Radiotherapy is superior to transarterial chemoembolization as adjuvant therapy after narrow-margin hepatectomy in patients with hepatocellular carcinoma: A single-center prospective randomized study.

BACKGROUND: This study was recruited to compare the efficacy and safety of radiotherapy (RT) and transarterial chemoembolization (TACE) as postoperative adjuvant therapy after narrow-margin hepatectomy in hepatocellular carcinoma (HCC) patients. METHODS: This single-center prospective randomized study was conducted in the Cancer Hospital, Guang Xi Medical University, Nanning. A total of 72 patients who received treatment in this hospital between August 2017 and July 2019 were included and randomly allocated to TACE group (n = 48) and RT group (n = 24). Next, overall survival (OS) and progression-free survival (PFS) rates, recurrence patterns, financial burden, and safety were evaluated. RESULTS: The difference between the RT and TACE groups was not significant in one-, three-, and five-year OS (87.5%, 79.0%, and 62.5% vs. 93.8%, 75.9%, and 63.4%, respectively, P = 0.071) and PFS rates (79.0%, 54.2%, and 22.6% vs. 75.0%, 47.9%, and 32.6%, respectively, P = 0.071). Compared to the TACE group, the RT group had significantly lower intrahepatic recurrence rate (20.8% vs. 52.1%, P = 0.011), higher extrahepatic recurrence rate (37.5% vs. 14.6%, P = 0.034), and no marginal and diffuse recurrences (0% vs. 16.7%, P < 0.05). The mean overall treatment cost was higher (¥62,550.59 ± 4397.27 vs. ¥40,732.56 ± 9210.54, P < 0.01), the hospital stay (15.1 ± 3.7 vs. 11.8 ± 4.1 days, P < 0.01) was longer, and the overall treatment stay (13.3 ± 5.3 vs. 41.29 ± 12.4 days, P < 0.01) was shorter in the TACE group than in the RT group. Besides, both groups did not exhibit significant differences in the frequency and severity of adverse events. CONCLUSION: Both adjuvant TACE and RT can better the OS and PFS of patients with HCC. However, RT has a significantly better performance than TACE in terms of improving intrahepatic recurrence rate, treatment cost and hospital stay.

Prognostic role of serum carcinoembryonic antigen in patients receiving liver resection for colorectal cancer liver metastasis: A meta-analysis.

BACKGROUND: Carcinoembryonic antigen (CEA) is a broad-spectrum tumor marker for differential diagnosis, monitoring, and response assessment of a variety of malignancies. AIM: To evaluate whether serum CEA could predict the prognosis in patients with colorectal cancer liver metastasis (CRCLM) before and after liver resection (LR). METHODS: PubMed, Embase, Cochrane, and Web of Science were systematically searched to retrieve literature, with a search cut-off date of February 27, 2023. Articles were strictly screened for inclusion according to pre-specified inclusion and exclusion criteria. Data were pooled and analyzed using Stata 16.0. RESULTS: This meta-analysis included 36 studies involving a total of 11143 CRCLM patients. The results showed that a high pre-LR serum CEA level was correlated with poor overall survival (OS) [hazard ratio (HR) = 1.61, 95% confidence interval (CI): 1.49-1.75, P < 0.001] and recurrence-free survival (HR = 1.27, 95%CI: 1.11-1.45, P < 0.001) in CRCLM patients. A high post-LR serum CEA level predicted poor OS (HR = 2.66, 95%CI: 2.10-3.38, P < 0.001). A comparison by treatment modality, analysis modality, patient source, and cutoff-value showed that overall, high preoperative and postoperative serum CEA levels remained correlated with a poor prognosis. CONCLUSION: This study concluded that high pre-LR and post-LR serum CEA levels were significantly correlated with a poor prognosis in CRCLM patients.

Betaine Delayed Muscle Loss by Attenuating Samtor Complex Inhibition for mTORC1 Signaling Via Increasing SAM Level.

