[Effects of chronic intermittent hypoxia on atrial electrical remodeling in rats].

OBJECTIVE: The aim of this study was to investigate the effects of chronic intermittent hypoxia (CIH) on atrial electrical remodeling in Sprague-Dawley (SD) rats, which provide the explication for the mechanisms of CIH promoting atrial fibrillation (AF). METHODS: Eighty SD rats were randomly divided into 2 groups: control group and CIH group (n=40). CIH rats were subjected to CIH 8 h/d for 30 days. After the echocardiography and hemodynamics examination, cardiac electrophysiological experiments, histological experiments, and molecular biological experiments were executed. AF susceptibility was measured by isolated heart electrophysiological experiments. Masson's trichrome stain was used to assess the degree of atrial fibrosis. The protein expression levels of sodium voltage-gated channel alpha subunit 5 (SCN5A/Nav1.5), calcium voltage-gated channel subunit alpha1 C (CACNA1C/Cav1.2) and potassium voltage-gated channel subfamily D member 3 (KCND3/Kv4.3) were measured by Western blot. In whole-cell patch clamp experiments, current clamp mode was used to record AP, and APD90 and APD50 were analyzed and compared between the two groups. In voltage clamp mode, INa, ICa-L, Ito and their kinetic parameters were recorded and compared between the two groups. RESULTS: Compared to the control rats, atrial interstitial collagen deposition (P＜0.01) and AF inducibility (P＜0.05) were increased in CIH rats, whereas the expression levels of Nav1.5, Cav1.2 and Kv4.3 were decreased (P＜0.05). APD90 and APD50 in CIH rats' atrial myocytes were longer than those of control rats, and CIH rats showed decreased current density of INa, ICa-L(P＜0.01) and Ito(P＜0.01). CONCLUSION: CIH-induced changes in the protein expression levels of ion channel subunits, current intensity, APD, and AF susceptibility, which may be the mechanisms of CIH promoting AF.

Prognostic factors and therapeutic effects of different treatment modalities for colorectal cancer liver metastases.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors in China, and the liver is the most common metastatic site in patients with advanced CRC. Hepatectomy is the gold standard treatment for colorectal liver metastases. For patients who cannot undergo radical resection of liver metastases for various reasons, ablation therapy, interventional therapy, and systemic chemotherapy can be used to improve their quality of life and prolong their survival time. AIM: To explore the prognostic factors and treatments of liver metastases of CRC. METHODS: A retrospective analysis was conducted on 87 patients with liver metastases from CRC treated at the Liaoning Cancer Hospital and Institute between January 2005 and March 2011. According to different treatments, the patients were divided into the following four groups: Surgical resection group (36 patients); ablation group (23 patients); intervention group (15 patients); and drug group (13 patients). The clinicopathological data and postoperative survival of the four groups were analyzed. The Kaplan-Meier method was used for survival analysis, and the Cox proportional hazards regression model was used for multivariate analysis. RESULTS: The median survival time of the 87 patients was 38.747 ± 3.062 mo, and the 1- and 3-year survival rates were 87.5% and 53.1%, respectively. The Cox proportional hazards model showed that the following factors were independent factors affecting prognosis: The degree of tumor differentiation, the number of metastases, the size of metastases, and whether the metastases are close to great vessels. The results of treatment factor analysis showed that the effect of surgical treatment was better than that of drugs, intervention, or ablation alone, and the median survival time was 48.83 ± 4.36 mo. The drug group had the worst prognosis, with a median survival time of only 13.5 ± 0.7 mo (P < 0.05). For patients with liver metastases of CRC near the great vessels, the median survival time (27.3 mo) of patients undergoing surgical resection was better than that of patients using other treatments (20.6 mo) (P < 0.05). CONCLUSION: Patients with a low degree of primary tumor differentiation, multiple liver metastases (number of tumors > 4), and maximum diameter of liver metastases > 5 cm have a poor prognosis. Among drug therapy, intervention, ablation, and surgical treatment options, surgical treatment is the first choice for liver metastases. When liver metastases are close to great vessels, surgical treatment is significantly better than drug therapy, intervention, and ablation alone.

Antityrosinase mechanism of ellagic acid in vitro and its effect on mouse melanoma cells.

