OBJECTIVETo investigate the absolute bioavailability of caffeic acid in rats and its intestinal absorption properties.

METHODThe absolute bioavailability (Fabs) of caffeic acid was obtained after iv (2 mg x kg(-1)) or ig (10 mg x kg(-1)) administration to rats. The intestinal absorption of caffeic acid was explored by the recirculating vascularly perfused rat intestinal preparation. Caco-2 cell model was applied to measure the permeability of caffeic acid from apical to basolateral said (A-B) and from basolateral to apical said (B-A).

RESULTA two-compartment pharmacokinetic model was best to describe the pharmacokinetics of caffeic acid following iv or ig administration. The Fabs of caffeic acid was 14. 7% , and its intestinal absorption was 12.4%. The values of Papp A-->B and Papp B-->A of caffeic acid were retained stable while its concentration was changed. The efflux ratio values in this study surveyed were above 2.0, and suggesting caffeic acid was active transport.

CONCLUSIONCaffeic acid was shown to have poor permeability across the Caco-2 cells, low intestinal absorption and low oral bioavailability in rats.

Animals ; Biological Availability ; Caco-2 Cells ; Caffeic Acids ; metabolism ; pharmacokinetics ; Humans ; Intestinal Absorption ; Male ; Rats ; Rats, Sprague-Dawley

Aim To explore the anti-psoriatic effects of honokiol on the mouse model induced by imiquimod and the underlying mechanism. Methods The mice were randomly divided into control group, model group, liposome solvent control group, dexamethasone positive group and honokiol high, medium, low dose groups. The progress of the disease was observed by the psoriasis area and severity index (PASI). The morphological changes of the skin cells were observed by HE staining, and epidermis thickness was meas-ured. The expression of IL-17, IL-23, JAK, STAT3, TNF-α and NF-κB was semi-quantitively analyzed by immunohistochemistry. Results Compared to model group, the scaling and thickness of honokiol treated groups were alleviated. Inflammatory infiltration and micro abscess were reduced. The expressions of IL-17, IL-23, JAK, STAT3, TNF-α and NF-κB in model group were higher than those in honokiol-high and honokiol-medium group in a dose-dependent manner. Conclusion Honokiol can inhibit imiquimod-induced psoriasis-like lesions in mice by inhibiting the IL-17/IL-23 inflammatory axis.

OBJECTIVETo explore effect and the application value of continuous douche and vacuum sealing drainage (VSD) in refractory tissue, and joint infections after complete debridement.

METHODSAs retrospective analysis of treatment time and restoration or recurrence, from Jan. 2006 to Dec. 2007, 61 cases of refractory tissue, bone and joint infections underwent continuous douche and VSD combined with the treatment of anti-inflammatory and rehabilitation training after debridement in our hospital. The 61 patients included 39 males and 22 females with age ranging from 10 to 58 years with an average of (35 +/- 12) years, among whom 61 identified to have ankle ulcers combined with infections,open fracture combined with infections, sacrococcygeal pressure ulcers combined with infections, infections after hip replacement, infections after open fracture, and infections after skin avulsion postoperation were 11, 15, 9, 3, 5 and 18 cases respectively. The course was from 2 weeks to 11 months with an average of 4 months.

RESULTSIn all 61 patients,the mean healing time was 17, 36, 42, 24, 32, 29 and 28 days in ankle ulcers and infections, tibia and fibula open fracture and infections, femoral shaft fracture and infections, sacrococcygeal pressure ulcers and infections, infections after hip replacement, infections after open fracture, and infections after skin avulsion postoperation respectively. The replacement of VSD was 1, 2-4, 3-5, 1-3, 2-4, 2-3 and 1-3 times in each group respectively. There was no wound recurrence except for 2 cases with recurrent in 61 cases with external fixation nail hole semi-pathological fracture in 1 case of femoral shaft fracture and infection and 1 case of tibia and fibula fracture and infection after follow-up at least one year.

