ObjectiveTo explore the mechanism of the anti-cancer compound formula Feiyanning in inhibiting epithelial-mesenchymal transition （EMT） and invasion and metastasis of non-small cell lung cancer （NSCLC）. MethodsCell proliferation and activity were assessed using the cell counting kit-8（CCK-8） assay to evaluate the effect of Feiyanning on the proliferation of A549 and H1299 cells. Wound healing and Transwell assays were conducted to examine Feiyanning's impact on the metastasis of A549 and H1299 cells. The effects of Feiyanning on EMT and the transforming growth factor-β₁ （TGF-β₁）/Smad signaling pathway proteins in A549 and H1299 cells were detected by Western blot. Exogenous TGF-β₁ was used to induce EMT in A549 and H1299 cells. The effects of Feiyanning on TGF-β₁-induced NSCLC cell metastasis， EMT， and the TGF-β₁/Smad pathway proteins were assessed by wound healing assay， Transwell assay， and Western blot. In vivo， an A549 lung metastasis model was established via tail vein injection in nude mice. A total of 28 SPF male nude mice were randomly divided into four groups： Model （NC） group， Feiyanning low-dose （FYN1） group， Feiyanning high-dose （FYN2） group， and the positive control group （TGF-β receptor kinase inhibitor SB431542 group）. The corresponding interventions were performed. After 40 days， the mice were euthanized， and lung metastases were analyzed. The expression of E-cadherin， N-cadherin， p-Smad2， and p-Smad3 in each group was detected by immunohistochemistry （IHC）. ResultsAfter Feiyanning intervention， compared to the blank group， Feiyanning inhibited the proliferation of A549 and H1299 cells in a concentration-dependent manner （P<0.01）. The metastasis ability of Feiyanning-treated cells was significantly decreased compared to the blank group （P<0.01）. The expression of EMT marker proteins N-cadherin and zinc finger transcription factors （Zeb1， Snail， Slug） was significantly reduced in the Feiyanning groups compared to the blank group （P<0.05， P<0.01）. The expression of p-Smad2/3， Smad2/3， TβRI， and TβRⅡ， key proteins in the TGF-β₁/Smad signaling pathway， was also significantly decreased （P<0.01）. In the TGF-β₁-induced EMT model， compared to the TGF-β₁ group， the cell metastasis ability in the Feiyanning groups was reduced （P<0.01）， and the expression levels of N-cadherin， Zeb1， Snail， and Slug were significantly lower （P<0.01）. The expression levels of p-Smad2/3， Smad2/3， TβRI， and TβRⅡ were also significantly reduced （P<0.01）. In vivo results showed that compared to the model group， the number of lung metastases in the FYN1， FYN2， and SB431542 groups was reduced （P<0.01）， and the range of cell infiltration was narrowed. Immunohistochemical results showed that compared to the model group， the expression of E-cadherin in the FYN1， FYN2， and SB431542 groups was increased （P<0.01）， the expression of N-cadherin decreased （P<0.05， P<0.01）， and the expression of p-Smad2 and p-Smad3， key proteins of the TGF-β₁/Smad pathway， was reduced （P<0.01）. ConclusionFeiyanning inhibits the invasion and metastasis of NSCLC cells and EMT. The mechanism is related to the inhibition of TGF-β₁/Smad signaling pathway.

