Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer / 中华医学杂志(英文版)

BACKGROUND@#Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a micro-barrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.@*METHODS@#The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models.@*RESULTS@#Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.@*CONCLUSIONS@#The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Establishment of a Patient-Derived T-Cell Acute Lymphoblastic Leukemia Xenograft Model in Novel Immunodeficient NCG Mice / 中国实验血液学杂志

OBJECTIVE@#The leukemia cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) were inoculated into NCG mice to establish a stable human T-ALL leukemia animal model.@*METHODS@#Leukemia cells from bone marrow of newly diagnosed T-ALL patients were isolated, and the leukemia cells were inoculated into NCG mice via tail vein. The proportion of hCD45 positive cells in peripheral blood of the mice was detected regularly by flow cytometry, and the infiltration of leukemia cells in bone marrow, liver, spleen and other organs of the mice was detected by pathology and immunohistochemistry. After the first generation mice model was successfully established, the spleen cells from the first generation mice were inoculated into the second generation mice, and after the second generation mice model was successfully established, the spleen cells from the second generation mice were further inoculated into the third generation mice, and the growth of leukemia cells in peripheral blood of the mice in each group was monitored by regular flow cytometry to evaluate the stability of this T-ALL leukemia animal model.@*RESULTS@#On the 10th day after inoculation, hCD45+ leukemia cells could be successfully detected in the peripheral blood of the first generation mice, and the proportion of these cells was gradually increased. On average, the mice appeared listless 6 or 7 weeks after inoculation, and a large number of T lymphocyte leukemia cells were found in the peripheral blood and bone marrow smear of the mice. The spleen of the mice was obviously enlarged, and immunohistochemical examination showed that hCD3+ leukemia cells infiltrated into bone marrow, liver and spleen extensively. The second and third generation mice could stably develop leukemia, and the average survival time was 4-5 weeks.@*CONCLUSION@#Inoculating leukemia cells from bone marrow of patients with T-ALL into NCG mice via tail vein can successfully construct a patient-derived tumor xenografts (PDTX) model.

Efficacy of the biopsy strategy combining 6-core systematic and 3-core MRI-targeted biopsy in the detection of prostate cancer / 中华泌尿外科杂志

Objective:To investigate the efficacy of the biopsy strategy combining 6-core systematic and 3-core MRI-targeted biopsy on prostate cancer (PCa) detection in biopsy-na?ve patients.Methods:The clinical data of 121 biopsy-na?ve patients who underwent transperineal prostate biopsy in West China Hospital of Sichuan University from July 2018 to January 2020 were retrospectively analyzed. The average age was (64.7±9.1) years old. Pre-biopsy prostate-specific antigen (PSA) was (12.4±7.5)ng/ml, f/t PSA was 0.13±0.05. Prostate volume was (43.1±26.1) ml and PASD was (0.35±0.27) ng/ml 2. The prostate-imaging and data system (PI-RADS) score of MRI before biopsy was reported to be 3 for 29 patients (24.0%), 4 for 54 patients (44.6%) and 5 for 38 patients (31.8%). All 121 patients underwent 12-core systematic biopsy combined with a 3-core or 5-core MRI-targeted biopsy, of which 61 patients underwent 3-core targeted biopsy and 60 underwent 5-core targeted biopsy. There was no significant difference in the pre-biopsy clinical data between the two groups ( P>0.05). A 6-core systematic biopsy was redefined as the results of 6 cores among the 12-core systematic biopsy. We compared the detection rates among the single 12-core systematic biopsy, 6-core systematic biopsy, MRI-targeted biopsy (3-core or 5-core), and different systematic biopsy combing with targeted biopsy for any PCa and clinically significant PCa, and we also analyzed the cumulative cancer detection rates for MRI-targeted biopsy of different cores. Results:Of the 121 patients in this study, the biopsy results were negative for 43 patients (35.5%) and positive for 78 (64.5%). The detection rate of clinically significant PCa was 55.4% (67/121). The detection rate of the 6-core systematic biopsy combined with MRI-targeted biopsy was 62.0% (75/121) for PCa and 55.4% (67/121) for clinically significant PCa, which was of no difference compared with that for the 12-core systematic biopsy combined with MRI-targeted biopsy ( P>0.05), but the 6-core systematic biopsy combined with MRI-targeted biopsy avoided the overdiagnosis of 3 patients with Gleason score 3+ 3. The detection rate of PCa for MRI-targeted biopsy was 57.9% (70/121), including 42.1% (51/121) for the first core, 55.4% (67/121) for the first two cores, and 57.9% (70/121) for the first three cores. Compared with the single-core targeted biopsy for suspicious lesions, the first 2-core targeted biopsy ( OR=1.7, 95% CI 1.0-2.8) and 3-core targeted biopsy ( OR=1.9, 95% CI 1.1-3.1) can significantly increase the detection rate of PCa, while the fourth or fifth core of targeted biopsy can not increase the detection rate additionally (60%, 36/60). Conclusion:For patients with suspected PCa, the prostate biopsy strategy combing 6-core systematic and 3-core MRI-targeted biopsy performs no inferior than the current 12-core systematic biopsy combined with MRI-targeted biopsy.

