anti-CCP antibody positive and negative patients were also compared. RESULTS: Among the 77 patients, 15 were RF or anti-CCP antibody positive, of whom 8 were only RF positive and 2 were only anti-CCP antibody positive, and both of RF and anti-CCP antibody were positive in 5 cases. The RF or anti-CCP antibody positive PsA patients were older than those in the negative group [(58.2±14.8) years vs. (46.69±12.27) years, P=0.002]. And metacarpophalangeal joints, elbow joints and shoulder joints were more likely to be involved in RF or anti-CCP antibody positive PsA patients. PsA patients in the anti-CCP antibody positive group were older than those in the negative group [(62.43±14.34) years vs. (47.59±12.75) years old, P=0.005]. The positive rate of RF and serum level of fibrinogen in the anti-CCP antibody positive group were higher than those in the negative group. The PsA patients in the anti-CCP antibody positive group were all polyarthritis, while 68.6% patients in the negative group were polyarthritis, but there was no statistical difference between the two groups. There was no statistical difference in sausage fingers/toes, changes in nails and enthesitis, and bone erosion on radiographs between the RF or anti-CCP antibody positive and negative PsA patients. There was also no statistical difference in sausage fingers/toes, bone erosion on radiographs, and changes in nails and enthesitis between the anti-CCP antibody positive and negative patients. CONCLUSION: RF and anti-CCP antibodies can be detected in the serum of some PsA patients. RF or anti-CCP antibody positive PsA patients were older than those in negative PsA patients. Metacarpophalangeal joints, elbow joints and shoulder joints were more likely to be involved in RF or anti-CCP antibody positive PsA patients. Anti-CCP antibody positive PsA patients were older and had higher levels of RF positive rate and fibrinogen level.

[The dosimetry comparison study between 3D print template and free-hand guided of precision (125)I seeds implantation on superficial metastatic carcinoma].

Objective: To compare the dose difference of (125)I seeds implantation on superficial metastatic carcinoma between 3D print template guided operation and traditional implantation. To investigate the accuracy of seeds implantation according preplan guided by 3D print template. Methods: A total of 21 cases of patient with 27 lesions underwent (125)I seeds implantation from January 2015 to May 2018 in Hebei General Hospital were analyzed retrospectively. In which, ten lesions underwent seeds implantation guided by 3D print template (template group) and 17 lesions underwent free-hand traditional implantation (traditional group). All patients had been fixed as the position of operation and then performed CT scan. After preplan was designed, the 3D templates were printed in template group. Postplan was performed after the operation.The dose volume histogram, D90 was calculated. The D90 pre and post operation were collected and compared in each group. The difference of D90 and the percentage difference of D90 between pre and post operation were calculated by the formula D90d=D90post-D90pre, D90d%=(D90post-D90pre)/D90pre×100%, and compared the difference between two groups. Results: The mean D90 pre and post operation in template group were (92±26) and (93±27) Gy respectively, t=-0.749, P=0.473. The mean D90 pre and post operation in traditional group were (104±29) and (104±26) Gy respectively, t=-0.139, P=0.891. The difference of D90 in two groups were (3.1±2.4) and (10.0±8.7) Gy, Z=-2.5, P=0.012. The percentage difference of D90 in two groups were 3.1%±1.9% and 9.5%±7.9%, Compared with the traditional group, the template group had smaller fluctuations, and the difference was statistically significant (Z=-2.7, P=0.006) (all P<0.05). Conclusions: The dose parameters of 3D template guided seeds implantation between postplan and preplan are nearly consistent.3D template has good repeatability, which provides a theoretical basis for the popularization of 3D printing technology.

MiR-155-5p affects Wilms' tumor cell proliferation and apoptosis via targeting CREB1.