SCOPE: The muscle loss during aging results from the blunt of protein synthesis and poses threat to the elderly health. This study aims to investigate whether betaine affects muscle loss by improving protein synthesis. METHODS AND RESULTS: Male C57BL/6J mice are raised from age 12 or 15 months. Mice are fed with AIN-93M diet without or with 2% w/v betaine in distilled water as control group or betaine intervention group (Bet), respectively. Betaine supplementation to mice demonstrates better body composition, grip strength, and motor function. Muscle morphology upregulates expression of myogenic regulate factors, and elevates myosin heavy chain and also improves in Bet group. Betaine promotes muscle protein synthesis via tethering mammalian target of rapamycin complex1 protein kinase (mTORC1) on the lysosomal membrane thereby activating mTORC1 signaling. All these effects aforementioned are time-dependent (p < 0.05). Ultrahigh-performance liquid chromatography results show that betaine increases S-adenosyl-l-methionine (SAM) via methionine cycle. SAM sensor-Samtor-overexpression in C2C12 cells could displace mTORC1 from lysosome thereby inhibiting the mTORC1 signaling. Addition of betaine attenuates this inhibition by increasing SAM level and then disrupting interaction of Samtor complex. CONCLUSIONS: These observations indicate that betaine could promisingly promote protein synthesis to delay age-related muscle loss.

Exome sequencing identified a novel missense mutation c.464G>A (p.G155D) in Ca2+-binding protein 4 (CABP4) in a Chinese pedigree with autosomal dominant nocturnal frontal lobe epilepsy.

The aim of this study was to identify disease-causing gene mutations in a Chinese family affected with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), a 4-generation pedigree of 27 members in the Southern Chinese Han population, including 11 individuals diagnosed with ADNFLE. DNA samples were collected from 15 family members, chinese han people, including seven affected and eight unaffected individuals. None of these patients had night blindness or visual disorders. Four affected individuals were screened for mutations using whole-exome sequencing, and 13 potentially interesting mutations shared by all the four affected individuals were validated using the Sanger sequencing method. Only one novel missense mutation c.464G>A (p.G155D) in the CABP4 gene, encoding the neuronal Ca2+-binding protein 4 (CaBP4), was present in all seven affected individuals in this family as revealed by PCR with blood DNA samples using CABP4 primers. The mutation was also found in one young unaffected family member, but was absent from 300 unrelated control subjects. The p.G155D mutation, located near the Ca2+ binding motif EF-hand 1 and the L-type Ca2+ channel (Cav1.4) binding motif within the N-terminal lobe of CaBP4, is predicted to affect protein function according to the bioinformatics tools PolyPhen-2 and SIFT. These findings suggest that mutations in the CABP4 gene may be linked to ADNFLE.

[Effect of Ilepcimide Combined Western Drugs on Serum Level of Neuron Specific Enolase in Treating Epilepsy Children Patients].

Objective To observe changes of serum neuron specific enolase (NSE) level in children patients with epilepsy by additional use of ilepcimide (piperine derivative). Methods Totally 107 epilepsy children patients were assigned to the test group (77 cases) and the control group (30 cases) ac- cording to random digit table. Children patients in the control group received anti-epileptic Western drugs only. Those in the test group additionally took ilepcimide, 5 mg/kg per day as initial dose, taken in two times. The dose was gradually added to those without control of epilepsy attack. Added dose within a week should not exceed 10 mg/kg per day. The therapeutic course for all was one year. Electoencephalo- gram (EEG) was performed before treatment, half a year after treatment, and one year after treatment, respectively. Serum NSE level was detected using electrochemiluminescence. Efficacy was assessed after 1-year treatment. Results The total effective rate was 65. 0% (50177) in the test group, with statistical difference as compared with that in the control group [30. 0% (9/30), P <0. 01 ]. Compared with before treatment, serum NES-level obviously decreased in the test group after 0. 5-year treatment and 1- year treatment respectively (P <0. 05, P <0. 01). Besides, serum NES level was lower after 1-year treatment than after 0. 5-year treatment (P <0. 05, P <0. 01). There was no statistical difference in serum NES level between the test group and the control group at each time point (P >0. 05). Results of EEG were obviously superior in the test group (3 with normal range EEG, 5 critically abnormal EEG, 69 abnormal EEG) to the control group (2 with normal range EEG and 75 abnormal EEG) after 1-year treatment, with statistical difference (Z= -2. 33, P <0. 05). There was no statistical difference in EEG results of the control group between before treatment (all abnormal EEG) and after 1-year treatment (3 critically abnormal EEG and 27 abnormal EEG) (Z = -1. 732, P > 0. 05). Conclusion Adding ilepcimide (piperine derivative) for epilepsy children patients could lower serum NSE level and the frequency of seizures, and improve results of EEG.

