OBJECTIVE:To establish physiological pharmacokinetic (PBPK) model of cefdinir in healthy volunteers,and to predict pharmacokinetic process of cefdinir in volunteers after oral administration. METHODS:Using“toubao dini”“cefdinir”“logP”“pKa”as keywords,related literatures about physico-chemical constants of cefdinir were retrieved from CNKI,ScienceDi-rect,PubMed and other databases;according to related guidelines and preliminary clinical trial plan of FDA,GastroPlusTM 8.6 soft-ware was used to establish PBPK model of oral administration of cefdinir;the effectiveness of the model was evaluated by multiple error. The model was used to simulate the absorption of cefdinir in the gastrointestinal tracts. The bioequivalence of test preparation and reference preparation were evaluated through single and population(n=500)simulation tests using cmax and AUC0-∞ of cefdinir reference preparation (capsule and granular formulation) as factors when release rate t85%=15 min (i.e. accumulatively released 85% within 15 min). RESULTS:The blood concentration-time curves of cefdinir predicted by PBPK model fitted well with mea-sured value(R2≥0.95);the pharmacokinetic parameters(cmax,tmax,AUC0-∞)were close to measured results,and the multiple er-rors were less than 2. After oral administration,cefdinir was mainly absorbed by the intestinal tract (45.6%),especially by seg-ment 1 of jejunum(14.8%);the absorption amount was significantly lower than the release amount of absorption site,and reached the maximal value(about 40%)within 4 h. The results of single simulation test showed that there was no statistical significance in cmax and AUC0-∞ between cefdinir test and reference preparations (P>0.05). The results of population simulation test showed that the relative bioavailability of cefdinir test particle and test capsule respectively were 99.01%-102.99% and 97.60%-105.90%;90%CI of cmax and AUC0-∞ values were within 80%-125% of reference preparation. CONCLUSIONS:The PBPK model is accurate and reliable in this study,can provide reference for pharmacokinetic study and bioequivalence evaluation of cefdinir preparations. Test preparation and reference preparation are equivalent.

Objective To evaluate postprandial pharmacokinetics and bioequivalence of two preparations of cefdinir capsules in Chinese healthy volunteers. Methods In a two-way cross-over study, 24 healthy male volunteers were divided into two groups randomly and a single dose of cefdinir capsules of test and reference preparation were administered orally, respectively.The concentration in plasma was determined by LC-MS/MS. Pharmacokinetic parameters and bioequivalence were calculated and evaluated by DAS. Results The main pharmacokinetic parameters of test and reference were as follows: AUCt (4.35±1.09) μg??h??mL-1 and (4.12±1.22) μg??h??mL-1, AUC0-∞(4.53±1.12) and (4.53±1.73) μg??h??mL-1, t1/2 (1.74±0.29) h and (2.13±1.65) h, tmax(4.44±0.86) h and (4.54 ±1.16) h, Cmax(900±250) ng??mL-1 and (876±269) ng??mL-1 . Conclusion The test and reference preparation of cefdinir capsules are bioequivalent.

Objective: To investigate the contamination levels and dietary intakes of seven mycotoxins in Chinese diets. Methods: In Chinese Total Diet Study, food aggregation was based on the food consumption of local residents, thus generating the sampling scheme. According to the sampling scheme, the food items were sampled at three survey points in each province and then mixed in the same proportion. The mixed dietary samples were prepared after being cooked and processed. The samples comprised of 13 categories of food: cereals, beans, potatoes, meat, eggs, aquatic products, milk, vegetables, fruits, saccharides, beverages and drinking water, alcohol, and condiments. Condiments were used in cooking, so there were in total 12 varieties of samples for determination. Altogether, the study included 240 mixed dietary samples from 20 provinces with 12 varieties. The contamination levels of the seven mycotoxins, including sterigmatocystin (SMC), citrinin (CIT), cyclopiazonic acid (CPA), moniliformin (MON), gliotoxin (GLIO), mycophenolateacid (MPA) and verruculogen (Verru), were analyzed by UPLC-MS/MS method, and dietary intakes of residents were estimated as well. Results: Among the detected seven mycotoxins, MPA,GLIO and Verru were not detected. The content range of CPA in beans was 0.47-1.57 μg/kg and in alcohol was 0.19-2.26 μg/kg, and the detection rate of CPA was 7.1% (17/240). The content of SMC in aquatic products of Guangxi, in saccharides of Beijing, and in beverages of Liaoning was 2.88 μg/kg, 0.01 μg/kg, and 0.53 μg/kg, respectively. The content range of SMC in aquatic products was 0.70-1.76 μg/kg, and the detection rate was 2.9% (7/240). In addition, the content of CIT in fruit of Sichuan was 5.31 μg/kg, and the content of MON in milk of Jilin was 3.60 μg/kg. According to the dietary exposure analysis, the exposure levels of the seven mycotoxins in China's general population were low. MPA, GLIO and Verru were not detected, and the exposure range of the other four mycotoxins were 0.000-8.132 (CIT), 0.000-27.448 (SMC), 0.000-3.026 (CPA), and 0.000-62.847 ng·kg^-1·d^-1 (MON), respectively. Conclusion In the detected seven mycotoxins, CPA, SMC, CIT and MON were detected only in the individual diet in some areas with a low dietary exposure level. However, the contamination level of CPA in alcohol merits attention.

