OBJECTIVETo investigate the clinicopathologic characteristics and prognosis of multiple primary synchronous colorectal carcinoma (synchronous CRC) and single colorectal carcinoma (single CRC).

METHODSClinicopathological data of 39 patients with synchronous CRC and 528 patients with single CRC from May 1996 to June 2001 were reviewed retrospectively.

RESULTSThe patients with synchronous CRC accounted for 6.9% of all the patients with colorectal carcinoma treated in our hospital during the same period. Compared with concurrent lesions, Dukes stage of the index lesions of synchronous CRC was more developed and the lymph node metastasis and vessel invasion occurred more frequently. In addition, it also had poorer differentiation. There were significant differences of Dukes stages and lymph node metastasis between the index lesions and single CRC. The incidence of adenomatous polyp in synchronous CRC was higher than that in single CRC(59.0% vs 25.0%,P<0.01). The sensitivity of preoperative colonoscopy examination was 76.9%, which was significantly higher than that of barium examination and exploration during operation. The total 5-year survival rate of synchronous CRC was significantly lower than that of single CRC (5.1% vs 28.2%,P=0.042), and no significant difference of total 5-year survival rate was found between single CRC patients and synchronous CRC patients undergone radical operation. Synchronous CRC patients undergone radical operation had longer survival as compared to those undergone palliative operation(P<0.01). Multivariate analysis indicated that Dukes stages, lymph node metastasis, vessel invasion and the type of operation were independent prognostic factors of synchronous CRC.

CONCLUSIONSSynchronous CRC and single CRC are not always similar in clinicopathologic characteristics and prognosis. Early finding, early diagnosis and radical operation are the keys to improve the survival rate of synchronous CRC.

Aged ; Colorectal Neoplasms ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Neoplasms, Multiple Primary ; pathology ; Prognosis ; Retrospective Studies ; Survival Rate

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.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.

Objective: To investigate the clinical characteristics, memory and neuroimaging features of nonlesional temporal lobe epilepsy (TLE-NL). Methods: Forty-four patients with TLE-NL and 53 patients with unilateral temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) were recruited from the Second Affiliated Hospital of Zhejiang University from September 1st 2012 to August 31st 2017. The clinical characteristics were systematically analyzed and compared between TLE-NL and TLE-HS. Twenty healthy volunteers were also recruited. Memory assessment and high resolution magnetic resonance imaging (MRI) scanning were completed in the patients and healthy volunteers. Volume and shape of the hippocampus were compared between patients and healthy volunteers. Results: Compared with the TLE-HS, TLE-NL patients showed later seizure onset ((24.3±12.6) vs (15.8±10.3) years; t=3.684, P<0.01), shorter duration of epilepsy ((4.00 (2.00, 8.75)) vs (14.00 (7.50, 22.00)) years; Z=-4.675, P<0.01), less history of febrile convulsions (4.5% (2/44) vs 62.3% (33/53); χ²=32.270, P<0.01) and lower incidence of pharmacoresistant epilepsy (47.7% (21/44) vs 84.9% (45/53); χ²=15.282, P<0.01). However, there were no statistically significant differences between TLE-NL and TLE-HS in sex ratio, family history of epilepsy, lateralization of the epileptogenic zone, presence of aura, seizure types and seizure frequency. TLE-NL patients had normal memory quotient compared to normal controls (105.2±17.4 vs 103.8±16.2; P=1.000), while TLE-HS patients had significant memory impairment compared to normal controls (84.5±20.3 vs 103.8±16.2; P<0.01). Compared to normal controls, TLE-NL patients did not have significant alteration in hippocampal volume and shape, while TLE-HS patients had significant atrophy in the ipsilateral hippocampus ((2 953±481) mm³ vs (4 431±505) mm³; P<0.01), and shape analysis showed significant atrophy in the head and body of the hippocampus. Conclusion TLE-NL has different characteristics compared with TLE-HS, including later seizure onset, shorter duration of epilepsy, less history of febrile convulsions, better response to antiepileptic drugs, and no significant memory impairment and hippocampal atrophy.

Three-dimensional printing is a technology that prints the products layer-by-layer, in which materials are deposited according to the digital model designed by computer aided design (CAD) software. This technology has competitive advantages regarding product design complexity, product personalization, and on-demand manufacturing. The emergence of 3D technology provides innovative strategies and new ways to develop novel drug delivery systems. This review summarizes the application of 3D printing technologies in the pharmaceutical field, with an emphasis on the advantages of 3D printing technologies for achieving rapid drug delivery, personalized drug delivery, compound drug delivery and customized drug delivery. In addition, this article illustrates the limitations and challenges of 3D printing technologies in the field of pharmaceutical formulation development.

Objective To translate the Water Orientation Test of Alyn 2 (WOTA2) into Chinese, and to study its reliability and validity for patients with spinal cord injury. Methods After authorizing, the English version WOTA2 scale and its training package were translated into Chinese. From January to September, 2018, 137 patients with spinal cord injury were evaluated with the Chinese version WOTA2 by two evaluators independently, and evaluated again three days later by one of the evaluators. The Cronbach's α, Spearman-Brown coefficient, intra-group correlation coefficient (ICC) and Kappa coefficient were calculated to evaluate the reliability. Content Validity Index (CVI) of items (I-CVI) and scale (S-CVI) were used to evaluate the content validity, and factors analysis was used to evaluate the structure validity. Results The Cronbach's α was 0.947 in all items of the scale, 0.890 in mental adjustment items and 0.954 in aquatic skills items. Pearson correlation coefficient of the half scales separated by odd and even items was 0.948, and the Spearman-Brown coefficient was 0.973. The ICC of test-retest was 0.965 in total score, 0.965 in centesimal system total score, 0.847 in mental adjustment score and 0.970 in aquatic skills score. The ICC of inter-testers was 0.964 in total score, 0.965 in centesimal system total score, 0.847 in mental adjustment score and 0.970 in aquatic skills score. The Kappa coefficient was 0.528 to 0.927 in test-retest and 0.528 to 0.927 in inter-testers. The I-CVI was 0.8 to 1.0 and S-CVI was 0.63. Factors analysis extracted four factors, which met the theory, and contributed 67% of cumulative variance. Conclusion The Chinese version WOTA2 is good in reliability and validity for patients with spinal cord injury, and can be used in the clinical practice of aquatic therapeutic exercise in China.