ObjectiveTo explore the mechanism of the anti-cancer compound formula Feiyanning in inhibiting epithelial-mesenchymal transition （EMT） and invasion and metastasis of non-small cell lung cancer （NSCLC）. MethodsCell proliferation and activity were assessed using the cell counting kit-8（CCK-8） assay to evaluate the effect of Feiyanning on the proliferation of A549 and H1299 cells. Wound healing and Transwell assays were conducted to examine Feiyanning's impact on the metastasis of A549 and H1299 cells. The effects of Feiyanning on EMT and the transforming growth factor-β₁ （TGF-β₁）/Smad signaling pathway proteins in A549 and H1299 cells were detected by Western blot. Exogenous TGF-β₁ was used to induce EMT in A549 and H1299 cells. The effects of Feiyanning on TGF-β₁-induced NSCLC cell metastasis， EMT， and the TGF-β₁/Smad pathway proteins were assessed by wound healing assay， Transwell assay， and Western blot. In vivo， an A549 lung metastasis model was established via tail vein injection in nude mice. A total of 28 SPF male nude mice were randomly divided into four groups： Model （NC） group， Feiyanning low-dose （FYN1） group， Feiyanning high-dose （FYN2） group， and the positive control group （TGF-β receptor kinase inhibitor SB431542 group）. The corresponding interventions were performed. After 40 days， the mice were euthanized， and lung metastases were analyzed. The expression of E-cadherin， N-cadherin， p-Smad2， and p-Smad3 in each group was detected by immunohistochemistry （IHC）. ResultsAfter Feiyanning intervention， compared to the blank group， Feiyanning inhibited the proliferation of A549 and H1299 cells in a concentration-dependent manner （P<0.01）. The metastasis ability of Feiyanning-treated cells was significantly decreased compared to the blank group （P<0.01）. The expression of EMT marker proteins N-cadherin and zinc finger transcription factors （Zeb1， Snail， Slug） was significantly reduced in the Feiyanning groups compared to the blank group （P<0.05， P<0.01）. The expression of p-Smad2/3， Smad2/3， TβRI， and TβRⅡ， key proteins in the TGF-β₁/Smad signaling pathway， was also significantly decreased （P<0.01）. In the TGF-β₁-induced EMT model， compared to the TGF-β₁ group， the cell metastasis ability in the Feiyanning groups was reduced （P<0.01）， and the expression levels of N-cadherin， Zeb1， Snail， and Slug were significantly lower （P<0.01）. The expression levels of p-Smad2/3， Smad2/3， TβRI， and TβRⅡ were also significantly reduced （P<0.01）. In vivo results showed that compared to the model group， the number of lung metastases in the FYN1， FYN2， and SB431542 groups was reduced （P<0.01）， and the range of cell infiltration was narrowed. Immunohistochemical results showed that compared to the model group， the expression of E-cadherin in the FYN1， FYN2， and SB431542 groups was increased （P<0.01）， the expression of N-cadherin decreased （P<0.05， P<0.01）， and the expression of p-Smad2 and p-Smad3， key proteins of the TGF-β₁/Smad pathway， was reduced （P<0.01）. ConclusionFeiyanning inhibits the invasion and metastasis of NSCLC cells and EMT. The mechanism is related to the inhibition of TGF-β₁/Smad signaling pathway.

Objective: Exploring the effect and mechanism of Xinyang Tablet on reduction of ferroptosis in myocardial cells from mice with chronic heart failure. Methods: Sixty C57BL/6J mice were randomly assigned to the sham, model, Xinyang Tablet low-dose (0.34 g/kg), Xinyang Tablet medium-dose (0.68 g/kg), Xinyang Tablet high-dose (1.36 g/kg), and perindopril (0.607 mg/kg) groups using a random number table method (10 mice in each group). Except for the sham group, all other groups underwent aortic arch constriction surgery to construct a chronic heart failure model. On the third day after completion of the modeling, each treatment group was administered the corresponding medication by gavage, while the sham and model groups were administered equal volumes of water by gavage once a day for eight consecutive weeks. After treatment, cardiac ultrasound was used to detect the structure and function of the mouse heart. Hematoxylin and eosin staining was used to detect pathological changes in mouse heart tissue. Masson staining was used to detect the proportion of fibrotic area of mouse heart tissue. Realtime fluorescence PCR was used to detect the mRNA expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), collagen 3α (Col3α), and myosin heavy chain 7 (MYH7) in mouse myocardial tissue. Transmission electron microscope was used to detect the ultrastructure of myocardial cell mitochondria. Reactive oxygen species (ROS) staining was used to detect the mean fluorescence intensity of ROS in myocardial tissue. Micro-determination was used to detect superoxide dismutase (SOD) activity in myocardial tissue. An immunofluorescence assay was used to detect the mean fluorescence intensity of phosphorylated histone deacetylase 2 (p-HDAC2) in myocardial cell. Western blotting was used to detect the protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), p-HDAC2, nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), glutathione peroxidase 4 (GPX4), and cystine glutamate reverse transporter (xCT) in