The activities of ellagic acid in inhibiting mushroom tyrosinase and cell proliferation were evaluated in this research. The results of enzyme kinetics indicated that ellagic acid could effectively inhibit tyrosinase activity. The value of the semi-inhibitory rate (IC50 ) was 0.2 ± 0.05 mM. Ellagic acid inhibited tyrosinase activity in a reversible manner and was a mixed tyrosinase inhibitor. Furthermore, ellagic acid had a good inhibitory effect on the proliferation of mouse melanoma B16 cells and could induce apoptosis. The results acquired from fluorescence spectroscopy revealed that the interaction of ellagic acid with tyrosinase depended on hydrogen bond and electrostatic force. In addition, computational docking showed that ellagic acid interacted with amino acid residues of tyrosinase (Asn19 and Lys372) by hydrogen bond and produced electrostatic interaction with amino residue Lys18. PRACTICAL APPLICATIONS: In the present research, the antityrosinase mechanism of ellagic acid and its effect on mouse melanoma cells were investigated. This study suggested that ellagic acid had a strong inhibitory activity against tyrosinase and cell proliferation,which laid an experimental foundation for the development of new drugs and whitening products. The combined multispectral methods used in this research can be applied to the screening of other antityrosinase inhibitors, further promoting the development and utilization of tyrosinase inhibitors.

Inhibition of α-glucosidase activity and non-enzymatic glycation by tannic acid: Inhibitory activity and molecular mechanism.

The inhibition of α-glucosidase and glycation is considered as an effective approach for the treatment of type 2 diabetes. In this study, multispectroscopic and molecular docking techniques were employed to investigate the inhibition of tannic acid on α-glucosidase and glycation. Kinetics analyses revealed that tannic acid had a significant inhibition on α-glucosidase (IC50 = 0.35 ±â€¯0.02 µM) in a reversible and mixed competitive manner. The results acquired from fluorescence quenching and ANS-binding fluorescence methods revealed that tannic acid could bind to α-glucosidase and reduce the hydrophobic area on the surface of the enzyme. In addition, synchronous fluorescence analysis showed that tannic acid decreased the hydrophobicity of α-glucosidase and changed the conformation of the enzyme. In vitro glycation assays showed that tannic acid had strong inhibitory effects on the formation of fructosamine, dicarbonyl compounds, and fluorescent AGEs. ANS-binding fluorescence analysis showed that tannic acid could bind to BSA and reduce the hydrophobicity of BSA in glycation. Moreover, the results of molecular docking showed the interaction between tannic acid and α-glucosidase was mainly driven by hydrogen bond, electrostatic, and hydrophobic interaction. And the interaction between tannic acid and BSA was mainly driven by hydrogen bond and hydrophobic interaction.

Clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization combined with radiotherapy in hilar cholangiocarcinoma.

BACKGROUND: Radical surgical resection is regarded as the best treatment for hepatic hilar cholangiocarcinoma. However, 60%-70% of patients have lost the chance of surgery at the time of diagnosis. Simple biliary stent or drainage tube placement may fail in a short time due to tumor invasion or overgrowth, bile accumulation, or biofilm formation. Effective palliative treatments to extend the effective drainage time are of great significance for improving the quality of life of patients and changing the prognosis of patients. AIM: To investigate the clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization (TACE) combined with radiotherapy in hilar cholangiocarcinoma. METHODS: A retrospective analysis was conducted on patients clinically diagnosed with hilar cholangiocarcinoma from June 2014 to January 2017 at the Liaoning Provincial Cancer Hospital. Patients were evaluated by specialists, and those who were not suitable for surgery or unwilling to undergo surgery and met the inclusion criteria were included in the study. There were a total of 72 patients (34 males and 38 females) with an average age of 59.9 years (range, 40-72 years). According to percutaneous transhepatic biliary angiography and the patients' wishes, stent implantation or biliary drainage tube implantation was used to relieve biliary obstruction. The patients were divided into either a control group or a combined treatment group according to their follow-up treatment. The control group consisted of a total of 35 patients who received simple biliary drainage tube placement and biliary stent implantation (7 patients with bilateral stents and 6 with a unilateral stent) and 22 patients receiving biliary drainage tube placement alone. The combined treatment group received TACE and extracorporeal radiotherapy after biliary drainage or biliary stent implantation and consisted of a total of 37 patients, including 21 patients receiving combined treatment after biliary stent placement (14 patients with bilateral stents and 7 with a unilateral stent) and 16 undergoing combined therapy after implanting the biliary drainage tube. In the combination treatment group, the TACE chemotherapy regimen employed gemcitabine and cisplatin, and the embolic agent was iodized oil. A particular dose was determined according to the patient's body surface area and the tumor staining indicated by DSA. In vitro radiotherapy was performed with intensity-modulated radiotherapy or three-dimensional conformal radiotherapy at an average dose of 48.3 Gy. Both groups were followed from stent implantation or drainage tube implantation until the patient quitted or died. The median length of follow-up observation was 13 mo. The differences in overall survival time and the effect of different jaundice reducing methods (single stent, double stent, or biliary drainage) on the patency time and survival time of biliary stents were compared between the two groups; the related factors affecting overall survival time were analyzed. RESULTS: The median survival time of the control group was 10.5 mo; the median survival time of patients with biliary stent implantation and those with percutaneous biliary drainage was 9.6 mo and 11.4 mo, respectively, and there was no statistically significant difference between them. The median survival time of the combined treatment group was 20.0 mo, which was significantly higher than that of the control group (P < 0.05). Among patients in the combined treatment group, the median survival time of patients who underwent biliary stent implantation and those who accepted percutaneous biliary drainage before the combination therapy was 19.5 mo and 20.1 mo, respectively, and there was no significant difference between them. In the combination treatment group, the mean time of median stent patency was 15.6 mo, which was significantly higher than that of the control group (7.0 mo; P < 0.05). The independent factors affecting survival time included age, whether to receive combination therapy, percutaneous biliary drainage tube implantation, and Bismuth-Corlette classification as type IV. CONCLUSION: Gemcitabine and cisplatin-based TACE combined with radiotherapy can prolong the survival of patients with hilar cholangiocarcinoma. Independent predictors of survival include selection of combination therapy, Bismuth-Corlette classification as type IV, selection of percutaneous biliary drainage tube implantation, and age.