Analysis of the CHRNA7 gene mutation and polymorphism in Southern Han Chinese patients with nocturnal frontal epilepsy.

OBJECTIVE: To detect the CHRNA7 gene mutation and polymorphism in Southern Han Chinese patients with nocturnal frontal lobe epilepsy (NFLE). METHODS: Blood samples were collected from 215 Southern Han Chinese patients with NFLE and 200 healthy Southern Han Chinese control subjects. Genomic DNA was extracted, and CHRNA7 whole genome exons were amplified by the polymerase chain reaction and subjected to Sanger sequencing. RESULTS: No CHRNA7 gene mutation was detected in all of the NFLE patients. However, five single nucleotide polymorphisms (SNPs) in sporadic cases were found, located in exons 5, 6, and 7 of the CHRNA7 gene. Among them, c.690G>A and c.698A>G are known SNPs, while c.370G>A, c.654C>T, and c.497-498delTG were newly discovered SNPs. These SNPs were also found in some of the healthy controls. CONCLUSIONS: No CHRNA7 gene mutation was identified in Southern Han Chinese patients with NFLE. The CHRNA7 gene is probably not responsible for NFLE in this population.

Patient-specific instrumentation does not improve accuracy in total knee arthroplasty.

Patient-specific instrumentation (PSI) has been introduced as a tool to increase the accuracy of total knee arthroplasty (TKA) compared with conventional instrumentation (CLI). However, previous studies have shown inconsistent results. The authors conducted a meta-analysis to compare the performance of PSI to CLI in TKA. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials electronic databases were systematically searched to identify eligible trials published between 2000 and March 2014. Two reviewers independently assessed methodological quality according to the Cochrane Handbook. Subgroup analyses were performed based on the different study designs (randomized, controlled trial [RCT] vs non-randomized, controlled trial [non-RCT]), preoperative magnetic resonance imaging vs computed tomography, and systems of PSI to explore the source of heterogeneity. Fourteen studies (7 RCTs and 7 non-RCTs) involving 1906 patients were included. There were no statistical differences with respect to the outliers of mechanical axis, coronal femoral component, sagittal femoral component, femoral component rotation, operative time, blood loss, and length of hospital stay between PSI and CLI groups. The number of outliers in coronal tibial components (odds ratio, 2.29; 95% confidence interval, 1.20 to 4.35; P=.01) and sagittal tibial components (odds ratio, 1.67; 95% confidence interval, 1.16 to 2.42; P<.01) was significantly lower in the CLI group than in the PSI group. Based on the numbers available, the use of PSI compared with CLI was not likely to improve the accuracy of component alignment and treatment effects of TKA. Further high-quality RCTs are warranted to confirm the authors' results.

Incidence of retear with double-row versus single-row rotator cuff repair.

Rotator cuff tears have a high recurrence rate, even after arthroscopic rotator cuff repair. Although some biomechanical evidence suggests the superiority of the double-row vs the single-row technique, clinical findings regarding these methods have been controversial. The purpose of this study was to determine whether the double-row repair method results in a lower incidence of recurrent tearing compared with the single-row method. Electronic databases were systematically searched to identify reports of randomized, controlled trials (RCTs) comparing single-row with double-row rotator cuff repair. The primary outcome assessed was retear of the repaired cuff. Secondary outcome measures were the American Shoulder and Elbow Surgeons (ASES) shoulder score, the Constant shoulder score, and the University of California, Los Angeles (UCLA) score. Heterogeneity between the included studies was assessed. Six studies involving 428 patients were included in the review. Compared with single-row repair, double-row repair demonstrated a lower retear incidence (risk ratio [RR]=1.71 [95% confidence interval (CI), 1.18-2.49]; P=.005; I(2)=0%) and a reduced incidence of partial-thickness retears (RR=2.16 [95% CI, 1.26-3.71]; P=.005; I(2)=26%). Functional ASES, Constant, and UCLA scores showed no difference between single- and double-row cuff repairs. Use of the double-row technique decreased the incidence of retears, especially partial-thickness retears, compared with the single-row technique. The functional outcome was not significantly different between the 2 techniques. To improve the structural outcome of the repaired rotator cuff, surgeons should use the double-row technique. However, further long-term RCTs on this topic are needed.

Does immobilization after arthroscopic rotator cuff repair increase tendon healing? A systematic review and meta-analysis.

