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BACKGROUND@#Cancer stem-like cells (CSCs) are a small subset of cells in tumors that exhibit self-renewal and differentiation properties. CSCs play a vital role in tumor formation, progression, relapse, and therapeutic resistance. B7-H3, an immunoregulatory protein, has many protumor functions. However, little is known about the mechanism underlying the role of B7-H3 in regulating gastric cancer (GC) stemness. Our study aimed to explore the impacts of B7-H3 on GC stemness and its underlying mechanism.@*METHODS@#GC stemness influenced by B7-H3 was detected both in vitro and in vivo . The expression of stemness-related markers was examined by reverse transcription quantitative polymerase chain reaction, Western blotting, and flow cytometry. Sphere formation assay was used to detect the sphere-forming ability. The underlying regulatory mechanism of B7-H3 on the stemness of GC was investigated by mass spectrometry and subsequent validation experiments. The signaling pathway (Protein kinase B [Akt]/Nuclear factor erythroid 2-related factor 2 [Nrf2] pathway) of B7-H3 on the regulation of glutathione (GSH) metabolism was examined by Western blotting assay. Multi-color immunohistochemistry (mIHC) was used to detect the expression of B7-H3, cluster of differentiation 44 (CD44), and Nrf2 on human GC tissues. Student's t -test was used to compare the difference between two groups. Pearson correlation analysis was used to analyze the relationship between two molecules. The Kaplan-Meier method was used for survival analysis.@*RESULTS@#B7-H3 knockdown suppressed the stemness of GC cells both in vitro and in vivo . Mass spectrometric analysis showed the downregulation of GSH metabolism in short hairpin B7-H3 GC cells, which was further confirmed by the experimental results. Meanwhile, stemness characteristics in B7-H3 overexpressing cells were suppressed after the inhibition of GSH metabolism. Furthermore, Western blotting suggested that B7-H3-induced activation of GSH metabolism occurred through the AKT/Nrf2 pathway, and inhibition of AKT signaling pathway could suppress not only GSH metabolism but also GC stemness. mIHC showed that B7-H3 was highly expressed in GC tissues and was positively correlated with the expression of CD44 and Nrf2. Importantly, GC patients with high expression of B7-H3, CD44, and Nrf2 had worse prognosis ( P = 0.02).@*CONCLUSIONS@#B7-H3 has a regulatory effect on GC stemness and the regulatory effect is achieved through the AKT/Nrf2/GSH pathway. Inhibiting B7-H3 expression may be a new therapeutic strategy against GC.
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Humans , Cell Line, Tumor , Neoplasm Recurrence, Local , NF-E2-Related Factor 2/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Stomach NeoplasmsABSTRACT
Gastrointestinal cancers are the common malignant tumors of the digestive system, and their morbidity and mortality are in the forefront of malignant tumors. Currently, cancer immunotherapy is the hottest topic in cancer research field. Although cancer immunotherapy has achieved some results in the fundamental research and clinical application of gastrointestinal tumors, there are still a series of problems that need to be resolved. In this article, we review the fundamental and clinical research progress of several common methods of cancer immunotherapy in the field of gastrointestinal tumors.
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Objective To explore the diagnostic value of digital breast tomosynthesis technique (DBT) in breast suspicious calcified lesions.Methods Clinical data of 135 patients using DBT and FFDM (Full field digital mammography) was respectively analyzed.Results Of the 135 cases,43 cases were malignant,and 92 cases were benign.The diagnostic sensitivity DBT and FFDM were 93.0％ (40/43)and 88.4％ (38/43),specificity were 88.0％ (81/92) and 75.0％ (69/92),accuracy were 89.6％ (121/135) and 79.3％ (107/135),the differences were statistically significant (P ＜0.05).The ROC curve area (AUC) of DBT and FFDM were 0.905 ± 0.026 and 0.817 ± 0.034 (P =0.000 2).In premenopausal,postmenopausal and breast density ACR3-4 cases,DBT accuracy is higher than FFDM (P ＜ 0.05).The BI-RADS classification difference of the benign calcified lesions was statistically significant (x2 =11.740,P =0.038 5).Conclusions Compared with the traditional FFDM,DBT has a higher value in the diagnosis of breast suspicious calcified lesions,especially for benign calcified lesions.
