Xenograft mice are preclinical animal models of tumors and are widely utilized in anti-tumor research. PK/PD modeling of anti-tumor agents is an approach that can capture the time profile of the "dose-plasma concentration-biomarker level-tumor volume" process based on experimental data from xenograft mice using a non-linear mixed-effect model. PK/PD modeling can help optimize the dosing regimen for anti-tumor therapy, evaluate any synergistic effect and help identify an optimal schedule for combination therapy, as well as providing a preliminary estimate of a drug's efficacy and anti-tumor potency in the human body. PK/PD modeling can also help by quantitatively explaining the mechanism of the tumor-inhibitory effect as indicated by changes in biomarker levels after a drug acts on its target. This article provides a systematic summary of the background, application range, and limitations of the mainstream anti-tumor agent PK/PD models. Recent advances in model structure development are reviewed in detail. Finally, we discuss promising applications of PK/PD models in anti-tumor medicine development from the perspective of a drug's mechanism of action, optimization of combination therapy schedules, and their clinical translation.

0.05). Significant increment of aggregation piles right after flights was shown in both groups (p0.05).

Objective: To explore the eff ect of Fasudil on the invasion and metastatic abilities of human high metastatic liver cancer cells (HCCLM3) and the underlying mechanisms. Methods: HCCLM3 cells were incubated with 100 μmol/L Fasudil. Fluorescence staining forF-actin and Transwell assay were performed to observe the invasion ability of HCCLM3 cells. HCCLM3 cells were divided into 3 groups: a negative control group, a Fasudil group and a BTB/POZ domain containing 7 (BTBD7)-siRNA group. Western blot assay was performed to detect the expression levels of BTBD7, ras homolog family member C (RhoC) and Rho-associated, coiled-coil containing protein kinase 2 (ROCK2), matrix metalloproteinases 2 (MMP2) and MMP9. Zymogram analysis method was performed to detect the expression activities of MMP2 and MMP9. hTe BTBD7-siRNA group was served as a positive control. Results: In HCCLM3 cells treated with Fasudil, the invasion ability was significant decreased compared with the control group, concomitant with the down-regulated expression levels of BTBD7, RhoC and ROCK2 protein as well as the decreased activities of MMP2 and MMP9. Conclusion: Fasudil plays an important role in interfering BTBD7-ROCK2 signaling pathway and suppressing the invasion and metastasis of hepatocellular carcinoma.

Radiopharmaceutical is an essential component of nuclear medicine and molecular imaging, as well as a key component of precision medicine. The United States Food and Drug Administration (FDA) has recently approved the marketing of several peptide-based radiopharmaceuticals, sparking a global trend of research in this area and propelling nuclear medicine into the precision theranostic era. This has created a new wave of technological competition in the field of nuclear medicine. It is the responsibility of Chinese scientists in the radiopharmaceutical field to capitalize on this opportunity, leverage the momentum, and strengthen their independent innovation capability in order to stay ahead in the future global nuclear science and technology competition. This review provides an overview of the remarkable progress made in the research, development, and translation of global peptide-based radiopharmaceuticals. It examines the advantages of peptide-based radiopharmaceuticals and outlines the current hot targets and progress in drug development in this field. Additionally, it proposes six opportunities for China to overtake others in the field of peptide-based radiopharmaceuticals and achieve technological self-reliance, based on interdisciplinary collaboration and independent innovation. Lastly, the future prospect of peptide-based radiopharmaceuticals is discussed.

Objective To investigate the effects of Lotensin on inflammatory factors, vascular endothelial function and heart function in patients with acute myocardial infarction. Methods 100 cases with acute myocardial infarction from March 2015 to January 2016 in the fifth central hospital of Tianjin were selected as the research object, which were randomly divided into the control group and the observation group. The control group were given routine treatment, at this basis, the observation group were given Lotensin. After treatment, the cardiac function, the levels of inflammatory factors, the blood vessel endothelial function, the serum NO and endothelin 1 and the therapeutic effect in the two groups were compared. Results LVESV, LVEDV (156.28±3.29、213.45±6.12) mL in the observation group were better than (162.98±4.16、202.83±7.16) mL in the control group (P<0.05). LVEF was (48.72± 2.13)% in the observation, which was higher than (40.62±3.29)% in the control group(P<0.05). Hs-CRP, IL-6 were (2.66±0.68) mg/L、(4.90±0.92) ng /L in the observation group , which were less than (6.35±1.50) mg/L、(9.38±2.01) ng/L in the control group (P<0.05). FMD(10.37±0.62)% in the observation group was bet er than (6.16±0.92)% in the control group (P<0.05)、 NO, ET-1 level (71.52±13.21) μmol/L、(56.27±7.10) ng/L in the observation group were bet er than (60.63 ±10.57) μmol/L、(69.72±9.50) ng/L in the control group (P<0.05). The total effective rate in the observation group was 94.00% (47/50), which was better than 62.00% (31/50) in the control group (P<0.05). Conclusion The effect is significant which Lotensin is used in the treatment of acute cerebral infarction, which can reduce inflammatory factors, improve endothelial function and cardiovascular function.

