Changes of intestinal wall barrier function and its correlation with susceptibility to infection in patients with cirrhotic portal hypertension / 中华肝脏病杂志

Objective: To investigate the changes of intestinal wall barrier function and its correlation with infection occurrence in patients with cirrhotic portal hypertension. Methods: 263 patients with cirrhotic portal hypertension were split into: the clinically evident portal hypertension (CEPH) combined with infection group (n = 74); CEPH group (n = 104); and Non-CEPH group (n = 85). Among them, 20 CEPH patients and 12 non-CEPH patients in non-infection status were subjected to sigmoidoscopy. Immunohistochemical staining was used to detect the expression of trigger receptor-1 (TREM-1), CD68, CD14, the inducible nitric oxide synthase molecule, and Escherichia coli (E.coli) in the medullary cells of the colon mucosa. An enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of soluble myeloid cell trigger receptor-1 (sTREM-1), soluble leukocyte differentiation antigen-14 subtype (sCD14-ST) and intestinal wall permeability index enteric fatty acid binding protein (I-FABP). Fisher's exact probability method, one-way ANOVA, Kruskal-Wallis-H test, Bonferroni method, and Spearman correlation analysis were used for statistical analysis. Results: The serum sTREM-1 and I-FABP levels were higher in CEPH patients than those of non-CEPH patients in the non-infectious state (P < 0.05), but the difference in blood sCD14-ST levels was not statistically significant (P > 0.05). Serum levels of sTREM-1, sCD14-ST, and I-FABP in infected patients were higher than those in patients without a concurrent infection (P < 0.05). Serum sCD14-ST levels were positively correlated with serum sTREM-1, C-reactive protein (CRP), and procalcitonin (PCT), and sTREM-1 levels were also positively correlated with CRP and PCT (r > 0.5, P < 0.001). The rates of CD68, inducible nitric oxide synthase, CD14-positive cells, and E.coli-positive glands were higher in the intestinal mucosa of the CEPH group than those of the control group (P < 0.05). Spearman's correlation analysis showed that the rate of E.coli-positive glands in CEPH patients was positively correlated with the expression of molecular markers CD68 and CD14 in the lamina propria macrophages. Conclusion: Patients with cirrhotic portal hypertension have increased intestinal permeability and inflammatory cells, accompanied by bacterial translocation. Serum sCD14-ST and sTREM-1 can be used as indicators to predict and evaluate the occurrence of infection in patients with cirrhotic portal hypertension.

Visual Detection of Vibrio parahaemolyticus using Combined CRISPR/Cas12a and Recombinase Polymerase Amplification / 生物医学与环境科学（英文）

Objective@#To establish an ultra-sensitive, ultra-fast, visible detection method for Vibrio parahaemolyticus (VP) .@*Methods@#We established a new method for detecting the tdh and trh genes of VP using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 12a (CRISPR/Cas12a) combined with recombinase polymerase amplification and visual detection (CRISPR/Cas12a-VD).@*Results@#CRISPR/Cas12a-VD accurately detected target DNA at concentrations as low as 10 -18 M (single molecule detection) within 30 min without cross-reactivity against other bacteria. When detecting pure cultures of VP, the consistency of results reached 100% compared with real-time PCR. The method accurately analysed pure cultures and spiked shrimp samples at concentrations as low as 10 2 CFU/g.@*Conclusion@#The novel CRISPR/Cas12a-VD method for detecting VP performed better than traditional detection methods, such as real-time PCR, and has great potential for preventing the spread of pathogens.