CONCLUSIONApplication of continuous douche and VSD can effectively decrease incidence of complications and promote the refractory tissue, bone and joint infections wound growth, healing and considerably shorten the healing time.

Adolescent ; Adult ; Bone Diseases ; pathology ; physiopathology ; surgery ; Child ; Debridement ; adverse effects ; Female ; Follow-Up Studies ; Humans ; Joint Diseases ; pathology ; physiopathology ; surgery ; Male ; Middle Aged ; Retrospective Studies ; Suction ; methods ; Therapeutic Irrigation ; methods ; Time Factors ; Wound Healing ; Young Adult

OBJECTIVE: To investigate whether heroin can directly induce apoptosis in primary cultured cortical neurons of rat's brain. METHODS: Cultured primary neurons cultures were obtained from cerebral cortex of embryo rats. After 7 days, the cells were incubated with different concentrations of heroin (purity-80%) for 24 hours. The neuronal survival was assessed by cell viability counting with fluorescent diacetate (FDA) staining. The morphological and biochemical changes were observed with Hoechst 33258 fluorescent staining and then analyzed by agarose gel electrophoresis, respectively. RESULTS: After treatment with different concentrations of heroin, the neurons showed a decreased survival rate in a dose dependent manner, and there was a significant difference in the survival rate between the heroin group and the control group (P < 0.05). When exposed to different concentrations of heroin, neurons exhibited the morphological and biochemical features of apoptosis, including cell shrinkage, neurite degeneration, network disappearance, condensation and aggregation of nuclear chromatin, and the formation of DNA ladders. With the increase of heroin concentration of rat's brain more apoptotic bodies were seen. CONCLUSION Heroin can directly induce apoptosis in primary cultured cortical neurons in rat's brain.
Animals ; Apoptosis/drug effects* ; Cell Nucleus/pathology* ; Cell Survival/drug effects* ; Cells, Cultured ; Cerebral Cortex/pathology* ; DNA Fragmentation/drug effects* ; Dose-Response Relationship, Drug ; Electrophoresis, Agar Gel/methods* ; Female ; Heroin/pharmacology* ; Male ; Neurons/pathology* ; Rats ; Rats, Sprague-Dawley ; Staining and Labeling

OBJECTIVETo study the CD8+ cell noncytotoxic antiviral response (CNAR) to HIV in nosocomial HIV infected individuals, and reveal the relationship between the CNAR and CD4+ cell count.

METHODCD8+ cells from HIV-1 sero-positive individuals were separated by immunomagnetic beads and mixed with CD4+ cells at different CD8 CD4 cell input ratios (2:1, 1:1, 0.5:1 and 0.25:1). Reverse transcriptase (RT) activity of cocultured supernatant was tested and compared with negative control and the suppression rate of HIV-1 replication was measured.

RESULTThe average CD8:CD4 cell input ratios to reach 80% suppression of HIV replication in the group with CD4 < 300/microl and CD4 > 300/microl were 2.4:1 and 1.3:1, respectively (P < 0.05).

CONCLUSIONCNAR activity in HIV infected individuals is associated with CD4+ cell count. The ability to suppress HIV replication in subjects with CD4 > 300 is stronger than those with CD4 < 300.

Adult ; Aged, 80 and over ; Anti-HIV Agents ; therapeutic use ; CD4-Positive T-Lymphocytes ; drug effects ; immunology ; CD8-Positive T-Lymphocytes ; drug effects ; immunology ; Cells, Cultured ; Cross Infection ; drug therapy ; immunology ; Female ; HIV ; drug effects ; immunology ; HIV Infections ; drug therapy ; immunology ; Humans ; Male ; Middle Aged