OBJECTIVE: The aim of this study was to explore the role of microRNA-155-5p (miR-155-5p) in regulating the proliferation and apoptosis of Wilm's tumor (WT), and to investigate the possible underlying mechanism. PATIENTS AND METHODS: The expression levels of miR-155-5p in 37 pairs of WT clinical samples, as well as WT cell line (G401), were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay and flow cytometry assay were used to detect the effects of miR-155-5p on cell proliferation, cycle and apoptosis. Target gene prediction software was applied to screen the potential downstream target gene of miR-155-5p. QRT-PCR, Western blot (WB) and luciferase reporter gene assay proved that cAMP-response element binding protein 1 (CREB1) was the target gene of miR-155-5p. Besides, rescue experiment was conducted to further explore the effect of CREB1 on WT cells. RESULTS: The expression levels of miR-155-5p in WT tissues and cells were both significantly down-regulated. Importantly, miR-155-5p was found to be involved in the malignant behavior of WT cells. MTT assay and flow cytometry assay demonstrated that miR-155-5p significantly inhibited the proliferation, caused stagnation of cells in G0/G1 phase, and promoted cell apoptosis. CREB1 was verified as a functional target gene of miR-155-5p, which was negatively regulated by miR-155-5p. Rescue experiments indicated that restoring the expression of CREB1 could interfere with the effects of miR-155-5p on WT cells. CONCLUSIONS: MiR-155-5p could regulate the proliferation, cell cycle and apoptosis of WT cells. These effects were achieved by regulating the expression of CREB1. Furthermore, our study might provide a new theoretical basis for the basic research of WT.

[The effect of pre-operation (125)I seed activity measuring on dose accuracy].

Objective: To measure the activity of (125)I seed and compare the dose difference of ten patients treated with seed implantation in pre-plan with actual seed activity and calibrate activity. Method: The activity of 100 seeds from company A and B was measured with a well-type ionization chamber 1 day before operation and named group A and B. The activity of two groups was compared and the error between actual and calibrate activity (22.2 MBq, group C) was calculated. Ten patients implanted with (125)I seeds from November 1 st to 30 th, 2017, solstice 30 were selected in Hebei General Hospital. Firstly, pre-plans were designed with 22.2 MBq, prescribed dose were 100-140 Gy. The dose parameters of 90% volume absorbed dose (D(90)), 150% volume fraction (V(150)) and 100% volume fraction (V(100)) were calculated. Then changed 22.2 MBq to actual activity of group A and B, calculated the dose parameters above again. Then dose parameters of D(90), V(150), V(100) in group C were compared with those in group A and B respectively. Result: The actual activity 1 day before the operation was(22.6±0.7)and(23.9±0.9)MBq in group A and B respectively. Compared with 22.2 MBq, the difference was statistically significant(t=5.7, P<0.05 and t=19.2, P<0.05), and the activity error of group B was greater than 5%. The D(90) of group A, B and C were (124.3±9.7) , (131.2±10.2) and (121.9±9.5) Gy respectively.The V(150) were 58.4%±9.4%, 63.7%±8.9% and 56.5%±9.2% respectively. The V(100) were 88.9%±5.0%, 92.0%±4.1%, 88.1%±5.2% respectively.The difference of D(90) between calibrate activity(group C) and actual activity(group A and B) were statistically significant (t=40.2, P<0.05 and t=40.3, P<0.05). The difference of V(150) between group C and group A and B were statistically significant (t=7.5, P<0.05 and t=24.7, P<0.05). The difference of V(100) between group C and group A and B were statistically significant (t=6.6, P<0.05 and t=7.3, P<0.05). Conclusion: There is difference between the actual activity and calibration activity. The difference affects the dose parameters in pre-plan.The seed activity should be measured before operation strictly and the pre-plan should be designed with the actual activity.

Role of MLL3 in regulating cardiac stem cells following cardiac cachexia.