Nicotine exacerbates tacrolimus-induced renal injury by programmed cell death

Background/Aims@#Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal injury. @*Methods@#Sprague-Dawley rats were treated daily with NIC, TAC, or both drugs for 4 weeks. The influence of NIC on TAC-caused renal injury was examined via renal function, histopathology, oxidative stress, mitochondria, endoplasmic reticulum (ER) stress, and programmed cell death (apoptosis and autophagy). @*Results@#Both NIC and TAC significantly impaired renal function and histopathology, while combined NIC and TAC treatment aggravated these parameters beyond the effects of either alone. Increased oxidative stress, ER stress, mitochondrial dysfunction, proinf lammatory and profibrotic cytokine expressions, and programmed cell death from either NIC or TAC were also aggravated by the two combined. @*Conclusions@#Our observations suggest that NIC exacerbates chronic TAC nephrotoxicity, implying that smoking cessation may be beneficial for transplant smokers taking TAC.

L-carnitine treatment attenuates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction

Background/Aims@#Accumulating evidence indicates that L-carnitine (LC) protects against multiorgan damage through its antioxidant properties and preservation of the mitochondria. Little information is available about the effects of LC on renal fibrosis. This study examined whether LC treatment would provide renoprotection in a rat model of unilateral ureteral obstruction (UUO) and in vitro. @*Methods@#Sprague-Dawley rats that underwent UUO were treated daily with LC for 7 or 14 days. The influence of LC on renal injury caused by UUO was evaluated by histopathology, and analysis of gene expression, oxidative stress, mitochondrial function, programmed cell death, and phosphatidylinositol 3-kinase (PI3K)/ AKT/forkhead box protein O 1a (FoxO1a) signaling. In addition, H2O2-exposed human kidney cells (HK-2) were treated with LC. @*Results@#LC treatment inhibited expression of proinflammatory and profibrotic cytokines, and was followed by a significant attenuation of tubulointerstitial inflammation and fibrosis. The increased oxidative stress caused by UUO was associated with mitochondrial dysfunction and excessive apoptosis and autophagy via PI3K/AKT/FoxO1a-dependent signaling, and this was abrogated by administration of LC. In H2O2-exposed HK-2 cells, LC decreased intracellular production of reactive oxygen species, and suppressed expression of profibrotic cytokines and reduced the number of apoptotic cells. @*Conclusions@#LC protects against the progression of tubulointerstitial fibrosis in an obstructed kidney.

Absorption and excretion of CT-707 in healthy male subjects studied by radioisotope tracer method / 中国临床药理学与治疗学

AIM: To study the absorption and excretion of CT-707 in healthy male subjects. METHODS: Six healthy male subjects received a single 300 mg (120 μCi) oral dose of radio-labeled CT-707 as a suspension in a fasted state. Blood, urine and feces were collected. Radioactivity concentrations were measured by liquid scintillation counting (LSC). The pharmacokinetic parameters of total radioactivity in plasma were calculated by WinNonlin (Pharsight version 8.1) software according to the non-compartment model. The recovery rate of total radioactivity in urine and feces was calculated according to the weight and radioactivity concentration of urine and feces collected at each time interval. RESULTS: After a single 300 mg oral of radio-labeled CT-707 552 h (23 d) as a suspension in a fasted state, the mean AUC

Clinical application of midpiece facial nerve dissection in regional parotidectomy / 华西口腔医学杂志

OBJECTIVE@#To propose and evaluate the clinical effect of midpiece facial nerve dissection through transparotid approach in regional parotidectomy.@*METHODS@#A total of 136 patients with benign parotid tumors were categorized into three groups according to the way of facial nerve dissection: anterograde dissection from main trunk (anterograde, n=70), retrograde dissection from distal branches (retrograde, n=34), and midpiece dissection through transparotid approach (middle dissection, n=32). Surgery duration, facial nerve injury, salivary fistula, earlobe sensation, Frey's syndrome, and aesthetic evaluation were compared.@*RESULTS@#The surgery duration in the middle dissection group was significantly shorter than that in the other two groups. The proportion of salivary fistula was higher in the anterograde group (9 cases, 12.9%; P<0.05) compared with that in the other groups. Postoperative facial nerve injury was similar between the middle dissection (1 case, 3.1%) and anterograde groups (3 cases, 4.3%) with lower injury rate compared with the retrograde group (7 cases, 20.6%). The anterograde group had more cases of hypoesthesia of the earlobe (12 cases, 17.1%; P<0.05) than the other two groups. Aesthetic score was higher in the anterograde and middle dissection groups compared with that in the retrograde group (P<0.05).@*CONCLUSIONS@#Midpiece facial nerve dissection is technically feasible and clinically viable in regional parotidectomy.