Objective To explore the clinical efficacy of one-stage anterolateral-posterior approach debridement,bone graft and internal fixation in treatment of thoracolumbar spinal tuberculosis.Methods From January 2010 to December 2014,56 cases of thoracolumbar spinal tuberculosis were retrospectively analyzed, including 31 males and 25 females,aged 18 -72 years (mean 43.1 years).All patients were managed by standard courses of chemotherapy with quadruple anti-TB drugs for 2 - 4 weeks.Patients were treated by anterolateral debridement,autologous iliac bone graft fixed by absorbable screw fixation,and posterior pedicle screw fixation via multi-split muscle gap (Wiltse approach).We recorded the operation time,the amount of bleeding,bone graft fusion,postoperative erythrocyte sedimentation rate (ESR),Cobb angle,VAS score,and American Spinal Injury Association (ASIA)score to evaluate the surgical results.Results The average operation time was 175-290 min, with an average of (248±42)min.The bleeding volume was 300 -900 mL with an average of (420 ±68)mL.The average follow-up time was (24 ± 5.2 )months,bone fusion rate was 100%,and fusion time was (4.7 ± 0.5 ) months.At the last follow-up,the average Cobb angle was (8.2±3.1)°,VAS was (2.1±0.8),and ESR was (17± 4.2)mm/h.The ASIA neurological functions were all classified as Grade E except for 3 cases of Grade D.All these were significantly different from the preoperative ones.Six patients had complications of different degree but without serious complications.Conclusion One-stage anterolateral debridement,autologous iliac bone graft fixedby absorbable screw fixation,and posterior pedicle screw fixation via multi-split muscle gap (Wiltse approach)can completely remove the tuberculosis lesions and achieve ideal kyphosis correction,high bone graft fusion,and satisfactory neurological function recovery.Absorbable screws can be safely applied to the bone graft site after debridement.