Objective:To explore the clinical application value of MRI-PDFF on different liver segments for the evaluation of non-alcoholic fatty liver disease (NAFLD).Methods:178 volunteers from March 2019 to February 2020 were included. PDFF values ??of all nine segments of the liver were measured using CSE3.0T MRI scan. The obtained average value was used to represent the average liver fat content. PDFF values of each or combined liver segment were equally compared with the average value to observe the representativeness of fat content. Receiver operating characteristic curve was used to analyze the diagnostic performance of each liver segment, and the Youden index was used to calculate the cutoff value. Paired-sample t-test or non-parametric Kruskal-Wallis test were used to compare measurement data among groups.Results:178 volunteers average liver fat content ranged from 0.89% to 42.61% with MRI-PDFF, and 71.35% (127/178) of the volunteers had PDFF > 5%. There was no significant difference between SIII, SIVb, SV, and SVIII liver segments when compared with the average value ( P > 0.05). PDFF values ??of SI, SII, and SIV a liver segments were all lower than the average value, while the PDFF values ??of SVI and SVII liver segments were all higher than the average value ( P ??< 0.05). MRI-PDFF sensitivity value for diagnosing liver steatosis of nine liver segments was 85.8% ~ 94.5%, and the specificity was higher than 96.0%. Among them, the SV liver segment had the highest sensitivity (94.5%), and the corresponding optimal diagnostic threshold value was 5.13%. Compared with single and combined liver segment, the PDFF value of SII, SV, SVI combined liver segment had the highest diagnostic performance for fatty liver, with the sensitivity and specificity of 96.9%, and 100%, respectively, and the corresponding optimal diagnostic threshold value was 5.17%. Conclusion:Compared with single and other combined liver segments, MRI-PDFF values of SII, SV, and SVI combined liver segments have higher sensitivity and specificity for the diagnosis of NAFLD, and it can be used as the first choice for the determination of liver fat content with MRI.

Objective: To understand the status and health risk assessment of dietary fipronil contamination among 20 provinces of China. Methods: A total of 13 kinds of dietary samples in Chinese total diet study include cereals, legumes, potatoes, meats, eggs, aquatics, dairies, vegetables, fruits, sugars, beverages and water, alcohols, condiments and their corresponding products. Among them, condiments were used in the preparation of 12 other sample categories; thus, the actual mixed dietary samples of each province covered 12 groups. A total of 240 mixed dietary samples were collected from 20 provinces in China from 2009 to 2013. After the sample extraction and cleanup, dietary samples were analyzed for the residues of fipronil and its metabolites to obtain the contamination levels of fipronil residues using liquid chromatography-high resolution mass spectrometry. The dietary intake of adult residents was estimated based on food consumption of general population of China. Results: Among the 240 dietary samples, the detection rate of fipronil was 10.4% (25 samples), and the detection rates of fipronil metabolites, i.e. fipronil desulfinyl, fipronil sulfone and fipronil sulfide were 20.4% (49 samples), 40.0% (96 samples) and 8.8% (21 samples), respectively. According to the dietary exposure analysis, the average lower and upper dietary exposure levels of fipronil residues in adult residents of China were 11.34 and 12.35 ng·kg^-1·d^-1, accounting for 5.7% and 6.2% of acceptable daily intake (ADI), respectively. The highest adult dietary intake of fipronil residues was found in Hunan province, with a value of 72.98 ng·kg^-1·d^-1, accounting for 36.5% of ADI. Vegetables were the main dietary source of fipronil residues, which contributed to 71.0% of the total intake dose. Conclusion Fipronil residues were detected in varying degrees in dietary samples, yet the health risk caused by the dietary intake of adult residents among 20 provinces of China is low.