Intermedin promotes hepatocellular carcinoma cell proliferation through the classical Wnt signaling pathway.

The proliferative activity of hepatic carcinoma cells is directly associated with tumorigenesis, tumor development, metastasis and invasion. A variety of cytokines and peptides serve important roles in the development of hepatic carcinoma. The aim of the present study was to examine the effect of intermedin (IMD) on hepatic carcinoma cell proliferation and its mechanism of action. HepG2 hepatic carcinoma cell lines were treated with human recombinant IMD1-53 and its receptor antagonist IMD17-47. Cell proliferation was detected using a Cell Counting kit-8. The activation of the classical Wnt signaling pathway was demonstrated by the ratio of TOPflash:FOPflash luciferase activity. The expression of c-Myc and cyclin D1 downstream of the Wnt signaling pathway were detected using reverse transcription-quantitative polymerase chain reaction analysis. It was demonstrated that IMD may promote the proliferation of HepG2 cells in a time-dependent manner, and that the IMD receptor antagonist IMD17-47 could eliminate this promotion. IMD may activate classical Wnt signaling pathway transcriptional activity and the mRNA levels of certain downstream target genes. Furthermore, blocking of the Wnt signaling pathway may inhibit IMD-induced HepG2 cell proliferation to a certain extent. IMD may promote hepatic carcinoma cell proliferation by binding with receptor antagonist IMD17-47 and activating the Wnt signaling cascade, thus providing a novel avenue for the treatment of hepatic carcinoma.

Intermedin promotes hepatic carcinoma cell proliferation through upregulation of miR-155.

OBJECTIVE: MicroRNAs (miRNAs) plays an important role in the development of malignant carcinoma. The small peptide intermedin (IMD) can promote hepatic carcinoma cell proliferation. The aim of the present study is to examine the effect of miR-155 on IMD-stimulated hepatic carcinoma cell proliferation. METHODS: Proliferation of hepatic carcinoma SMMC7721 cells was detected by CCK-8, expression of proliferating cell nuclear antigen (PCNA) and miR-155 was detected by real-time PCR. RESULTS: We found that IMD promotes the proliferation of SMMC7721 cells in a time and dose-dependent manner. IMD can upregulate the expression of miR-155, and blocking of miR-155 can inhibit the IMD-induced SMMC7721 cell proliferation to some extent. CONCLUSION: This study demonstrated that IMD can promote the proliferation of human hepatic carcinoma cell line SMMC7721 cells through upregulation of miR-155. This study may contribute to hepatic cancer prevention and therapy.

[Application of Le Fort â ¢ osteotomy with minimal invasive approach in the treatment of midfacial hypoplasia].

Objective: To describe a minimal invasive approach in the Le Fort Ⅲ osteotomy procedure. Methods: 33 cases with midfacial hypoplasia were treated by Le Fort Ⅲ osteotomy.Incisions were performed with minimal invasive approach,through lower eyelid,intraoral and upper eyelid crease or medial part of eyebrow instead of coronal incision.After the completion of osteotomy,distraction osteogenesis or orthognathic procedures were followed. Results: The midfacial segments achieved enough advancement without obvious relapse.Bleeding and operative time were reduced compared with coronal approach.No obvious scar was left. Conclusion: The Le Fort Ⅲ osteotomy procedure could be successfully performed through minimal approach with steady results and minimal scars.

