Objective To evaluate the analytical variables of the reversed-phase high pressure liquid chromatography (HPLC) with 5-Fluorouracil(5-Fu) as an internal standard for determining creatinine in human serum and urine. The method was used as a candidate reference method for accuracy assessment of routine creatinine test kits.Methods We tested the accuracy, precision, linearity of the reversed-phase HPLC.We analyzed split samples of a panel of 85 patients’ serum and 94 patients’ urine and compared the results of the routine test kits and HPLC by means of bias plots (percentage differences of results) and standard linear regression.Results The linear range of HPLC method was up to 2 210 ?mol/L, the within-run CV(n=5) was below 2.5% and the between-day CV(n=10) was less than 4.5%. The analytical recovery rate was 96.3%～102.4%. All of the test kits correlated very well with HPLC.Conclusions We recommend the reversed-phase HPLC with 5-Fu as an internal standard as a candidate reference method for determining creatinine in human serum and urine.The enzymatic method with creatininase coupled sarcosine oxidase is suitable for routine work in clinical laboratories.

Objective To investigate the effects of simvastatin on the bone loss and deterioration of bone quality with different intervention programs. Methods Thirty two 3?month?old female Sprague?Dawley ( SD ) rats were randomized into 4 groups of 8 animals in each: All rats but those in the sham group ( A) received bilateral ovariectomy, and treated by vehicle (B), simvastatin (5 mg/kg/day) at first half period (C) or at latter half period (D). The rats in group C received simvastatin by a gavage after the OVX operation immediately, and stopped at 10 weeks after OVX. The rats in group D began to receive simvastatin treatment from 10 weeks after OVX and ended at 20 weeks after OVX. At week 20, all rats were sacrificed and the concentrations of serum PINP and ICTP were detected by ELISA, L3 vertabra was used to detect the bone mineral density, L4 vertebra was used to analyze the maximum loading and elastic modulus by compression test, and the microstructure of the L5 vertebra was detected by micro?computed tomography. Results 1. ELISA analysis:the concentrations of serum P1NP and ICTP in the groups A, B and C were significantly higher than that of group A (P<0?05). 2. BMD test showed that the rats in group B had significantly lower BMD than the other 3 groups (P<0?05), while the BMD of groups C and D were markedly lower than that of group A (P<0?05). 3. Biomechanical test:the maximum load and elastic modulus of L4 vertebrae in the group B were significantly lower than the other 3 groups ( P<0?05), and those of the groups C and D were markedly lower than that in the group A (P<0?05). 4. micro?CT:BV/TV and Tb. N in the sham operated rats were significantly higher than those of the other 3 groups, while the opposite trends was found in Tb. Sp (P<0?05), and the Tb. Sp in the groups C and D were significantly lower than that of group B (P<0?05). Conclusions Our data demonstrate that bone loss and deterioration of bone micro?structure and biomechanical properties occurred at 20 weeks after ovariectomy, both the first?half?period and latter?half?period treatment by simvastatin may partially prevent these changes, but can not restore the BMD to normal level.

Objective To investigate the measurement of serum calcium by flame atomic absorption spectrometry (FAAS) and to validate the method for use as a candidate reference method. Methods Serum was diluted by 50 fold with 50 mmol/L hydrochloric acid containing 10 mmol/L LaCl3 and analyzed for calcium on an AA 6800 atomic absorption spectrophotometer. Dilution solutions and FAAS conditions were optimized and the performance of the method was evaluated. Results The method showed within-run, between-run and total CVs of 0. 31%～0.38%, 0.16%～0.30% and 0.35%～0.49%, respectively, and analytical recoveries ranging 98.9%～101.1%. No significant interferences were detected. Conclusions A FAAS method for the measurement of serum calcium has been established. The method is simple and accurate and may be used as a candidate reference method for serum calcium.

Objective To investigate the precision and trueness of results from six imported commercial systems for measurement of gamma-glutamyltransferase (GGT) in serum in order to provide reference for the clinical laboratories to verify the target accuracy. Methods Five fresh frozen human serum samples that differed in catalytic concentration were analyzed in two candidate domestic reference laboratories and the target values for GGT were assigned using IFCC reference measurement procedure. The same samples were tested by six commercial systems which were calibrated using the matched calibrator. Each system consisted of five instruments in five laboratories, which had been well maintained before measurement. The data was collected. Precision from the same manufacturer and different manufacturers and biases between target values and mean values from each system were calculated. Results The differences of the mean values for five levels of commercial systems varied from 16. 1% to 35.4%. For the five levels, the coefficients of variation (CVs) of the results from all measurement system were from 5.3% to 8. 8% , and CVs from each level were A 2. 17%- 5.07%, B 4. 21%-10. 98%, C 0. 52%-2. 38%, D 1.35%-2. 59%, E 0. 23%-1..54%-), F 1.83%-2. 38%. Biases between the mean values of each commercial systems and the target values were A 0. 43% -8.41% ), B -1.49% - -13.04% ), C 11.20% -17.73% ), D 0. 19% -4. 62% ), E -0. 30% - -2. 63% ), F 4). 46%-7.90%, respectively. The investigation showed that biases of two manufacturers were less than a quarter of the total allowable error (TAE) of The Clinical Laboratory Improvement Amendments of 1988 (CLIA'88) in the whole range of investigated concentrations and the other two manufacturers' biases could meet a quarter of TAE in a relative limited range. The biases of two manufacturers were near or more than half of TAE in most levels. It also revealed that the biases of more than half of manufacturers were more than a quarter of TAE in the low or high level of investigated concentrations. Conclusions The mean values of each manufacturer were significantly different. The variances of commercial systems from different manufacturers were much higher than those from the same manufacturer. Some imported commercial systems for measurement GGT should be better calibrated with the reference method, especially in the whole measurement linearity.