Objective:To investigate the safety and short-term efficacy of laparoscopic pro-ximal gastrectomy (LPG) for proximal gastric cancer and adenocarcinoma of esophagogastric junction.Methods:The retrospective cohort study was conducted. The clinicopathological data of 385 patients with proximal gastric cancer and adenocarcinoma of esophagogastric junction who underwent LPG in the 15 medical centers, including the First Affiliated Hospital of Xiamen University et al, from January 2014 to March 2022 were collected. There were 304 males and 81 females, aged (63±9)years. Of the 385 patients, 335 cases undergoing LPG were divided into the laparoscopic group and 50 cases undergoing open proximal gastrectomy were divided into the open group. Observation indicators: (1) intraoperative and postoperative situations; (2) follow-up; (3) stratified analysis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Repeated measurement data were analyzed using the repeated ANOVA. Results:(1) Intraoperative and postoperative situations. The operation time, cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis, cases with postoperative pathological staging as stage 0?Ⅰ and stage Ⅱ?Ⅲ, duration of postoperative hospital stay, cases with postoperative early complications were (212±96)minutes, 270, 65, 177, 107, 10(range, 8?14)days, 40 in patients of the laparoscopic group, with 51 cases missing the data of postoperative pathological staging. The above indicators were (174±90)minutes, 39, 11, 22, 28, 10(range, 8?18)days, 10 in patients of the open group. There were significant differences in the opera-tion time and postoperative pathological staging between the two groups ( t=2.62, χ2=5.93, P<0.05), and there was no significant difference in the reconstruction of digestive tract, duration of post-operative hospital stay, postoperative early complications between the two groups ( χ2=0.19, Z=0.40, χ2=2.50, P>0.05). (2) Follow-up. Of the 385 patients,202 cases were followed up during the post-operative 12 months, including 187 cases in the laparoscopic group and 15 cases in the open group. Cases with reflux esophagitis, cases with esophageal anastomotic stenosis were 48, 11 in patients of the laparoscopic group, versus 5, 2 in patients of the open group, showing no significant difference in the above indicators between the two groups ( P>0.05). The body mass index (BMI), hemoglobin (Hb), albumin (Alb) at postoperative 6 months and 12 months were (21±3)kg/m 2, (130±15)g/L, (40±4)g/L and (21±3)kg/m 2, (132±14)g/L, (41±4)g/L in patients of the laparoscopic group, versus (21±3)kg/m 2, (121±19)g/L, (37±5)g/L and (21±3)kg/m 2, (125±21)g/L, (43±6)g/L in patients of the open group. There were significant differences in postoperative Hb between the two groups ( Fgroup=5.88, Ftime=5.49, Finteraction=19.95, P<0.05) and there were significant differences in time effect of postopera-tive BMI and Alb between the two groups ( Ftime=9.53, 49.88, P<0.05). (3) Stratified analysis. ① Incidence of postoperative of reflux esophagitis and esophageal anastomotic stenosis in patients with different reconstruction of digestive tract. Of the 202 patients, cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis were 168 and 34, respectively. The incidence rates of postoperative of reflux esophagitis were 26.79%(45/168)and 23.53%(8/34)in cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis, showing no significant difference between them ( χ2=0.16, P>0.05). Cases undergoing esophageal anastomotic stenosis were 13 in patients with reconstruction of diges-tive tract as esophagogastric anastomosis. ② The BMI, Hb, Alb in patients with different reconstruc-tion of digestive tract. The BMI, Hb, Alb were (24±3)kg/m 2, (135±20)g/L, (41±5)g/L in the 168 patients with reconstruction of digestive tract as esophagogastric anastomosis before the operation, versus (23±3)kg/m 2, (130±19)g/L, (40±4)g/L in the 34 patients with reconstruction of digestive tract as esophageal-jejunal anastomosis before the operation, showing no significant difference between them ( t=1.44, 1.77, 1.33, P>0.05). The BMI, Hb, Alb at postoperative 6 months and 12 months were (21±3)kg/m 2, (128±16)g/L, (39±4)g/L and (21±3)kg/m 2, (131±16)g/L, (41±4)g/L in the 168 patients with reconstruction of digestive tract as esophagogastric anastomosis, versus (20±4)kg/m 2, (133±13)g/L, (43±3)g/L and (21±3)kg/m 2, (135±12)g/L, (44±3)g/L in the 34 patients with reconstruction of digestive tract as esophageal-jejunal anastomosis. There were significant differences in the group effect and time effect of postoperative Alb between patients with different reconstruction of diges-tive tract ( Fgroup=15.82, Ftime=5.43, P<0.05), and there was also a significant difference in the time effect of postoperative BMI between them ( Ftime=4.22 , P<0.05). Conclusion:LPG can be used to the treatment of proximal gastric cancer and adenocarcinoma of esophagogastric junction, with a good safety and short-term efficacy.

OBJECTIVETo investigate the expression of vasoactive intestinal peptide (VIP) in gastric adenocarcinoma, and to evaluate the correlation of VIP level with clinical pathologic parameters.

METHODSThe level of VIP in sera from gastric adenocarcinoma patients and healthy people was investigated by ELISA. Moreover, the differential gene expression between gastric adenocarcinoma, gastric dysplasia, and the corresponding normal gastric mucosa were determined by RT-PCR. Western Blot was also used to measure the expression of VIP in the gastric adenocarcinoma and the normal gastric mucosa.

RESULTSThe serum level of VIP was (5.794 +/- 0.014) ng/ ml in normal control and was (14.437 +/- 0.825) ng/ml in gastric adenocarcinoma patients, showing significant difference (P < 0.05). Meanwhile,the V/B of gastric adenocarcinoma tissues was greater than that of gastric dysplasia and the corresponding normal gastric mucosa (P <0.01), the values of V/B were 1.5261 +/- 0.3028, 0.9334 +/- 0.2872,and 0.9051 +/- 0.2794, respectively. The values of V/B between normal gastric mucosa and gastric dysplasia were not different significantly (P > 0.05). There were significantly negative correlation between the VIP mRNA expression of the differentiation degree of tumor (P < 0.05). The VIP mRNA expression was higher in gastric adenocarcinoma with lymph node metastasis than that without lymph node matastsis (P < 0.05). The VIP protein expression of the gastric adenocarcinoma tissues was greater than that of normal control.

