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.

Objective To investigate the efficacy and safety,as well as surgical essentials of upper urinary tract calculi (calculi being≤2 cm in diameter) complicated with pre-surgical uncertain pyonephrosis through one-stage renal calculi removal by percutaneous nephrolithotomy and suction device.Methods Retrospective analysis was used to detect the thirty-three cases with upper urinary tract calculi complicated with pre-surgical uncertain pyonephrosis collected from August 2010 to March 2016 in Yellow River Sanmenxia Hospital Affiliated to Henan University of Science and Technology,all the cases in the group had no pre-surgical fever,no apparent infection by blood-urine routine test,different degrees of hydronephrosis and no indications of pyonephrosis confirmed by CT and color Doppler ultrasonography,no pre-surgical anti-infection cure,pyonephrosis was found during the operation.First of all,a suction device was used to suck pus through percutaneous renal channel,rinsing repeatedly with small amount of fluid until the sucked rinsing fluid was clear;then,the one-stage calculi was removed by percutaneous renal lithotripsy,and the pus was sent to be cultured during the surgery,and the cases were treated by postoperative intravenous anti-infection for seven to seventeen days.Operation condition,postoperative blood routine,temperature,calculi removal and other clinical recovery conditions should be carefully observed.Results All the 33 cases underwent the one-stage single channel percutaneous nephrolithotom,the surgery was successful,the operation lasted 28-59 minutes,with an average of 41 minutes per case.Within the first-week of operation,CT reexamination showed the stone-free rate was 90.9% (30/33),and three cases had residual stone,the maximum diameter was about 6mm;seven cases had high fever within 3 days after the surgery (21.2%),and the temperature in four cases was higher than 38.5℃(12.1%) and two cases had fever within 3-6 days after surgery (6.1%),the highest temperature reached 38.0℃,and no fever existed after 6 days.Compared with preoperative values,the postoperative blood routine indicated that the surgery-relevant hemoglobin has decreased to (6.16±5.21) g/L;three days after surgery,white blood cell count was (7.16±4.86) 109/L.There were no severe complications such as sepsis,septic shock,renal abscess,hemorrhage.All cases were followed up for 6 to 36 months and no secondary pyonephrosis or renal dysfunction occurred during that period.Conclusion The treatment of upper urinary tract calculi,complicated with pyonephrosis without pre-surgical fever through one-stage renal calculi removal by percutaneous nephrolithotomy and suction device is effective and safe,it can be used as the routine method in basic hospitals and more attention should be paid to the operation and renal pelvic pressure in order to avoid the occurrence of complication.

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.

Carcinoma, Papillary ; diagnosis ; pathology ; Female ; Humans ; Jugular Veins ; pathology ; Male ; Middle Aged ; Neoplastic Cells, Circulating ; Retrospective Studies ; Thyroid Neoplasms ; diagnosis ; pathology

Objective To explore the causes of death of patients with cerebral hemorrhage of hypertension in recent 6 years and the countermeasure of decrease death rate.Methods The clinical data,different kinds of treatment and curative effects of the patients of two groups,admitted in recent six years,with cerebral hemorrhage of hypertension was refrospectively analysied.Results Of 157 cases of cerebral hemorrhage of hypertension in group A,there were 69 cases died(44%).Of 158 cases of cerebral hemorrhage of hypertension in group B,there were 48 cases died(30.4%).Death rate between the two of group had significant difference(P

Objective To explore the aestivation and lethal hyperthermy temperature of Oncomelania hupensis in summer,which is one of important ecology indexes,in order to understand the potential impact of global warming on the distribution of Oncomelania snail in mainland China. Methods Oncomelania hupensis hupensis snails were collected from the marshland region in Jiangsu Province and the aestivation and lethal hyperthermy temperature were examined by increasing temperature gradually in laboratory. Results The lethal hyperthermy temperatures of 50% Oncomelamia snails in dry and wet environment was 40.01℃ ( 95% of confidence interval from 39.76-40.27℃) and 42.13℃( 95% of confidence interval from 41.59-42.68℃), respectively. The logistic regression equations between temperature and mortality were d=101/(1+e 61.402269-1.535058X) (F=69.997,P

Objective To determine the effective accumulated temperature of Oncomelania hu-pensis during the period of development of generations in the natural environment. Methods The snails, Oncumelania hupensis, were raised in natural breeding site, the developing duration and accumulated temperature for .snails' development from eggs to adult that began to lay eggs were estimated based on the formula T=?(Ti-C). Results The average developing duration was (334.22?7. 52) days, average accumulated temperature was (5 821.38?70.05) day degree, and average effective accumulated temperature was (3 846.28?32. 59) day degree. Conclusion The method to estimate the effective accumulated temperature is quite accuracy, which provides theoretical parameters in developing the prediction model on transmission of schistosomiasis japonica affected by weather warming.

