Objective To investigate the expression of heat shock protein(HSP)70 and HSP90 in patients with atrophic gastritis(AG)or gastric cancer(GC)and its significance.Methods One hundred and forty-one patients including 35 with superficial gastritis(CSG),66 with AG(miner in 21,medium in 30 and severe in 15)and 40 with GC were enrolled with mean age of 47.8,56.1 or 59.4 years,respectively.H.pylori positive patients were 12 with CSG and 28 with AG.The quantity analysis of HSP90 and HSP70 were detected by immunohistochemistry,whereas their mRNA and protein expressions were measured by Western bolt and real-time PCR,respectively.Results The mRNA expression of HSP70 was significantly higher in CSG(1.31±0.80)and AG(1.41±0.80)than that in GC(1.18±0.70,P＜0.05),but was significantly lower in miner(1.32±0.70)and medium(1.34±0.60)AG than that in severe AG(2.20±0.80,P＜0.05).The mRNA expression of HSP90 was kept on increasing in order of CSG(1.27±0.60),AG(1.53±0.80)and GC(1.84±0.70); or in order of miner(1.33±0.60),medium(1.47±0.90)and severe(2.75±0.70)(P＜0.05).The patients infected with H.pylori had higher expression of HSP90 compared with those without H. pylori infection (P＜0.05). Conclusion The synchronous increase of HSP90 and HSP70 indicates the aggravation of AG. When HSP90 is up-regulated and HSP70 is down-regulatied, it may predict the occurrence of cancer.

Background Idiopathic orbital inflammatory pseudotumor (IOIP) is a commom orbital disease,with serious eye symptoms and replase tendency,and its pathogenesis is still unclear.Nuclear factor-κB (NF-κB)-related proteins participate in many important pathophysiological process,however,whether NF-κB plays a role in the IOIP process is worthy of attention.Objective This study was to explore the roles of NF-κB pathway in IOIP pathogenesis.Methods Twenty-four IOIP specimens were collected during surgery in Beijing Tongren Hospital from September 2010 to May 2016.The histopathological characteristics of IOIP were examined by hematoxylin and eosin staining.The expression and location of NF-κB/p65,p-p65,p50 and inhibitor of κB (IκB-ot) were detected by immunohistochemistry and verified by immunocytochemistry and Western blot assay.Results The histopathological features of IOIP were numerous small lymphocyte infiltraion and fibrous tissue proliferation,and a lot of epithelioid cells were seen in lacrimal gland-involved specimens.NF-κB/p65 was positively expressed in the cytoplasm of all 24 specimens and the nucleus in 15 specimens with the expressing rate of 62.5％.p50 was expressed in the cytoplasm in 22 specimens with the expressing rate of 91.7％ and in the nucleus in 17 specimens with the expressing rate of 70.8％.The positive expression of p-p65 was found in 22 specimens with the expressing rate of 91.7％,and IκB-α was expressed in the cytoplasm of 11 specimens with the expressing rate of 45.8％.These results were confirmed by immunocytochemistry and Western blot assay.Conclusions NF-κB pathway is activiated during IOIP process,and NF-κB pathway may be involved in the pathogenesis of IOIP.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.

Objective: To explore the prognostic value of CD34, CD2, CD56 expressions and FLT3-ITD mutation in adults with acute promyelocytic leukemia (APL) . Methods: The immuno-phenotypic and molecular characteristics of 137 adult patients with APL (from January 2010 to March 2016, in Henan Provincial People’s Hospital) were investigated. And the relationships between CD34, CD2, CD56 expressions, FLT3-ITD mutation and the outcomes of high WBC counts at onset, complete remission (CR) rate, early mortality, relapse rate (RR) , overall survival (OS) , disease free survival (DFS) were explored. Results: ①Among the 137 patients, the positive ratios of CD34, CD2, CD56 expressions and mutation rate of FLT3-ITD were 26.3%, 25.5%, 10.2% and 17.5%, respectively. The morbidities of positive CD34, CD2, CD56 expressions and FLT3-ITD mutation in the high-risk group were 43.2%, 47.7%, 18.2% and 27.3% respectively, while those in the low-/intermediate-risk groups were 18.3%, 15.1%, 6.5% and 12.9%, respectively (P<0.05) . ②At a median follow-up of 41 months, the total CR rate of the 137 adults APL patients was 96.9%, early mortality 6.6% and relapse rate 7.3% respectively. And RR of positive CD34 or CD2 expression patients was higher than negative CD34/CD2 expression ones (18.8% vs 3.3%, χ²=8.462, P=0.004; 16.1% vs 4.3%, χ²=4.382, P=0.028, respectively) . In addition, the early mortality of patients with positive CD56 expression or FLT3-ITD mutation was extremely higher than in negative ones (21.4% vs 4.9%, χ²=5.610, P=0.018; 16.7% vs 4.4%, χ²=4.833, P=0.028, respectively) . ③The whole OS and DFS were 88.3% and 84.7%, respectively. Wherein, OS and DFS in patients with CD34⁺, CD56⁺ or FLT3-ITD mutation were worse (P<0.05) . Conclusions Positive CD34, CD2, CD56 expression and FLT3-ITD mutation were latent poor prognostic factors in adults with APL.