Construction and application value of CT-based three-dimensional digital model of small bowel for predication of small bowel length before bariatric surgery / 中华消化外科杂志

Objective:To construct a computed tomography (CT)-based three-dimensional digital model of small bowel, and investigate its application value for predication of small bowel length before bariatric surgery.Methods:The retrospective and descriptive study was conducted. The clinical data of 3 patients with obesity who were admitted to the Daping Hospital of Army Medical University from December 2018 to January 2019 were collected. There were 2 males and 1 female, aged from from 24 to 44 years, with a median age of 25 years. Patients underwent abdominal enhanced CT examination before operation, and the three-dimensional digital models of small bowel for each patient were constructed respectively. Of the 3 patients, 2 underwent sleeve gastrectomy and 1 underwent Roux-en-Y gastric bypass. The 3 patients were numbered as No.1, No.2, and No.3 according to the operation time. Observation indicators: (1) construction of three-dimensional digital model of small bowel and preoperative prediction of small bowel length; (2) intraoperative measurement of small bowel length and the relative error between preoperative prediction of small bowel length and intraoperative measurement of small bowel length. Count data were represented as absolute numbers or percentages.Results:(1) Construction of three-dimensional digital model of small bowel and preoperative prediction of small bowel length: the three-dimensional digital models of small bowel for each patient were constructed respectively before operation. The volume of small bowel, area of each cross-section for the 10 cross-sections of small bowel, average area of cross-section of small bowel, preoperative prediction of small bowel length in the three-dimensional digital model of small bowel of No.1 patient were 1 312 985 mm 3, 174 mm 2, 154 mm 2, 143 mm 2, 172 mm 2, 345 mm 2, 213 mm 2, 357 mm 2, 173 mm 2, 382 mm 2, 154 mm 2, 227 mm 2, 578 cm. The above indicators of No.2 patient were 1 817 224 mm 3, 274 mm 2, 196 mm 2, 487 mm 2, 413 mm 2, 520 mm 2, 254 mm 2, 231 mm 2, 170 mm 2, 212 mm 2, 168 mm 2, 293 mm 2, 620 cm. The above indicators of No.3 patient were 2 183 019 mm 3, 320 mm 2, 408 mm 2, 281 mm 2, 222 mm 2, 194 mm 2, 219 mm 2, 188 mm 2, 419 mm 2, 326 mm 2, 235 mm 2, 281 mm 2, 777 cm. (2) Intraoperative measurement of small bowel length and the relative error between preoperative prediction of small bowel length and intraoperative measurement of small bowel length: the length of small bowel measured intraoperatively for No.1, No.2, and No.3 patients were 570 cm, 600 cm, and 780 cm, respectively. The relative error between preoperative prediction of small bowel length and intraoperative measurement of small bowel length of No.1, No.2, and No.3 patients were 1.40%、3.33%、0.38%, respectively. Conclusion:Three-dimensional digital model of the small bowel can predict the small bowel length before bariatric surgery.

Inactivation of Poliovirus by Ozone and the Impact of Ozone on the Viral Genome / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the mechanisms underlying ozone-induced inactivation of poliovirus type 1 (PV1).@*METHODS@#We used cell culture, long-overlapping RT-PCR, and spot hybridization assays to verify and accurately locate the sites of action of ozone that cause PV1 inactivation. We also employed recombinant viral genome RNA infection models to confirm our observations.@*RESULTS@#Our results indicated that ozone inactivated PV1 primarily by disrupting the 5'-non-coding region (5'-NCR) of the PV1 genome. Further study revealed that ozone specifically damaged the 80-124 nucleotide (nt) region in the 5'-NCR. Recombinant viral genome RNA infection models confirmed that PV1 lacking this region was non-infectious.@*CONCLUSION@#In this study, we not only elucidated the mechanisms by which ozone induces PV1 inactivation but also determined that the 80-124 nt region in the 5'-NCR is targeted by ozone to achieve this inactivation.

