Objective To evaluate the safety and efficacy of intravenous dalteparin compared with unfractionated heparin in patients underwent coronary angiogram with or without percutaneous coronary intervention(PCI).Methods A total of 87 patients who underwent one-stage elective PCI were randomized to intravenously unfractionated heparin(UFH,10 000 IU) group or dalteparin group.The dalteparin group was further divided into low dose dalteparin(5 000 IU) group or high dose dalteparin(10 000 IU) group according to whether the patients underwent PCI procedure.Blood samples for anti-Xa levels and ACTs were assayed at baseline and at 10 min,20 min,1 hour,2 hours and 4 hours after all dalteparin or UFH doses were administered.Results Baseline characteristics were similar across the three groups.In all groups,ACTs reached the maximum at 10 min after the total doses given,with the highest value in the UFH group and lowest in the low dose dalteparin group(524.68 ?278.32 s vs 191.26?39.35 s vs 304.20?42.71 s,P0.05).Conclusion Both 5 000 IU and 10 000 IU dalteparin injected through sheath before PCI or coronary angiography could reach an anti-Xa levels similar to that achieved by 10 000 IU UFH.

OBJECTIVETo determine the O/W partition coefficient of geniposide in fructus gardeniae extract and investigate the absortion kinetics of geniposide in whole small intestine and different intestinal segments of rats.

METHODThe shake-flask method was employed to determine the O/W partition coefficient of geniposide; an in situ intestinal perfusion model was employed to investigate the absorptive kinetics of geniposide.

RESULTThe partition coefficient (P) of geniposide was 0.1077, logP was -0.9678; the absorptive rate constants (K) of geniposide at the concentration of 0.078, 0.311, 0.780 g x L(-1) were (0.130 +/- 0.007), (0.056 +/- 0.003), (0.031 +/- 0.006) h, respectively. The K of geniposide were (0.019 +/- 0.003), (0.015 +/- 0.002), (0.012 +/- 0.002) h at duodenum, jejunum, ileum, respectively.

CONCLUSIONAccording to the P and the logP, it could be indicated that the absorption of geniposide at small intestine was poor absorption; The absorption rate was increased with the decrease of the extract concentration; Their absorption was first-order process besides the passive diffusion mechanism, and facilitated diffusion and active transport may also take part in the transport process. Geniposide was absorbed at all smallintestinal segments of rats, but the duodenal absorption ratewas higher more than other section.

Animals ; Drugs, Chinese Herbal ; chemistry ; pharmacokinetics ; Gardenia ; chemistry ; Intestinal Absorption ; drug effects ; Intestines ; drug effects ; physiology ; Iridoids ; chemistry ; pharmacokinetics ; Kinetics ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Objective:To explore the relationship among the supratrochlear and supraorbital neurovascular bundles and the corrugator muscle, in order to provide anatomical basis for eyebrow operations.Methods:From July to October 2019, the upper eyelids and forehead of 10 adult skull specimens (20 sides) were dissected layer by layer in the anatomy laboratory of Weifang Medical College. The line of bilateral inner canthus was taken as the X-axis and the facial midline as the Y-axis to establish the coordinate system. The coordinate parameters of supratrochlear nerve, supratrochlear artery, medial branch of supraorbital nerve, lateral branch of supraorbital nerve and supraorbital artery were measured to obtain the range of its trajectory, and their level and their adjacent relationship with the corrugator muscle were observed.Results:The corrugator muscle started from the upper part of the nasal process of the frontal bone near the medial margin of the orbit and was (4.32±0.98) mm from the midline. The base of the corrugator muscle start was (9.91±1.41) mm wide. The corrugator muscle run obliquely upward, through orbicularis oculi muscle and frontal muscle, and stopped at subcutaneous of the outer 1/3 of eyebrow. The trapezoid area was composed of the line of 15 mm above the inner canthus line, (16.58±1.70) mm and (16.17±1.42) mm from the facial midline as the lower base and the line of 30 mm above the inner canthus line, (13.74±1.54) mm and (14.21±2.42) mm from the facial midline, which was the dangerous area for the supratrochlear neurovascular bundles walking in corrugator muscle. The trapezoid area was composed of the line of 22.5 mm above the inner canthus line, (26.03±1.55) mm and (28.11±2.46) mm from the facial midline as the lower base and the line of 40 mm above the inner canthus line, (31.23±3.19) mm and (38.20±2.94) mm from the facial midline, which was the dangerous area for the supraorbital neurovascular bundles.Conclusions:Familiar with the relationship among the supratrochlear and supraorbital neurovascular bundle and the corrugator muscle can avoid dangerous areas and reduce superficial and deep neurovascular injury during operation.

