Adolescent ; Bone Screws ; Child ; Female ; Femoral Neck Fractures ; surgery ; Fracture Fixation, Internal ; instrumentation ; Humans ; Male

OBJECTIVE To map a comprehensive metabolic pathway of herbacetin in rats, specifically, to elucidate the biotransformation of herbacetin in vivo and to simultaneously monitor the pharmacokinetic process of both parent drug and its major metabolites. METHODS liquid chromatography/ion trap mass spectrometry (LC/MSn) and ultra-liquid chromatography coupled with mass spectrometry (UPLC/MS) were combined in the current study for qualitative and quantitative determinations of herbacetin and its metabolites in bile, urine and feces after both oral and intravenous administration of herbacetin to rats. Enzyme kinetic studies on the intestinal and hepatic metabolism of herbacetin were further conducted to elucidate metabolic profiles of herbacetin in rat tissues and organs. Additionally, plasma concentration profiles of herbacetin and its metabolites in rats were obtained to characterize the overall pharmacokinetic behavior of herbacetin. RESULTS It was found that herbacetin was excreted primarily from rat urine in the form of glucuronide-conjugations. Subsequent in vitro enzyme kinetic studies and in vivo pharmacokinetic investigations suggested an extensive hepatic metabolism of herbacetin and the high exposure of herbacetin- glucuronides in systemic circulation. The clearance, half- life and bioavailability of herbacetin in rats were determined as (16.4±1.92)mL·kg-1·min-1, (11.9±2.7)min, and 1.32%, respectively. On basis of these findings, a comprehensive metabolic pathway of herbacetin in rats was composed. In addition, a physiology based pharmacokinetic (PBPK) model was successfully developed with the aid of the GastroPlus to simulate the pharmacokinetic process of herbacetin in rats. Application of the PBPK modeling can provide a useful starting point to understand and extrapolate pharmacokinetic parameters among different species, populations, and disease states. CONCLUSION After oral administration, herbacetin was subjected to colonic degradation and extensive first pass metabolism, with glucuronidation as its dominating in vivo metabolic pathway.

OBJECTIVE To investigate the effect of hypoxia on the pharmacokinetic process of salidrosidein rats and to explore its underlying mechanisms. METHODS The Caco-2 cell monolayerwas exposed to 1% oxygen (O2) concentration for 24 h to build the hypoxiccell model. The transportation mode of salidroside was investigated with the aid of this hypoxia model by detecting the apparent permeability coefficient(Papp). Healthy Sprague Dawley (SD) rats were exposed to 9% O2 for 72 h for the construction of hypoxic rat model. Liver sample was subsequently collected from the hypoxic rats with an aim to identify enzymes responsible for salidroside metabolism. The expression levels of sali?droside-transporting and salidroside-metabolizing enzymes, including Sodium-dependent glucose cotrans?porters (SGLT1), β-glucosidase (GBA3)and sulfotransferase (SULT2A1), were thereafter detected by RT-PCR and Western blot. The metabolic activity of GBA3 and SULT2A1 was monitored by rat liver microsome incubation.In addition, the renal function of rats under hypoxia was assessed by detecting concentrations of blood urea nitrogen and creatinine. RESULTS The AUC and t1/2 values of salidroside in hypoxic rats were more than doubled, while the in vivo clearance was significantly reduced. Mechanistic study demonstrated that the PappA- B/PappB- A eualsto 10.3, indicating the potential active transport of salidrosile. The expression of SGLT1 and GBA3 was significantly decreased, which indicated a reduced metabolism of salidroside under hypoxia. Moreover, rat under hypoxia was found to suffer from renal dysfunction, with an abnormal value of blood urea nitrogen. CONCLUSION Due to the reduced metabolism and the abnormal renal function under hypoxia, the systemic exposure of salidroside in rats was signifi?cantly enhanced.

Objective To study osteoporosis in patients receiving androgen deprivation therapy (ADT) with prostate cancer, and determine whether once-weekly oral alendronate can prevent bone loss in men receiving ADT. Methods One hundred and twelve men with nonmetastatic prostate cancer receiving ADT were divided into two groups from April 2007 to April 2008, 56 cases in each group. Group A took alendronate (70 rng once-weekly orally) and calcium supplement, group B received calcium supplement only. Bone mineral density (BMD) were measured both before and 6 months, 12 months after treatment for both groups. Results There were no statistically differences in age, persistence time of castration, prostate specific antigen level and adverse effect between two groups(P＞ 0.05). At baseline, 39.3%(44/112) of men had osteoporosis and 51.8%(58/112) had low bone mass. After 12 months treatment, in group A, BMD increased 3.7% (95% CI 2.80% to 4.60% ,P＜0.01 ) at the spine,0.7%(95% CI 0.10% to 1.40% ,P=0.031)at the total hip and 1.6% (95% CI0.40% to 2.80%,P =0.008) at the femoral neck. In group B decreased 1.4% (95% CI-2.70% to -0.03%, P = 0.045 ) at the spine, 0.7% (95% CI - 1.50% to -0.01%,P = 0.052) at the total hip and 0.7% (95% CI -1.50% to 0.10%, P = 0.081 ) at the femoral neck. The estimated changes in BMD were significantly different between two groups (P ＜ 0.01 ). Conclusions It suggests that ADT induce bone loss which should be treated in early stage. Bone loss that occurred with ADT is prevented and improved with once-weekly oral alendronate.

