Pharmacokinetics (PK) is the study of the absorption, distribution, metabolism, and excretion (ADME) processes of a drug. Understanding PK properties is essential for drug development and precision medication. In this review we provided an overview of recent research on PK with focus on the following aspects: (1) an update on drug-metabolizing enzymes and transporters in the determination of PK, as well as advances in xenobiotic receptors and noncoding RNAs (ncRNAs) in the modulation of PK, providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy; (2) current status and trends in assessing drug-drug interactions, especially interactions between drugs and herbs, between drugs and therapeutic biologics, and microbiota-mediated interactions; (3) advances in understanding the effects of diseases on PK, particularly changes in metabolizing enzymes and transporters with disease progression; (4) trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies; (5) emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes, especially non-P450s. Existing challenges and perspectives on future directions are discussed, and may stimulate the development of new research models, technologies, and strategies towards the development of better drugs and improved clinical practice.

OBJECTIVE: To discuss whether grade B pancreatic fistula after pancreaticoduodenectomy(PD)can be graded according to the severity and to provide reference for accurate evaluation and treatment.METHODS: The clinical data of 343 patients underwent PD surgery in the First Affiliated Hospital of Harbin Medical University from December2012 to June 2016 were retrospectively collected,among which 72 cases followed grade B pancreatic fistula. Grade B pancreatic fistula after operation was divided into severe groups of which imaging-assisted interventional therapy was needed and mild group. The total medical cost,length of hospital stay,drainage time,ICU transfer,introperitoneal effusion,introabdominal infection,abdominal hemorrhage,biliary fistula,delayed gastric emptying,number of types and incidence of complications except pancreatic fistula,incidence of pancreatic fistula as the most serious complications,postoperative morbidity index(PMI),fistula average complication burden(ACB)were statistically analyzed between two groups.RESULTS: Univariate analysis revealed that there were significant differences between two groups in the total medical cost(84,000 yuan vs. 132,000 yuan),length of hospital stay(29.0 days vs. 42.0 days),drainage time(20.5 d vs.53.0 d),introperitonal effusion rate(41.1% vs. 87.5%),introabdominal infection rate(10.7% vs. 43.8%),abdominal hemorrhage rate(7.1% vs. 56.3%),the number of other types of complications except pancreatic fistula(1 vs. 4),pancreatic fistula as the most serious complications(53.6% vs. 87.5%),PMI(0.22±0.08 vs. 0.37±0.00),ACB(0.19±0.08 vs. 0.37±0.00),and the P-values were less than 0.05 respectively.CONCLUSION: The severity of grade B pancreatic fistula of ISGPS update classification is heterogeneous,which can be divided into mild and severe groups. It provides a reference for precise and individualized treatment for grade B pancreatic fistula.

Seasonal outbreaks of airsacculitis in China's poultry cause great economic losses annually. This study tried to unveil the potential role of Avian metapneumovirus (AMPV), Ornithobacterium rhinotracheale (ORT) and Chlamydia psittaci (CPS) in avian airsacculitis. A serological investigation of 673 breeder chickens and a case-controlled study of 430 birds were undertaken. Results showed that infection with AMPV, ORT, and CPS was highly associated with the disease. The correlation between AMPV and CPS were positively robust in both layers and broilers. Finally, we determined the co-infection with AMPV, ORT, and CPS was prevalent in the sampled poultry farms suffering from respiratory diseases and the outbreak of airsacculitis was closely related to simultaneous exposure to all three agents.
Air Sacs ; microbiology ; pathology ; Animals ; Antibodies, Bacterial ; blood ; Antibodies, Viral ; blood ; Case-Control Studies ; Chickens ; Chlamydia ; Chlamydia Infections ; microbiology ; pathology ; veterinary ; Coinfection ; Flavobacteriaceae Infections ; microbiology ; pathology ; veterinary ; Humans ; Metapneumovirus ; Ornithobacterium ; Paramyxoviridae Infections ; pathology ; veterinary ; virology ; Poultry Diseases ; microbiology ; pathology ; virology ; Respiratory Tract Diseases ; microbiology ; veterinary ; virology ; Seroepidemiologic Studies