BACKGROUND:Gait deviations are the important diagnosis criteria and surgical indications of cervical myelopathy. Conventional three-dimensional gait laboratory failed to apply in clinics due to complex operations and time consuming. In recent years, a portable gait analyzer based on the micro-sensors is emerging and developing, it has been verified by clinical practice, al owing gait analysis in the ward.
OBJECTIVE:To quantitatively analyze gait characteristics of patients with cervical spondylotic myelopathy (CSM) by a portable gait analyzer.
METHODS:From March 2013 to November 2013, 15 CSM patients and 30 healthy subjects were enrol ed in the study. The involved patients were accompanied by gait abnormalities. A portable gait analyzer was used for gait analysis. Subjects walked on a 30-meter corridor back and forth for 120 meters. Total y 12 gait parameters were involved in this study, including seven common parameters (single limb support, double limb support, gait cycle, speed, cadence, step length and stride length) and five new parameters (pul ing acceleration, swing power, ground impact, foot fal , and pre-swing angle). Three patients underwent cervical decompression surgery. The gait characteristics were re-evaluated one week later, carrying neck support.
RESULTS AND CONCLUSION:The double limb support and gait cycle duration of CSM group were significantly longer than control group (P<0.05). Speed, cadence, step length, stride length, swing power, ground impact, foot fal , and pre-swing angle of CSM patients were significantly smal er than healthy subjects (P<0.05). No differences were found in single limb support and pul ing acceleration (P>0.05). after cervical decompression surgery, the mean remission rate of Japanese Orthopedics Association scores was 32.5%and lower limb acceleration was improved obviously in the graph one week after surgery. Varying degree of correlation was seen between Japanese Orthopedics Association scores and the detected 12 gait parameters in CSM patients. The portable gait analyzer can effective measure the pathological gait deviation in CSM patients with abnormal gaits, and assists to evaluate the lower limb functions.

Some problems were found for argument in the teaching of The Therapeutics of Acupuncture & Moxibustion, the new centurial national advanced Chinese medical school's planning material, including errors in compiling, some concepts lacking definition, and some acupuncture treatment methods in the material deviating off clinical practice, etc.. Study on these problems so as to make the teaching material more perfect, more scientific, accurate and authoritative.
Acupuncture ; education ; Acupuncture Therapy ; Humans ; Medicine, Chinese Traditional ; Moxibustion ; Teaching Materials

OBJECTIVETo investigate the expression of thymidylate synthase (TS) in patients with advanced lung adenocarcinoma and its relation with the therapeutic effect of pemetrexed.

METHODSThe clinicopathological data of 38 patients with stage IIIIB/IV lung adenocarcinoma receiving pemetrexed treatment were retrospectively analyzed. The tumor samples of the patients were collected for detecting TS expression using RT-PCR, and the therapeutic effect of the treatment was analyzed.

RESULTSTS positivity was found in 26.32 (10/38) of the patients. TS positivity was not correlated to gender, TNM stage or PS score. The total response rate of pemetrexed treatment (CR+PR) was 34.21 (13/38) in these patients, and the rate was 39.29% (11/28) in TS-negative patients, as compared to 20.00% (2/10) in the positive patients (P=0.087). Patients with low TS expression had significantly higher control rate by pemetrexed treatment than those with TS overexpression [89.29% (25/28) vs 40.00% (4/10), P=0.002].

CONCLUSIONTS expression may serve as a potential indicator of chemosensitivity to pemetrexed in patients with advanced lung adenocarcinoma.

Adenocarcinoma ; drug therapy ; enzymology ; Antineoplastic Agents ; therapeutic use ; Female ; Folic Acid Antagonists ; therapeutic use ; Glutamates ; therapeutic use ; Guanine ; analogs & derivatives ; therapeutic use ; Humans ; Lung Neoplasms ; drug therapy ; enzymology ; Male ; Middle Aged ; Pemetrexed ; Retrospective Studies ; Thymidylate Synthase ; metabolism

OBJECTIVE: To evaluate the forensic application value of 30 insertion/deletion (InDel) loci included in Investigator DIPplex Kit in Han and She nationalities of Eastern China. METHODS: A total of 565 unrelated individuals in Han nationality and 119 ones in She nationality of Eastern China were investigated using Investigator DIPplex Kit. Allele frequencies, population genetics parameters of the 30 InDel loci were statistically calculated. RESULTS: In Han nationality, the mean Ho was 0.413 3, the mean DP was 0.551 1, the mean PIC was 0.320 0. And in She nationality, the mean Ho was 0.389 6, the mean DP was 0.543 3, the mean PIC was 0.310 0. No deviation from Hardy-Weinberg equilibrium was observed in Han and She nationalities (P > 0.05). CONCLUSION The 30 loci in Investigator DIPplex Kit show good genetic diversity in Han and She nationalities, and could be used as a supplemental tool for some special paternity cases.
Asian People/genetics* ; China ; Ethnicity/genetics* ; Female ; Forensic Genetics ; Gene Frequency ; Genetic Variation ; Genetics, Population ; Humans ; INDEL Mutation/genetics* ; Polymorphism, Genetic

Cyclooxygenase 2 ; metabolism ; Cyclooxygenase Inhibitors ; pharmacology ; Hep G2 Cells ; Humans ; Nitrobenzenes ; pharmacology ; Radiation Tolerance ; drug effects ; Sulfonamides ; pharmacology