INTRODUCTION: To determine whether immobilization after arthroscopic rotator cuff repair improved tendon healing compared with early passive motion. MATERIALS AND METHODS: A systematic electronic literature search was conducted to identify randomized controlled trials (RCTs) comparing early passive motion with immobilization after arthroscopic rotator cuff repair. The primary outcome assessed was tendon healing in the repaired cuff. Secondary outcome measures were range of motion (ROM) and American Shoulder and Elbow Surgeons (ASES) shoulder scale, Simple Shoulder Test (SST), Constant, and visual analog scale (VAS) for pain scores. Pooled analyses were performed using a random effects model to obtain summary estimates of treatment effect with 95% confidence intervals. Heterogeneity among included studies was quantified. RESULTS: Three RCTs examining 265 patients were included. Meta-analysis revealed no significant difference in tendon healing in the repaired cuff between the early-motion and immobilization groups. A significant difference in external rotation at 6 months postoperatively favored early motion over immobilization, but no significant difference was observed at 1 year postoperatively. In one study, Constant scores were slightly higher in the early-motion group than in the immobilization group. Two studies found no significant difference in ASES, SST, or VAS score between groups. CONCLUSION: We found no evidence that immobilization after arthroscopic rotator cuff repair was superior to early-motion rehabilitation in terms of tendon healing or clinical outcome. Patients in the early-motion group may recover ROM more rapidly. LEVEL OF EVIDENCE: Level II; systematic review of levels I and II studies.

[Clinical features and mutation analysis of CHRNA4 gene for families and sporadic cases affected with autosomal dominant nocturnal frontal lobe epilepsy].

OBJECTIVE: To investigate mutations of CHRNA4 gene in Chinese patients with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). METHODS: Two hundred and fifty-seven patients (including 215 sporadic and 42 familial cases) were analyzed. Mutational screening was performed by sequencing all of the 6 exons of the CHRNA4 gene including the donor and acceptor splice sites. RESULTS: The results have excluded the involvement of any known mutations of the CHRNA4 gene. A novel synonymous mutation c.570C>T(D190D) and 6 single nucleotide polymorphisms (SNPs) of the CHRNA4 gene were detected in 6 sporadic cases, including c.639T/C, c.678T/C, c.1209G/T, c.1227T/C, c.1659G/A, and c.1629C/T. The SNP D190D was hererozygous and absent in 200 healthy controls. CONCLUSION: This results suggested that mutations of the CHRNA4 gene may be rare in southern Chinese population with ADNFLE. The synonymous mutation D190D has not been reported previously. Its impact on the pathogenesis of ADNFLE warrant further study.

[Problems and solutions in minimally invasive process of posterior discectomy for lumbar disc herniation].

OBJECTIVE: To analyze the problems and complications of posterior discectomy for lumbar disc herniation. METHODS: From January 2005 to June 2010, 497 patients with lumbar disc herniation were treated by posterior discectomy, which data were analyzed retrospectively. There were 395 males and 102 females,ranging in age from 20 to 78 years with an average of 43.7 years. Among them, 405 cases were in single gap, 86 cases were in double gaps and 6 cases were in three gaps. The complication of operation and solution was analyzed. RESULTS: The mean operative time was 70 min (from 45 to 210 min), and the mean hospitalization was 10 d (from 5 to 20 d). Forty-seven cases suffered operative complications. There were 16 cases of wrong location of segments (14 cases occurred in operation and 2 occurred after operation), 15 cases of less alleviation or aggravation of nerve symptoms (12 cases were poor alleviation and 3 cases were aggravation), 10 cases of urinary retention, 5 cases of cerebrospinal fluid leakage and 1 case of infection. CONCLUSION: Minimally invasive process of posterior discectomy in treating lumbar disc herniation may complicate with many problems. The operative effects can be improved and the complication can be decreased if the ability of location is improved,surgical indications is correct and the operation is exactly performed.

[The first exploration of a minimally invasive lysis subcutaneouly for the treatment of gluteal muscle contracture based on relatively safe region around standard injection point of gluteal muscle].