Objective To investigate the effect of long?term exposure to environmental cadmium on eight mineral element's metabolic balance of human body. Methods To choose a high cadmium area polluted by smelting and mining north of Guangdong province and a cadmium?free area with a similar economic level, and living and eating habit of residents as a contrast from April 2011 to August 2012. Stratified random sampling and clustered sampling method were adopted to choose the non?occupationally cadmium?exposed respondents who have lived in local area for more than 15 years, older than 40 years, having local rice and vegetable as the main dietary source, with simple and relatively stable diet, and without diabetes, kidney disease, thyroid disease, liver disease or other history of chronic disease. This study included 298 respondents, of whom 155 were in cadmium exposure group and 143 in control group. Questionnaires was used to acquire their health status and their morning urine samples were collected. Electrolytically coupled plasma mass spectrometry (ICP?MS) was used to test the concentrations of sodium (Na), magnesium (Mg), phosphorus (P), potassium (K), calcium (Ca), copper (Cu), zinc (Zn) and iodine (I). The Mann?Whitney U test method was used to compare the differences of concentrations of urinary cadmium, Na, Mg, P, K, Ca, Cu, Zn, I, and the ratio of Na to K (Na/K), Ca to P (Ca/P) between exposed group and control group.χ2 test was used to compare the abnormal rate of urinary cadmium between exposed group and control group. Pearson correlation and multiple regression method were used to investigate the relationship between urinary cadmium levels, gender, age, smoking, passive smoking, and minerals. Results The urinary cadmium level P50 (P25-P75) in exposed group was 5.45 (2.62-10.68)μg/g·cr, which was higher than that of the control group, which was 1.69 (1.22-2.36)μg/g · cr (Z=-10.49, P<0.001). The abnormal rate of urinary cadmium was 51.6%(80/155), which was higher than that of the control group (2.8%(4/143)) (χ2=87.56,P<0.001). The urinary Ca, Cu, Zn, and I level P50 (P25-P75) of exposed group were 173.80 (114.40-251.70), 20.55 (14.95-28.44), 520.23 (390.25-647.15), and 246.94 (203.65-342.97)μg/g · cr, which were higher than those in control group (142.42 (96.87-179.11), 15.44 (12.26-20.98), 430.09 (309.85-568.78) and 213.85 (156.70-281.63) μg/g · cr, respectively) (Z values were-4.33,-5.04,-3.47 and-4.24, all P values<0.001). The urinary P, K level P50 (P25-P75) of exposed group were 582.50 (463.20-742.8), 890.10 (666.00-1 305.40) μg/g · cr, which were lower than control group (694.50 (546.20-851.17), 1 098.58 (904.53-1 479.18) μg/g · cr) (Z values were-3.36,-4.02, all P values <0.001). on Based the results of Pearson correlation analysis, urinary cadmium was positively correlated with urinary Ca, Cu, Zn, and I, and the correlation coefficients were 0.31, 0.61, 0.38, and 0.25, respectively(all P values<0.05). Based on the results of multiple regression analysis, urinary cadmium levels contributed most to the metabolic balance of urinary Ca, Cu, Zn and I. The standardized regression coefficients were 0.31, 0.59, 0.39, and 0.24, respectively (all P values<0.001). Conclusion Long?term environmental exposure to cadmium affected the metabolic balance of Ca, Cu, Zn and I in human body.