Increasing attention has been focused on the antitumor activity of artemisinin derivatives in recent years, for artemisinin had been reported to have cytotoxic effects against HL-60, P388 and MCF-7 tumor cells. We report here the synthesis and evaluation for antitumor activity of a series of artemisinin-ether derivatives bearing tetrahydropyrrole, morpholine, piperidine, substituted piperidines and azoles with various linkers. Sixteen 10-O-substituted dihydroartemisinin derivatives were designed and synthesized, all of which have never been reported in literatures and whose antiproliferative effects on human breast cancer MCF-7, MCF-7/Adr and HL-60 cells were determined by MTT assay or direct cell counting. Each of these artemisinin derivatives possessed better effects than dihydroartemisinin evidently against HL-60 and MCF-7 cells growth, while less potent than doxorubicin. All target compounds exhibited significantly improved potency compared to DHA and doxorubicin on the doxorubicin-resistant MCF-7/Adr cells, so did they in their sensitive counterparts MCF-7 cells. Among them, compounds GF02, GH04 and ZH04 showed strong activity against these three cell lines growth. Further research is undergoing.
Antineoplastic Agents ; chemical synthesis ; chemistry ; Artemisinins ; chemical synthesis ; chemistry ; Breast Neoplasms ; pathology ; Cell Proliferation ; Doxorubicin ; Drug Design ; HL-60 Cells ; drug effects ; Humans ; MCF-7 Cells ; drug effects

OBJECTIVETo explore the relationship between the expression of Survivin and Ki67 with prognosis of pancreatic endocrine tumors (PETs).

METHODSImmunohistochemistry for Survivin and Ki67 was performed in 25 cases of normal pancreatic tissues and 81 cases of PETs by tissue microarrays and to observe the expression and evaluate the relationship with prognosis.

RESULTS(1)The expression of Survivin and Ki67 in PETs was significantly higher than that in normal pancreatic tissues (P <0.01); (2)The expression of Survivin and Ki67 in PETs was correlated with tissue grading and the TNM-staging (P < 0.05), but not related with tumor size, location and functional status. In addition, the expression of nuclear Survivin was association with lymph node metastasis (P < 0.05). (3)The high expression of Ki67 was related with the expression of nuclear Survivin, but not related with the expression of cytoplasmic Survivin.

CONCLUSIONSurvivin and Ki67 were both expressed in PETs, which were closely related to the clinical pathological characteristics. They could be used as new indicators in the evaluation of prognosis of PETs. The expression of Survivin in nucleus had more diagnostic significance than that in cytoplasm, and that could be highly correlated with lymph node metastasis, which would be used as a new marker of poor prognosis.

Biomarkers, Tumor ; metabolism ; Cell Nucleus ; metabolism ; Cytoplasm ; metabolism ; Humans ; Immunohistochemistry ; Inhibitor of Apoptosis Proteins ; metabolism ; Ki-67 Antigen ; metabolism ; Lymphatic Metastasis ; Neoplasm Staging ; Pancreatic Neoplasms ; diagnosis ; Prognosis

OBJECTIVEAdhesive or too highly located folds upper eyelid and even blepharoptosis are common complications of double eyelid operation. To correct such deformities.

METHODWe shifted down the double eyelid line, removed adhesion thoroughly, relieved orbital fat and restarted the volume with infraorbicularis oculi fat flap.

RESULTWe had treated 32 case in past two years. The results were satisfying.

CONCLUSIONThe method are acted easy and gained fine result, so behaving to extend application.

Adipose Tissue ; transplantation ; Adult ; Blepharoplasty ; methods ; Eye Abnormalities ; etiology ; surgery ; Eyelids ; abnormalities ; pathology ; Female ; Humans ; Oculomotor Muscles ; surgery ; Postoperative Complications ; surgery ; Tissue Adhesions ; Young Adult

OBJECTIVETo evaluate the aesthetic outcome after application of rectangle periosteous flap to cover corrugator.