Pharmacokinetics of levornidazole disodium phosphate in monkey / 药学学报

This study was carried out to investigate the pharmacokinetics/bioequivalence of levornidazole disodium phosphate by using stable isotope labeled drug, evaluated the pharmacokinetic profile and confirmed the prodrug characteristics of levornidazole disodium phosphate in monkey. Levornidazole (Drug A) and stable isotope 15N labeled levornidazole disodium phosphate (Drug B) were mixed with equal mole amount (experiment I); stable isotope 15N labeled levornidazole disodium phosphate (Drug B) and levornidazole disodium phosphate (Drug C) were mixed with equal mole amount, respectively. After giving the mixed drugs to the monkey, the concentration of 15N-levornidazole disodium phosphate, levornidazole disodium phosphate, 15N-levornidazole and levornidazole in plasma samples of pre-dosing and 24 h after administration were analyzed by a liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method. Pharmacokinetic calculations were performed through non-compartmental analysis using WinNonlin software. Two-sided 90% confidence intervals (CI) were used to evaluate the bioequivalence of two drugs. The results showed that levornidazole disodium phosphate was metabolized to levornidazole rapidly after administration, the body exposure were increased with the dosage. The method of bioequivalence used in this study was different from the traditional two periods, crossover design. By using the method of this study, the effects of administration period, intra-individual variability, and sequence of administration on bioequivalence were avoided. The results of this study had successfully supported the pharmacokinetic and bioequivalence study of this drug in human using the same approach.

Osteopractic total flavone promoting rat extra-articular tendon-bone healing through mTOR pathway / 中国骨伤

<p><b>OBJECTIVE</b>To explore function and related molecular mechanism of osteopractic total flavone (OTF) on tendon healing in rats.</p><p><b>METHODS</b>Ten male rats aged for 8 weeks were collected and weighted from 180 to 220 g. Tendon stem cells were cultivated, the third tendon stem cells were used for experiment. OTP treated with 0, 0.1, 1, 10 ng/ml were added into tendon stem cells, and expression change of ALP, Runx2, OCN, VEGF, P-S6, P-4E/BP1 were detected after 14 days. Forty male rats aged for 8 weeks (weighted 180 to 220 g) were established extra-articular tendon-bone transplanting healing model, and divided into experimental group and control group. Experimental group were treated with OTF(100 mg·kg⁻¹·d⁻¹), while control group was treated by normal saline with the same volume. Tendon-bone healing degree were detected by biomechanical testing at 3 and 6 weeks after surgery, histological detection were applied to detect tendon-bone healing and number of new vessles.</p><p><b>RESULTS</b>After treated by OTP, ALP staining and active index detection showed there were statistical differences among 0, 0.1, 1, 10 ng/ml group. After 14 days' cultivation, western blotting results showed mTOR downstream marker protein P-S6 protein expression were gradually increased with increase of density of OTP, expression of P-4E/BP1 was reduced, while expression of Runx2, OCN, VEGF were increased. Biological detection results showed that there was no significant difference in mechanical strength between experimental group(0.78±0.05) N/mm and control group (0.51±0.02) N/mm at 3 weeks after surgery, while mechanical strength in experimental group (1.36±0.09) N/mm was higher than control group (1.01±0.08) N/mm at 6 weeks after surgery. Histological results showed maturity of tendon-bone surface cell were higher at 3 and 6 weeks in experimental group, sharpey fiber growth more density, calcification extent of mesenchyme was high, and new bone, vessels were increased.</p><p><b>CONCLUSIONS</b>OTF could promote osteogenic differentiation of tendon stem cells through mTOR signaling in vitro, and stimulate tendon-bone healing in bone tunnel and enhance connection quality between tendon and bone.</p>