Objective To investigate dynamic change of cadmium body burden and renal dysfunction among residents living in cadmium?polluted areas. Methods From April to July of 2011, the cadmium?polluted areas of northern Guangdong province in China was chosen as the study site. Based on the levels of cadmium pollution in soil and rice, the survey areas were divided into low exposed group (average concentration of cadmium was 0.15-0.40 mg/kg, 0.5-1.0 mg/kg in rice and soil, respectively) and high exposed group (average concentration of cadmium was >0.40 mg/kg, >1.0 mg/kg in rice and soil, respectively). Stratified random sampling and cluster sampling method of epidemiological investigations were carried out among 414 local residents who lived in cadmium exposure areas for more than 15 years, aged above 40, and without occupational cadmium exposure, including 168 and 246 residents in low and high exposed group, respectively. From March to June of 2014, 305 respondents of those who participated in 2011 were successfully traced, including 116 and 189 respondents in low and high exposed group, respectively. We used health questionnaires to acquire their health status. Home?harvested rice and vegetable samples were collected using quartering method for detection of cadmium level, including 190 rice samples, 161 vegetable samples in 2011 and 190 rice samples, 153 vegetable samples in 2014. Urine specimens of residents were collected for the detection of urinary cadmium and creatinine as well as renal dysfunction biomarkers, namely, N?acetyl?beta?D?glucosamidase (NAG) andβ2?microglobulin (β2?MG), respectively. In 2011 and 2014, Chi?square test was used to investigate the differences of abnormality of cadmium concentration in rice, vegetables and urinary cadmium,β2?MG,and NAG that were expressed as odds ratio (OR) and 95%confidence intervals (95%CI). Results In 2011 and 2014, cadmium concentration P50 (P25-P75) in rice was 0.43 (0.17-1.10) mg/kg,and 0.42 (0.20-1.14) mg/kg, respectively (Z=-0.77, P=0.440). In 2011 and 2014, cadmium concentrations P50 (P25-P75) in vegetables were 0.13 (0.07-0.34) mg/kg,and 0.25 (0.12-0.59) mg/kg, respectively, with abnormal rates of 38.5%(62/161) and 60.8%(93/153), respectively. In 2014, both average concentration and abnormal rate of cadmium in vegetables were higher than those in 2011 (Z=-4.69,P<0.001 andχ2=15.58, P<0.001). Concentrations of urinary cadmium P50 (P25-P75) in high exposed group were 7.90 (3.96-14.91)μg/g creatinine, 8.64 (4.56-17.60)μg/g creatinine in 2011 and 2014, respectively. Contrary to that in 2011, urinary cadmium of high exposed group was significantly increased in 2014 (Z=-2.80 ,P=0.005). In 2011 and 2014, concentrations of β2?MG, NAG P50 (P25-P75) were 0.15 (0.07-0.29)μg/g creatinine, 0.15 (0.07-0.45)μg/g creatinine,and 7.12 (5.05-10.65) U/g creatinine, 13.55 (9.1-19.84) U/g creatinine, respectively, with abnormal rates of 7.5% (23/305), 15.1% (46/305) ,8.2%(25/305) , and 33.8% (103/305), respectively. Compared with baseline in 2011, average concentrations ofβ2?MG, NAG significantly increased in 2014 (Z=-2.263,P=0.024 and Z=-12.52,P<0.001), and abnormal rates ofβ2?MG, NAG were also higher in 2014 (χ2=15.61,P<0.001 andχ2=64.72,P<0.001), with odds ratio (OR) of 2.00 (95%CI:1.23-3.24) and 4.12 (95%CI:2.87-5.92). Conclusion Environmental cadmium pollution of crops such as rice and vegetables in survey areas continued to remain high. Body burden of cadmium might kept at sustainably high levels and renal dysfunction was worsened after continuous, long?term cadmium exposure. Our results suggested that NAG might be more sensitive than β2?MG to serve as an indicator for an individual's future tubular function.