Coptis chinensis is widely used as Chinese medicine herbs and serious soil problems occur after continual cultivation of this medicinal plant. In the preset experiment, fibrous root extract of C. chinensis (REC) was added into soil to study the effect of REC on microbes and enzyme activity in soil. The results showed that both bacteria and actinomycetes decreased by about 2 times in contrast to fungi, which increased by about 3 folds. Phosphorus bacteria, potassium bacteria, azotobacter, ammonia bacteria, and nitrifying bacteria were also reduced significantly by REC, suggesting the inhibition of nitrogen biofixation and supply, mobilization of phosphorus and potassium, ad plant growth promotion as REC added into soil. There were multiple influences of REC on soil enzyme activities. Invertase activity was stimulated, while urease was inhibited and dehydrogenase unchanged by REC, indicating the interference of biochemical reactions in soil. In addition, type and total content of phosphorus lipid fatty acids (PLFAs) , the signature of microbes, decreased while the ratio of bacterium to fungus PLFAs increased as REC increased in soil, which suggested that fungi increased relatively with bacteria decreased thereby leading to easy occurrence of crop fungus diseases following cultivation of C. chinensis. The decrease in diversity and evenness indexes of microbial community in soil by REC indicated soil ecosystem deterioration and reduction of microbial groups and densities in soil. Therefore, allelopathic chemicals released from the roots of C. chinensis could change microbial community structure and resulted in serious soil problems by continual cropping of this medicinal plant.
Coptis ; Ecosystem ; Plant Extracts ; pharmacology ; Plant Roots ; Soil ; chemistry ; Soil Microbiology

Objective To investigate whether there existed a healthy obese subtype.Methods A total of 116 healthy subjects were recruited.They were divided into 3 groups according to BMI and metabolic disorders:40 cases of normal weight and metabolic normality (NMN),36 cases of obesity and metabolic normality (OMN) and 40 cases of obesity and metabolic abnormality (OMA).Anthropometic parameters as height,weight,waist circumference,hip circumference and blood pressure was recorded.Blood glucose,lipids,insulin,high-sensitivity C-reactive protein (hs-CRP) was detected.Body fat distribution was detected by dual-energy X-ray absorptiometry (DXA).Serum von Willebrand factor (vWF),a marker of endothelial dysfunction,were detected by ELISA.Results Both serum vWF levels in OMN group [(733.6±86.2)U/L] and OMA group[(809.2 ±46.3)U/L] are higher than that in NMN group [(466.9 ±65.3)U/L,P ＜0.05] with serum vWF level in OMA group is higher than in OMN group (P ＜ 0.05).Among android fat mass percentage (AFM％),BMI,waist height ratio,waist circumference,hs-CRP,weight,hip circumference and trunk fat mass,AFM％,BMI and hs-CRP are main influencing factors of vWF.Conclusions Endothelial dysfunction existed in obese adults regardless of their metabolic status.There is no healthy obese subtype.AFM％,BMI and hs-CRP are the main influencing factors of endothelial dysfunction.

Bone marrow mesenchymal stem cells (MSCs), multipotent stem cells, can replicate as undifferentiated cells and have the potential to differentiate into different lineages of mesenchymal tissues, including bone, cartilage,endothelial, neural, smooth muscle, skeletal myoblasts, and cardiac myocyte cells. The ischemia-induced death of cardiomyocytes results in scar formation and reduced contractility of the ventricle. Several preclinical and clinical studies have supported the notion that MSCs therapy may be used for cardiac regeneration.When transplanted into the infracted heart, MSCs prevent deleterious remodeling and improve recovery, but the mechanism is not clear. In this work,we review evidence and new prospects that support the use of MSCs in cardiomyoplasty.