Objective:To establish a prediction method of diopter based on sequence of ocular biological parameters.Methods:A stratified random cluster sampling method was used to extract the dataset. The dataset consisted of data collected from January 2022 to January 2023 by the Eye & ENT Hospital, Fudan University, from children aged 5 to 13 years in 2 key schools and 2 general schools of Yangpu District, Shanghai. Children’s ocular biological parameters, including sex, age, diopter, axial length, corneal curvature, and anterior chamber depth were collected. The slope of the optimally fitted straight line was calculated using the least squares method. The least square-back propagation (BP) neural network model was established by combining baseline data and the pre-processed rate of the change of ocular biological parameters. The dataset was divided into the training set and the validation set according to the ratio of 8:2 for five-fold cross-validation. The model performance was evaluated by using the mean absolute error (MAE), mean squared error (MSE), root mean square error (RMSE), correlation coefficient R, and coefficient of determination R2. Results:The optimal performances of R2, R, RMSE, MAE, and MSE of the least square-BP neural network model were 0.96, 0.981 9, 0.214 2, 0.139 9 D, 0.045 9, respectively. The regression equation between the predicted value and the true value of the diopter was y=0.97 x+ 0.014 8, R2=0.97, with good correlation. In the internal verification, MAE values of the diopter at three, six, nine, and twelve months of follow-up were 0.110 1, 0.136 0, 0.153 7, and 0.184 8 D, respectively, which achieved clinically acceptable performance (less than 0.25 D). In the external validation, the errors were less than 0.25 D at all ages. Conclusions:A prediction method of diopter based on sequence of ocular biological parameters was successfully developed.

OBJECTIVETo investigate the profile of promoter methylation and expression of SHP-1 gene in the progression of chronic myeloid leukemia (CML).

METHODSThe expression level of SHP-1 mRNA and protein in bone marrow or peripheral blood mononuclear cells from CML patients were detected by Western blot and SYBR Green-based qRT-PCR. The methylation status of SHP-1 were assessed by methylation-specific polymerase chain reaction (MSP) assay. K562 cells were infected with the lentiviral plasmids pEX-SHP-1-puro-Lv105 (K562-SHP-1) or pEX-EGFP-puro-Lv105 (K562-EGFP). The levels of proteins and phosphorylated proteins were detected by Western blot. qRT-PCR assay was used to test the level of BCR-ABL mRNA.

RESULTSThe relative levels of SHP-1 mRNA were sharply decreased in advanced stages CML compared to chronic phase (CP)-CML (0.79±0.37 vs 1.18±0.64, P= 0.009). The level of SHP-1 protein was lower in advanced stages CML compared to CP-CML (0.57±0.02 vs 1.02±0.04, P=0.039). The frequency of SHP-1 gene promoter methylation at selected loci in CP-CML was 23.8% (10/42), and the methylated regions were detected in all advanced CML samples (P<0.01). SHP-1 was stably transfected into K562 cells and selected with puromycin. Overexpression of SHP-1 inhibited the proliferation and induced the apoptosis of K562 cells, meanwhile leaded to G0/G1 phase arrest. After transfection, the level of BCR-ABL mRNA was not affected in K562-SHP-1 cells (1.32±0.34) compared to K562-EGFP cells (1.18±0.20, P=0.644), but overexpression of SHP-1 caused a slight decrease in BCR-ABL protein in K562-SHP-1 cells compared to K562 -EGFP cells (0.78±0.15 vs 1.27±0.24, P=0.040). Overexpression of SHP-1 resulted in a remarkable decrease in MYC protein, phosphorylated forms of JAK2, STAT5, Akt and MAPK. However, the un-phosphorylated forms of these molecules were not significantly affected.

CONCLUSIONDecreased expression of SHP-1 caused by aberrant promoter hypermethylation may play a key role in the progression of CML by dysregulation of BCR-ABL, Akt, MAPK, MYC, JAK2 and STAT5 signaling.

Apoptosis ; DNA Methylation ; Disease Progression ; Fusion Proteins, bcr-abl ; Humans ; Janus Kinase 2 ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukocytes, Mononuclear ; Phosphorylation ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 ; RNA, Messenger