OBJECTIVE: To explore the solution of choosing the minimally invasive incision site for gluteal muscle contracture patient based on standard injection point of gluteal muscle. METHODS: from September 2008 to August 2010, 25 patients (14 males and 11 females with an average of 16.5 years, ranging from 12 to 26 years) with injected gluteal muscle contracture were prospectively studied. The course of disease was from 6 to 12 years. Firstly, the connective skin Surface line from anterior superior iliac spine to coccyx (line AD) was delineated and the point (point O) was marked out as the standard gluteal muscle injection site which was on the one-third of the distance from the anterior superior iliac spine(point A) to the coccyx (point D). Secondly, the anterior and posterior edge lines of surface projection of the gluteal muscle contracture banding (line a, line p) were delineated. Thirdly, the distance from B to O and C to O (B is the point of intersection of line a and line AD,C is the point of intersection of line P and line AD)were measured which was the intersection of line a,p and line AD to point O. Lastly, the minimally invasive surgery was operformed via the skin entry of point C. RESULTS: OB = (0 +/- 0.76) cm, OC = (2.86 +/- 0.78) cm, BC = (2.86 +/- 1.01) cm,the mean postoperative drainage was less than 10 ml,there was no nerve damage,hematoma and other complications. All patients achieved the function of squatting in 4 to 6 days. CONCLUSION: The solution of choosing the minimally invasive incision site based on standard injection point of gluteal muscle has advantages of positioning precisely,handling easily, recoverying quickly, less trauma and safety, etc.

Assessment of the effect of betaine on p16 and c-myc DNA methylation and mRNA expression in a chemical induced rat liver cancer model.

BACKGROUND: The development and progression of liver cancer may involve abnormal changes in DNA methylation, which lead to the activation of certain proto-oncogenes, such as c-myc, as well as the inactivation of certain tumor suppressors, such as p16. Betaine, as an active methyl-donor, maintains normal DNA methylation patterns. However, there are few investigations on the protective effect of betaine in hepatocarcinogenesis. METHODS: Four groups of rats were given diethylinitrosamine (DEN) and fed with AIN-93G diets supplemented with 0, 10, 20 or 40 g betaine/kg (model, 1%, 2%, and 4% betaine, respectively), while the control group, received no DEN, fed with AIN-93G diet. Eight or 15 weeks later, the expression of p16 and c-myc mRNA was examined by Real-time PCR (Q-PCR). The DNA methylation status within the p16 and c-myc promoter was analyzed using methylation-specific PCR. RESULTS: Compared with the model group, numbers and areas of glutathione S-transferase placental form (GST-p)-positive foci were decreased in the livers of the rats treated with betaine (P < 0.05). Although the frequency of p16 promoter methylation in livers of the four DEN-fed groups appeared to increase, there is no difference among these groups after 8 or 15 weeks (P > 0.05). Betaine supplementation attenuated the down-regulation of p16 and inhibited the up-regulation of c-myc induced by DEN in a dose-dependent manner (P < 0.01). Meanwhile, increases in levels of malondialdehyde (MDA) and glutathione S-transferase (GST) in model, 2% and 4% betaine groups were observed (P < 0.05). Finally, enhanced antioxidative capacity (T-AOC) was observed in both the 2% and 4% betaine groups. CONCLUSION: Our data suggest that betaine attenuates DEN-induced damage in rat liver and reverses DEN-induced changes in mRNA levels.

[The effect of anthocyanins on cholesterol efflux from mouse peritoneal macrophage-derived foam cells and its possible molecular mechanism].

OBJECTIVE: To investigate the potential role of anthocyanins on modulating cholesterol efflux in mouse peritoneal macrophage-derived foam cells and related molecular mechanisms. METHODS: The macrophages were isolated from pathogen-free NIH mice and were loaded with 50 microg/ml oxLDL for 24 hours, newly formed foam cells were then treated with anthocyanins (cyanidin-3-glucoside, Cy-3-g; or peonidin-3-glucoside, Pn-3-g) at the concentrations of 1 micromol/L, 10 micromol/L, 100 micromol/L for 0 to 36 hours, respectively. The enzymatic-fluorescent method was used to determine cholesterol content in culture medium. ABCA1 expressions at mRNA and protein level were detected by real-time PCR and confocal microscope. RESULTS: Cholesterol efflux of macrophage-derived foam cells increased in a time- and dose-dependent manner post anthocyanins treatment. ABCA1 expressions at mRNA and protein levels were also significantly enhanced after anthocyanins treatment in these cells and these effects could be blocked by co-treatment with DIDS, an inhibitor of the transport activities of ABCA1 and blocker of apoAI-mediated cholesterol efflux. CONCLUSION: These data demonstrate that anthocyanins induce cholesterol efflux from mouse peritoneal macrophage-derived foam cells via regulating ABCA1 expression.

