A phase III randomized, double-blind, placebo-controlled trial of the denosumab biosimilar QL1206 in postmenopausal Chinese women with osteoporosis and high fracture risk.

The current study evaluated the efficacy and safety of a denosumab biosimilar, QL1206 (60 mg), compared to placebo in postmenopausal Chinese women with osteoporosis and high fracture risk. At 31 study centers in China, a total of 455 postmenopausal women with osteoporosis and high fracture risk were randomly assigned to receive QL1206 (60 mg subcutaneously every 6 months) or placebo. From baseline to the 12-month follow-up, the participants who received QL1206 showed significantly increased bone mineral density (BMD) values (mean difference and 95% CI) in the lumbar spine: 4.780% (3.880%, 5.681%), total hip :3.930% (3.136%, 4.725%), femoral neck 2.733% (1.877%, 3.589%) and trochanter: 4.058% (2.791%, 5.325%) compared with the participants who received the placebo. In addition, QL1206 injection significantly decreased the serum levels of C-terminal crosslinked telopeptides of type 1 collagen (CTX): -77.352% (-87.080%, -66.844%), and N-terminal procollagen of type l collagen (P1NP): -50.867% (-57.184%, -45.217%) compared with the placebo over the period from baseline to 12 months. No new or unexpected adverse events were observed. We concluded that compared with placebo, QL1206 effectively increased the BMD of the lumbar spine, total hip, femoral neck and trochanter in postmenopausal Chinese women with osteoporosis and rapidly decreased bone turnover markers. This study demonstrated that QL1206 has beneficial effects on postmenopausal Chinese women with osteoporosis and high fracture risk.

Current and Emerging Technology for Continuous Glucose Monitoring.

Diabetes has become a leading cause of death worldwide. Although there is no cure for diabetes, blood glucose monitoring combined with appropriate medication can enhance treatment efficiency, alleviate the symptoms, as well as diminish the complications. For point-of-care purposes, continuous glucose monitoring (CGM) devices are considered to be the best candidates for diabetes therapy. This review focuses on current growth areas of CGM technologies, specifically focusing on subcutaneous implantable electrochemical glucose sensors. The superiority of CGM systems is introduced firstly, and then the strategies for fabrication of minimally-invasive and non-invasive CGM biosensors are discussed, respectively. Finally, we briefly outline the current status and future perspective for CGM systems.

Inhibiting MMP13 Attenuates Deep Vein Thrombosis in a Mouse Model by Reducing the Expression of Pdpn.

OBJECTIVE: Matrix metalloproteinase 13 (MMP13) is an extracellular matrix protease that affects the progression of atherosclerotic plaques and arterial thrombi by degrading collagens, modifying protein structures and regulating inflammatory responses, but its role in deep vein thrombosis (DVT) has not been determined. The purpose of this study was to investigate the potential effects of MMP13 and MMP13-related genes on the formation of DVT. METHODS: We altered the expression level of MMP13 in vivo and conducted a transcriptome study to examine the expression and relationship between MMP13 and MMP13-related genes in a mouse model of DVT. After screening genes possibly related to MMP13 in DVT mice, the expression levels of candidate genes in human umbilical vein endothelial cells (HUVECs) and the venous wall were evaluated. The effect of MMP13 on platelet aggregation in HUVECs was investigated in vitro. RESULTS: Among the differentially expressed genes, interleukin 1 beta, podoplanin (Pdpn), and factor VIII von Willebrand factor (F8VWF) were selected for analysis in mice. When MMP13 was inhibited, the expression level of PDPN decreased significantly in vitro. In HUVECs, overexpression of MMP13 led to an increase in the expression level of PDPN and induced platelet aggregation, while transfection of PDPN-siRNA weakened the ability of MMP13 to increase platelet aggregation. CONCLUSIONS: Inhibiting the expression of MMP13 could reduce the burden of DVT in mice. The mechanism involves downregulating the expression of Pdpn through MMP13, which could provide a novel gene target for DVT diagnosis and treatment.

[Effect of different nitrogen forms and concentrations on biomass and alkaloids of isatidis folium].