The purpose of this study is to design push-pull osmotic pump (PPOP) tablets of famotidine using the expert system for the formulation design of osmotic pump of poor water-soluble drug which had been established by the authors. Firstly, the parameters which were requisite of the system input were obtained from literatures and experimental tests. Then the parameters were input into the system, and the program was run. The system displayed the designed formulations sequential. Finally, famotidine PPOP was prepared according to the designed formulations and the in vitro dissolution was carried out. It was found out that the target formulation of famotidine PPOP which could release for 24 hours was obtained in a very short period. Meanwhile, the practicability of the established expert system was proved.

Objective Alendronate is widely used as an anti-osteoporosis agent , while simvastatin , as a lipid-lowering drug , is being considered beneficial for bone formation .The present study aims to compare the effects of simvastatin and alendronate on bone loss in ovariectomized ( OVX) rats. Methods Thirty-two female SD rats were equally randomized into a sham operation , an OVX mod-el, a simvastatin ( OVX +S), and an alendronate ( OVX +A) group.All the rats but those in the sham operation group underwent dual ovariectomy .The animals of the OVX model and OVX +S groups were treated intragastrically with vehicle and simvastatin at 5 mg per kg of the body weight per day , respectively , while those of the OVX+A group injected subcutaneously with alendronate at 70μg per kg of the body weight per week .After 12 weeks of intervention , all the rats were sacrificed for detection of the serum concentrations of PINP and ICTP by ELISA, analysis of bone mineral density and bone histo-morphometry parameters of L 4 vertebrae , determination of the maximum loading and elastic modulus of L 5 vertebrae by compression test. Results The serum concentrations of P1NP and ICTP were significantly lower in the sham operation than in the other three groups (P<0.05), and that of ICTP markedly lower in the OVX +A than in the OVX model and OVX +S groups (P<0.05).Bone mineral density was remarkably lower in the OVX model ([0.238 ±0.007] g/cm2 ) than in the sham operation ([0.276 ±0.015] g/cm2), OVX+S ([0.250 ±0.014] g/cm2) and OVX+A groups ([0.269 ±0.014] g/cm2) (P<0.05), lower in the OVX+S than in the sham operation and OVX +A groups (P<0.05), but with no statistically significant difference between the latter two (P>0.05).Bone histomorphometry showed significantly lower BV /TV in the OVX model than in the sham operation and OVX +A groups ([19.9 ±1.69]%vs [29.03 ±2.59]%and [27.05 ±1.91]%, P<0.05), but markedly higher Tb.Sp in the former than in the latter two groups ([357.33 ±26.55] μm vs [211.17 ±16.56] μm and [252.50 ±19.35] μm, P<0.05).The maximum load and elastic modulus of L5 vertebrae were significantly lower in the OVX model rats than in the other three groups (P <0.05). Conclusion Both simvastatin and alendronate can inhibit bone loss in OVX rats , with comparable effects of preventing the deteriora-tion of biomechanical properties , but the latter is evidently more effective in maintaining bone mineral density .

Colorectal Cancer (CRC) is a kind of molecular diversified neoplasm.For nonmetastatic early CRC patients who received surgery based systemic treatment,the 5 years survival rate is as high as 50％-80％.However,only chemotherapy is available for majority of metastatic advanced CRC patients.The effect of chemotherapy is disappointing.Numerous studies have demonstrated that some patients with metastatic advanced CRC can benefit from anti-EGFR and anti-VEGF monoclonal antibodies.Here,we give a brief overview about the clinical research of the detection of KRAS,BRAF,MSI and HER2in guiding treatment with targeted drugs in metastatic advanced CRC