OBJECTIVETo observe the influence of ingredients in Xingnaojing,such as moschus, borneol and radix curcumae on intestine absorption kinetics of gardenia extract.

METHODAn in situ intestinal perfusion model of rats was employed to investigate the absorption of geniposide in gardenia extract.

RESULTWhile gardenia extract was administered solely, the absorptive rate constant (K) of geniposide was (0.055 +/- 0.006) h(-1); But while the extract was co-administered with radix curcumae,moschus and borneol, the K were (0.060 +/- 0.001), (0.066 +/- 0.008), (0.072 +/- 0.010) h(-1), respectively. The K was (0.076 +/- 0.011) h(-1) while the extract in total formulation for Xingnaojing.

CONCLUSIONThe K, while the extract is co-administered with borneol or total formulation is significantly higher than solely used. Borneol and complex prescription can significantly increase the intestinal absorption of geniposide in gardenia extract.

Animals ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; pharmacology ; Gardenia ; chemistry ; Intestinal Absorption ; drug effects ; Iridoids ; pharmacokinetics ; Linear Models ; Male ; Plant Extracts ; pharmacokinetics ; Rats ; Rats, Wistar

Objective To explore the risk factors that may cause recurrent retinal detachment in rhegmatogenous retinal detachment(RRD)patients after surgery.Methods A total of 403 patients(403 eyes)with RRD diagnosed in the Department of Ophthalmology of the First Affiliated Hospital of Soochow University from October 2020 to April 2022 were included in this study.Among them,35 patients underwent the scleral buckling,79 patients underwent the pars plana vit-rectomy(PPV)+intravitreal gas tamponade,222 patients underwent the PPV+intravitreal silicone oil tamponade,and 67 patients underwent the PPV+vitreous silicone oil tamponade+silicone oil removal.The postoperative follow-up lasted for at least 3 months.Risk factors affecting one-time retinal reattachment after RRD surgery were analyzed by univariate and multivariate Logistic analyses,and Logistic regression was applied to construct a risk prediction model.Results Among the 403 eyes with RRD,369 eyes had retinal reattachment on the first try,and 34 eyes did not,with a one-time reat-tachment rate of 91.6％.The univariate analysis showed that the differences in axial length(AL),surgical approach,loca-tion of the tear,and size of the tear between patients with one-time retinal reattachment and those without reattachment were statistically significant(all P＜0.05).From the regression equation,it was found that the risk of non-reattachment af-ter RRD surgery of patients with an AL ≥ 26 mm was 4.248 times higher than those with an AL＜26 mm(P＜0.05).The multivariate Logistic regression analysis showed that AL,location of the tear,size of the tear,and surgical approach were risk factors for non-reattachment after RRD surgery(all P＜0.05).The Hosmer-Lemeshow test yielded P=0.165.The re-sults of the receiver operating characteristic curve analysis showed that the area under the curve to predict whether retinal re-detachment occurs after RRD surgery was 0.892(95％CI:0.832-0.953),and the sensitivity and specificity were 79.4％and 87.3％,respectively(P＜0.05).Conclusion AL is an independent risk factor for retinal re-detachment after RRD surgery.The prediction model constructed based on AL,location of the tear,size of the tear,and the surgical method can accurately predict whether retinal detachment will occur after RRD surgery.