Effect of Celastrol Based on IRAK4/ERK/p38 Signaling Pathway on Proliferation and Apoptosis of Multiple Myeloma Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of celastrol on the proliferation and apoptosis of human multiple myeloma (MM) cell lines, reveal the relationship between IRAK4/ERK/p38 signaling pathway and celastrol regulating the proliferation and apoptosis of H929 and ARP-1 cells, and explore whether celastrol combined with bortezomib has synergistic effect. @*METHODS@#CCK-8 method was used to detect the viability of MM cell lines H929 and ARP-1 treated by different concentrations of celastrol, bortezomib, and their combination, and the synergistic effect was determined by Kim's formula. The apoptosis rate of H929 cells and necrosis rate of ARP-1 were detected by Annexin V/PI method. The expression of key proteins and apoptosis proteins in IRAK4/ERK/p38 signaling pathway were detected by Western blot. @*RESULTS@#Celastrol could significantly inhibit the proliferation of H929 and ARP-1 cells (r=0.9018, r=0.9244) and induce apoptosis in a time-dependent manner. Compared with the control group, celastrol could significantly up-regulate the expression of PARP and cleaved caspase-3 while down-regulate the expression of p-IRAK4, p-ERK, and p-p38 in H929 and ARP-1 cells. Celastrol and bortezomib alone inhibited the proliferation of H929 and ARP-1 cells. Compared with celastrol and bortezomib alone, their combination had lower cell survival rate and higher apoptosis rate (P<0.05). @*CONCLUSION@#Celastrol can inhibit the proliferation and promote the apoptosis of H929 and ARP-1 cells, which may be related to inhibiting the phosphorylation of IRAK4 and blocking the activation of IRAK4/ERK/p38 signaling pathway. Celastrol combined with bortezomib has synergistic effect, which can more effectively inhibit the proliferation and induce apoptosis of H929 and ARP-1 cells.

Analysis of Serum Metabonomics in Patients with Multiple Myeloma Based on Liquid Chromatography-Mass Spectrometry / 中国实验血液学杂志

OBJECTIVE@#To observe the changes of serum metabolites in patients with multiple myeloma (MM) by metabonomics, and explore the potential biomarkers for diagnosis, prognosis, and progression of MM.@*METHODS@#Serum samples were collected from 26 patients with MM and 50 healthy controls. The data detected by liquid chromatography-mass spectrometry (LC-MS) was input into SIMCA-14.0 software for multivariate statistical analysis. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to analyze the changes of metabolites.@*RESULTS@#The metabolic change of uric acid and trans-vaccenic acid in serum samples of MM patients was 9.39 times and 2.77 times of these in healthy people, respectively, which were significantly higher than those of healthy people, and the difference was statistically significant(P<0.01).@*CONCLUSION@#Uric acid and trans-vaccenic acid are expected to be important metabolic indicators for the diagnosis, prognosis, and efficacy evaluation of MM, thus providing some clues for the pathogenesis of MM.