A surgical protocol for bicondylar four-quadrant tibial plateau fractures.

PURPOSE: Bicondylar tibial plateau fractures involving four articular quadrants are severe and complex injuries, and they remain a challenging problem in orthopaedic trauma. The aim of this study was to introduce a new treatment protocol with dual-incision and multi-plate fixation in the floating supine patient position as well as to report the preliminary clinical results. METHODS: From January 2006 to December 2011, 16 consecutive patients with closed bicondylar four-quadrant tibial plateau fractures (Schatzker type VI, OTA/AO 41C2/3) were treated with posteromedial inverted L-shaped and anterolateral incisions. With the posteromedial approach, three quadrants (posteromedial, anteromedial and posterolateral) can be exposed, reduced and fixed with multiple small antiglide plates and short screws in an enclosure pattern. With the anterolateral approach, after articular elevation and bone substitute grafting, a strong locking plate with long screws to the medial cortex is used to raft-buttress the reduced lateral plateau fracture, hold the entire reconstructed tibial condyles together, and contact the condyles with the tibial shaft. All patients were encouraged to exercise knee motion at an early stage. The outcome was evaluated clinically and radiologically after a minimum two-year follow-up. RESULTS: The average operation time was 98 ± 26 minutes (range 70-128) and the average duration of hospitalization was 29 ± 8.6 days (range 20-41). Three cases used five plates, nine cases used four plates, and four cases used three plates. All patients were followed for a mean of 28.7 ± 6.1 months (range 26-38). Fifteen incisions healed initially, while one patient developed a medial wound dehiscence and was successfully managed by debridement. All patients achieved radiological fracture union after an average of 20.2 weeks. At the two-year follow up, the average knee range of motion (ROM) was 98° ± 13.7 (range 88-125°), with a Hospital for Special Surgery (HSS) knee score of 87.7 ± 10.3 (range 75-95), and SMFA score of 21.3 ± 8.6 (range 12-33). CONCLUSION: For bicondylar four-quadrant tibial plateau fractures, the treatment protocol of multiple medial-posterior small plates combined with a lateral strong locking plate through dual incisions can provide stable fracture fixation to allow for early stage rehabilitation. Good clinical outcomes can be anticipated.

Effect of preparation conditions and washing of activated carbon from paper mill sewage sludge on its adsorptive properties.

Sludge-based activated carbon (SAC) was prepared from paper mill sewage sludge by physical activation with steam for wastewater treatment in this study. The effects of preparation variables, including carbonization temperature, carbonization time, activation temperature and activation time, on iodine number and yield were investigated through orthogonal experiments. The influences of washing by deionized water and acid on the characteristics and adsorption capacities of SAC for phosphate, methylene blue and reactive red 24 were also studied. The results indicated that the optimal preparation conditions were: carbonization temperature of 350 °C, carbonization time of 40 min, activation temperature of 800 °C and activation time of 20 min. The characteristics and adsorption capacities of SAC were obviously different before and after washing, especially by acid. The surface area was improved and adsorption capacities for dyes increased after washing, while adsorption capacity for phosphate decreased. The maximum adsorption capacities provided strong evidence of the potential of SAC as an alternative adsorbent for wastewater treatment.

Microbial treatment of the monosodium glutamate wastewater by Lipomyces starkeyi to produce microbial lipid.

The monosodium glutamate (MSG) wastewater as a medium was treated by Lipomyces starkeyi to produce microbial lipid in the study. The effect of related factors (initial glucose concentration, inoculation concentration, initial culture pH, and cultivation time) on biomass, lipid production and lipid content was discussed, respectively. According to the experiments, the optimal fermentation conditions were determined: addition of 80g/L glucose, 10% inoculation concentration, initial pH about 5.0, incubation time 96h. Under this condition, the biomass production reached up to 4.61g/L, lipid production and lipid content was 1.14g/L and 24.73%, respectively. Simultaneously, protein and COD removal rate was 78.60% and 74.96%, respectively. The main composition of fatty acid in the resultant lipid was analyzed by gas chromatography-mass spectrometry, which showed: oleic acid (C18:1) 35.85%, palmitic acid (C16:0) 19.91%, palmitoleic acid (C16:1) 17.65%, and myristic acid (C14:0) 16.03%.

[Study on the extraction of total flavonoids from Mentha spicata by ultrasonic method].