mouse myocardial tissue. Results: Compared to the sham group, the model group showed a decrease in left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), an increase in left ventricular end-systolic diameter(LVESD) and left ventricular end-diastolic diameter (LVEDD), an increase in the proportion of cardiac fibrosis area, an increase in relative expression levels of ANP, BNP, Col3α, and MYH7 mRNA, an increase in ROS mean fluorescence intensity, a decrease in SOD activity, an increase in mean fluorescence intensity of p-HDAC2, an increase in relative expression levels of p-HDAC2 and NOX1 proteins, and a decrease in relative expression levels of Nrf2, GPX4, and xCT proteins (P<0.05). Myocardial fibrosis lesions are obvious, with disordered mitochondrial arrangement, decreased volume and shrinkage, increased membrane density, and reduced mitochondrial cristae. Compared to the model group, the LVEF and LVFS of mice in each dose group of Xinyang Tablet and the perindopril group increased, LVESD and LVEDD decreased, the proportion of fibrotic area of heart tissue decreased, the relative expression levels of ANP, BNP, Col3α, MYH7 mRNA decreased, ROS mean fluorescence intensity decreased, SOD activity increased, mean fluorescence intensity of p-HDAC2 decreased, relative expression levels of p-HDAC2 and NOX1 proteins decreased, and relative expression levels of Nrf2 and xCT proteins increased (P<0.05). Myocardial fibrosis was reduced, the mitochondrial arrangement was more regular, the mitochondria enlarged, the membrane density was reduced, and mitochondrial cristae increased. Compared to the model group, the relative expression level of the GPX4 protein in myocardial tissue increased in the Xinyang Tablet medium-, high-dose, and the perindopril groups (P<0.05). Conclusion Xinyang Tablet can improve ferroptosis and ventricular remodeling in mice with chronic heart failure by regulating the HDAC2-mediated Nrf2 antioxidant pathway.

A three-dimensional(3D)medical image segmentation network(CA-SegResNet)which incorporates a 3D coordinate attention mechanism is proposed to address the issue of segmenting identified vertebral bones from spinal computed tomography(CT)images.The network extracts image features through a deep residual convolutional neural network and fuses the feature maps from each encoder layer with the input of the corresponding decoder layer.Subsequently,a 3D coordinate attention module is introduced to capture inter-channel relationships as well as directional and positional information,establishing long-range dependencies across different spatial directions,thereby enabling precise segmentation of the identified vertebral bones.For the segmentation tasks involving the identified cervical vertebra(the 7th cervical vertebra)and the identified thoracic vertebra(the 12th thoracic vertebra)across 105 cases,CA-SegResNet achieves average Dice similarity coefficients(DSC)of 0.934 5 and 0.918 9 on the test set,with average Hausdorff distances(HD)of 7 and 8 mm.Compared with U-Net results,the average DSC is improved by 0.014 5 and 0.0463,while average HD is reduced by 176 and 388 mm.The results demonstrate that the network can realize the precise segmentation of identified vertebral bones from CT images.

OBJECTIVE To study the pharmacokinetics of small molecule inhibitor SYHA1809 in Beagle dogs. METHODS LC-MS/MS method was adopted. Beagle dogs were randomly divided into single intravenous administration group （3.75 mg/kg）， single low-dose intragastric administration group （3.75 mg/kg）， single medium-dose intragastric administration group （7.5 mg/kg）， single high-dose intragastric administration group （15 mg/kg） and multiple intragastric administration group （7.5 mg/kg， once a day， for 7 consecutive days）， with 6 dogs in each group， half male and half female. The plasma samples of Beagle dogs were collected in each group according to the set time point， and underwent LC-MS/MS quantitative analysis after preprocessing. The pharmacokinetic parameters were calculated by using Phoenix WinNonlin 8.0 software using obtained data. RESULTS After intravenous injection， CL of SYHA1809 in Beagle dogs was （2.70±0.48） mL/（min·kg）， steady-state distribution volume was 0.757 L/kg， and t1/2 was （3.35±1.36） h； after single intragastric administration of low-dose， medium-dose and high-dose of SYHA1809， average tmax was （0.53±0.02） h， and the blood drug concentration increased with the increase of dose； after single intragastric administration of 3.75 mg/kg SYHA1809， the absolute bioavailability was 83.5%； within the dose range of 3.75-15 mg/kg， the increase in cmax and AUC of SYHA1809 was positively correlated with the dose； after intragastric administration of 7.5 mg/kg SYHA1809 for 7 consecutive days， the pharmacokinetic parameters of SYHA1809 were comparable to those of a single intragastric administration of the same dose， with no statistically significant difference （P＞0.05）. CONCLUSIONS SYHA1809 is absorbed rapidly in Beagle dogs， shows the dose-dependent blood concentration， high bioavailability， no obvious accumulation after multiple intragastric administration， and good pharmacokinetic behavior.

