OBJECTIVE:To determine the plasma concentration of Phencynonate hydrochloride(PCH)in dogs,and to calcu-late pharmacokinetic parameters. METHODS:6 Beagle dogs were given PCH tablets(2 mg and 4 mg)intragastrically. The blood samples were collected 5 min before medication and 0.17,0.25,0.5,0.75,1.0,1.25,1.5,2,3,4,6,8,10,12,14,16,18, 24 and 36 h after medication,2 ml each time. Using penehyclidine hydrochloride as internal standard,HPLC-MS/MS method was adopted to determine the plasma concentration of PCH. The medication plans were interchanged 2 weeks later. The pharmacokinetic parameters were calculated using DAS 2.0 software. RESULTS:The linear range of PCH was 0.1-15 ng/ml(r=0.999 6);the low-est limit of quantification was 0.1 ng/ml;the methodology recovery were 97.30%-103.20%;the extraction recovery were 52.30%-60.11%(RSD<11%,n=5). The main pharmacokinetic parameters of low and high doses were as follows as t1/2α of (0.678±0.525)and(0.405±0.465)h,tmax of(1.042±0.401)and(0.900±0.418)h,cmax of(14.063±6.29)and(31.580±9.673) mg/L,AUC0-36 h of(48.186±14.776)and(79.269±34.649)mg·h/L. CONCLUSIONS:The method is simple,sensitive and speci-fic,and can be used for pharmacokinetic study of PCH in dogs.

Objective To optimize the preparation of liensinine HP-β-CD inclusion compound; To investigate its dissolution performance in vitro. Methods The inclusion compound of liensinine was prepared by using saturated water solution method; the cumulative dissolution (45 min) was used as an indicator and Box-Behnken design was adopted to evaluate the influence of feed ratio, mixing time and inclusion temperature on preparation process. Results were analyzed by multiple linear and binomial fitting; response surface methodology was used to screen the optimal inclusion process; predictive parsing and verification experiment were conducted; SEM, DSC, IR, and XRD were applied for the structural characterization of inclusion compound of liensinine. Results The optimal preparation process was: HP-β-CD was 4.5 times the amount of liensinine feeding amount; mixing time was 3.7 h; inclusion temperature was 52 ℃. HP-β-CD inclusion compound of liensinine formed. Conclusion Optimal inclusion process is stable and feasible, which can significantly improve the dissolution of liensinine and increase its bioavailability.

Objective To explore the microsurgical technique and clinical value of endoscope-assisted microsurgery via the transsphe-noidal approach to the clivus. Methods According to the results of microanatomy of endoscope-assisted via the transsphenoidal approach to sellar and clival area, the clinical data of 12 cases (8 with invasive pituitary adenoma, 3 with chordoma, 1 with chondroma) treated by transsphenoidal approach were studied retrospectively. All cases were followed-up 3 months to 6 years after operation. Results The tumor was totally removed in 8 patients, removed subtotally in 3 patients, and removed partially in 1 patient. 6 patients occurred transient diabetes insipidus, 2 patients with transient cerebrospinal rhinorrhoea. There were no death or intracranial infection. Postoperative follow-up was performed for 3 months to 6 years, No recurrence occurred except for enlargement of 1 chordoma. Conclusion Transsphenoidal approach satisfactorily and quickly reaches and helps remove the larger tumors in sellar and clival area without severe complication. It has the advantages of low incidence of surgical complication and high total removal rate. Endoscope-assisted may be helpful for this approach.

Objective To further research the urinary monitoring of the maternal thyroid functional status ,the levels of urine thyroid hormones were analyzed during pregnancy .Methods This study recruited 30 cases of healthy pregnant women at 9-12 ges-tational weeks .Their random urine specimens were collected every four weeks until delivery .The concentrations of urine thyrotro-pin(uTSH) ,urine free triiodothyronine(uFT3) and urine free tetraiodothyronine(uFT4) were detected by electrochemical lumines-cence immunoassay(ECLIA) .The urine retinol binding protein(uRBP) was detected by enzyme immunoassay (EIA) .After correc-ted by uRBP ,the statistical analysis was done to analyze the variation of the ratio of uTSH and uRBP (uTSH/uRBP) ,the ratio of uFT3 and uRBP(uFT3/uRBP)and the ratio of uFT4 and uRBP(uFT4/uRBP)during pregnancy .Results The median levels of u-rine thyroid hormone parameters were obtained from the healthy pregnant women every four weeks and were compared among dif-ferent stages .The difference of uFT3/uRBP and uFT4/uRBP was statistically significant (F= 6 .222 ,P< 0 .05 ;F= 5 .078 ,P<0 .05) ,and the levels of them varied linearity during pregnancy (F=27 .480 ,P<0 .05 ;F=23 .959 ,P<0 .05) .The difference of uT-SH/uRBP had no statistical significance(F=2 .731 ,P=0 .054) .Conclusion After corrected by uRBP ,the levels of uFT3 and uFT4 of healthy pregnant women decreased linearity among different gestational stages ,and the levels of uTSH had no noticeable change .