[Relationship between paraoxonase 1 55 Met/Leu, paraoxonase 2 148 Ala/Gly genetic polymorphisms and coronary artery disease].

OBJECTIVE: To study the relationships between paraoxonase 1 55 Met/Leu (PON1 55Met/Leu), paraoxonase 2 148 Ala/Gly(PON2 148Ala/Gly) genetic polymorphisms and coronary artery disease(CAD), plasma activities of paraoxonase (PON), total superoxide dismutase (T-SOD), as well as plasma concentration of maleic dialdehyde (MDA). METHODS: The PCR-RFLP method was applied to identify the genetic polymorphisms of PON1 55Met/Leu and PON2 148Ala/Gly, and the colorimetry way was used to detect plasma activities of PON, T-SOD and plasma MDA concentration of 262 CAD patients and 100 controls. RESULTS: Comparing with control, the CAD patient had the obviously lower activities of enzymes PON (349.27+/- 138.36 nmol/min.mL vs 454.75+/- 166.00 nmol/min.mL, P< 0.001) and T-SOD (23.61+/- 16.51 U/mL vs 44.01+/- 22.68 U/mL, P< 0.001) while getting the plasma MDA concentration increased markedly(2.47+/- 0.73 nmol/mL vs2.15+/- 0.55 nmol/mL, P< 0.01). The CAD patient had more LM genotype and M allele of PON1 55Met/Leu(24.8% vs 1.4%, P< 0.001 and 12.4% vs 0.5%, P was 0.001 respectively), GG and AG genotype and G allele of PON2 148 Ala/Gly(11.8% vs 5.0%, P< 0.001; 48.1% vs 24.0%, P< 0.001 and 36.0% vs 17.0%, P< 0.001 respectively) than control did. The activities of plasma PON and T-SOD were lower in individuals with PON??1 55 LM genotype than those with LL genotype(304.73+/- 125.04 vs 394.84+/- 154.87 nmol/min.mL and 24.89+/- 16.14 vs 30.22+/- 21.29 U/mL, P< 0.001 and P< 0.05 respectively). The activity of plasma PON was also lower in individuals with PON2 148 GG/AG genotype than that with AA genotype(281.47+/- 84.70 vs 356.00+/- 145.95 vs 417.34+/- 159.00 nmol/min.mL, P< 0.001). Logistic regression analysis showed that PON1 55 LM genotype (OR 29.08, 95%CI 2.88-294.04, P was 0.004) and M allele(OR 15.17, 95%CI 1.32-174.29, P was 0.029), PON2 148 GG/AG genotype (OR 2.32, 95%CI 1.52-3.54, P< 0. 001) and G allele (OR 3.24, 95%CI 1.38-7.61, P was 0.007) were independent risk factors for CAD. CONCLUSION: The CAD patient has the obviously low activities of plasma PON and T-SOD but on the contrary, get the plasma MDA concentration increased markedly. PON1 55 LM genotype and M allele, PON2 148 GG/AG genotype and G allele are the risk factors for coronary artery disease, and the activity of plasma PON is also markedly reduced in individuals with above genotypes.

[Study of the association between paraoxonase1 55 Met/Leu, paraoxonase2 148 Ala/Gly and manganese superoxide dismutase (MnSOD) 9 Ala/Val genetic polymorphisms and coronary heart disease].