The optimal conditions of total flavonoids extraction from Mentha spicata were identified by orthogonal test. The results showed that the ethanol concentration and the ultrasonic time had significant effect on the extraction of total flavonoids and the optimum conditions of extraction were A3B3C1D1, which were as follows: the ethanol concentration was 50%, the ultrasonic time was 40 min, the solid-liquid ratio was 1 g: 50 mL and the temperature of extraction was 60 degrees C, On the basis of the extracting method above, the content of total flavonoids in Mentha spicata was 0.0951 mg/mg. The linear equation was A = 11.51143C - 0.00029, r = 0.9999. This method is simple, quick and accurate with good prosperity.

[The association between polymorphism of the serotonin 2A, 2C receptor genes and obstructive sleep apnea-hypopnea syndrome in Han population].

OBJECTIVE: To investigate the association between polymorphisms of the serotonin 2A, 2C receptor genes and obstructive sleep apnea-hypopnea syndrome (OSAHS), and therefore to explore the genotypes related to OSAHS. METHODS: The T102C and A1438G polymorphisms of the serotonin 2A receptor genes and the G796C polymorphisms of the serotonin 2C receptor genes were identified by polymerase chain reaction-restricted fragment length polymorphism assay in 119 unrelated subjects (including 65 OSAHS patients and 54 normal controls) of "Han" population of China. The genotype distribution and the allele frequencies of the polymorphisms were compared between the OSAHS group and the control group. The effects of polymorphisms in the OSAHS group on parameters of polysomnography and indexes correlated with obesity were analyzed. RESULTS: There was no significant difference in genotype distribution and allele frequencies of the T102C polymorphisms of the serotonin 2A receptor genes between the two groups; the frequencies of TT/TC/CC genotype and T/C allele were 27.7% (18/65), 46.2% (30/65), 26.1% (17/65), 50.8% (66/130) and 49.2% (64/130), respectively in the OSAHS group; but were 27.8% (15/54), 51.8% (28/54), 20.4% (11/54), 53.7% (58/108) and 46.3% (50/108), respectively in the control group (chi(2) = 0.616 and 0.203, respectively, P > 0.05). The G796C polymorphisms of the serotonin 2C receptor genes were as follows: the frequencies of male's G/C allele, female's GG/GC genotype and G/C allele were 88.9% (48/54), 11.1% (6/54), 63.6% (7/11), 36.4% (4/11), 81.8% (18/22) and 18.2% (4/22), respectively in the OSAHS group; but were 90.5% (38/42), 9.5% (4/42), 66.7% (8/12), 33.3% (4/12), 83.3% (20/24) and 16.7% (4/24), respectively in the control group (chi(2) = 0.007, 0.002 and 0.064, respectively, P > 0.05). The frequencies of AA genotype and A allele in the A1438G polymorphisms of the serotonin 2A receptor genes in the OSAHS group [63.1% (41/65) and 74.6% (97/130), respectively] were significantly higher than those of the control one [27.8% (15/54) and 40.7% (44/108), respectively; chi(2) = 18.779 and 28.035, respectively, P < 0.01]. The OSAHS patients with AA genotype had higher obstructive apnea-hypopnea index (OAHI) and longest apnea time (LAT) than those with AG/GG genotype [OAHI were (40 +/- 9)/h, (25 +/- 9)/h and (20 +/- 11)/h, respectively, t = 6.674 and 7.753, respectively, P < 0.05; LAT were (94 +/- 10) s, (88 +/- 9) s and (75 +/- 12) s, respectively, t = 3.278 and 5.682, respectively, P < 0.05]. The lowest saturation of blood oxygen in patients with AA genotype was significantly lower than that in patients with AG/GG genotype [(69 +/- 12)%, (78 +/- 10)% and (80 +/- 9)%, respectively, t = 4.025 and 4.153, respectively, P < 0.05]. There was no significant difference in body mass index [(26.9 +/- 2.8) kg/m(2), (25.2 +/- 2.7) kg/m(2) and (26.0 +/- 3.7) kg/m(2), respectively], neck circumference [(43.3 +/- 2.7) cm, (42.6 +/- 1.8) cm and (42.8 +/- 2.1) cm, respectively] and waist/hip rate (0.89 +/- 0.12), (0.92 +/- 0.11) and (0.90 +/- 0.09), respectively, F = 0.859, 1.296 and 1.078, respectively, P > 0.05). CONCLUSION: The T102C polymorphisms of the serotonin 2A receptor gene and the G796C polymorphisms of the serotonin 2C receptor gene may be not associated with OSAHS in subjects of "Han" population of China. The 1438 AA genotype of the serotonin 2A receptor gene may be involved in OSAHS, and the A allele may be an important candidate gene for OSAHS.