BACKGROUND:It is presumed that urinary trypsin inhibitor could have protective effects on local and systemic tissues and could inhibit osteoclast proliferation and activation under long-term chronic inflammation conditions and in ischemic and anoxic environment which was induced by prosthetic wear. OBJECTIVE:To investigate the inhibitory effect of ulinastatin on receptor activator for nuclear factor-κb ligand-induced differentiation, proliferation and osteoclastogenesis of RAW264.7 cells and its effects on matrix metal oproteinase-2, matrix metal oproteinase-9 expression level and activity. METHODS:Mouse monocyte/macrophage cellline RAW264.7 was treated with different concentrations of urinary trypsin inhibitor (0, 500, 5 000 U/mL) for 24, 48 and 72 hours. Experiments were divided into four groups:the blank group (RAW264.7 cells), receptor activator for nuclear factor-κb ligand-induced group (0 U/mL ulinastatin), 500 U/mL ulinastatin group and 5 000 U/mL ulinastatin group. RESULTS AND CONCLUSION:(1) MTT results indicated that there was no significant difference on the proliferation of RAW264.7 cells treated with urinary trypsin inhibitor at 0-5 000 U/mL (P>0.05) (2) Tartrate-resistant acid phosphatase staining results revealed that compared with receptor activator for nuclear factor-κb ligand-induced group, the number of tartrate-resistant acid phosphatase-positive cells was significantly less in the ulinastatin group (P<0.05), showing a time-dose dependent manner. (3) Immunohistochemisical results found that compared with receptor activator for nuclear factor-κb ligand-induced group, the percentage of matrix metal oproteinase-9-positive cells was apparently lower in the ulinastatin group. (4) Western blot assay results demonstrated that matrix metal oproteinase-9 expression was low in the RAW264.7 cells alone. At 48 hours after addition of receptor activator for nuclear factor-κb ligand, matrix metal oproteinase-9 protein expression was large. At 72 hours after culture in the 5 000 U/mL ulinastatin group, matrix metal oproteinase-9 protein expression was evidently reduced. (5) Gelatin zymography results showed that compared with the receptor activator for nuclear factor-κb ligand-induced group, matrix metal oproteinase-9 expression was significantly lower in the 5 000 U/mL ulinastatin group (P<0.05). Results suggested that urinary trypsin inhibitor inhibited receptor activator for nuclear factor-κb ligand-induced osteoclastogenesis and diminished matrix metal oproteinase-9 expression and activity.

Objective:To explore the effect of sarpogrelate on platelet function in patients at the bridging stage before coronary artery bypass grafting (CABG).
Methods: A total of 40 consecutive patients with peripheral artery stent and scheduled for CABG in our hospital from 2011-05 to 2013-04 were enrolled in this study. The patients were randomly divided into 2 groups, Low molecular weight heparin (LMWH) alone group, n=19 and Sarpogrelate+LMWH group, n=21. The medications started at 5-7 days before CABG and stopped at 24 h before CABG. The platelet inhibition rates (platelet aggregation induced by collagen+ serotonin) were examined and compared between 2 groups at the baseline (before randomization), 24h and 1h before CABG respectively.
Results: The platelet inhibition rates were similar between 2 groups at the baseline (87.33 ± 6.82) % vs (86.11 ± 6.87) %, P=0.577 and 1h before CABG (62.60 ± 12.39) % vs (56.19 ± 14.99) %, P=0.148. At 24h before CABG, the platelet inhibition rate in Sarpogrelate+LMWH group was higher than that in LMWH alone group (83.87 ± 8.99)%vs (63.13 ± 10.88)%, P<0.001. Compared with the baseline, the falling range of platelet inhibition was lower in Sarpogrelate+ LMWH group at 24h before CABG, (3.46 ± 6.18) % vs (22.98 ± 9.43) %, P<0.001 and the falling range was similar between 2 groups at 1h before CABG (24.73 ± 14.19)%vs (29.92 ± 14.28)%, P=0.257.
Conclusion: Sarpogrelate + LMWH may result better platelet inhibition rate with quicker recovery of platelet function upon the medication stopping, which might be a feasible management in patients at the bridging stage before CABG.

