Trends, implications and references of curriculum update in American medical schools in recent ten years (2010-2018) / 中华医学教育探索杂志

Nearly a decade of curriculum update in American medical colleges and universities are summarized in this paper. This paper introduces the situation of sampling survey of colleges and universities. The results show the diversity of medical curriculum integration, reflecting the concept of multi-disciplinary integration of basic disciplines, clinical disciplines and public health and social sciences, and giving experiences such as early clinical practice, providing personalized talent cultivation approaches, and designing competency-oriented curriculum system. Combined with the current situation of medical education curriculum reform in China, it's suggested to explore the construction of medical curriculum system with Chinese characteristics, so as to contribute to the cultivation of excellent physicians for implementing Healthy China Initiative.

Tumor-Associated Macrophages Derived TGF-β‒Induced Epithelial to Mesenchymal Transition in Colorectal Cancer Cells through Smad2,3-4/Snail Signaling Pathway / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We investigated the role of tumor-associated macrophages (TAMs) on the epithelial to mesenchymal transition (EMT) of colorectal cancer cells and determined the potential mechanism involved in the metastatic process. MATERIALS AND METHODS: In this study, flow cytometry was used to detect the expression of target proteins. We used transwell assay to evaluate the migration of cancer cells under specific conditions. Using real-time polymerase chain reaction, we examined the expressions of cytokines and EMT-related markers in mRNA level. Animal assay was performed for analysis in vivo and hematoxylin and eosin was used to visualize the effect of TAMs on tumor metastasis. We also used immunohistochemistry and Western blotting to detect the expression of target proteins. RESULTS: Here, we observed enrichment of TAMs in colorectal tumor tissues, resulting in high metastasis in clinical therapy. Moreover, those TAMs could facilitate the EMT progression of colorectal cancer cells, which is induced by the transforming growth factor-β (TGF-β) derived from TAMs, leading to the invasion and migration of cancer cells. CONCLUSION: Our results demonstrated that TAMs contributed the EMT progression through a TGF-β/Smad2,3-4/Snail signaling pathway, and disrupting this pathway with TGF-β receptor inhibitor could suppress metastasis, readjusting our focus to the connection of TAMs and cancer metastasis.

Multicenter postmarketing clinical study on using pegylated recombinant human gran-ulocyte-colony stimulating factor to prevent chemotherapy-induced neutropenia / 中国肿瘤临床

Objective: To investigate the efficacy and safety of using pegylated recombinant human granulocyte-colonystimulating factor (PEG-rhG-CSF) in preventing neutropenia in multiple chemotherapy cycles. Methods: A multicenter, prospective, open-label, singlearmstudy was designed. Patients with malignant tumors, such as lung, ovarian, and colorectal cancers, who received multiple cycles of chemotherapy with the prophylactic use of PEG-rhG-CSF for 2-4 consecutive cycles participated in the study. Results: After the prophylactic use of PEG-rhG-CSF, the incidence of grade IV neutropenia decreased from 4.76% (13/273) in the first cycle to 1.83% (5/273), 1.15% (2/174), and 2.08% (2/96) in subsequent cycles. Meanwhile, the incidence of grade III neutropenia decreased from 11.36% (31/ 273) in the first cycle to 6.23% (17/273), 2.87% (5/174), and 3.13% (3/96) in subsequent cycles. The incidence of febrile neutropenia (FN) during the first cycle was 0.73% (2/273). The duration of FN was 2 days in one case and 5 days in another case. FN was not observed during the second, third, or fourth cycle. After the secondary prophylactic use of PEG-rhG-CSF, the incidence of grade IV neutropenia decreased from 25% (7/28) to 3.57% (1/28), 0% (0/28), and 6.67% (1/15) in subsequent cycles. Meanwhile, the incidence of grade III neutropenia decreased from 71.43% (20/28) to 10.71% (3/28), 14.29% (4/28), and 0% (0/15) in subsequent cycles. The proportion of patients who received antibiotic therapy during the entire chemotherapy period was 10.48% (44/420). Conclusion: The application of PEG-rhG-CSF once per chemotherapy cycle can effectively reduce the occurrence of neutropenia in patients under multiple cycles of chemotherapy treatment with good safety.