Characteristics of unintentional burns among left-behind children and their parents/guardians’ cognitive level of burns / 中国学校卫生

Objective@#To explore the characteristics and influencing factors of unintentional burns among left-behind children in rural areas of northern Guizhou, from the perspective of parents and children, to formulate strategies to prevent children from burns.@*Methods@#A total of 508 left-behind children were recruited by using a multistage cluster sampling method, and 196 left-behind children’s families were also investigated with a self-designed questionnaire.The relative factors of burns were analyzed by unconditional logistic regression and multiple regression analysis.@*Results@#The report rate of burns among left-behind children was 12.20%(62/508). Left-behind girls were a risk factor for burns(OR=1.81). The time of employment >5 years and the higher of the score of burn-related knowledge were the protective factors(OR=0.23, 0.38)(P<0.05). Only 64.80% of left-behind children’s main guardians had a burns-related knowledge score of 60 or more. The age of their main guardian, the number of minor children, and whether understand of unintentional injury were the influencing factors of burns score.@*Conclusion@#The report rate of burns among left-behind children in rural areas in northern Guizhou is still high; parents/guardians have a low cognition level of burns. The knowledge of burns should be strengthened and left-behind children should be cared to reduce the incidence of burns.

Transurethral resection of the prostate is an independent risk factor for biochemical recurrence after radical prostatectomy for prostate cancer / 亚洲男科学杂志(英文版)

Biochemical recurrence (BCR) is important for measuring the oncological outcomes of patients who undergo radical prostatectomy (RP). Whether transurethral resection of the prostate (TURP) has negative postoperative effects on oncological outcomes remains controversial. The primary aim of our retrospective study was to determine whether a history of TURP could affect the postoperative BCR rate. We retrospectively reviewed patients with prostate cancer (PCa) who had undergone RP between January 2009 and October 2017. Clinical data on age, prostate volume, serum prostate-specific antigen levels (PSA), biopsy Gleason score (GS), metastasis stage (TNM), D'Amico classification, and American Society of Anesthesiologists (ASA) classification were collected. Statistical analyses including Cox proportional hazard models and sensitivity analyses which included propensity score matching, were performed, and the inverse-probability-of-treatment-weighted estimator and standardized mortality ratio-weighted estimator were determined. We included 1083 patients, of which 118 had a history of TURP. Before matching, the non-TURP group differed from the TURP group with respect to GS (P= 0.047), prostate volume (mean: 45.19 vs 36.00 ml, P < 0.001), and PSA level (mean: 29.41 vs 15.11 ng ml-1, P= 0.001). After adjusting for age, PSA level, T stage, N stage, M stage, and GS, the TURP group showed higher risk of BCR (hazard ratio [HR]: 2.27, 95% confidence interval [CI]: 1.13-3.94, P= 0.004). After matching (ratio 1:4), patients who underwent TURP were still more likely to develop BCR according to the adjusted propensity score (HR: 2.00, 95% CI: 1.05-3.79, P= 0.034). Among patients with PCa, those with a history of TURP were more likely to develop BCR after RP.

The relationship between the level of serum lipid and homocysteine with cerebral infarction / 预防医学

Objective To investigate the correlation between cerebral infarction and homocysteine (Hcy) level and atherosclerosis index (ASI) , and to provide reference for prevention and treatment of cerebral infarction. Methods 2525 patients hospitalized with cerebral infarction and 8151 healthy subjects were included in the study, the blood serum homocysteine and blood lipid levels were detected by enzymatic cycling and enzymatic method, and the ASI was calculated according to the results of blood lipid test. The risk factors of cerebral infarction were analyzed by logistic regression analysis model. Results The Physical examination Health Group male 4952, female 3199, average (45.65±10.77) years old, in the cerebral infarction Group male 1590 cases, female 935, average (65.47±12.16) years old. A total of 360 patients with high homocysteine were detected in the Health examination group, the detection rate was 4.42%, the cerebral infarction group detected 268 patients with high homocysteine, the detection rate was 10.61%, and the difference was statistically significant (P<0.01) . Logistic regression analysis showed that age (OR=1.147, 95%CI: 1.140~1.154), homocysteine (OR=1.022, 95% CI: 1.010 ~1.035) and total cholesterol (OR=2.815, 95% CI: 2.603 ~3.045) level, ASI (OR=1.914, 95%CI: 1.794~2.042) are the risk factors of cerebral infarction, women (OR=0.694, 95%CI: 0.606~0.697) are the protective factors for the occurrence of cerebral infarction. Conclusion Serum homocysteine and total cholesterol levels, ASI elevated can increase the risk of cerebral infarction, regular detection of serum homocysteine and lipid levels can help early detection and prevention of cerebral infarction.