OBJECTIVE: Cardiac cachexia is a form of serious illness that results with terminal stage of heart failure. It is associated with unreasonable weight loss and muscle loss with poor prognosis. Cardiac stem cells play a major role in repairing, damaged cardiac tissue and they are regulated by different mechanisms. In the present study, we investigated the role of MLL3 in regulating cardiac stem cells following cardiac cachexia. MATERIALS AND METHODS: To effectively study the cardiac cachexia, we established a Dahl rat model that produces symptoms similar to cachexia. Using histology, we analyzed the acute and chronic stage of cardiac cachexia. Immunohistochemistry and Western blotting were used to analyze the expression of MLL3 and Oct-4. RESULTS: The rat develops an acute form of cachexia after 2 months of fed with high-salt (8% NaCl) diet, which is characterized by inflammation and tissue damage that are observed through the histological sectioning. The chronic cardiac cachexia developed after 5 months of high-salt diet and histologically it shows tissue loss. At the molecular level the stem cell marker, Oct-4, shows elevated expression at acute stage, but down regulated latter in the chronic stage of cardiac cachexia. Also, MLL3 shows a similar pattern of upregulated expression in acute stage of cachexia, but significantly down regulated in the chronic stage of cachexia that implies their role in regulating the cardiac stem cell and their proliferation. CONCLUSIONS: Our results show that the cardiac stem cells in association with MLL3 support in maintaining homeostatic after initial pathological stages of cachexia but not in the chronic stage of cachexia.

[Expression of CXCL16/CXCR6 in fibroblast-like synoviocytes in rheumatoid arthritis and its role in synoviocyte proliferation].

OBJECTIVE: It has been found that serum CXCL16 concentration in rheumatoid arthritis (RA) patients are significantly higher than those in osteoarthritis (OA) and normal subjects, and are positively correlated with disease activity and bone erosion. However, how is CXCL16 involved in the pathogenesis of RA is unclear. To evaluate the expression of CXCL16 and its receptor CXCR6 in fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) patients, and to explore the role of CXCL16 in the proliferation of RA-FLS. METHODS: FLS were isolated from knee synovial tissues obtained from 8 patients of RA, 7 osteoarthritis (OA) and 3 normal controls. The diagnosis of RA was in line with the 1987 American Rheumatology Association (ACR) RA classification criteria, osteoarthritis met the 1996 ACR revised knee osteoarthritis classification criteria. Control synovium were obtained from trauma caused knee joint injury in healthy individuals who required surgery. Human knee FLS were cultured by tissue explants adherent method.FLS between passages 3 and 5 were used in the experiment. Expression of CXCL16 and its receptor CXCR6 were performed in Western blot analysis. FLS proliferation following stimulation with TNF-α and different concentrations of CXCL16 was examined by cell counting kit-8 (CCK-8). Expression of phosphorylated AKT (pAKT) in RA-FLS stimulated by CXCL16 was quantified by Western blot. Different concentrations of recombinant human CXCL16 were added to the culture medium of RA-FLS. After 48 h culture, supernantants were collected, and TNF-α, IL-6, RANKL and MMP3 in culture supernatants of RA-FLS were determined by enzyme-linked immunosorbent assays (ELISA) operated following the kit instructions. RESULTS: Expression of CXCL16 and CXCR6 in RA-FLS was significantly higher than that of OA and controls (P<0.05), but no significant difference was found between OA-FLS and control FLS. Proliferation of RA-FLS was markedly up-regulated after stimulation of CXCL16 (P <0.05). In the case of the CXCL16 stimulated OA-FLS and control FLS, the FLS proliferation remained basically unchanged. Expression of phosphorylated AKT in RA-FLS increased remarkably in condition of CXCL16 (50,100, 200 µg/L) stimulation. The levels of IL-6 and RANKL in culture supernatants of RA-FLS were obviously increased under CXCL16 (200 µ g/L) stimulation, while TNF-α and MMP-3 levels in the culture supernatants remained unchanged after CXCL16 (200 µg/L) stimulation. CONCLUSION: This study shows that the expression of CXCL16 and its receptor was highly elevated in RA-FLS. Recombinant CXCL16 promoted RA-FLS proliferation and activation in vitro. All these indicate that CXCL16 play an important role in the pathogenesis of RA, anti-CXCL16 treatment may help to relieve inflammation and bone damage of RA patients. However, due to the limitations of this study, the role of CXCL16 and its receptors in RA-FLS remains to be elucidated by further research.