Uncertainty Evaluation for the Determination of Pseudo-ginsenoside GQ in Human Plasma by HPLC-MS/MS / 医药导报

Objective To evaluate the uncertainty of the pseudo-ginsenoside GQ (PGQ) concentration in human plasma by HPLC-MS/MS.Methods The whole process of PGQ determination by HPLC-MS/MS in human plasma was evaluated and the uncertainty caused by repeatability,weighing,standard solution preparation,biological sample preparation,extraction recovery process,recovery,instrument precision and calibration curve fitting were evaluated,respectively.The combined and expanded uncertainty values were both calculated.Results The expanded uncertainty values for low (15.16 ng·mL-1),medium (2 516.67 ng·mL-1) and high (3 902.00 ng·mL-1) levels of PGQ were 1.39,177.74 and 262.69 ng·mL-1,respectively (P =95 ％,k =2).Conclusion The uncertainty of the PGQ determination in human plasma by HPLC-MS/MS is mainly caused by recovery,repeatabihty and sample preparation at low concentration,by sample preparation and recovery at medium and high concentration.

Recent advances in the application of growth factors in spinal cord injury / 天津医药

The incidence of spinal cord injury is increasing year by year, and more and more attentions have been paid. Growth factors can promote the regeneration of nerve fibers and synapses, and they also play an important role in the treatment of spinal cord injury and the recovery of neurological function. The growth factor itself has a short half-life, so it is necessary to use growth factor gene vectors to transfect stem cells and nanoparticles to deliver growth factors or biocompatible scaffolds to support growth factors to treat spinal cord injuries. With the development of the research on growth factors, the application of single growth factor is difficult to meet the need of treatment to spinal cord injury. To explore the synergistic effect of various growth factors in order to achieve a better therapeutic effect is a promising research direction in the future. The purpose of this review is to summarize the therapeutic effects of growth factors on spinal cord injury including brain-derived neurotrophic factor, neurotrophic factor 3, nerve growth factor, basic fibroblast growth factor and synergy therapy of growth factors.

Recent advances in the application of growth factors in spinal cord injury / 天津医药

The incidence of spinal cord injury is increasing year by year, and more and more attentions have been paid. Growth factors can promote the regeneration of nerve fibers and synapses, and they also play an important role in the treatment of spinal cord injury and the recovery of neurological function. The growth factor itself has a short half-life, so it is necessary to use growth factor gene vectors to transfect stem cells and nanoparticles to deliver growth factors or biocompatible scaffolds to support growth factors to treat spinal cord injuries. With the development of the research on growth factors, the application of single growth factor is difficult to meet the need of treatment to spinal cord injury. To explore the synergistic effect of various growth factors in order to achieve a better therapeutic effect is a promising research direction in the future. The purpose of this review is to summarize the therapeutic effects of growth factors on spinal cord injury including brain-derived neurotrophic factor, neurotrophic factor 3, nerve growth factor, basic fibroblast growth factor and synergy therapy of growth factors.

Over expression lung cancer-1 is sa soic ated with poor prognosis in colorectal cancer / 实用肿瘤学杂志

Objective The overexpression lung cancer1( OLC1) protein is overexpressed in a variety of human tumors.The purpose of the present study is to determine whether increased expression of OLC1 is associat-ed with colorectal cancer.Methods OLC1 expression was assayed in 150 colorectal cancer tissues by immuno-histochemical staining(IHC).Multivariate and univariate analyses were performed to determine the association between OLC1 expression and prognosis.Results Immunohistochemical results revealed that 107 out of 150 colorectal cancer patients had increased levels of OLC1.OLC1 expression was significantly correlated with UICC stage(P<0.001)and histological differentiation(P<0.001)in colorectal cancer patients.The 5-year overall survival( OS) rates in patients with strong positive and less OLC1 staining were 16.6%and 95.3%,respectively (P<0.0001).Conclusion OLC1 overexpression is an important factor in colorectal carcinoma prognosis and can be an interesting potential novel biomarker for colorectal cancer.