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Objective To evaluate the diagnostic value of breast mass-like lesions by digital breast tomosynthesis technique (DBT) versus full field digital mammography (FFDM).Methods 182 breast mass cases undergoing respectively DBT and FFDM diagnosis were reviewed to evaluate the the sensitivity,specificity and accuracy,breast BI-RADS classification and differences of edge character.Results Of the 182 cases,101 cases were malignant,81 cases were benign.DBT and FFDM in malignant mass detection rate were 95.0％ and 95.0％ respectively,the benign tumor detection rate were 80.2％ and 80.2％ respectively,the difference was statistically significant (P ＜ 0.05).The diagnostic sensitivity was 93.1％ (94/101) and 82.2％ (83/101),specificity was 66.7％ (54/81) and 53.1％ (43/81),accuracy was 81.3％ (148/182) and 69.2％ (126/182),all the differences were statistically significant (P ＜ 0.05).The BI-RADS classification difference of the malignant mass was statistically significant (x2 =12.912,P =0.044 5),and the benign mass was also statistically significant (x2 =12.739,P =0.026 0).The clear edge benign tumors detected by DBT and FFDM respectively were 65 and 45 cases (x2 =10.224,P =0.001 4).The spicule sign detected by DBT and FFDM respectively in malignant tumors were 71 and 50 cases (x2 =8.244,P =0.004 1).Conclusion DBT compared to traditional FFDM photography improves the lesion visibility,increases the diagnostic sensitivity and specificity,conducing to the identification of benign and malignant lesions.
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Objective:To prepare celecoxib nanosuspension ( CXB-NSs) and study the pharmacokinetics of CXB-NSs in rats. Methods:CXB-NSs were prepared by an anti-solvent precipitation and high pressure homogenization method. The particle size, polydispersion index ( PdI) and zeta potential of the nanosuspension were studied. Totally 12 Wistar rats were randomly divided into CXB-NSs group and CXB suspension group, and gastric drug dose was 100 mg·kg-1 . CXB concentration in plasma was determined by HPLC and the pharmacokinetic parameters were calculated by 3P97 software. Results: The particle size, polydispersion index, zeta potential of CXB-NSs was (442. 5 ± 61. 9) nm, 0. 312 ± 0. 057 and ( -31. 6 ± 3. 9) mV, respectively. AUC (0-t) of CXB suspension and CXB-NSs was (5.13 ±0.77) and (13.51 ±3.18) mg·L-1·h, half time (t1/2) was (12.31 ±1.91) and (12.73 ±1.83) h, Tmax was (2. 48 ± 0. 37) and (1. 41 ± 0. 27) h and Cmax was (0. 94 ± 0. 31) and (2. 38 ± 0. 25) mg·L-1 , respectively. Conclusion:CXB-NSs can remarkably increase bioavailability in rats.
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BACKGROUND:Chinese herbs for kidney nourishment can promote the proliferation and differentiation of spermatogonial stem cel s. OBJECTIVE:To verify the effect of seminiferous capsule extract on spermatogonial stem cel proliferation. METHODS:Spermatogonial stem cel s were isolated from the testis of male mice and synchronized by serum-free medium fol owed by an addition of 10, 50, 100 mg/L seminiferous capsule extracts. After 24 hours of culture, viability, proliferation and cel cycle of spermatogonial stem cel s were observed. RESULTS AND CONCLUSION:Compared with the control group, seminiferous capsule extracts promoted the cel number, viability and proportion at S stage. The number of BrdU-labeled spermatogonial stem cel s was increased significantly after intervention with seminiferous capsule extracts, especial y at the concentration of 50 mg/L. These findings indicate that seminiferous capsule extracts can promote the proliferation and viability of spermatogonial stem cel s.
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BACKGROUND:To establish a rapid and effective method to obtain sufficient spermatogonial stem cels that can meet the clinical need is urgent to be solved in the spermatogonial stem cel transplantation. OBJECTIVE:To study the effect of rhodiola polysaccharide on the proliferation of spermatogonial stem celsin vitro. METHODS:Under sterile conditions, spermatogonial stem cels and Sertoli cels were isolated from the testis of mice, and spermatogonial stem cels were seeded onto the feed layer of Sertoli cels. Then, the co-cultured cels were assigned into experimental group 1 (simple cel culture medium), experimental group 2 (cel culture medium containing 150 mg/L rhodiola polysaccharide) and experimental group 3 (cel culture medium containing 150 mg/L rhodiola polysaccharide, 1 U/L leukemia inhibitory factor and 10 μg/L glial cel line-derived neurotrophic factor). After 7 days of co-culture, flow cytometry was used to detect cel proliferation in vitro, and cel viability and positive expression of GFRa-1, Thy-1 and C-kit were calculated. RESULTS AND CONCLUSION:After 7 days of co-culture, the cels grew rapidly and presented with colony and thyrsiform growth, and the number of cel masses increased significantly, al of which were in line with the proliferative features of spermatogonial stem cels. The GFRa-1, Thy-1 and C-kit proteins were expressed in the cel membrane and cytoplasm, mainly in the cel membrane. The viability of spermatogonial stem cels and positive expression of GFRa-1 and Thy-1 were ranked as folows: experimental group 3 > experimental group 2 > experimental group 1, and there were significant differences between groups (P < 0.05). The positive expression of C-kit had no difference between experimental groups 1 and 2, but it was significantly higher in the experimental group 3 than the other two groups (P < 0.05). These findings indicate that rhodiola polysaccharide used alone or combined with leukemia inhibitory factor and glial cel line-derived neurotrophic factor can enhance the proliferative ability of spermatogonial stem celsin vitro.