OBJECTIVE:To investigate the effects of neoadjunctive chemotherapy(NAC)of docetaxel and epirubicin com-bined with cyclophosphamide on clinical efficacy and tumor markers of breast cancer patients with different molecular types. METH-ODS:A total of 88 female patients with locally advanced breast cancer collected from our hospital during Jan. 2014-Jan. 2016 were divided into Luminal A type(23 cases),Luminal B type(21 cases),basal-like type(11 cases),HER2-over expressing type(18 cases)and normal breast-like type(15 cases)according to molecular type. All patients were given Docetaxel injection+Epirubicin hydrochloride injection+Cyclophosphamide for injection for consecutive 6 cycles(21 d as a cycle). Total response rates and patho-logical complete remission(pCR)rates were compared among breast cancer patients with different molecular types. The expression of serum tumor markers [CEA,CA125,CA153] were compared before and after treatment,and the occurrence of ADR was record-ed. RESULTS:Total response rate of 88 patients was 63.64%,among which that of basal-like breast cancer patients was 72.73%, significantly higher than other molecular types,with statistical significance(P<0.05). There was no statistical significance in total response rates of pairwise molecular type comparison(P>0.05). The pCR rate of 88 patients was 27.27%,and that of basal-like breast cancer patients was the highest(45.45%). There was statistical significance in pCR rates of pairwise molecular type compari-son(P<0.05),except there was no significant difference in pCR rate between HER2-over expressing type and normal breast-like type(P>0.05). Before treatment,there was no statistical significance in the expression of CEA,CA125 and CA153 in breast can-cer patients with different molecular types(P>0.05). After treatment,the expression of CEA,CA125 and CA153 in different mo-lecular types were decreased significantly,with statistical significance(P<0.05). There was no statistical significance in the expres-sion of above markers among different molecular types(P>0.05). There was no statistical significance in the incidence of ADR among different molecular types(P>0.05). CONCLUSIONS:NAC plan of docetaxel and epirubicin combined with cyclophospha-mide can reduce the expression of tumor markers and shows certain therapeutic efficacy for breast cancer patients with different mo-lecular types. Total response rate and pCR rate of basal-like type are better than those of other molecular types,so NAC plan is the preferred treatment for basal-like type breast cancer.

Objective To assess the clinical factors impacting on the effective time of endocrine therapy for patients with prostate cancer.Methods The chnical data of 432 patients with prostate cancer who accepted endocrine therapy were analyzed retrospectively.The endpoint of the study was failure of endocrine therapy which was defined as continuous elevation of prostate specific antigen (PSA) from nadir for 2 times and more than 0.2 μg/L.The clinical data such as age,clinical stage,lymph node metastasis,bone metastasis,Gleason score,initial PSA,and PSA nadir were collected and their rehtionship with the effective time of endocrine therapy were further assessed via COX regression model.Results Age of onset was 57-88(73.70 ± 7.28) years.Initial PSA was 10.30-588.10(27.15 ± 75.90) μ g/L.The effective time of endocrine therapy was 3-62 (27.01 ± 13.10) months.Univariate regression analysis showed that initial PSA,clinical stage,Gleason score,PSA nadir,lymph node metastasis,bone metastasis were correlated with the effective time of endocrine therapy (P ＜ 0.01).Multivariate regression analysis showed that only Gleason score was correlated with the effective time of endocrine therapy(P=0.001).Compared with patients with Gleason score equal to or less than 3+4,patients with Gleason score equal to or more than 4+3 showed 2.49 fold increased risk of therapy failure (OR =2.49,95％ CI 1.44-4.30).Conclusion Gleason score has close relationship with the effective time of endocrine therapy for patients with prostate cancer,Gleason score equal to or more than 4+3 is an indicator for poor response to endocrine therapy.