Objective To investigate the effect of long?term exposure to environmental cadmium on eight mineral element's metabolic balance of human body. Methods To choose a high cadmium area polluted by smelting and mining north of Guangdong province and a cadmium?free area with a similar economic level, and living and eating habit of residents as a contrast from April 2011 to August 2012. Stratified random sampling and clustered sampling method were adopted to choose the non?occupationally cadmium?exposed respondents who have lived in local area for more than 15 years, older than 40 years, having local rice and vegetable as the main dietary source, with simple and relatively stable diet, and without diabetes, kidney disease, thyroid disease, liver disease or other history of chronic disease. This study included 298 respondents, of whom 155 were in cadmium exposure group and 143 in control group. Questionnaires was used to acquire their health status and their morning urine samples were collected. Electrolytically coupled plasma mass spectrometry (ICP?MS) was used to test the concentrations of sodium (Na), magnesium (Mg), phosphorus (P), potassium (K), calcium (Ca), copper (Cu), zinc (Zn) and iodine (I). The Mann?Whitney U test method was used to compare the differences of concentrations of urinary cadmium, Na, Mg, P, K, Ca, Cu, Zn, I, and the ratio of Na to K (Na/K), Ca to P (Ca/P) between exposed group and control group.χ2 test was used to compare the abnormal rate of urinary cadmium between exposed group and control group. Pearson correlation and multiple regression method were used to investigate the relationship between urinary cadmium levels, gender, age, smoking, passive smoking, and minerals. Results The urinary cadmium level P50 (P25-P75) in exposed group was 5.45 (2.62-10.68)μg/g·cr, which was higher than that of the control group, which was 1.69 (1.22-2.36)μg/g · cr (Z=-10.49, P<0.001). The abnormal rate of urinary cadmium was 51.6%(80/155), which was higher than that of the control group (2.8%(4/143)) (χ2=87.56,P<0.001). The urinary Ca, Cu, Zn, and I level P50 (P25-P75) of exposed group were 173.80 (114.40-251.70), 20.55 (14.95-28.44), 520.23 (390.25-647.15), and 246.94 (203.65-342.97)μg/g · cr, which were higher than those in control group (142.42 (96.87-179.11), 15.44 (12.26-20.98), 430.09 (309.85-568.78) and 213.85 (156.70-281.63) μg/g · cr, respectively) (Z values were-4.33,-5.04,-3.47 and-4.24, all P values<0.001). The urinary P, K level P50 (P25-P75) of exposed group were 582.50 (463.20-742.8), 890.10 (666.00-1 305.40) μg/g · cr, which were lower than control group (694.50 (546.20-851.17), 1 098.58 (904.53-1 479.18) μg/g · cr) (Z values were-3.36,-4.02, all P values <0.001). on Based the results of Pearson correlation analysis, urinary cadmium was positively correlated with urinary Ca, Cu, Zn, and I, and the correlation coefficients were 0.31, 0.61, 0.38, and 0.25, respectively(all P values<0.05). Based on the results of multiple regression analysis, urinary cadmium levels contributed most to the metabolic balance of urinary Ca, Cu, Zn and I. The standardized regression coefficients were 0.31, 0.59, 0.39, and 0.24, respectively (all P values<0.001). Conclusion Long?term environmental exposure to cadmium affected the metabolic balance of Ca, Cu, Zn and I in human body.

Objective To investigate dynamic change of cadmium body burden and renal dysfunction among residents living in cadmium?polluted areas. Methods From April to July of 2011, the cadmium?polluted areas of northern Guangdong province in China was chosen as the study site. Based on the levels of cadmium pollution in soil and rice, the survey areas were divided into low exposed group (average concentration of cadmium was 0.15-0.40 mg/kg, 0.5-1.0 mg/kg in rice and soil, respectively) and high exposed group (average concentration of cadmium was >0.40 mg/kg, >1.0 mg/kg in rice and soil, respectively). Stratified random sampling and cluster sampling method of epidemiological investigations were carried out among 414 local residents who lived in cadmium exposure areas for more than 15 years, aged above 40, and without occupational cadmium exposure, including 168 and 246 residents in low and high exposed group, respectively. From March to June of 2014, 305 respondents of those who participated in 2011 were successfully traced, including 116 and 189 respondents in low and high exposed group, respectively. We used health questionnaires to acquire their health