Effector cells derived from naive T cells used in tumor immunotherapy of mice bearing B16 melanoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Adoptive cell transfer (ACT) immunotherapy has been used clinically for years to treat malignancies. Improving the killing efficiency of effector cells, such as tumor-specific cytotoxic T lymphocytes (CTLs), is an important component for enhancing the clinical response of cancer immunotherapy. Hence, we explored a novel method for preparing cancer-specific CTLs using naive T lymphocytes.</p><p><b>METHODS</b>C57BL/6 mice bearing B16 melanoma tumors were pretreated with cyclophosphamide (CTX) by peritoneal injection. The immunosuppressive influence of CTX on tumor regression and the tumor microenvironment was assessed. Naive T cells and T cell pools were isolated via negative selection using immunomagnetic beads. The proliferative potential and cytokine production of different T cell subpopulations were evaluated in vitro. Tumor-specific CTLs derived from naive T cells (naive CD4+ T cells: naive CD8+ T cells = 2:1) and pooled T cells were generated in vitro, respectively. B16 melanoma-bearing C57BL/6 mice were pretreated with CTX, followed by ACT immunotherapy using dendritic cell-induced CTLs. The homing abilities of the effector cells and interleukin-2 (IL-2), interferon-γ, granzyme B, and perforin mRNA levels in tumor tissues were evaluated, and the change in tumor volume was measured.</p><p><b>RESULTS</b>Mice receiving CTX peritoneal pretreatment injections did not display tumor regression compared with control mice. However, a significant downregulation of splenic Tregs and tumor growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) serum levels was observed (P < 0.05). Naive T cells showed a stronger proliferative capacity and elevated cytokine production than did pooled T cells (P < 0.05). In addition, effector cells generated from naive T cells displayed more potent antitumor activity in vivo than those derived from pooled T cells (P < 0.05).</p><p><b>CONCLUSION</b>Effector cells derived from the naive T cells possess a stronger proliferative potential, homing capacity, and enhanced cytokine production, which leads to a superior antitumor response.</p>

Mitoxantrone inhibits growth of melanoma by increasing expression of calreticulin / 中国肿瘤生物治疗杂志

Objective: To investigate the effect of mitoxantrone (MIT) on calreticulin (CRT) expression in B16 cells, and to observe the immune effect of B16-membrane antigen vaccine highly expressing CRT on B16 tumor-bearing mice. Methods: The expression of CRT on membrane of B16 cells was detected by immunofluorescence after treatment with different concentrations of MIT. B16-implanted mouse model was established, and the growth of B16-implanted tumors and CRT expression in B16-implanted tumor tissues were observed after treatment with different concentrations of MIT. Membrane antigen vaccines from both normal B16 cells and MIT-treated B16 cells were prepared, and mice were immunized before B16 cell implantation. The infiltration of immune cells into B16 tumor tissues and the ratios of CD4~+ and CD8~+ T cells in the spleen of B16 tumor-bearing mice were examined by immunohistochemistry and flow cytometry, respectively. Results: Flow cytometry results showed that MIT dose-dependently increased CRT expression on B16 cell membrane, with CRT expression in control and high dosage MIT groups being (29.40±3.57)% and (72.20±2.94)% (P<0.05), respectively. MIT also increased CRT expression in B16 tumor tissues, with those in the control and high dosage MIT groups being 3.21±1.37 and 9.17±1.06 (P<0.05), respectively. MIT effectively inhibited the growth of B16 tumors (P<0.05). Compared with normal B16 cell membrane antigen vaccine, the vaccine highly expressing CRT increased the numbers of DCs and T cells in B16 tumors tissues and the ratios of CD4~+ and CD8(+) T cells in the spleen (P<0.05). Conclusion: MIT can increase CRT expression on membrane of B16 cells. B16-membrane antigen vaccine highly expressing CRT can enhance the infiltration of DCs and T cells in melanoma, thus improving the immune effect of B16-membrane antigen vaccine.

Effects of traditional Chinese drugs Shuganyishen, on Ishikawa cell line / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effects of the traditional Chinese drugs, Shuganyishen, on Ishikawa cell line.</p><p><b>METHOD</b>Rat blood serum was prepared by using Chinese drugs serum pharmacology method, in which, Shuganyishen was contained or not contained. Ishikawa cells were subjected into five groups: (1) normal cells group (NCG), (2) rat blood serum without Shuganyishen group (NSGG) as negative control, (3) Shuganyishen group (SGG), (4) Cisplatin group (DDPG) as positive control, and (5) Shuganyishen with Cisplatin group (S&CG). MTT assay was used to evaluate the inhibition effect on cell growth in each group. The mRNA expression of estrogen receptor alpha and beta (ERalpha and ERbeta) in each group was detected by RT-PCR.</p><p><b>RESULT</b>Effective inhibition of cell growth was found in the groups of SGG and S&CG, respectively (P < 0.05), which had no significant difference from positive control by MTT. The mRNA expression of ERbeta was slightly going up, while the expression of ERalpha was hardly effected in SGG by RT-PCR. Interestingly in S&CG, the mRNA expression of ERalpha was significantly down-regulated (P < 0.05), but the mRNA expression of ERbeta remained no change. As the positive control, the mRNA expression of ERalpha and ERbeta was significantly down-regulated in DDPG (P < 0.5).</p><p><b>CONCLUSION</b>Traditional Chinese drugs, Shuganyishen, may inhibit Ishikawa cell growth and had no effects on the expression of ERalpha, furthermore, can reverse the inhibition of ERbeta expression by Cisplatin.</p>