Objective:To investigate the efficacy of continuous intravenous injection of hyaluronidase (HAase) combined with urokinase (UK) in the treatment of ischemia of hyaluronic acid (HA) arterial embolized skin flap.Methods:(1)Establish an animal model of superficial abdominal artery embolization with HA: 24 SD rats were used to make a square island flap (2 cm×2 cm, the width of the pedicle is 2 mm) on the left and right sides of the abdominal white line with superficial epigastric artery as feeding artery. The left and right flaps of rats were used as experimental group and control group. After the preparation of the experimental skin flap, HA 10 μl was injected into the superficial abdominal artery, while the self-control flap was only made and the vessels were peeled off without embolization.(2)The rats were randomly divided into A, B, C and D groups by drawing lots with 6 rats in each group, After the successful establishment of embolic animal model of 45 min, HAase(2 000 IU/kg)+ UK(50 000 IU/kg), HAase(2 000 IU/kg), UK(50 000 IU/kg) and normal saline were continuously infused through caudal vein with microinjection pump. The volume of solution in each group was 6 ml in 12 minutes. The general condition of rats and the skin color, edema, congestion and skin necrosis in the operation area of rats were observed, which were photographed and compared immediately, and at 3 days, 5 days and 7 days after embolization. The images were analyzed by Photoshop software, and the percentage of survival area of the flap after operation 7 days, was measured by pixel method. The percentage of survival area was compared by single factor analysis of variance (ANOVA) and head-to-head comparison by LSD- t test. Results:Immediately after operation, all the flaps in the four groups were pale and there was no obvious swelling. All the flaps showed different degrees of swelling within 3 days after operation, and the swelling basically disappeared within 3-5 days after operation, and gradually changed from dark red ecchymosis to dark purple or black. Seven days after operation, the necrotic area flap gradually hardened and its boundary was obvious. The skin flaps of the 4 groups showed different degrees of necrosis. The postoperative reaction of the flap was the slightest in group A, the performance of group B and C was similar, which were both between group A and group D, and there was the heaviest postoperative reaction in group D. At 7 days after operation, the percentage of survival area of flaps in groups A, B, C and D was 90.30%±5.95%, 52.63%±6.90%, 51.14%±5.95% and 7.70%±2.18%, respectively. The percentage of survival area of skin flap in group A was significantly higher than that in groups B, C and D (analysis of ANOVA: P<0.01; LSD- t test: P<0.01). Conclusions:Continuous intravenous infusion of HAase combined with UK can effectively alleviate the flap ischemia caused by HA artery embolism, increase tissue perfusion and increase the survival area of the flap.

Objective:To investigate the efficacy of continuous intravenous injection of hyaluronidase (HAase) combined with urokinase (UK) in the treatment of ischemia of hyaluronic acid (HA) arterial embolized skin flap.Methods:(1)Establish an animal model of superficial abdominal artery embolization with HA: 24 SD rats were used to make a square island flap (2 cm×2 cm, the width of the pedicle is 2 mm) on the left and right sides of the abdominal white line with superficial epigastric artery as feeding artery. The left and right flaps of rats were used as experimental group and control group. After the preparation of the experimental skin flap, HA 10 μl was injected into the superficial abdominal artery, while the self-control flap was only made and the vessels were peeled off without embolization.(2)The rats were randomly divided into A, B, C and D groups by drawing lots with 6 rats in each group, After the successful establishment of embolic animal model of 45 min, HAase(2 000 IU/kg)+ UK(50 000 IU/kg), HAase(2 000 IU/kg), UK(50 000 IU/kg) and normal saline were continuously infused through caudal vein with microinjection pump. The volume of solution in each group was 6 ml in 12 minutes. The general condition of rats and the skin color, edema, congestion and skin necrosis in the operation area of rats were observed, which were photographed and compared immediately, and at 3 days, 5 days and 7 days after embolization. The images were analyzed by Photoshop software, and the percentage of survival area of the flap after operation 7 days, was measured by pixel method. The percentage of survival area was compared by single factor analysis of variance (ANOVA) and head-to-head comparison by LSD- t test. Results:Immediately after operation, all the flaps in the four groups were pale and there was no obvious swelling. All the flaps showed different degrees of swelling within 3 days after operation, and the swelling basically disappeared within 3-5 days after operation, and gradually changed from dark red ecchymosis to dark purple or black. Seven days after operation, the necrotic area flap gradually hardened and its boundary was obvious. The skin flaps of the 4 groups showed different degrees of necrosis. The postoperative reaction of the flap was the slightest in group A, the performance of group B and C was similar, which were both between group A and group D, and there was the heaviest postoperative reaction in group D. At 7 days after operation, the percentage of survival area of flaps in groups A, B, C and D was 90.30%±5.95%, 52.63%±6.90%, 51.14%±5.95% and 7.70%±2.18%, respectively. The percentage of survival area of skin flap in group A was significantly higher than that in groups B, C and D (analysis of ANOVA: P<0.01; LSD- t test: P<0.01). Conclusions:Continuous intravenous infusion of HAase combined with UK can effectively alleviate the flap ischemia caused by HA artery embolism, increase tissue perfusion and increase the survival area of the flap.