BACKGROUND: Management of gastric leak after sleeve gastrectomy (SG) is challenging due to its unpredictable outcomes. We aimed to summarize the characteristics of SG leaks and analyze interventions and corresponding outcomes in a real-world setting. METHODS: To retrospectively review of 15,721 SG procedures from 2010 to 2020 based on a national registry. A cumulative sum analysis was used to identify a fitting curve of gastric leak rate. The Kaplan-Meier method and log-rank tests were performed to calculate and compare the probabilities of relevant outcomes. The logistic regression analysis was conducted to determine the predictors of acute leaks. RESULTS: A total of 78 cases of SG leaks were collected with an incidence of 0.5% (78/15,721) from this registry (6 patients who had the primary SG in non-participating centers). After accumulating 260 cases in a bariatric surgery center, the leak rate decreased to a stably low value of under 1.17%. The significant differences presented in sex, waist circumference, and the proportion of hypoproteinemia and type 2 diabetes at baseline between patients with SG leak and the whole registry population ( P = 0.005, = 0.026, <0.001, and = 0.001, respectively). Moreover, 83.1% (59/71) of the leakage was near the esophagogastric junction region. Leakage healed in 64 (88.9%, 64/72) patients. The median healing time of acute and non-acute leaks was 5.93 months and 8.12 months, respectively. Acute leak (38/72, 52.8%) was the predominant type with a cumulative reoperation rate >50%, whereas the cumulative healing probability in the patients who required surgical treatment was significantly lower than those requring non-surgical treatment ( P = 0.013). Precise dissection in the His angle area was independently associated with a lower acute leak rate, whereas preservation ≥2 cm distance from the His angle area was an independent risk factor. CONCLUSIONS Male sex, elevated waist circumference, hypoproteinaemia, and type 2 diabetes are risk factors of gastric leaks after SG. Optimizing surgical techniques, including precise dissection of His angle area and preservation of smaller gastric fundus, should be suggested to prevent acute leaks.
Humans ; Male ; Retrospective Studies ; Diabetes Mellitus, Type 2/complications* ; Obesity, Morbid ; Anastomotic Leak/epidemiology* ; Gastrectomy/methods* ; Reoperation/methods* ; Registries ; Laparoscopy/methods* ; Treatment Outcome

Objective:To compare the effects of rosuvastatin and atorvastatin on coronary artery bypass grafting (CABG) on the incidence of acute kidney injury (AKI), and assess the independent risk factors of AKI.Methods:We retrospectively collected 550 patients aged 18 years or older who underwent CABG from May 2014 to May 2020. They were divided into the rosuvastatin group ( n=322), atorvastatin group ( n=125) and non statins group ( n=103) according to whether rosuvastatin or atorvastatin was routinely used before operation. Demographic data, clinical data before and after CABG and laboratory results were collected. Blood urea nitrogen (BUN), serum creatinine (Scr), creatinine clearance rate (Ccr) and incidence of postoperative AKI were compared among the three groups. Univariate analysis and binary logistic regression analysis were used to investigate the effect of statins on AKI in patients undergoing CABG. Results:Compared with preoperation, BUN showed no significant change ( P>0.05), while Scr was increased and Ccr was decreased significantly (both P<0.01); BUN in the rosuvastatin group was decreased significantly ( P<0.01), whereas Scr and Ccr had no significant change ( P>0.05); Scr in the atorvastatin group was increased significantly ( P<0.01), but there was no significant difference in BUN and Ccr ( P>0.05). BUN and Scr in the non statins group were increased significantly (both P<0.01), while Ccr was decreased significantly ( P<0.01). After operation, BUN and Scr in the rosuvastatin group and atorvastatin group were significantly lower than those in the non statins