METHODSOn the basis of regular rhytidectomy, a inter-eyebrow periosteous flap is applied to cover the fascia flap of corrugator by means of turnover. This manipulation helps to separate the skin from the muscle and prevent the re-adherence between the skin and muscle.

RESULTSThe approach was applied on 15 cases. The follow-up ranged from 6 months to 1 year. The results were satisfactory.

CONCLUSIONSThe method is effective in elimination of inter-eyebrow crease.

Adult ; Female ; Humans ; Middle Aged ; Muscle, Skeletal ; transplantation ; Periosteum ; transplantation ; Reconstructive Surgical Procedures ; methods ; Rhytidoplasty ; methods ; Skull ; Surgical Flaps ; Treatment Outcome

OBJECTIVETo discuss the clinical manifestations, therapeutic strategy and prognosis of patients with severe acute respiratory syndrome (SARS) older than 60 years.

METHODSElderly patients diagnosed as SARS in Peking Union Medical College Hospital were compared with younger patients.

RESULTSTwenty-four elderly patients and 53 younger patients were analysed. Elderly patients had more coexisting conditions, such as hypertension, diabetes, coronary heart disease, and renal disease than control group (P < 0.05). Rate of respiratory failure in elderly patients was higher than that in control group (P < 0.05). Elderly patients had more respiratory symptoms, such as cough, sputum, and shortness of breath (P < 0.05). Rate of lymphocytopenia and thrombocytopenia in elderly patients was higher than that in control group. All patients were given ribavirin and antibiotics. More patients in elderly group were given 3rd generation cephalosporin and imipenem. Mortality rate in elderly group was higher than that in control group (33.3% vs 3.8%, P < 0.05). Univariate analysis showed that age, respiratory failure, and thrombocytopenia were risk factors of death, but logistic analysis did not find any independent risk factor.

CONCLUSIONSThough the elderly patients have a lower morbidity of SARS, they have more coexisting conditions. The therapy of elderly patients is more difficult than that of control group, and the mortality in elderly patients is high.

Age Factors ; Aged ; Antiviral Agents ; therapeutic use ; Diabetes Complications ; Female ; Humans ; Hypertension ; complications ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Ribavirin ; therapeutic use ; Risk Factors ; Severe Acute Respiratory Syndrome ; complications ; diagnosis ; drug therapy

OBJECTIVETo compare the protective activity of liver injury induced by D-galactosamine (GalN) between Huangqin-Tang and their metabolites by human intestinal bacteria(HIB).

METHODThe liver injuries in conventional and pseudo-germfree mice were induced by GalN. After oral administration of Huangqin-Tang and their metabolites mixtures by HIB, the serum transaminase (ALT and AST) activities were detected.

RESULTIn conventional mice, large and medium doses (20 and 10 g.kg-1) of Huangqin-Tang decoction significantly reduced the increase of serum ALT activity after 18 h GalN treatment. In pseudo-germfree mice, metabolites significantly reduced the ALT levels. However, Huangqing-Tang didn't affect the ALT levels in this kind of mice. To all of the animals, AST levels remained the same after oral Huangqin-tang or their metabolites.

CONCLUSIONThe metabolism by intestinal bacteria plays a role in pharmacological effects of constituents of Chinese herbal medicine. The metabolites of the constituents by intestinal bacteria were the real active components in vivo.

Administration, Oral ; Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Bacteria ; metabolism ; Chemical and Drug Induced Liver Injury ; Drugs, Chinese Herbal ; isolation & purification ; metabolism ; pharmacology ; Galactosamine ; Intestines ; microbiology ; Liver Diseases ; metabolism ; Male ; Mice ; Plants, Medicinal ; chemistry ; Protective Agents ; metabolism ; pharmacology