This paper aims to explore the main points of diagnosis， treatment and misdiagnosis of conversion disorder characterized by paroxysmal abdominal pain. The general hospitals had a high misdiagnose rate and no effective symptomatic treatment for conversion disorder patients with physical discomfort as main symptoms， which leading to heavy physical and mental burden of patients and waste of medical resources， so this paper retrospectively analyzed the etiology， diagnostic process， treatment and therapeutic effect of a case of conversion disorder with paroxysmal abdominal pain as the main symptom. Case analysis showed that the physical discomfort as chief complain of conversion disorder patients affected the rate of early correct diagnosis and treatment， so clinicians' ability of diagnosis and differential diagnosis of conversion disorder needs to be strengthened. At the same time， cognitive behavioral therapy （CBT） is effective in the clinical treatment and recurrence prevention of conversion disorder.

Objective:To evaluate the cost effectiveness of primary prophylaxis (PP) with pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF), PP with recombinant human granulocyte colony stimulating factor (rhG-CSF) and no prophylaxis in women with early-stage breast cancer in China.Methods:Two phase Markov models were constructed for a hypothetical cohort of patients aged 45 with stage Ⅱ breast cancer. The first phase modelled costs and outcomes of 4 cycles docetaxel combined with cyclophosphamide [TC×4, febrile neutropenia (FN) risk>20%] chemotherapy, which assumptions based on literature reviews, including FN rates [base-case (deterministic sensitivity analysis range), 0.29 (0.24-0.35)] and related events [FN case-fatality, 3.4 (2.7-4.1)]. Second phase modelled the long term survival which was link with the relative dose intensity (RDI) [mortality hazard ratio ( HR) of RDI < 85% vs ≥85%, 1.45 (1.00-2.32)]. Clinical effectiveness, therapeutic costs, and economic utilities were estimated from peer-reviewed publications and expert opinions in case of unavailability of published evidences. Results:Compared to rhG-CSF PP and no prophylaxis, the cost of PEG-rhG-CSF PP increased to 5 208.19 RMB and 5 222.73 RMB, respectively. The quality-adjusted life-years (QALYs) enhanced to 0.066 and 0.297, respectively. Accordingly, the incremental cost effectiveness ratios (ICERs) are 79 146.3 RMB and 17 558.77 RMB per QALY, which were both below the willingness to pay (WTP) threshold of three times GDP per capita (18, 000 RMB) recommended by the WHO. Sensitivity analysis suggested that the more clinically effective the primary prophylaxis with PEG-rhG-CSF is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. And the lower the mortality HR of RDI<85% vs ≥85% is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. Conclusion:Although the cost of PP PEG-rhG-CSF is higher, considering the additional benefits, the administrating of PP PEG-rhG-CSF is likely to be a cost-effective alternative to PP rhG-CSF and no prophylaxis in patients with early stage breast cancer whose FN risks are more than 20% in China.

Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.