OBJECTIVE: In order to provide theoretical basis of improving nitrogen utilization efficiency in Isatis indigotica, the biomass and active components in Isatidis Folium under different nitrogen forms and concentrations were analyzed. METHOD: I. indigotica was cultivated by sand culture in greenhouse, and the experiment was designed with orthogonal test L25 (5(6)). As an index to the biomass and indigo, indirubin, the effects on the I. indigotica by three factors [NO3(-) -N, NH4(+) -N, CO(NH2)2] at five different levels were studied. RESULT: There were significant difference of the biomass and active components by different nitrogen forms and concentrations. The effect of amide nitrogen [CO(NH2)2] on biomass of Isatidis Folium was the most apparent, and the effect of ammonium nitrogen on indirubin was more obvious. Considering the biomass and active ingredient, one combination was optimized, which was (NH4)2SO(4)-7.5 mmol x L(-1), KNO(3)-2.5 mmol x L(-1), CO(NH2)(2)- 5 mmol x L(-1). CONCLUSION: It is important to promote the growth in pre-stage of I. indigotica, and cost-effective combination of balanced nitrogen fertilizer could reasonably promote the growth, and improve the contents of active components and individual biomass.

Treatment of Gustilo grade III leg fractures by external fixation associated with limited internal fixation.

OBJECTIVE: To explore the clinical effects of external fixation associated with limited internal fixation on treatment of Gustilo grade III leg fractures. METHODS: From July 2006 to December 2008, 40 cases of Gustilo grade III leg fractures were emergently treated in our unit with external fixation frames. Soft tissue injuries were grouped according to the Gustilo classification as IIIA in 17 cases, IIIB in 13 cases, and IIIC in 10 cases. All the patients were debrided within 8 hours, and then fracture reposition was preformed to reestablish the leg alignment. Limited internal fixation with plates and screws were performed on all the Gustilo IIIA cases and 10 Gustilo IIIB cases at the first operation. But all the Gustilo IIIC cases and 3 Gustilo IIIB cases who had severe soft tissue injuries and bone loss only received Vacuum-sealing drainage (VSD). Broad-spectrum antibiotics were regularly used and VSD must be especially maintained easy and smooth for one week or more after operation. Limited internal fixation and transplanted free skin flaps or adjacent musculocutaneous flaps were not used to close wounds until the conditions of the wounds had been improved. RESULTS: The first operations were completed within 90-210 minutes (170 minutes on average). The blood transfusions were from 400 ml to 1500 ml (those used for anti-shock preoperatively not included). All the 40 patients in this study were followed up for 6-28 months, 20.5 months on average. The lower limb function was evaluated according to the comprehensive evaluation standards of leg function one year after operation and the results of 28 cases were excellent, 9 were good and 3 were poor. CONCLUSION: External fixation associated with limited internal fixation to treat Gustilo grade III leg fractures can get satisfactory early clinical therapeutic effects.

Expression changes and roles of matrix metalloproteinases in a rat model of traumatic deep vein thrombosis.

OBJECTIVE: To study the expression changes of matrix metalloproteinases (MMPs) in traumatic deep vein thrombosis (TDVT) in a rat model with the aid of gene chip technology and to explore the roles of MMPs in TDVT. METHODS: Totally 150 Sprague Dawley rats were randomly divided into control group (n equal to 10) and model group (n equal to 140). Rat models of TDVT were established by clamping the femoral vein and fixing the bilateral hind limbs. Then fixation of the hip spica with plaster bandage was conducted. According to the observation phases and/or biological situations of the femoral vein thrombosis, the model rats were further divided into 7 groups. Vascular tissues were obtained from each group through noninvasive incision into the femoral vein at corresponding time points. We adopted the Trizol one-step method for total RNA extraction, Affymetrix RAT 230 2.0 array for detection of RNA expressions and fold change (FC) analysis for changes of differential expressions of MMPs in each group. The main outcome parameters measured included expressions of MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11, MMP-12, MMP-13, MMP-14, MMP-16, MMP-23 and MMP-24. Gene array data of these MMPs were analyzed by the Affymetrix Microarray Analysis software (Version 5.0). RESULTS: FC analysis showed differential expressions of MMPs in each group during the course of TDVT. At the initial period of thrombosis, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11, and MMP-24 had significantly high expression, while MMP-12, MMP-13, MMP-14, MMP-16 and MMP-23 had relatively low expression. MMPs were all highly expressed at the peak time of thrombosis. In the process of thrombus resolution, MMP-2, MMP-10, MMP-16 and MMP-24 have relatively low expression, while MMP-12, MMP-13, MMP-14, MMP-16 and MMP-23 have significantly high expression. CONCLUSION: MMPs may affect the process of TDVT through transcription regulation of the fibrinolysis-anti-fibrinolytic system during the course of thrombosis and thrombus resolution.