Comminuted fracture of distal femur is a common lower limb injury from traffic accidents, especially from motor accidents. Routine dynamic condylar screw (DCS) or 95-degree condylar plate (CP) sometimes cannot solve the bone defect in the center of alignment and contralateral diaphysis for the reason of absent screw anchor point, especially for AO C2.2-2.3 types. Many authors recommended open reduction and fixation with less invasive stabilization system (LISS) as the treatment of choice, but there are still problems in fusion and alignment. In this study, we reported our experiences with the use of bone splint technique in the high-energy commimuted fracture of distal femur with central and medial bone defect in adolescents.
Adolescent ; Adult ; Bone Plates ; Female ; Femoral Fractures ; surgery ; Fracture Fixation, Internal ; methods ; Fractures, Comminuted ; surgery ; Humans ; Male ; Splints

OBJECTIVETo explore clinical effect of vacuum sealing drainage (VSD) combined with discontinuous windowing technique for repairing large area exposed wounds of Achilles tendon.

METHODSFrom July 2009 to May 2014, 11 patients with large exposed wounds of Achilles tendon were treated, including 5 males and 6 females with an average age of 43 years old (aged from 7 to 65 years old). Among them, 4 cases were skin necrosis caused by heavy objects abrasion and contusion; 3 cases were caused by distal tibiofibula fractures; 3 cases were caused by bicycle-spoke injuries; 1 case was caused by diabetes. Areas of exposed Achilles tendon were from 6 cmx3 cm to 14 cmx5 cm without tendon rupture or bone exposed. After debridement, discontinuous fenestration on Achilles tendon was made by knife blade parallel with longitudinal axis of Achilles tendon, combined with Vacuum Sealing Drainage (VSD) treatment.

RESULTSAfter drainage treatment with one VSD cycle (5 to 7 days), abundant fresh granulation tissues were growing on all wounds and survived well after the second phase dermatoplasty. All patients were followed up for 12 to 24 months, the color of skin flap was good, the texture was soft without burst. At 3 to 4 months after operation, subcutaneous fat was appeared under the flap, the skin was sliding, movement of ankle joints was good. No delayed Achilles tendon rupture were occurred.

CONCLUSIONVacuum sealing drainage (VSD) combined with discontinuous fenestration is a simple, safe and effective method for repairing large area exposed wounds of Achilles tendon,which could minimize the secondary damage caused by wounds of skin flap grafting.

Achilles Tendon ; injuries ; surgery ; Adolescent ; Adult ; Aged ; Child ; Drainage ; methods ; Female ; Humans ; Male ; Middle Aged ; Vacuum

AIMTo determine the relationship between C3435T mutation in exon 26 of the human multidrug resistant 1 gene and cyclosporine (CsA) pharmacokinetic (PK) parameters among healthy Chinese volunteers by nonlinear mixed effect model (NONMEM).

METHODSTwenty healthy subjects were given orally a single dose of 500 mg CsA in microemulsion solution. Blood CsA concentrations were measured with HPLC and the genotype for the C3435T polymorphism of MDR1 gene was determined with the PCR and restriction fragment length polymorphism. The results were further confirmed by sequencing. NONMEM was performed to assess the effect of genotype on CsA PK profile.

RESULTSMDR1 C3435T genotype was identified as the best predictor of CsA systemic exposure. The relative bioavailability of CsA was 40% higher in subjects who carried at least one 3435C allele compared to that of TT type individuals in the study population.

CONCLUSIONThe MDR1 C3435T genotype offers a potential basis of mechanism to explain inter-subject differences in CsA oral bioavailability.

Administration, Oral ; Adult ; Biological Availability ; Cyclosporine ; administration & dosage ; pharmacokinetics ; Exons ; Genes, MDR ; genetics ; Genetics, Population ; Genotype ; Humans ; Male ; Mouth ; metabolism ; Polymorphism, Genetic

OBJECTIVETo explore feasibility of applying evidence grading system in clinical decision-making analysis.

METHODSUsing grading system as well as a quantitative approach to generate the threshold NNT((T)), and conducting clinical decision-making analysis through one study on Asymptomatic carotid atherosclerosis.

RESULTSNNT((T)) was 12, comparing with no-intervention in the ACA study that NNT = 6. NNT < NNT((T)) indicated the benefits of intervention outweigh the risks and costs.

CONCLUSIONTo obtain the rate of adverse event and the specifying approximate cost were vital in the process of applying grading system in clinical decision-making.

Advance Care Planning ; Algorithms ; Carotid Artery Diseases ; economics ; therapy ; Decision Making, Organizational ; Evidence-Based Medicine ; methods ; Health Care Costs ; Humans ; Models, Theoretical