BACKGROUND:Previous studies have indicated that ulinastatin can inhibit RANKL-induced osteoclastogenesis on RAW264.7 cells and also lower matrix metal oproteinase-9 expression and activity. However, it remains be unclear whether ulinastatin has the intervention effect on polymethyl methacrylate (PMMA)-induced MC3T3-E1 mouse preosteoblast apoptosis or not. ＜br> OBJECTIVE:To explore the intervention role of ulinastatin on the PMMA-induced MC3T3-E1 mouse preosteoblast apoptosis and its effects on type I col agen, osteocalcin, matrix metal oproteinase-2 mRNA expression. ＜br> METHODS:MC3T3-E1 mouse preosteoblasts at passages 6 and 7 were divided into four groups:blank group (only cultured MC3T3-E1 mouse preosteoblast), PMMA-induced group (MC3T3-E1 mouse preosteoblast+1 g/L PMMA bone cement suspension), low dose ulinastatin group (MC3T3-E1 mouse preosteoblast+1 g/L PMMA bone cement suspension+500 U/mL ulinastatin) and high dose ulinastatin group (MC3T3-E1 mouse preosteoblast+1 g/L PMMA bone cement suspension+5 000 U/mL ulinastatin). MTT method was adopted to detect the proliferation activity of proliferative activity of MC3T3-E1 mouse preosteoblast;alizarin red staining method was used to observe mineralization nodules of MC3T3-E1 mouse preosteoblast among different groups;the change of apoptosis rate for MC3T3-E1 cells was detected by flow cytometry analysis;semi-quantitative RT-PCR was taken to analyze type I col agen, osteocalcin, matrix metal oproteinase-2 mRNA expression level in MC3T3-E1 mouse preosteoblasts among different groups. ＜br> RESULTS AND CONCLUSION:Compared with the blank group, PMMA significantly inhibited the proliferation activity of MC3T3-E1 mouse preosteoblast (P＜0.05), and however significantly promoted cells apoptosis (P＜0.05). After addition of different concentrations of ulinastatin (500, 5 000 U/mL), the proliferation activity of MC3T3-E1 mouse preosteoblasts significantly raised (P＜0.05), and cells apoptosis rate significantly decreased (P＜0.05), showing the dose and time-dependent relation. Type I col agen and osteocalcin mRNA expression levels both significantly decreased after co-culture in PMMA group compared with the blank group (P＜0.05), matrix metal oproteinase-2 mRNA expression level, however, significantly increased (P＜0.05). After intervention with 5000 U/mL ulinastatin, type I col agen and osteocalcin mRNA expression levels both significantly increased, while matrix metal oproteinase-2 mRNA expression level significantly decreased (P＜0.05). PMMA group showed no obvious mineralization nodules. Yet, mineralization nodules were formed in the blank group, high and low dose ulinastatin groups. These results indicate that ulinastatin could have the inhibitory effect on the PMMA-induced MC3T3-E1 mouse preosteoblast apoptosis, and it could promote type I col agen and osteocalcin mRNA expression and yet suppress matrix metal oproteinase-2 mRNA expression.