[Significance of antibodies to the citrullinated glucose-6-phosphate isomerase peptides in rheumatoid arthritis].

OBJECTIVE: To detect the anti-citrullinated glucose-6-phosphate isomerase (GPI) 70-88 peptide antibody (anti-C-GPI(70-88) antibody), anti-citrullinated GPI 435-453 peptide antibody (anti-C-GPI(435-453) antibody), anti-GPI 70-88 peptide antibody (anti-GPI(70-88) antibody) and anti-GPI 435-453 peptide antibody(anti-GPI(435-453) antibody) in the serum of rheumatoid arthritis (RA) patients, and examine the diagnostic values of the anti-C-GPI peptide antibodies in RA. METHODS: The anti-C-GPI(70-88) antibody, anti-C-GPI(435-453) antibody, anti-GPI(70-88) antibody and anti-GPI(435-453) antibody were detected by enzyme-linked immunosorbent assay (ELISA) in 191 RA patients, 129 other rheumatic diseases and 74 healthy controls. The clinical and laboratory data of the patients with RA were collected, and the values of anti-C-GPI peptide antibodies in the diagnosis of RA and the relationships of anti-C-GPI peptide antibodies with the clinical and laboratory parameters analyzed. RESULTS: (1) The mean titers of the anti-C-GPI(70-88) antibody and the anti-C-GPI(435-453) antibody in the RA patients (respectively, 68.71 ± 4.20 and 51.78 ± 3.13) were significantly higher than those with other rheumatic diseases and healthy individuals (P <0.05). However, the mean titers of the anti-GPI(70-88) antibody and anti-GPI(435-453) antibody in the RA patients were similar to those with other rheumatic diseases and healthy individuals. (2) The diagnostic sensitivity and specificity of the anti-C-GPI(70-88) antibody for RA were 41.88% and 84.50% respectively; and the diagnostic sensitivity and specificity of the anti-C-GPI(435-453) antibody for RA were 46.05% and 86.05% respectively. The sensitivity of combined detection of the two anti-C-GPI peptide antibodies was 50.79%, and the specificity was 81.40%. (3) The positive rates of the anti-C-GPI(70-88) antibody and the anti-C-GPI(435-453) antibody were 35% and 45% respectively in those patients with negative anti-cyclic citrullinated peptide antibody, anti-keratin antibody, and rheumatoid factor. (4) There was no significant difference in clinical and laboratory indicators between the anti-C-GPI(70-88) antibody or anti-C-GPI(435-453) antibody positive group and negative group. CONCLUSION: The anti-C-GPI(70-88) antibody and anti-C-GPI(435-453) antibody can be detected in the serum of RA patients, and C-GPI may be involved in the pathogenesis of RA. There is a certain diagnostic significance for the sera-negative RA.

[Role of galectin-1 in regulation of umbilical cord mesenchymal stem cells on T cells of rheumatoid arthritis].