Multi-slice spiral CT 3-dimensional reconstruction technique to treat multi-segmental degenerative spinal stenosis with traumatic instability of lower cervical spine.

OBJECTIVE: To study the feasibility of multi-slice spiral computed tomography (MSCT) 3-dimensional reconstruction technique in assisting cervical pedicle screw fixation (PSF) and double-door laminoplasty to treat multi-segmental degenerative spinal stenosis with traumatic instability (MDSTI) of lower cervical spine. METHODS: From September 2006 to August 2007, PSF combined with double-door laminoplasty was performed in 9 patients with MDSTI of lower cervical spine. MSCT 3-dimensional reconstruction techniques, including volume rendering (VR) and multi-planar reconstruction (MPR), were used to assist preoperative diagnosis and measurement to guide the procedure. MPR was performed after operation. In coronal view, the degree of screw perforation was measured precisely and the different positions of pedicle screws were divided into three grades according to Richter's method. In axial view, the canal sagittal diameter and transverse area of every laminoplasty level were measured. RESULTS: Nine patients with MDSTI of lower cervical spine underwent PSF (total 44 screws). According to the classification of Richter, 72.7% (32/44) was in Grade 1 and 27.3% (12/44) was in Grade 2. No screw perforation occurred in Grade 3 and no screw revision was done for misplacement. No iatrogenic damage was observed. Double-door laminoplasty was performed in total 42 volumes. The postoperative sagittal diameter and transverse area of cervical spinal canal were significantly increased (P<0.05). The confidence intervals of mean increased ratio were 23.43%-40.65% in sagittal diameter and 23.18%-42.07% in transverse area. Six months after laminoplasty, based on MSCT axial view, complete union between "open door" and allograft bone was obtained in 76.19% of volumes (32/42), and allograft bone was absorbed partly in 23.81% (10/42). A solid union in bilateral gutters was achieved in all cases. They were followed up from 6 months to 1 year (mean 7.8 months). Postoperative neural function recovery in two cases improved 2 ASIA grade, 5 cases improved 1 grade and 2 cases remained the same as preoperative grade. No cases had lower ASIA grade. CONCLUSION: Assisted with MSCT 3-dimensional reconstruction technique, PSF combined with double-door laminoplasty can be performed more safely and effectively to treat patients with MDSTI of lower cervical spine.

[Effect of sophocarpine on HERG K+ channels].

Human ether-a-go-go-related gene (HERG) encodes the rapid component of the cardiac delayed rectifier K+ current, which has an important effect on both proarrhythmia and antiarrhythmia. To investigate the effect of sophocarpine (SC) on HERG channel stably expressing in human embryonic kidney-293 (HEK293) cells, whole-cell patch-clamp technique was used to record HERG current and kinetic curves. As the result, it was found that SC inhibited HERG current in a concentration-dependent manner (10, 30, 100, and 300 micromol x L(-1)). At 0 mV, 10, 30, 100, and 300 micromol x L(-1) SC respectively inhibited IHERG by Istep ( 10.7 +/- 2.8)% , (11.3 +/- 5.5)% , (47.0 +/- 2.3)% and (53.7 +/- 2.5)% , and Itail (1.1 +/- 3.0)%, (17.1 +/- 3.3)%, (32.7 +/- 1.9)% (P < 0.05, n = 12) and (56.0 +/- 2.4)% (P < 0.05, n = 13). The time constants of inactivation, recovery from inactivation and onset of inactivation were accelerated. SC did not change other channel kinetics (activation and deactivation). It is concluded that SC inhibited the transfected HERG channels by influencing the inactivation state, which is the probable anti-arrhythmic mechanism.

Gene expression profile related to inflammation in rat model of traumatic deep vein thrombosis.