group (all P<0.01); Ccr was significantly higher than that in the non statins group ( P<0.01). BUN and Scr were not significantly different between the rosuvastatin and atorvastatin groups ( P>0.05), but Ccr was significantly higher than that in the atorvastatin group ( P< 0.05). There were significant differences in BUN, Scr and Ccr among the three groups ( χ2=48.925, 22.677 and 34.426, all P<0.01). The incidence of AKI among 550 patients was 15.1% (83/550), of which 9.6% (31/322) in the rosuvastatin group, 16.0% (20/125) in the atorvastatin group and 31.1% (32/103) in the non statins group. The incidence of AKI in the rosuvastatin and atorvastatin groups was significantly lower than that in the non statins group ( χ2=28.412, 7.282, P<0.01). Multivariate regression analysis showed that hypertension ( OR=3.555, 95% CI: 1.959-6.451, P<0.01), NHYAⅢ/Ⅳ ( OR=2.438, 95% CI: 1.187-5.008, P=0.015), and increased serum creatinine level ( OR=1.018, 95% CI: 1.003-1.032, P=0.016), and intraoperative cardiopulmonary bypass ( OR=2.936, 95% CI: 1.454-5.927, P=0.003) were independent risk factors for AKI after CABG, while preoperative conventional statin therapy ( OR=0.490, 95% CI: 0.247-0.974, P=0.042) and increased serum albumin level ( OR=0.920, 95% CI: 0.856-0.990, P=0.026) were protective factors for AKI after CABG. Conclusions:The incidence of AKI after CABG is common. Rosuvastatin or atorvastatin and increased preoperative serum albumin level can protect renal function and reduce the incidence of AKI, which are the protective factors of AKI after CABG. The hypertension, NHYAⅢ/Ⅳ, increased preoperative serum creatinine level and cardiopulmonary bypass are the independent risk factors of AKI after CABG.

Objective    To investigate the safety and effectiveness of the multi-artery graf tstrategy for coronary bypass (MICS-CABG) with small incision in the left chest, and to provide experience for the promotion of this technique. Methods    The clinical data of 64 patients with MICS-CABG in Department of Cardiac Surgery of Peking University Third Hospital from December 2015 to November 2019 were retrospectively analyzed. There were 54 males and 10 females, aged 36-77 (61.1±8.7) years. The left lateral thoracic incision (5-8 cm) was made through the 5th intercostal incision, and the operation was performed under off-pump CABG. With the help of the chest wall suspension device and the heart fixator, the proximal anastomosis of the ascending aorta, anastomosis of the target vessels of the left anterior descending (LAD), left circumflex (LCX) and right coronary artery (RCA) systems were completed. The number of grafts was 2-4 (2.3±0.5) including 2 grafts in 45 patients, 3 grafts in 17 patients and 4 grafts in 2 patients. Three patients were treated with percutaneous intervention (PCI) hybridization and 62 patients were treated with total artery bypass graft. Coronary angiography was performed within 7 days after the operation to evaluate the graft patency rate. The incidence of major adverse cardiac and cerebrovascular events (MACCE) was recorded in the follow-up. The MACCE rate was calculated by Kaplan-Meier method. Results    None of the patients was transferred to thoracotomy and no intra-aortic balloon counterpulsation (IABP) or extracorporeal membrane oxygenation (ECMO) was used during the operation.  Incision infection was in 1 patient and reoperation in 2 patients (all were postoperative hemorrhage). Within 30 days after surgery, MACCE occurred in 1 patient, including 1 patient of non-fatal myocardial infarction. The overall patency rate of angiography bypass was 96.2%, and the patency rate of anterior descending branch bypass was 98.2%. Follow-up was performed from 12 to 60 months (median follow-up time was 28 months). The loss rate was 7.8% (5/64). The incidence of MACCE was 84.9% (95%CI 79.5%-90.3%). Conclusion    The MICS-CABG can achieve completed re-vascularization and totally artery-CABG and the short-term and medium-term clinical results of the operation are good.