OBJECTIVE: The therapeutic potential of umbilical cord mesenchymal stem cells (UC-MSCs) in rheumatoid arthritis (RA) has attracted more and more attention, because of it can suppress the various inflammatory effects of T cells. Galectin-1 is highly expressed in UC-MSCs, as the first lectin mediating the immunomodulatory effect of MSCs. Our study will investigate the effects of galectin-1 in regulation of UC-MSCs on rheumatoid arthritis T cells. METHODS: Lentivirus transfected shRNA technique was used to knock down the expression of galectin-1 in UC-MSCs to construct UC-MSCs(Gal-1-). The effects of UC-MSCs and UC-MSCs(Gal-1-) on CD4+ T cells in RA patients were investigated by contact system, including negative control group (CD4+ T cells), positive control group [CD4+ T-phytohemagg lutinin (PHA)], UC-MSCs-CD4+ T cells co-culture group, UC-MSCs(control shRNA)-CD4+ T cells co-culture group, and UC-MSCs(Gal-1-)-CD4+ T cells co-culture group. The proliferation of CD4+ T cells was detected by MTS assay. The level of tumor necrosis factors α (TNF-α) in cells supernatant was detected by enzyme linked immunosorbent assay (ELISA). The effect of UC-MSCs on helper T cell (Th) subset was detected by flow cytometry. RESULTS: In vitro, UC-MSCs were capable of inhibiting PHA induced proliferation of CD4+ T cells from RA patients, but UC-MSCs(Gal-1-) did not show the significant inhibitory effect. Galectin-1 affect the TNF-α level of CD4+ T cells regulated by UC-MSCs. UC-MSCs and UC-MSCs(control shRNA) significantly inhibited the expression of TNF-α in PHA-induced CD4+ T cells. However, UC-MSCs(Gal-1-) had no significant inhibitory effect. Furthermore, the Th1 cells were also significantly suppressed by UC-MSCs and UC-MSCs(control shRNA) (4.83%±1.37% and 5.13%±0.87%,P=0.012 and P=0.018). These was no significant difference in the proportion of the Th1 cells between the control group and UC-MSCs(Gal-1-) group (8.51%±2.04% and 6.41%±0.96%,P=0.101). The Th2 cells were protected after silence galectin-1 in UC-MSCs, whereas there was no significant difference. The proportion of Th17 was decreased by co-culture with UC-MSCs and UC-MSCs (control shRNA), but these was also no significant difference. CONCLUSION: UC-MSCs can inhibit the proliferation and differentiation of CD4+ T cells from RA patients, but these effect declined after knocking down the expression of galectin-1. Galectin-1 maybe take part in the regulation of UC-MSCs on rheumatoid arthritis CD4+ T cells.

[Role of hypoxia-inducible factor in the pathogenesis of rheumatoid arthritis].

Rheumatoid arthritis (RA) is a destructive chronic autoimmune disease characterized by synovium inflammation, cartilage destruction, bone erosion and the presence of autoantibodies. Hypoxia is a prominent micro-environmental feature in a range of disorders including RA. A combination of increased oxygen consumptionby inflamed resident cells and infiltrating immune cells along with a disrupted blood supply due to vascular dysfunction contribute to tissue hypoxia in RA. Hypoxia in turn regulates a number of key signaling pathways that help adaptation. The primary signaling pathway activated by hypoxia is the hypoxia-inducible factor (HIF) pathway. It has been shown that HIFs are highly expressed in the synovium of RA. HIFs mediate the pathogenesis of RA through inducing inflammation, angiogenesis, cell migration, and cartilage destruction, and inhibiting the apoptosis of synovial cells and inflammatory cells. HIF expressed in RA can be regulated in both oxygen-dependent and independent fashions, like inflammatory cytokines, leading to the aggravation of this disease. Considering the vital role of HIF in the pathogenesis of RA, we reviewed the new advances about hypoxia and RA. In this review, we firstly discussed the hypoxia-inducible factor and its regulation, and then, the pathologic role of hypoxia in RA, mainly elucidating the role of hypoxia in synovitis and cartilage destruction and immune cells. Finally, we provided evidence about the potential therapeutic target for treating RA.

[Frequency and clinical features of ASXL2 gene mutation in acute myeloid leukemia patients with AML1- ETO fusion gene positive].