Giant ossifying fibroma of nasal cavity and nasal sinuses: one case report / 临床耳鼻咽喉头颈外科杂志

A 39 years old male patient was admitted with the right of facial abnormalities and gradually protruding in right eye more than 30 years. CT shows high mixed density, clear boundary, and the right eye was crowded to the right. Giant tumor had completely been excised, and the result was fine. The outline figure and function of patients were obviously improved. The pathological examination after resection showed ossifying fibroma.

Myoepithelioma of nasal cavity: a case report / 临床耳鼻咽喉头颈外科杂志

Myoepithelioma is an uncommon benign tumor that most likely occurs in the salivary gland. Extra-salivary myoepithelioma are sporadic and rare, especially the quantities occur in the sinonasal cavity are fewer in related literature reported. In this paper, we present a rare case of benign myoepithelioma that occurred in the nasal cavity, and the related process of pathogenesis, diagnosis, treatment and prognosis are discussed.

Changes in Wnt pathway inhibiting factors in nitrosamine-induced esophageal precancerosis lesions and effect of gexia zhuyu decoction / 中国中药杂志

<p><b>OBJECTIVE</b>To discuss the changes in Wnt pathway inhibiting factors in esophageal precancerosis lesions induced by methyl benzyl nitrosamine (MBNA) and the effect of Gexia Zhuyu decoction.</p><p><b>METHOD</b>Wistar rats were subcutaneously injected with MBNA (3.5 mg x kg(-1) for twice per week to establish the model. Since the 1st day after the model establishment, they were orally administered with Gexia Zhuyu decoction (16, 8 mg x kg(-1)). At the 10th week, esophageal tissues were collected to observe the pathological changes of esophageal mucosa, detect SFRP1, sFRP4, Axin1, Axin2 and GSK-3β mRNA levels.by fluorescent quantitation PCR analysis and β-catenin protein level by Western blotting.</p><p><b>RESULT</b>Being induced by MBNA, rats in the model group showed slight atypical hyperplasia in the histopathological examination. Compared with the normal group, Gexia Zhuyu decoction dose high and low groups showed no significant pathomorphological and histological changes. The model group showed lower gene transcription levels of esophageal tissues sFRP1, sFRP4, Axin1 and Axin2 (P < 0.05 or P < 0.01) and higher β-catenin protein expression level (P < 0.01) than the normal control group. The Gexia Zhuyu decoction low dose group showed higher gene transcription levels of esophageal tissues sFRP1, sFRP4, Axin1 and Axin2 (P < 0.05 or P < 0.01) and lower β-catenin protein expression level (P < 0.01) than the normal control group.</p><p><b>CONCLUSION</b>Up-regulated β-catenin protein level and down-regulated Wnt pathway could enhance Wnt pathway activity of MBNA-induced esophageal precancerous lesions. Gexia Zhuyu decoction could down-regulate the β-catenin protein level and up-regulate the transcription level of Wnt pathway inhibiting factors, but could not block MBNA-induced esophageal precancerosis lesions.</p>

Clinical and biological features in refractory anemia with ringed sideroblasts with fluctuant platelet counts / 中国实验血液学杂志

The objective of this study was to explore the differences between refractory anemia with ringed sideroblast (RARS) and RARS associated with marked thrombocytosis (RARS-T) in the clinical, biological features and prognosis. The morphological changes of cells were observed by bone marrow smear and biopsy. Immunologic phenotype was analyzed by flow cytometry, and chromosome was examined by conventional chromosomal analysis. JAK2 V617F and MPL W515L mutations were screened by allele-specific polymerase chain reaction (AS-PCR) and sequence analysis. The results showed that this case was clinically diagnosed as RARS with thrombophilia, the level of serum potassium was positively related with platelet counts. When platelets increased, the clusters of atypical giant platelets and megakaryocytes were observed in peripheral blood and bone marrow examined by bone marrow smear and bone marrow biopsy respectively, JAK2 V617F and MPL W515L mutations were negative. It is concluded that RARS may transform into RARS-T accompanied with megakaryocyte proliferation, large atypical platelets and negative JAK2 V617F. Preventing thrombophilia and monitoring relative gene mutations are necessary when atypical giant platelets and fluctuant platelet counts occurred in process of RARS with tendency to RARS-T.