Interaction of butylphthalide with rat and human liver CYP450 isoenzymes / 药学学报

The work aims to study the drug metabolizing enzymes involved in the metabolism of butylphthalide and evaluate the induction and inhibition activities of butylphthalide on CYP450 isoenzymes by using in vitro (liver microsome incubation system of rats and human) and in vivo (CYP induced model of rats) method. Butylphthalide was incubated with selective inhibitors of CYP450, and its metabolic rate was determined to identify the metabolizing isoenzymes of NBP in rat (normal and induced rats) and human liver microsomes. The in vitro inhibition effect of butylphthalide on 6 main liver microsomal CYP450 isoenzymes was evaluated by using probe drugs; the induction and inhibition activities in vivo of butylphthalide on CYP450 isoenzymes were evaluated by NBP ig dosing (160 mg x kg(-1)) and iv dosing (20 mg x kg(-1)) in rats. After adding the specific inhibitors of CYP2C11, 2E1 and 3A 1/2 for rat, CYP2C19, 2E1 and 3A4/5 for human, the metabolism of NBP in rat and human liver microsomes were reduced 38.8%, 86.2%, 78.4% and 51.0%, 92.0%, 58.9% of control, respectively. The metabolic rates of NBP in CYP2E1 and 3A 1/2 induced rat liver microsomes were increased 25.5% and 68.9%. High concentration of NBP (≥ 200 μmol x L(-1), in vitro) could inhibit the activities of CYP1A2, 2C6, 2C11 and 2D2 in rats, and high concentration of NBP ( ≥ 15 μmol x L(-1), in vitro) could inhibit the activity of CYP2C19 in human. All the results indicated that NBP should be mainly metabolized by CYP2E1, 2C11 and 3A 1/2 in rats and CYP2E1, 2C19 and 3A4/5 in human. High concentration of NBP could inhibit human CYP2C19 in vitro. No significant induction/inhibition effects of NBP were observed on rat liver CYP450 isoforms after ig 160 mg x kg(-1) NBP or iv 20 mg x kg(-1) NBP.

Quantification of sitagliptin in human plasma and urine by LC-MS/MS method and its application / 药学学报

A rapid and sensitive liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method for quantification of sitagliptin in human plasma and urine had been developed. This method was applied to the pharmacokinetics study of sitagliptin tablet after single- and multiple-dosing in Chinese population. Plasma samples were prepared by a liquid-liquid extracted method, and urine samples were diluted. Compounds were analyzed by multiple reaction monitoring (MRM) mode with a electrospray ionization (ESI) interface. Mobile phase consisted of methanol and water (85 : 15, v/v). The linear concentration range of calibration curve was 0.5-1 000 ng.mL-1. and 0.2-100 µg.mL , intra-run/between-run accuracy was 98.98%-103.69% and 97.63%-102.29%, intra-run/between-run precision was <5.51% and 4.26% for plasma and urine sample, respectively. The stability of sitagliptin stock solution was tested for 55 days at -30 °C. Sitagliptin was stable when stored under the following conditions: 24 hours in the autosampler after sample preparation; 24 hours at room temperature, after 3 freeze and thaw cycles (from -30 °C to room temperature), 40 days at -30 °C for plasma and urine samples. The absolute recovery in plasma was 71.1%, and no matrix effect was founded. This method was proved simple, specific, sensitive, rapid and suitable for pharmacokinetics study of sitagliptin in human being.