OBJECTIVE: To investigate frequency and clinical features of additional sex combs-like 2 (ASXL2) gene mutation in acute myeloid leukemia (AML) patients with AML1-ETO fusion gene and to analyze the relationship between ASXL2 gene mutation and c- kit gene mutation. METHODS: Mutation analysis of exon 11 and 12 of ASXL2 gene in 59 de novo AML patients was performed by using polymerase chain reaction (PCR) followed by sequence analysis. The clinical features, survival curve and c-kit gene mutation in ASXL2 gene mutation positive and negative patients were compared. RESULTS: In a total of 59 AML patients with AML1-ETO fusion gene positive, 11.9% (7/59) patients harboured ASXL2 gene mutations. The hemoglobin levels of patients with mutated ASXL2 gene [56.2 (38.0- 72.0) g/L] were significantly lower than those with wild type ASXL2 [69.0(37.2-154.0) g/L] (P=0.038). Differences were not observed in white blood cell counts, platelet counts, the proportion of acidophilic cell, and the proportion of primitive cell in the marrow between patients with mutant ASXL2 and ones without mutant ASXL2 (P>0.05). None of all 59 patients suffered from liver, spleen, central nervous system metastases in both groups. Moreover, enlarged lymph nodes was similar between patients with mutant ASXL2 and ones without mutant ASXL2 (P=0.859). Immunophenotypic analysis: in positive group CD33 positive expression was significantly lower than that of negative group (P=0.033). cCD3 was not expressed in both groups. Expression levels of CD117, cMPO, HLA-DR, CD34, CD38, CD13, CD44, CD15, CD64, CD11b, CD56, CD19, cCD79a and CD7 were similar between patients with mutant ASXL2 and ones without mutant ASXL2 (P>0.05). All of 59 patients were in remission (P=0.577). Overall survival was similar between patients with mutant ASXL2 and ones without mutant ASXL2 (P=0.631). The mutation rates of c- kit in positive group and negative group were 14.3% and 29.4%, without statistical significance (P= 0.697). CONCLUSIONS: ASXL2 mutation may be a new event that can cooperate with AML1-ETO to induce leukemia. Patients in AML1- ETO positive AML with ASXL2 mutation show specific clinical characteristics of hemoglobin levels and expression level of CD33. ASXL2 gene mutations and c-kit gene mutations may not have a specific correlation between them.

Different dietary energy intake affects skeletal muscle development through an Akt-dependent pathway in Dorper × Small Thin-Tailed crossbred ewe lambs.

The objective of this experiment was to investigate the mechanisms through which different levels of dietary energy affect postnatal skeletal muscle development in ewe lambs. Twelve Dorper × Small Thin-Tailed crossbred ewe lambs (100 d of age; 20 ± 0.5 kg BW) were selected randomly and divided into 2 groups in a completely randomized design. Animals were offered identical diets at 100% or 65% of ad libitum intake. Lambs were euthanized when BW in the ad libitum group reached 35 kg and the semitendinosus muscle was sampled. Final BW and skeletal muscle weight were decreased (P < 0.01) by feed restriction. Both muscle fiber size distribution and myofibril cross-sectional area were altered by feed restriction. Insulin-like growth factor 1 (IGF-1) messenger RNA (mRNA) content was decreased (P < 0.05) when lambs were underfed, whereas no difference for IGF-2 mRNA expression was observed (P > 0.05). Feed restriction altered phosphor-Akt protein abundance (P < 0.01). Moreover, the mammalian target of rapamycin (mTOR) pathway was inhibited by feed restriction, which was associated with decreased phosphor-mTOR, phosphorylated eukaryotic initiation factor 4E binding protein 1 (phosphor-4EBP1), and phosphorylated ribosomal protein S6 kinase (phosphor-S6K). Both mRNA expression of myostatin and its protein content were elevated in feed-restricted ewe lambs (P < 0.05). In addition, mRNA expression of both muscle RING finger 1 and muscle atrophy F-box was increased when ewe lambs were underfed. In summary, feed restriction in young growing ewe lambs attenuates skeletal muscle hypertrophy by inhibiting protein synthesis and increasing protein degradation, which may act through the Akt-dependent pathway.

[Discovery of a novel spliceosome of ABL gene (ABL(Δexon7+35INS)) and its association with TKIs resistance in chronic myeloid leukemia].

