A Decade of Scientific and Technological Innovation at Chinese Academy of Medical Sciences & Peking Union Medical College: Retrospect and Prospect.

Focusing on the reform initiatives of Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC) in medical scientific and technological innovation from perspectives of deepening the reform and optimizing the ecosystem of science and technology innovation, this article summarizes the highlights of CAMS & PUMC's efforts in safeguarding people's health and promoting the Healthy China 2030 strategy through scientific and technological innovation in the fields including basic research, disease prevention and treatment, and medical technology in the past ten years. These achievements embody the endeavors and responsibility of CAMS & PUMC in realizing self-reliance and self-improvement of Chinese medical science and technology and highlight its contributions to the development of medical science and technology of China.

The Key Genes for Perineural Invasion in Pancreatic Ductal Adenocarcinoma Identified With Monte-Carlo Feature Selection Method.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive form of pancreatic cancer. Its 5-year survival rate is only 3-5%. Perineural invasion (PNI) is a process of cancer cells invading the surrounding nerves and perineural spaces. It is considered to be associated with the poor prognosis of PDAC. About 90% of pancreatic cancer patients have PNI. The high incidence of PNI in pancreatic cancer limits radical resection and promotes local recurrence, which negatively affects life quality and survival time of the patients with pancreatic cancer. OBJECTIVES: To investigate the mechanism of PNI in pancreatic cancer, we analyzed the gene expression profiles of tumors and adjacent tissues from 50 PDAC patients which included 28 patients with perineural invasion and 22 patients without perineural invasion. METHOD: Using Monte-Carlo feature selection and Incremental Feature Selection (IFS) method, we identified 26 key features within which 15 features were from tumor tissues and 11 features were from adjacent tissues. RESULTS: Our results suggested that not only the tumor tissue, but also the adjacent tissue, was informative for perineural invasion prediction. The SVM classifier based on these 26 key features can predict perineural invasion accurately, with a high accuracy of 0.94 evaluated with leave-one-out cross validation (LOOCV). CONCLUSION: The in-depth biological analysis of key feature genes, such as TNFRSF14, XPO1, and ATF3, shed light on the understanding of perineural invasion in pancreatic ductal adenocarcinoma.

Fast-track multidisciplinary treatment versus conventional treatment for colorectal cancer: a multicenter, open-label randomized controlled study.

BACKGROUND: Laparoscopic surgery, fast-track perioperative treatment and XELOX chemotherapy are effective strategies for shortening the duration of hospital stay for cancer patients. This trial aimed to clarify the safety and efficacy of the fast-track multidisciplinary treatment (FTMDT) model compared to conventional surgery combined with chemotherapy in Chinese colorectal cancer patients. METHODS: This trial was a prospective randomized controlled study with a 2 × 2 balanced factorial design and was conducted at six hospitals. Patients in group 1 (FTMDT) received fast-track perioperative treatment and XELOX adjuvant chemotherapy. Patients in group 2 (conventional treatment) received conventional perioperative treatment and mFOLFOX6 adjuvant chemotherapy. Subgroups 1a and 2a had laparoscopic surgery and subgroups 1b and 2b had open surgery. The primary endpoint was total length of hospital stay during treatment. RESULTS: A total of 374 patients were randomly assigned to the four subgroups, and 342 patients were finally analyzed, including 87 patients in subgroup 1a, 85 in subgroup 1b, 86 in subgroup 2a, and 84 in subgroup 2b. The total hospital stay of group 1 was shorter than that of group 2 [13 days, (IQR, 11-17 days) vs. 23.5 days (IQR, 15-42 days), P = 0.0001]. Compared to group 2, group 1 had lower surgical costs, fewer in-hospital complications and faster recovery (all P < 0.05). Subgroup 1a showed faster surgical recovery than that of subgroup 1b (all P < 0.05). There was no difference in 5-year overall survival between groups 1 and 2 [87.1% (95% CI, 80.7-91.5%) vs. 87.1% (95% CI, 80.8-91.4%), P = 0.7420]. CONCLUSIONS: The FTMDT model, which integrates laparoscopic surgery, fast-track treatment, and XELOX chemotherapy, was the superior model for enhancing the recovery of Chinese patients with colorectal cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01080547 , registered on March 4, 2010.

Macular integrity assessment to determine the association between macular microstructure and functional parameters in diabetic macular edema.