Prevention and Treatment of Atherosclerosis by Three Different Chinese Medical Compounds: a Mechanism Study / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of Buyang Huanwu Decoction (BHD), Xuefu Zhuyu Decoction (XZD), and Sijunzi Decoction (SD) contained serums on expressions of Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signals, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), tumor necrosis factor-α (TNF-α), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and to explore possible anti-atherosclerotic mechanisms.</p><p><b>METHODS</b>Twenty New Zealand rabbits were divided into 4 groups at random, i.e., the normal control group, the BHD group (6.7 g/kg), the XZD group (3.6 g/kg), and the SD group (1.6 g/kg), 5 in each group. All medication lasted for 7 successive days. Two h after the final medication, about 50 mL blood was withdrawn from rabbit heart for preparing serums. Human umbilical vein endothelial cell ECV304 were cultured in vitro for 18 h and randomly divided into the blank control group, the model group, the Western medicine (WM) control group, the BHD group, the XZD group, and the SD group at random. ECV304, except in the blank control group, were stimulated with lipopolysaccharide (LPS) for 2 h. Those in the WM control group and CM groups were treated respectively with corresponding CM contained serum for 24 h. Finally gene and protein expressions of TLR4, myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor-associated factor-6 (TRAF-6), NF-κB, LOX-1, TNF-α, ICAM-1, and VCAM-1 were detected by fluorescent quantitative PCR and Western blot.</p><p><b>RESULTS</b>Compared with the blank control group, mRNA expressions of TLR4, MyD88, TRAF-6, NF-KB, LOX-1 , TNF-cx, ICAM-1, and VCAM-1 increased significantly; protein expressions of TLR4, NF-κB, LOX-1, TNF-α, ICAM-1, and VCAM-1 also increased significantly in the model group (P < 0.01). Compared with the model group, mRNA and protein expressions of each index could be significantly inhibited in the BHD group, the XZD group, and the WM control group (P < 0.05). Besides, mRNA and protein expressions of each index could be significantly elevated more in the BHD group and the XZD group than in the WM control group (P < 0.05). No statistical difference existed in each index between the SD group and the rest groups (P > 0.05).</p><p><b>CONCLUSIONS</b>The mechanism of BHD and XZD for fighting against atherosclerosis might be associated with inhibiting TLR4/NF-κB signal transduction pathway and expressions of its downstream inflammatory factors such as LOX-1, TNF-α, ICAM-1, and VCAM-1. But SD showed no associated effect on atherosclerosis.</p>

Quantification of sitagliptin in human plasma and urine by LC-MS/MS method and its application / 药学学报

A rapid and sensitive liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method for quantification of sitagliptin in human plasma and urine had been developed. This method was applied to the pharmacokinetics study of sitagliptin tablet after single- and multiple-dosing in Chinese population. Plasma samples were prepared by a liquid-liquid extracted method, and urine samples were diluted. Compounds were analyzed by multiple reaction monitoring (MRM) mode with a electrospray ionization (ESI) interface. Mobile phase consisted of methanol and water (85 : 15, v/v). The linear concentration range of calibration curve was 0.5-1 000 ng.mL-1. and 0.2-100 µg.mL , intra-run/between-run accuracy was 98.98%-103.69% and 97.63%-102.29%, intra-run/between-run precision was <5.51% and 4.26% for plasma and urine sample, respectively. The stability of sitagliptin stock solution was tested for 55 days at -30 °C. Sitagliptin was stable when stored under the following conditions: 24 hours in the autosampler after sample preparation; 24 hours at room temperature, after 3 freeze and thaw cycles (from -30 °C to room temperature), 40 days at -30 °C for plasma and urine samples. The absolute recovery in plasma was 71.1%, and no matrix effect was founded. This method was proved simple, specific, sensitive, rapid and suitable for pharmacokinetics study of sitagliptin in human being.