status. Home?harvested rice and vegetable samples were collected using quartering method for detection of cadmium level, including 190 rice samples, 161 vegetable samples in 2011 and 190 rice samples, 153 vegetable samples in 2014. Urine specimens of residents were collected for the detection of urinary cadmium and creatinine as well as renal dysfunction biomarkers, namely, N?acetyl?beta?D?glucosamidase (NAG) andβ2?microglobulin (β2?MG), respectively. In 2011 and 2014, Chi?square test was used to investigate the differences of abnormality of cadmium concentration in rice, vegetables and urinary cadmium,β2?MG,and NAG that were expressed as odds ratio (OR) and 95%confidence intervals (95%CI). Results In 2011 and 2014, cadmium concentration P50 (P25-P75) in rice was 0.43 (0.17-1.10) mg/kg,and 0.42 (0.20-1.14) mg/kg, respectively (Z=-0.77, P=0.440). In 2011 and 2014, cadmium concentrations P50 (P25-P75) in vegetables were 0.13 (0.07-0.34) mg/kg,and 0.25 (0.12-0.59) mg/kg, respectively, with abnormal rates of 38.5%(62/161) and 60.8%(93/153), respectively. In 2014, both average concentration and abnormal rate of cadmium in vegetables were higher than those in 2011 (Z=-4.69,P<0.001 andχ2=15.58, P<0.001). Concentrations of urinary cadmium P50 (P25-P75) in high exposed group were 7.90 (3.96-14.91)μg/g creatinine, 8.64 (4.56-17.60)μg/g creatinine in 2011 and 2014, respectively. Contrary to that in 2011, urinary cadmium of high exposed group was significantly increased in 2014 (Z=-2.80 ,P=0.005). In 2011 and 2014, concentrations of β2?MG, NAG P50 (P25-P75) were 0.15 (0.07-0.29)μg/g creatinine, 0.15 (0.07-0.45)μg/g creatinine,and 7.12 (5.05-10.65) U/g creatinine, 13.55 (9.1-19.84) U/g creatinine, respectively, with abnormal rates of 7.5% (23/305), 15.1% (46/305) ,8.2%(25/305) , and 33.8% (103/305), respectively. Compared with baseline in 2011, average concentrations ofβ2?MG, NAG significantly increased in 2014 (Z=-2.263,P=0.024 and Z=-12.52,P<0.001), and abnormal rates ofβ2?MG, NAG were also higher in 2014 (χ2=15.61,P<0.001 andχ2=64.72,P<0.001), with odds ratio (OR) of 2.00 (95%CI:1.23-3.24) and 4.12 (95%CI:2.87-5.92). Conclusion Environmental cadmium pollution of crops such as rice and vegetables in survey areas continued to remain high. Body burden of cadmium might kept at sustainably high levels and renal dysfunction was worsened after continuous, long?term cadmium exposure. Our results suggested that NAG might be more sensitive than β2?MG to serve as an indicator for an individual's future tubular function.

OBJECTIVE To investigate and analyze the operational costs and current charging policies of pharmacy intravenous admixture service （PIVAS） in China， and provide a reference for promoting high-quality and sustainable development of PIVAS. METHODS Questionnaires were distributed in 30 provinces， autonomous regions， and municipalities across the country through the “Wenjuanxing” platform from May 6th to July 1st， 2022. The operational costs， charging status and suggestions of PIVAS were investigated and analyzed. RESULTS A total of 761 PIVAS participated in the survey nationwide， including 666 tertiary medical institutions， 93 secondary medical institutions， and 2 primary medical institutions. Approximately 60.58% of PIVAS had implemented a charging system that allowed charges. Among them， most PIVAS required inspection and evaluation before charging. The annual operating cost of PIVAS in China was approximately 2 098 100 yuan， with the integrated operating cost comprising 89.36% of the total， while the dispensing cost accounted for only 10.64%. Human costs emerged as the highest annual consumption （74.20%）， followed by decoration and facility maintenance costs （4.77%） and equipment acquisition costs （3.44%）. Regarding charges for different drugs nationwide， common drugs had an average charge standard of 4.39 yuan per bag while antibacterial drugs averaged 5.01 yuan per bag； hazardous drugs had an average charge of 23.17 yuan per bag， whereas parenteral nutrition solutions averaged 38.75 yuan per bag. However， the recommended average charges of the four drugs mentioned above were 6.71， 9.63， 38.35 and 44.03 yuan per bag， respectively. CONCLUSIONS At present， there is no unified inspection and evaluation standard and charging standard in China. Moreover， the current charging standard is lower than the recommended standard. It is necessary to combine operational costs and develop more reasonable and fair charging standards.