Effect of gene gun transduction of K-RAS Antisense gene on the expression of K-RAS P21 protein in human pancreatic carcinoma cells / 基础医学与临床

Objective To observe the effect of gene gun transduction of K-RAS Antisense gene on the expression of K-RAS P21 protein in human pancreatic carcinoma cells.Methods K-RAS Antisense gene was transduced into pancreatic carcinoma cells by gene gun transduction, the expression of K-RAS P21 protein on BxPC-3、AsPC-1 and MiaPaCa-2 pancreatic carcinoma cells line were examined by western blot and immunocytochemistry staining. Results The expression of K-RAS P21 protein in AsPC-1 and MiaPaCa-2 pancreatic carcinoma cells was obviously lower after the transduction of specific K-RAS Antisense gene,which has little impact on BxPC-3 pancreatic carcinoma cells. Conclusion Gene gun transduction of K-RAS Antisense gene is a potential method for treatment of pancreatic carcinoma.

Celecoxib suppresses xenograft tumor of colon cancer in nude mice / 第三军医大学学报

Objective To evaluate the effects of celecoxib on tumor growth,COX-2 and survivin expressions and angiogenesis in nude mice. Methods Xenograft animal model was established by injecting human colon cancer HT-29 cells into the BALB/c nude mice subcutaneously. Fifty mice were randomly divided into 4 groups 16 d after injection:control group,celecoxib group(receiving 25,50,75,100 mg?kg-1?d-1 for 35 d). Tumor volumes were measured every week. The expression level of COX-2,survivin and the microvessel density (MVD) of the xenograft tumor tissues were measured by immunohistochemistry,and mRNA level of VEGF by RT-PCR. Results Celecoxib at dose of 25,50,75 and 100 mg?kg-1?d-1 inhibited the tumor volume by 34.94%,39.20%,53.50%,59.20% respectively,and showed more effective in suppressing the tumor growth than the control group(P

Experimental study on hemorheological and pathological changes following severe myocardial contusion / 中华创伤杂志(英文版)

OBJECTIVE: To investigate the mechanism of severe myocardial contusion in rabbits. METHODS: A total of 32 New Zealand rabbits were randomly divided into 2 groups, the severe myocardial contusion group (the experimental group, n=16) and the sham-impact control group (the control group, n=16). Hemorheological parameters, interleukin-8 (IL-8) in serum, the water contents of myocardium and polymorphonuclear neutrophil (PMN) infiltration in contused myocardium were observed at 24 hours after the experiment. RESULTS: As compared with the control group, the hemorheological parameters in the experimental group including the whole blood viscosity (etab), erythrocyte aggregation index (EAI), hematocrit (HCT), serum fibrinogen (Fib), Casson viscosity (Gammay) and erythrocyte sedimentation rate (ESR), significantly increased. The IL-8, PMN infiltration and the water contents of the contused myocardium also significantly increased. CONCLUSIONS: It suggests that the hemorheological disorder, increase of IL-8 in serum, and PMN infiltration in contused myocardium may contribute to the development of cardiac edema and secondary myocardial damage following severe myocardial contusion in rabbits.

Expression of GLUT4 in endometrium of rats with polycystic ovary syndrome / 中国病理生理杂志

AIM: To explore the expression of glucose transporter 4 (GLUT4) in the endometrium of rats with polycystic ovarian syndrom (PCOS) and evaluate the relationship between GLUT4 expression and insulin resistance (IR). METHODS: 54 female SD rats of 85 days were randomized to control group (n=20), PCOS model group (n=17) and metformin treatment group (n=17). The rats in the latter two groups were induced by Poretsky's method for PCOS model, followed by placebo or metformin, respectively. After 14 days of treatment, the rats were sacrificed and the expression of GLUT4 in endometrium was detected by ElivisionTM Plus two steps immunohistochemical staining. RESULTS: The expression of GLUT4 and insulin receptor(INS-R) proteins of endometrial glandulan epitheliu in PCOS rats were significantly lower (P