Interaction of butylphthalide with rat and human liver CYP450 isoenzymes / 药学学报

The work aims to study the drug metabolizing enzymes involved in the metabolism of butylphthalide and evaluate the induction and inhibition activities of butylphthalide on CYP450 isoenzymes by using in vitro (liver microsome incubation system of rats and human) and in vivo (CYP induced model of rats) method. Butylphthalide was incubated with selective inhibitors of CYP450, and its metabolic rate was determined to identify the metabolizing isoenzymes of NBP in rat (normal and induced rats) and human liver microsomes. The in vitro inhibition effect of butylphthalide on 6 main liver microsomal CYP450 isoenzymes was evaluated by using probe drugs; the induction and inhibition activities in vivo of butylphthalide on CYP450 isoenzymes were evaluated by NBP ig dosing (160 mg x kg(-1)) and iv dosing (20 mg x kg(-1)) in rats. After adding the specific inhibitors of CYP2C11, 2E1 and 3A 1/2 for rat, CYP2C19, 2E1 and 3A4/5 for human, the metabolism of NBP in rat and human liver microsomes were reduced 38.8%, 86.2%, 78.4% and 51.0%, 92.0%, 58.9% of control, respectively. The metabolic rates of NBP in CYP2E1 and 3A 1/2 induced rat liver microsomes were increased 25.5% and 68.9%. High concentration of NBP (≥ 200 μmol x L(-1), in vitro) could inhibit the activities of CYP1A2, 2C6, 2C11 and 2D2 in rats, and high concentration of NBP ( ≥ 15 μmol x L(-1), in vitro) could inhibit the activity of CYP2C19 in human. All the results indicated that NBP should be mainly metabolized by CYP2E1, 2C11 and 3A 1/2 in rats and CYP2E1, 2C19 and 3A4/5 in human. High concentration of NBP could inhibit human CYP2C19 in vitro. No significant induction/inhibition effects of NBP were observed on rat liver CYP450 isoforms after ig 160 mg x kg(-1) NBP or iv 20 mg x kg(-1) NBP.

Validation study of prediction models of hepatitis B virus-related hepatocellular carcinoma / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To validate two previously published models (REACH-B score and CU-HCC score) for predicting the risk of developing hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>In-patients of the Liver Center of First Affiliated Hospital Fujian Medical University who tested positive for hepatitis B surface antigen (HBsAg;more than 6 months) and were admitted for treatment between October 1,2004 and May 1,2014 were enrolled for study. The 627 study participants were grouped according to presence of HCC (151 in the HCC case group, and 476 in the non-HCC control group). Relevant clinical data from 3 and 5 years prior to the current hospital admission were collected retrospectively and assessed using the REACH-B and CU-HCC scoring systems. A subset of the study participants (65 HCC cases, and 94 non-HCC controls) was used for the verification analysis of prediction for 5-year risk of HBV-related HCC.T-test, rank sum test, chisquare test and the receiver operating characteristic curve were used for statistical analyses.</p><p><b>RESULTS</b>For the REACH-B score,prediction of 3-year risk of developing HCC had an area under the curve (AUC) of 0.78,a sensitivity of 73.00% and a specificity of 78.70%.In male patients with alanine aminotransferase (ALT) more than or equal to 45 U/L, the REACH-B score prediction of 3-year risk of developing HCC had an AUC of 0.89, a sensitivity of 87.09% and a specificity of 83.86%. The REACH-B score prediction of 5-year risk of HCC had an AUC of 0.79,a sensitivity of 73.60% and a specificity of 75.53%; the CU-HCC score prediction of 5-year risk of HCC had an AUC of 0.76, a sensitivity of 78.40% and a specificity of 77.40%.</p><p><b>CONCLUSION</b>Both the REACH-B and CUHCC scoring systems can be used for HCC prediction among patients at the First Affiliated Hospital Fujian Medical University. For male patients with ALT more than or equal to 45 U/L,the REACH-B score may be a more sensitive predictor for 3-year risk of developing HBV-related HCC.</p>