OBJECTIVE: To study the relationship between inflammation and traumatic deep vein thrombosis (TDVT). METHODS: A rat model of deep venous thrombosis was established by directly clamping femoral vein. Based on the different biological situations of femoral vein thrombosis and observation phases, 150 SD rats were divided into 7 groups. Inflammatory cells in vein wall of each group were counted. The fold change and cluster analysis were applied to study the change of gene expression during the development of venous thrombosis. Especially, the genes related to inflammation, fibrinolysis, coagulation of endothelium were analyzed in detail. RESULTS: The inflammation cells in femoral vein wall were mostly neutrophilic granulocytes in Groups B, C and D, while they were lymphocytes in Groups E, F and G. Compared with Groups A, B, E and G, the inflammation cell counts in Groups C, D and F were much higher (P less than 0.05). The results of fold-change analysis showed that 2 504 genes (Log 2 ratio > or = 1 or < or = 1) presented different expressions in the process of TDVT. Most of these genes'functions were not clarified so far and the genes with known functions were involved in inflammation, DNA-dependent transcription regulation, blood coagulation, fibrinolysis, etc. Among them, 23 genes related to inflammation had different expressions during TDVT. The cluster analysis showed that the expression changes of several genes, such as IL-1 alpha, IL-1 beta, IL-6, Cinc2, corresponded with the development of femoral vein thrombosis. CONCLUSION: There is a close relationship between the genes related to inflammation and deep vein thrombosis induced by direct vascular trauma.

Application of spiral CT image 3D reconstruction in severe talar neck fracture.

OBJECTIVE: To explore the application of the spiral computerized tomography (CT) image three-dimensional (3D) reconstruction technique associated with the conventional radiography in the diagnosis and treatment of severe talar neck fracture. METHODS: Using the multi-slice spiral CT image 3D reconstruction technique, we analysed 11 cases of talar neck fracture. The fractures were reduced and fixed through a minimal incision and internal fixation with titanium cannulated lag screws. RESULTS: In the 11 cases, the results of CT image 3D reconstruction were in concordance with plain radiograph in 6 case of Hawkins type II. And the remaining 5 cases of Hawkins types III and IV could not be classified exactly only by radiographs, one of whom was misdiagnosed. After using the CT image 3D reconstruction, the 5 cases were classified exactly before osteosynthesis. The classifications of these 11 cases were confirmed finally by surgical findings. The duration of operation were 45-140 min, averaging 81 min (including the duration of C-arm fluoroscopy). X-ray exposure time was 6-58 seconds, averaging 22 seconds. The blood loss was less than 100 ml. The fracture union was achieved in 3 months. No nonunion, talus avascular necrosis or joint surface collapse occurred. Postoperative follow-up was from 1 to 25 months. According to Hawkins score, excellent result was found in 6 type II cases and 1 type III case; good result in 1 type III case with both medial and lateral malleolar fracture, 1 type III with medial malleolus fractures and 1 open type III; fair result in 1 open type IV with lateral malleolus fracture. CONCLUSIONS: By using the multi-slice spiral CT image 3D reconstruction associated with radiography to diagnose and treat severe talar neck fractures, the accuracy of diagnosis can be improved obviously. Based on this technique, more consummate operational plan can be designed and performed so as to achieve a better therapeutic effect.

[The delivery mechanism of micro-porous osmotic pump tablets].

To investigate the delivery mechanism of micro-porous osmotic pump tablets ( MPOP), taking tramadol hydrochloride ( TR) as the model drug, tramadol hydrochloride micro-porous osmotic pump tablets (TR MPOP) were prepared with compressible starch as diluent, cellulose acetate as coating material, polyethylene glycol 400 as pore-forming agents. The equilibrium solubility and osmolality of TR were determined. The effects of fillers in tablet cores, coating levels, and osmotic pressures of release media on expansion behavior of preparations were described. The influences of the category, osmolality, and pH value of release media, release methods, and release conditions on release curves of tablets were evaluated. Based on several models, the delivery pattern of TR MPOP was fitted. The equilibrium solubility in water and osmolality of TR were (775.8 +/- 17.7) g x L(-1) and 4.036 Osmol x kg(-1), respectively. During the drug-release period, it was observed that the tablets expanded markedly in response to the expansion characteristics of compressible starch and the osmotic pressure difference across the membrane. When osmotic pressure of release media increased, the significant change of the equilibrium solubility of TR was not found, but the release rates of TR MPOP decreased significantly. The delivery rate was not influenced by the pH of release mediums, dissolution methods and paddle stirring rates. The drug release profile conformed to the model of zero order in 8 h. The pore-forming agents were dissolved in release medium, which caused micro-pores. The expansion of tablets made the size of micropores bigger, and then the drug-releasing pores were obtained. It was proved that the drivers of drug delivering from TR MPOP were mainly the difference of osmotic pressure, and secondly the difference of solubility. TR MPOP were the controlled-release preparation.

A Gelated Colloidal Crystal Attached Lens for Noninvasive Continuous Monitoring of Tear Glucose.