CONCLUSIONThis findings provide a direct evidence to support the possibility that VIP play a cofactor role in the pathogenesis of gastric adenocarcinoma.

Adenocarcinoma ; blood ; genetics ; Gastric Mucosa ; metabolism ; Gene Expression ; Humans ; RNA, Messenger ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Stomach Neoplasms ; blood ; genetics ; Vasoactive Intestinal Peptide ; blood ; genetics

AIM:To investigate the changes of short-chain acyl-CoA dehydrogenase(SCAD)in hypertensive vascular remodeling and to explore the relationship between SCAD and vascular remodeling in hypertension.METHODS:The spontaneously hypertensive rats(SHR;24 weeks old)and Wistar rats(24 weeks old)were used as experimental con-trol groups.The SHR and Wistar rats of 16 weeks old were trained by swimming as experimental groups.The systolic pres-sure was measured periodically.The thickness of vascular wall and the diameter of the vascular lumen were measured.The contents of ROS and ATP,the enzyme activity of SCAD, and the expression of SCAD at mRNA and protein levels in the aorta were determined.The free fatty acid in the serum and aorta was also measured.RESULTS:Compared with Wistar group,the diameter of vascular lumen decreased in SHR group.The thickness of vascular wall,the ratio of vascular wall and the diameter of vascular lumen,and the blood pressure in SHR group were increased significantly(P<0.05).Com-pared with SHR group,the diameter of vascular lumen increased in SHR +swim group.The thickness of vascular wall,the ratio of vascular wall and the diameter of vascular lumen,and the blood pressure in SHR +swim group were decreased sig-nificantly.Compared with control group, the expression of SCAD at mRNA and protein levels, the enzyme activity of SCAD,and the content of ATP were decreased in SHR group.However,the free fatty acid in the serum and aorta,and the content of ROS in the aorta were increased in SHR group.The expression of SCAD at mRNA and protein levels,the en-zyme activity of SCAD,the content of ATP were increased in Wistar +swim group and SHR +swim group.However, the free fatty acid in serum and aorta,and the content of ROS in the aorta were decreased in Wistar +swim group and SHR+swim group.CONCLUSION: Decrease in SCAD expression may be associated with hypertensive vascular remodeling. Swimming training can reverse hypertensive vascular remodeling by increasing the expression of SCAD in the aorta.

Pancreatic lipase (PL), a crucial enzyme in the digestive system of mammals, has been proven as a therapeutic target to prevent and treat obesity. The purpose of this study is to evaluate and characterize the PL inhibition activities of the major constituents from Fructus Psoraleae (FP), one of the most frequently used Chinese herbs with lipid-lowering activity. To this end, a total of eleven major constituents isolated from Fructus Psoraleae have been obtained and their inhibition potentials against PL have been assayed by a fluorescence-based assay. Among all tested compounds, isobavachalcone, bavachalcone and corylifol A displayed strong inhibition on PL (IC < 10 μmol·L). Inhibition kinetic analyses demonstrated that isobavachalcone, bavachalcone and corylifol A acted as mixed inhibitors against PL-mediated 4-methylumbelliferyl oleate (4-MUO) hydrolysis, with the K values of 1.61, 3.77 and 10.16 μmol·L, respectively. Furthermore, docking simulations indicated that two chalcones (isobavachalcone and bavachalcone) could interact with the key residues located in the catalytic cavity of PL via hydrogen binding and hydrophobic interactions. Collectively, these finding provided solid evidence to support that Fructus Psoraleae contained bioactive compounds with lipid-lowering effects via targeting PL, and also suggested that the chalcones in Fructus Psoraleae could be used as ideal leading compounds to develop novel PL inhibitors.