Background:Pulmonary arterial hypertension (PH) is a progressive disease with limited therapeutic options,ultimately leading to right heart failure and death.Recent findings indicate the role of the Warburg effect (aerobic glycolysis) in the development of PH.However,the effect of the glycolysis inhibitor 3-bromopyruvate (3-BrPA) on the pathogenesis of PH has not been well investigated.This study aimed to determine whether 3-BrPA inhibits PH and its possible mechanism.Methods:PH was induced in adult Sprague-Dawley rats by a single intraperitoneal injection of monocrotaline (MCT).3-BrPA,or phosphate-buffered saline (PBS) was administered via intraperitoneal injection every other day from the first day of MCT-injection to 4 weeks of follow-up,and indices such as right ventricular systolic pressure (RVSP),right ventricular hypertrophy index (RVHI),pulmonary arteriolar remodeling indicated by percent media thickness (％ MT),lactate levels and glucose consumption,were evaluated.Pulmonary arteriolar remodeling and right ventricular hypertrophy were observed in hematoxylin-eosin-stained lung sections.Western blotting,immunohistochemistry,and/or immunofluorescence analyses were used to measure the expression of relevant proteins.A cytochrome C release apoptosis assay and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining were used to measure cell apoptosis.Results:MCT-induced PH showed a significant increase in glucose consumption (0 vs.4 weeks:0.87 ± 0.23 vs.2.94 ± 0.47,P =0.0042) and lactate production (0 vs.4 weeks:4.19 ± 0.34 vs.8.06 ± 0.67,P =0.0004).Treatment with 3-BrPA resulted in a concomitant reduction in glucose consumption (1.10 ± 0.35 vs.3.25 ± 0.47,P =0.0063),lactate production (5.09 ± 0.55 vs.8.06 ± 0.67,P =0.0065),MCT-induced increase in RVSP (39.70 ± 2.94 vs.58.85 ± 2.32,P =0.0004),pulmonary vascular remodeling (％ MT,43.45％±1.41％ vs.63.66％±1.78％,P＜0.0001),and right ventricular hypertrophy (RVHI,38.57％ ± 2.69％ vs.62.61％ ± 1.57％,P ＜ 0.0001) when compared with those of the PBS-treated group.3-BrPA,a hexokinase 2 inhibitor,exerted its beneficial effect on PH by decreasing aerobic glycolysis and was also associated with inhibiting the expression of glucose transporter protein-1,inducing apoptosis,and suppressing inflammation.Conclusions:3-BrPA might have a potential beneficial effect on the PH treatment.

Objective:To evaluate the clinical efficiency and prognostic factors of autologous peripheral blood stem cell trans-plantation (APBSCT) in 30 cases of multiple myeloma (MM). Methods:Two of the 30 patients received the second treatment of APB-SCT because of relapse after the first treatment. Thus, a total of 32 case-times of APBSCT were studied. Combination chemotherapy was inducted regularly before APBSCT (11 patients used bortezomib as an induction drug), and chemotherapy combined with the G-CSF regimen was used to mobilize peripheral blood stem cells. Preconditioning was based on melphalan. Results:Mononuclear cells in harvest were 6.41 × 108/kg, and CD34+cells in harvest were 4.75 × 106/kg. The median times of neutrophil and platelet engraftment were 9.5 and 11 d, respectively. The complete remission (CR) and very good partial remission (VGPR) rates were 37.5%and 34.4%af-ter APBSCT, respectively. The median overall survival (OS) was 67.27 months in all patients, and the median progression-free survival (PFS) was 29.77 months. The median PFS rates were 29 and 20 months in the patients who achieved CR and PR, respectively, and the median PFS was not observed in the patients who achieved VGPR. Statistical differences in PFS were detected between the CR+VGPR and PR groups (P=0.025). The CR rates were 63.6%and 23.8%in the bortezomib (bortezomib-based chemotherapy) and non-bortezo-mib groups (P=0.034), respectively. The median OS and PFS were not obtained in the bortezomib group, whereas the median PFS was 22 months in the non-bortezomib group (P=0.045). Conclusion: MM patients treated with bortezomib-based chemotherapy followed by APBSCT had prolonged PFS. APBSCT can improve the response and survival of MM patients.

Objective:To systematically evaluate the effect of decision aid tools for advance care planning (ACP) in patients with cancer.Methods:Randomized controlled trials about the effect of decision aid tools for ACP in patients with cancer were retrieved from Embase, PubMed, CINAHL, the Cochrane Library, PsycINFO, Chinese Biomedical Literature Database, VIP, China National Knowledge Internet and Wanfang Data. The retrieval time was from inception to February 23, 2022. Literature screening, quality evaluation and data consolidation were carried out independently by two researchers. Then, RevMan 5.3 software was used for Meta analysis.Results:A total of 13 researches were included, involving 2 151 cancer patients. Meta-analysis showed that the signing of advance directives ( OR=1.81, 95% CI 1.22-2.69, Z=2.95, P<0.01) and knowledge scores related to ACP( MD=0.58, 95% CI 0.35-0.81, Z=4.90, P<0.01) in experimental group was higher than that in control group, but receiving cardiopulmonary resuscitation treatment before death ( MD=0.33, 95% CI 0.21-0.53, Z=4.64, P<0.01) and the level of decision confliction ( MD=-3.69, 95% CI-6.43--0.95, Z=2.64, P<0.01) in experimental group was lower than those in control group, and the differences were statistically significant. Conclusions:Existing evidence shows that decision aid tools can improve cancer patients′ awareness of ACP, help patients to join in ACP discussions and sign advanced directives, reduce patients' preference for cardiopulmonary resuscitation treatment before death and reduce decision-making conflicts.