Patients of diabetes mellitus urgently need noninvasive and continuous glucose monitoring in daily point-of-care. As the tear glucose concentration has a positive correlation with that in blood, the hydrogel colloidal crystal integrated into contact lens possesses promising potential for noninvasive monitoring of glucose in tears. This paper presents a new glucose-responsive sensor, which consists a crystalline colloidal array (CCA) embedded in hydrogel matrix, attached onto a rigid gas permeable (RGP) contact lens. This novel sensing lens is able to selectively diffract visible light, whose wavelength shifts between 567 and 468 nm according to the alternation of the glucose concentration between 0 and 50 mM and its visible color change between reddish yellow, green, and blue. The detection limit of responsive glucose concentration can be reduced to 0.05 mM. Its combination with a contact lens endows it with excellent biocompatibility and portability, which shows great possibility for it to push the development of glucose-detecting devices into new era.

Simultaneous Optimization of Multiple Response Variables for the Gelatin-chitosan Microcapsules Containing Angelica Essential Oil.

Angelica essential oil (AO), a major pharmacologically active component of Angelica sinensis (Oliv.) Diels, possesses hemogenesis, analgesic activities, and sedative effect. The application of AO in pharmaceutical systems had been limited because of its low oxidative stability. The AO-loaded gelatin-chitosan microcapsules with prevention from oxidation were developed and optimized using response surface methodology. The effects of formulation variables (pH at complex coacervation, gelatin concentration, and core/wall ratio) on multiple response variables (yield, encapsulation efficiency, antioxidation rate, percent of drug released in 1 h, and time to 85% drug release) were systemically investigated. A desirability function that combined these five response variables was constructed. All response variables investigated were found to be highly dependent on the formulation variables, with strong interactions observed between the formulation variables. It was found that optimum overall desirability of AO microcapsules could be obtained at pH 6.20, gelatin concentration 25.00%, and core/wall ratio 40.40%. The experimental values of the response variables highly agreed with the predicted values. The antioxidation rate of optimum formulation was approximately 8 times higher than that of AO. The in-vitro drug release from microcapsules was followed Higuchi model with super case-II transport mechanism.

miR-10b promotes invasion by targeting KLF4 in osteosarcoma cells.

OBJECTIVE: Osteosarcoma is a common malignancy with high rate of metastasis. miR-10b has been reported to be expressed in many types of tumors abnormally and be associated with cancer carcinogenesis and progression. But the function of miR-10b in osteosarcoma is still unknown. So this study was aimed to investigate the role of miR-10b in osteosarcoma development. METHODS: miR-10b expression in osteosarcoma tissues and osteosarcoma cells were detected using real time PCR. The effects of miR-10b on osteosarcoma cells proliferation, apoptosis, migration and invasion were detected using CCK-8 assay, flow cytometry, wound-healing assay and transwell assay, respectively. The relationship between miR-10b and KLF4 was evaluated using dual-luciferase assay, correlation analysis. RESULTS: miR-10b was highly expressed in osteosarcoma tissues and osteosarcoma cells. Furthermore, inhibition of miR-10b in osteosarcoma cells depressed the cells proliferation, migration and invasion but promoted cells apoptosis. In addition, KLF4 was down-regulated by miR-10b and miR-10b expression was negatively related to KLF4 expression in osteosarcoma tissue, miR-10b participated in the process of osteosarcoma cells invasion by regulating KLF4 expression. CONCLUSION: miR-10b is overexpressed in osteosarcoma and KLF4 is the direct target gene of miR-10b. Furthermore, miR-10b promotes osteosarcoma cells progression by downregulating KLF4 expression. These results suggest that miR-10b functions as an oncomiR and play an important role in osteosarcoma cellular processes at least partially through regulating KLF4; miR-10b may be a therapeutic target for osteosarcoma treatment.

Lower cervical spine injury treated with lateral mass plates and pedicle screws through posterior approach.