OBJECTIVE: To explore whether the ABL(Δexon7) and ABL(35INS) spliceosome contributed to TKIs resistance. METHODS: Screening ABL(Δexon7) and ABL(35INS) in 74 normal people and 76 CML patients (53 patients in remission and 23 patients with TKIs resistance) by using polyacrylamide gel electrophoresis combined with cloning sequencing. RESULTS: A novel spliceosome ABL(Δexon7+ 35INS) (ABL(Δexon7) and ABL(3)5INS existed at the same time) was identified and the mutation was detected in 8 (10.8%) of 74 normal people, 4 (7.5%) of 53 remission patients and 2 (8.7%) of 23 resistant patients. While 47 (63.5%) cases expressed ABL(Δexon7) and 8 (10.8% ) cases expressed ABL(35INS) in 74 healthy people, 30 (56.6%) cases expressed ABL(Δexon7) and 5 (9.4% ) cases expressed ABL(35INS) in 53 remission patients, 12 (52.2%) cases expressed ABL(Δexon7) and 3(13.0%) cases expressed ABL(35INS) in 23 resistant patients. Three kinds of spliceosome in all groups had no statistical difference. CONCLUSION: ABL(Δexon7+ 35INS), ABL(Δexon7) and ABL(35INS) may be not uncommon in ABL gene and were unrelated to resistance in CML with TKIs treatment. ABL(35INS) were often accompanying with exon 7 deletion.

[Dose comparison between pre and post operation of 125I seeds implantation guided by 3D print tamplate].

OBJECTIVE: To compare the dose difference between pre and post operation of (125)I seeds implantation guided by 3D print tamplate and investigate the dose accuracy. METHODS: From August 2015 to November 2015, a total of 9 patients were selected and underwent 3D print tamplate guided (125)I seeds implantation in Hebei General Hospital. All patients had been fixed as the position of operation and then performed CT scan. After preplan was designed, the 3D tamplates were printed. The tumors were punctured through needles holes predesigned. Another CT scan was used to confirm the locations of needles and then seeds were implanted into tumor according to preplan. Postplan was performed after the operation. The D90, V90, V100, V150 and seeds number pre and post operation were collected and compared. RESULTS: The mean D90, V90, V100, V150 and seeds number preoperation was (7 684±3 279)cGy, 93.2%±0.8%, 89.8%±0.9%, 62.8%±4.7% and 58±17 respectively. The mean D90, V90, V100, V150 and seeds number postoperation was (7 531±3 523) cGy, 92.4%±2.0%, 88.0%±2.5%, 61.9%±5.3% and 56±17 respectively. The difference of all data between pre and post operation was not statistically significant (all P> 0.05). CONCLUSIONS: The dose parameters in postplan show no difference compared with preplan. For the fixed tumor, 3D print tamplate guided seeds implantation may become an easy repeated and standard procedure.

Wortmannin enhances cisplatin-induced apoptosis in human ovarian cancer cells in vitro.

OBJECTIVE: The PI3K/Akt signaling pathway is constitutively activated in some ovarian cancers; when activated, it promotes invasion and inhibits chemotherapy-mediated apoptosis in cancer cells. The fungal metabolite wortmannin is the currently known inhibitors that show fairly high specificity for PI3K.We examined whether PI3K/Akt activity correlates with invasion and apoptotic resistance to chemotherapy in cultured human ovarian cancer cells, and whether inhibition of PI3K/Akt by wortmannin inhibits invasion and enhances cisplatin-induced apoptosis in cultured human ovarian cancer cells. MATERIALS AND METHODS: The cisplatin-sensitive A2780 ovarian adenocarcinoma cell line and its daughter line, A2780cis was evaluated for basal Akt activity. Chemotherapy-induced cell death was evaluated following down-regulation of Akt activity by wortmannin treatment or upregulation of Akt activity by myr-Akt treatment. Invasion and migration were assessed using Boyden chamber assays RESULTS: Inhibiting or activation of PI3K/Akt signaling pathway by wortmannin had little effect on the basal level of apoptosis in ovarian cancer cells, but increased the apoptotic effect of chemotherapy in A2780cis cells, decreased the apoptotic effect of chemotherapy in cisplatin-sensitive A2780 cells. Cisplatin resistant cells display increased potential for migration and invasion. CONCLUSIONS: The antiapoptotic effect of AKT activation in ovarian cancer cells confer invasive ability and resistance to apoptosis. Wortmannin is as adjuncts to conventional chemotherapy in the treatment of ovarian cancer.