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Objective To discuss the protein level of hypoxia-inducible factor 1-alpha(HIF-1α),glucose transporter-1 (Glut-1)and vascular endothelial growth factor(VEGF) in breast cancer tissue in diabetic patients and its significance.Methods HIF-1α,Glut-1 and VEGF protein levels were measured by immunohistochemical staining in 112 cases of primary breast cancer tissues.CD31 labeled vascular endothelial cells were used to evaluate micro vascular density (MVD).The correlation between the effect of blood sugar control and clinicopathological parameters was analyzed.Results The expression of HIF-1α,Glut-1 and VEGF protein in breast cancer tissues of diabetic patients was significantly higher than that in breast cancer tissues of non-diabetic patients(t =2.255,P =0.030; t =2.154,P=0.038; t =2.225,P =0.032).HIF-1α was positively correlated with Glut-1 and VEGF in diabetic patients with breast cancer (r =0.561,P =0.003 ; r =0.435,P =0.014).The level of MVD in breast cancer tissues of diabetic patients was obviously higher than that in the non-diabetic patients with breast cancer(t =9.458,P =0.000).The effect of blood sugar control was significantly correlated with lymph node metastasis and tumor stage in diabetic patients with breast cancer(x2 =4.689,P =0.030; x2 =5.051,P =0.025).Conclusion Hypoxia-related factors including HIF-1α,Glut-1 and VEGF and MVD are upregulated in diabetic patients with breast cancer,and the effect of blood sugar control is correlated with lymph node metastasis and tumor stage,suggesting diabetes mellitus may promote tumor progression through high glucose and hypoxia in breast cancer.
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Objective To compare the efficacy of the radical resection by laparoscopy versus open approach in perioperative period on the patients with rectal carcinoma,and investigate the feasibility,safety and oncological clearance of the laparoscopy.Methods The clinical data of 44 patients who underwent radical resection of rectal carcinoma by laparoscopy in our hospital were reviewed and compared with another 53patients who underwent an open approach in the same period.The surgery-related data,postoperative recovery status,tumor radical resection index,and postoperative complications by laparoscopy were analyzed by statistics,and compared with those by open approach,and evaluated the deference of too kinds of operation.Results This study showed a longer surgical time (260.45 ± 67.46) min vs ( 179.25 ± 40.92) min,P ＜0.05,a less intra-operative blood loss( 125.20 ±61.80) mL vs ( 198.02 ± 131.24) mL,P ＜0.05,in laparoscopic group compared with open approach.Meanwhile,it also showed an earlier recovery of bowel functions for discharge gas from anus,taking in food,and out-of-bed activity (4.34 ± 1.55) d vs(5.45 ± 1.55) d,P ＜0.05,in the laparoscopic group compared with open approach.There was no statistical difference of incidence of post-operative complications (5 cases vs 11 cases,P ＞0.05) between the two groups and the laparoscopic approach was also equal to the open approach as regard to post-operative stay (15.34 ±6.62) d vs (16.82±5.73) d,P ＞0.05,and demand of intra-operative blood transfusion (4 case vs 8 cases,P＞0.05 ).Conclusions Compared with open surgery,the radical resection of rectal carcinoma by laparoscopy has shown obvious advantages in smaller incision,less blood loss,less pain,earlier recovery of bowel and bladder functions,and earlier out-of-bed activity.And it is also possible by laparoscopy approach to decrease the post-operative complications and post-operative stay.Meanwhile,there is no significant deference on oncological clearance for laparoscopy compared with open approach during perioperative period,while the long term follow-up data is still needed to support the results.
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Objective To find an efficient plan for the arrangement of the beds in hospital so that the beds-operating efficiency can be raised and the requirement of patients can be perfectly met. Methods According to the data analyzed via the method of mathematical statistics, optimizing model was built and automatic stimulation program was generated as well as conducted by matlab software. Results The characteristics of bed-occupation condition was acquired by data analysis, the result of optimizing model was stimulated by program and the most efficient plan emerges which was obviously better than the original FCFS (First Come First Serve) Plan. Conclusion The mathematical model built up is of great maneuverability in the practical situation to ameliorate the management efficiency of hospital beds considerably.