OBJECTIVE: To treat injury of the lower cervical spine C6 to C7 with cervical lateral mass plates and T1 pedicle screws through posterior approach. METHODS: The data of 8 patients with lower cervical spine C6 or C7 injury (6 patients with fracture and dislocation in C6 and C7 and 2 with fracture in C7) were analyzed retrospectively in this study. For the preoperative American Spinal Injury Association (ASIA) classification, Grade C was found in 3 cases and Grade D in 5 cases. Screws were placed on the lateral masses and the first thoracic pedicle with Margerl technique. Lamina or facet bone allografting was used to achieve a long-term stability. RESULTS: All the 8 patients were followed up for 5-37 months (mean: 15 months). No operative death occurred. There were no examples of aggravation of spinal cord injury or vertebral artery injury, cerebrospinal fluid leak, nerve roots injury, screw malposition or back-out, loose of alignment or implant failure. Clinical symptoms and ASIA classification were improved in all the patients. Postoperative MRI scanning confirmed the satisfactory screw placement in all the cases. CONCLUSIONS: Lateral mass plates and pedicle screws through posterior approach are safe and beneficial for patients with lower cervical spine C6 or C7 injury.

[The use of lateral mass screws and pedicle screws for the treatment of injury of lower cervical spine].

OBJECTIVE: To discuss the effect of the use of the cervical lateral mass plates screws and T(1) pedicle screws for the treatment of C(6) to C(7) injury through posterior approach. METHODS: There were 8 patients in the study group; Each of them had been injured with low cervical spine C(6) or C(7). There were 6 cases with C(6)-C(7) injury and 2 cases with C(7) injury. According to ASIA classification, 3 cases were in grade C and 5 cases in D. The lateral mass screws were placed on the lateral masses using Margel technique. Lamina or facet bone allografting were used to achieve a long-term stability. RESULTS: All 8 patients were followed up from 5 to 37 months (mean 15 months). No operative death occurred. There were no cord or vertebral artery injury, cerebrospinal fluid leak, nerve roots injury, screw malposition or back out, loose of alignment or implant failure. Clinical symptom and ASIA classification were improved in all patients. Postoperative MRI scanning confirmed satisfactory screw placement in all cases. CONCLUSION: This technique is safe and benefit to patients with low cervical spine C(6) or C(7) injury.

Econazole Nitrate Induces Apoptosis in MCF-7 Cells via Mitochondrial and Caspase Pathways.

Econazole nitrate (EN), a synthetic compound, is now in use as a routine antifungal drug. EN was shown to have antitumor effect, the tumor cell killing mechanisms, however, remain unclear. In this research, the apoptosis-inducing effect of EN on MCF-7 cells was investigated. The results showed that EN inhibited the proliferation of MCF-7 cells in a time- and dose-dependent manner by MTT method and colony forming assay. MCF-7 cells treated with EN showed typical characteristics of apoptosis including the morphological changes and DNA fragmentation. Meanwhile, the loss of mitochondrial membrane potential was showed by flow cytometry. In addition, western blot analysis showed that EN resulted in the decrease expression of procaspase-3, procaspase-9 and bcl-2. In conclusion, these findings suggest that EN may be an effective way for treating human breast cancer. The anti-tumor mechanisms of EN might involve mitochondrial and caspase pathways.

Comparative effects of sophocarpine and sophoridine on hERG K+ channel.

Human ether-à-go-go-related gene (hERG) has an important role in the repolarization of the cardiac action potential. Sophocarpine and sophoridine are quinolizidine alkaloids and their structures are similar. Our aim was to investigate the effects of sophocarpine or sophoridine on hERG-encoded K(+) channels and the underlying structure-activity relationships. The effects of sophocarpine and sophoridine were examined on stably expressed hERG channels in HEK293 cells using a whole-cell patch clamp technique and Western blot analysis. The oil-water partition coefficients of sophocarpine and sophoridine were determined by a validated RP-HPLC method. At 300 microM, fractional block was 60.9+/-1.4% for sophocarpine versus 41.9+/-2.0% for sophoridine. Compared with sophocarpine, voltage-dependence of hERG channels inhibition by sophoridine was more notable. Sophoridine altered the activation properties, but not sophocarpine. Sophocarpine shifted the inactivation curve in a negative direction, but not sophoridine. Both drugs had no significant effect on the expression of hERG protein. The partition coefficients for the n-octanol/water system of sophocarpine and sophoridine at 37 degrees C were 16.03+/-0.42 and 1.94+/-0.03, respectively. In summary, sophocarpine and sophoridine are low potency blockers of hERG channels that functions by changing the channel kinetics, and sophocarpine is a more potent blocker of hERG K(+) channels than sophoridine, which may be due to higher hydrophobic nature of sophocarpine compared with sophoridine. Sophocarpine may have a higher binding affinity for the inactivate state. In contrast, sophoridine has a higher binding affinity for the open state. Both drugs have no effect on the generation and trafficking of hERG protein.