Objective:To investigate the diagnosis and treatment of emergency inguinal hernia.Methods:The retrospective cross-sectional study was conducted. The clinical data of 236 patients with emergency inguinal hernia who were admitted to the First Affiliated Hospital of Soochow University from January 2015 to May 2020 were collected. There were 194 males and 42 females, aged (69±30)years. Hospitalized patients received routine blood biochemistry test and imaging examinations for evaluation of characteristics of hernia contents and intestinal obstruction. Manual reduction and surgical treatment were selected according to the conditions of patients. Observation indicators: (1) treatment; (2) follow-up. Follow-up using outpatient examination and telephone interview was performed to detect hernia recurrence and late-onset mesh infection up to August 2020. Measurement data were described as M (range) or M ( P25, P75), and comparison between groups was analyzed using the Wilcoxon rank sum test. Count data were represented as absolute numbers, and comparison between groups was done using the chi-square test. Results:(1) Treatment: of the 236 patients, 106 cases had successful manual reduction, 124 cases underwent emergency operation, 6 cases refused surgery. ① For 106 cases with successful manual reduction (including 4 cases guided by B-ultrasonography), the manual reduction time was 5 minutes (2 minutes,7 minutes). Ninety-three of 106 patients underwent selective operation after manual reduction, including 89 cases with indirect hernia, 2 cases with direct hernia and 2 cases with compound hernia. The time to selective operation was 3 days(2 days,5 days) after manual reduction. Patients underwent mesh repair, of which the operation time, volume of intraoperative blood loss, time to postoperative first flatus, duration of postoperative hospital stay were 44 minutes (29 minutes, 66 minutes),10 mL(5 mL,20 mL), 1 day(1 day,2 days), 1 day(1 day,2 days), respectively. Eleven patients didn't undergo selective operation. Two patients with abdominal pain and fever after manual reduction were diagnosed with perforation of intestine by emergency surgical exploration, and then underwent partial intestinal resection combined with high ligation of hernial sac. ② There were 93 of 124 patients undergoing emergency operation with indirect hernia, 18 cases with femoral hernia, 6 cases with obturator hernia, 6 cases with compound hernia and 1 case with direct hernia. There were 54 of 124 patients undergoing open operation, including 21 cases with Bassini surgery, 18 cases with Lichtenstein surgery, 9 cases with Mc Vay surgery, 6 cases with high ligation of hernia sac. There were 70 patients undergoing laparoscopic operation, including 57 cases with laparoscopic transperitoneal preperitoneal hernia repair (TAPP), 10 cases with laparoscopic explora-tion + tissue repair and 3 cases with laparoscopic exploration + closure of inner inguinal ring. The operation time, volume of intraoperative blood loss, time to postoperative first flatus, cases with short-term postoperative complications were 60 minutes (50 minutes,76 minutes), 20 mL(14 mL,30 mL), 2 days(1 day,2 days), 15 cases for patients undergoing open surgery, respectively. The above indicators were 56 minutes (47 minutes,77 minutes), 20 mL(10 mL,25 mL), 2 days(1 day,2 days), 21 cases for patients under-going laparoscopic surgery. There was no significant difference in the above indicators between the two groups ( Z=?0.88, ?1.37, ?1.56, χ2=0.07, P>0.05). Cases with intraoperative placement of mesh and duration of hospital stay were 18 cases and 5 days(3 days,8 days) for patients undergoing open surgery, versus 57 cases and 3 days(2 days,5 days) for patients undergoing laparoscopic surgery, showing significant differences between the two groups ( χ2=29.50, Z=?4.32, P<0.05). (2) Follow-up: of 236 patients, 192 were followed up for 2?60 months, with a median follow-up time of 19 months. Seven patients had recurrence of hernia after emergency operation, including 3 with high ligation of the hernia sac, 2 with Bassini surgery, 1 with Lichtenstein surgery, and 1 with laparoscopic exploration + closure of inner inguinal ring. One patient with late-onset mesh infection after Lichtenstein surgery was improved after mesh removal. No long-term complications such as hernia recurrence or late-onset mesh infection occurred to the 184 patients. Conclusions:Emergency inguinal hernia had different state of illness, manual reduction is suitable for partial patients with incarceration. Surgery is the first choice, and the surgical procedure needs to be individually selected.

AIM: To assess the bioequivalence of pramipexole hydrochloride tablets with reference(Sifrol). METHODS: A randomized, open-label, 2-period crossover study was conducted in 48 healthy Chinese volunteers under fasted or fed conditions (24 volunteers for each condition). In each session, the subjects received a single oral dose of 0.25 mg test (T) or reference (R) formulation. Pramipexole concentrations in plasma were determined by a validated HPLC-MS/MS. Pharmacokinetic parameters were calculated using a non-compartmental model through Phoenix WinNonlin version 6.4. Other statistic analysis were analyzed by using software of SAS 9.3. RESULTS: The pharmacokinetic parameters of test drug and reference drug under fasted condition(n=20) were: C