AIM: To respectively evaluate macular morphological features and functional parameters by using spectral-domain optical coherence tomography (SD-OCT) and macular integrity assessment (MAIA) in patients with diabetic macular edema (DME). METHODS: This prospective, non-controlled, open study included 61 eyes of 38 consecutive patients with DME. All patients underwent best-corrected visual acuity (BCVA) measurement, MAIA microperimetry, and SD-OCT. DME morphology, including central retinal thickness (CRT) and central retinal volume (CRV); integrity of the external limiting membrane (ELM) and photoreceptor inner segment/outer segment (IS/OS) junction; and the deposition of hard macular exudates were assessed within a 1000-µm central subfield area. MAIA microperimetry parameters evaluated were average threshold (AT)-retinal sensitivity, macular integrity index (MI), fixation points within a circle of radius 1° (P1) and 2° (P2), and bivariate contour ellipse area considering 63% and 95% of the fixation points (A63 and A95, respectively). RESULTS: MI was significantly higher in eyes with disrupted ELM or IS/OS, compared with eyes with intact ELM and IS/OS. Values of BCVA (logMAR), total AT, AT within 1000-µm diameter, P2, A63, A95, and CRT were significantly worse in eyes with disrupted IS/OS, compared with eyes with intact IS/OS. The values of BCVA (logMAR), AT within 1000-µm diameter, and CRT were significantly worse in eyes with disrupted ELM, compared with eyes with intact ELM. These parameters were not significantly different between eyes with or without hard macular exudate deposition. CRV was not significantly different in the presence or absence of the integrity of ELM, IS/OS, or deposition of hard macular exudates. At the center, nasal and temporal sectors of the fovea, significant negative correlations were observed between retinal thickness and AT of the corresponding area. At the inferior and superior sectors of the fovea, no correlations were observed between retinal thickness and AT of the corresponding area. In the intact IS/OS group, significant negative correlations were observed between CRT and central AT. There was no correlation between retinal sensitivity and thickness when the IS/OS layer was disrupted. Multiple linear regression analyses revealed that IS/OS integrity was an independent factor affecting MI. CONCLUSION: Functional (BCVA and visual field) and morphological parameters (retinal thickness) were significantly associated with an intact IS/OS. Local photoreceptor integrity was a strong predictor of local visual function throughout the retina. MI revealed the functional status in DME, reflecting the IS/OS juction status in the macula.

Quantitative assessment of tumor blood flow changes in a murine breast cancer model after adriamycin chemotherapy using contrast-enhanced destruction-replenishment sonography.

OBJECTIVES: The purpose of the study was to detect tumor blood flow changes after chemotherapy with contrast-enhanced destruction-replenishment sonography. METHODS: Twenty-four MCF-7 breast cancer-bearing nude mice were included in this study. Animals received either adriamycin or sterile saline and underwent contrast-enhanced sonography before and after treatment using a destruction-replenishment technique. A monoexponential function, y = A(1 - e(-ßt)), was used to fit the replenishment kinetics, where the plateau signal intensity A reflects the percent blood volume; the time constant ß reflects the average speed of blood; and their product A*ß reflects the nutrient blood flow. Tumor blood perfusion was compared to measurements of cell density and microvascular density. RESULTS: Volumes of the treated tumors were significantly reduced after 7 days of adriamycin treatment compared with the control tumors (P < .001). Before adriamycin administration, there was no significant difference in blood perfusion between the treated and control groups (P > .05). Treatment with adriamycin resulted in a significant decrease in A, ß, and A*ß (P <.001) compared with the control tumors. The tumor cell density and microvascular density estimated by pathologic slices were significantly lower in the treated tumors than in the control tumors (P <.001). CONCLUSIONS: Quantification of tumor blood flow using contrast-enhanced destruction-replenishment sonography shows the potential to evaluate tumor responses to chemotherapy.

Assessment of early tumor response to cytotoxic chemotherapy with dynamic contrast-enhanced ultrasound in human breast cancer xenografts.

There is a strong need to assess early tumor response to chemotherapy in order to avoid adverse effects from unnecessary chemotherapy and allow early transition to second-line therapy. This study was to quantify tumor perfusion changes with dynamic contrast-enhanced ultrasound (CEUS) in the evaluation of early tumor response to cytotoxic chemotherapy. Sixty nude mice bearing with MCF-7 breast cancer were administrated with either adriamycin or sterile saline. CEUS was performed on days 0, 2, 4 and 6 of the treatment, in which time-signal intensity (SI) curves were obtained from the intratumoral and depth-matched liver parenchyma. Four perfusion parameters including peak enhancement (PE), area under the curve of wash-in (WiAUC), wash-in rate (WiR) and wash-in perfusion index (WiPI) were calculated from perfusion curves and normalized with respect to perfusion of adjacent liver parenchyma. Histopathological analysis was conducted to evaluate tumor perfusion, tumor cell density, microvascular density (MVD) and proliferating cell density. Significant decreases of tumor normalized perfusion parameters (i.e., nPE, nWiAUC, nWiR and nWiPI) were noticed between adriamycin-treated and control groups (P<0.01) 2 days after therapy. There were significant differences of tumor volumes between control and treated groups on day 6 (P<0.001) while there were no significant differences in tumor volume on days 0, 2 and 4 (P>0.05). Significant decreases of tumor perfusion, tumor cell density, MVD and proliferating cell density were seen in adrianycin-treated group 2 days after therapy when compared to control group (P<0.001). Dynamic CEUS for quantification of tumor perfusion could be used for early detection of cancer response to cytotoxic chemotherapy prior to notable tumor shrinkage.