Objective To explore the factors, characteristics and imaging manifestations of ankle joint injury in amateur marathoners (no formal training and no marathon career). Methods From December 2018 to March 2019, the amateur marathon runners in Guangdong Zhuhai had been recruited as research subjects according to the study inclusion and exclusion criteria. The questionnaires were used to collect relevant data, and the subjects underwent MRI scans of the ankle joint. The ankle joint special phased array coils were used to perform fast spin echo sequence (TSE) coronal T1WI and proton density?weighted fat?suppression sequence (PDWI?FS). Axial, coronal and sagittal scans, three?dimensional?double echo steady?state sequence (3D?DESS) and three?dimensional variable flip angle fast spin echo sequence (3D?SPACE) scans were also acquired. The results of the examination were independently analyzed by two radiologists (5 and 17 years of work experience, respectively) on the ligament, tendon, bone marrow and ankle joint injuries. When they had inconsistent views, the diagnosis provided by the third radiologist (27 years of work experience) was considered a final diagnosis. The relationship between ankle injury and different running postures, the number of participating in marathons and training intensity was analyzed, and the independent sample χ2 was used for statistical analysis. The consistency of two radiologists was tested by Kappa test. Results According to the inclusion and exclusion criteria, 39 subjects were included, with 64 ankles totally, 35 right ankles and 29 left ankles. MRI showed that (1) Ligament injuries: 28 ankles were anterior talofibular ligament injuriy;50 ankles were posterior talofibular ligament injury; 60 ankles the calcaneofibular ligament injuries and 54 ankles were deltoid ligament injuries, without complete injury. (2) Tendon sheath effusion and injuries: peritendinous effusion was common, with 47 flexor hallucis longus tenosynovitis, 49 posterior tibialis tenosynovitis, 37 flexor digitorum longus tenosynovitis, 7 peroneus longus tenosynovitis and 5 peroneus brevis tenosynovitis. (3) Synovitis effusion: 43 posterior ankle synovitis and local effusion. (4) Others: cartilage injury in 2 ankles, bone marrow edema in 8 ankles, and among them stress fracture in 2 ankles. The two radiologists had good consistency with the Kappa value of 0.91. Regarding the running posture, the incidence of ligaments injuries was obviously higher in those who landed on the hind foot than in those landed on front and middle foot,and the difference was statistically significant(P=0.013, χ2 value was 6.191).The incidence of tendon injuries was higher in those who landed on the front middle foot than in those landed on the hind foot, and the difference was statistically significant (P=0.029, χ2 value was 4.775). Those with larger training (training running ≥300 km/month) had significant ankle injury (P=0.005, χ2 value was 7.844). Conclusion The MRI features of ankle joint injuries in amateur marathon volunteers are related to different running postures and training intensity.

Objective: To explore the factors, characteristics and imaging manifestations of ankle joint injury in amateur marathoners (no formal training and no marathon career). Methods: From December 2018 to March 2019, the amateur marathon runners in Guangdong Zhuhai had been recruited as research subjects according to the study inclusion and exclusion criteria. The questionnaires were used to collect relevant data, and the subjects underwent MRI scans of the ankle joint. The ankle joint special phased array coils were used to perform fast spin echo sequence (TSE) coronal T₁WI and proton density-weighted fat-suppression sequence (PDWI-FS). Axial, coronal and sagittal scans, three-dimensional-double echo steady-state sequence (3D-DESS) and three-dimensional variable flip angle fast spin echo sequence (3D-SPACE) scans were also acquired. The results of the examination were independently analyzed by two radiologists (5 and 17 years of work experience, respectively) on the ligament, tendon, bone marrow and ankle joint injuries. When they had inconsistent views, the diagnosis provided by the third radiologist (27 years of work experience) was considered a final diagnosis. The relationship between ankle injury and different running postures, the number of participating in marathons and training intensity was analyzed, and the independent sample χ² was used for statistical analysis. The consistency of two radiologists was tested by Kappa test. Results: According to the inclusion and exclusion criteria, 39 subjects were included, with 64 ankles totally, 35 right ankles and 29 left ankles. MRI showed that (1) Ligament injuries: 28 ankles were anterior talofibular ligament injuriy;50 ankles were posterior talofibular ligament injury; 60 ankles the calcaneofibular ligament injuries and 54 ankles were deltoid ligament injuries, without complete injury. (2) Tendon sheath effusion and injuries: peritendinous effusion was common, with 47 flexor hallucis longus tenosynovitis, 49 posterior tibialis tenosynovitis, 37 flexor digitorum longus tenosynovitis, 7 peroneus longus tenosynovitis and 5 peroneus brevis tenosynovitis. (3) Synovitis effusion: 43 posterior ankle synovitis and local effusion. (4) Others: cartilage injury in 2 ankles, bone marrow edema in 8 ankles, and among them stress fracture in 2 ankles. The two radiologists had good consistency with the Kappa value of 0.91. Regarding the running posture, the incidence of ligaments injuries was obviously higher in those who landed on the hind foot than in those landed on front and middle foot,and the difference was statistically significant(P=0.013, χ² value was 6.191).The incidence of tendon injuries was higher in those who landed on the front middle foot than in those landed on the hind foot, and the difference was statistically significant (P=0.029, χ² value was 4.775). Those with larger training (training running ≥300 km/month) had significant ankle injury (P=0.005, χ² value was 7.844). Conclusion The MRI features of ankle joint injuries in amateur marathon volunteers are related to different running postures and training intensity.