OBJECTIVE: To study the associations between paraoxonase, 55 Met/Leu (PON1 55 Met/ Leu), paraoxonase2 148 Ala/Gly (PON2 148 Ala/Gly) and manganese superoxide dismutase 9 Ala/Val (MnSOD 9 Ala/Val) genetic polymorphisms and coronary heart disease (CHD), plasma activities of paraoxonase (PON), total superoxide dismutase (T-SOD), MnSOD, as well as plasma concentration of maleic dialdehyde (MDA). METHODS: Using PCR-RFLP method to identify genotype of PON1 55 Met/Leu, PON2 148 Ala/Gly and MnSOD 9 Ala/Val genetic polymorphisms, and using colorimetry to detect plasma activities of PON, T-SOD, MnSOD and plasma concentration of MDA in 262 CHD patients and 100 controls. RESULTS: Compared with controls, the plasma activities of PON [(349.27 +/- 138.36 vs. 454.75 +/- 166.00) nmol x min(-1) x ml(-1), P < 0.001], T-SOD [(23.61 +/- 16.51 vs. 44.01 +/- 22.68) U/ml, P < 0.001] and MnSOD [(21.56 +/- 13.11 vs. 28.79 +/- 8.65) U/ml, P < 0.001] reduced obviously,while plasma MDA concentration increased markedly [(2.47 +/- 0.73 vs. 2.15 +/- 0.55)nmol/ml, P < 0.01] in CHD patients. There were more LM genotype and Met allele of PON, 55 Met/Leu (24.8% vs. 1.4%, P < 0.001 and 12.4% vs. 0.5%, P = 0.001, respectively), GG and AG genotype and G allele of PON2 148 Ala/Gly (11.8% vs. 5.0%, P < 0.001, 48.1% vs. 24.0%, P < 0.001 and 36.0% vs. 17.0%, P < 0.001, respectively) and AA genotype, A allele of MnSOD 9 Ala/Val genetic polymorphisms (64.2% vs. 43.0%, P = 0.001 and 80.0% vs. 67.0%, P = 0.014, respectively) in CHD patients than in controls. The activities of plasma PON and T-SOD were lower in individuals with PON1 55 LM genotype than those with LL genotype. The activity of plasma PON was also lower in individuals with PON2 148 GG/AG genotype than those with AA genotype. The activities of plasma PON and MnSOD depressed in individuals with MnSOD AA genotype compared with those with VV genotype. Logistic regression analysis demonstrated that PON1 55 LM genotype, PON2 148 GG/AG genotype and G allele were independent risk factors for CHD. CONCLUSION: The antioxidative ability decreased, while lipid superoxide increased in CHD patients. Gene polymorphisms of PON1 55 Met/Leu, PON2 148 Ala/Gly and MnSOD 9 Ala/Val seemed to involve in the morbidity of CHD by influencing the plasma activities of PON and MnSOD.

[Effects of LOX-1 on expression of adhesion molecules induced by ox-LDL in HUVECs].

OBJECTIVE: To investigate the effects of oxidized low-density lipoprotein receptor 1 (LOX-1) on secretion of adhesive molecules mediated by ox-LDL in human umbilical endothelial cells (HUVECs). METHODS: HUVECs with different concentration of ox-LDL (0, 10, 20, 50, 100 microg/ml) were incubated for 24 h, or HUVECs were pretreated with 250 microg/ml poly (I) or 250 microg/ml carrageenan for 2 h and then incubated with 50 microg/ml ox-LDL for another 24 h. Expression of LOX-1 was determined by realtime RT-PCR and Western blot. mRNA and protein of ICAM-1, VCAM-1 and E-selectin were examined by RT-PCR and Western blot respectively. RESULTS: Incubation of HUVECs with ox-LDL (10-100 microg/ml) enhanced the expressions of LOX-1, ICAM-1 and E-selectin in a concentration-dependent manner (P < 0.01). On the contrary, ox-LDL did not affect the expression of VCAM-1 by HUVECs. The expression of LOX-1, ICAM-1 and E-selectin induced by ox-LDL were reduced in HUVECs pretreated with 250 microg/ml poly (I) or 250 microg/ml carrageenan for 2 h and then incubated with 50 microg/ml ox-LDL for 24 h. This showed that both poly (I) and carrageenan obviously decreased the expression of LOX-1, ICAM-1 and E-selectin induced by ox-LDL. CONCLUSION: ox-LDL may upregulate the expression of LOX-1, ICAM-1 and E-selectin, and LOX-1 blocker may partly inhibit this upregulation. The results suggest that the expression of inflammatory molecules induced by ox-LDL in HUVECs is mediated by LOX-1.

Dietary fatty acids regulate cholesterol induction of liver CYP7alpha1 expression and bile acid production.

In the present study we investigated the effects of dietary fats containing predominantly PUFA, monounsaturated FA (MUFA), or saturated FA (SFA) on lipid profile and liver cholesterol 7alpha-hydroxylase (CYP7alpha1) mRNA expression and bile acid production in C57BL/6J mice. The animals (n = 75) were randomly divided into five groups and fed a basic chow diet (AIN-93G) (BC diet), a chow diet with 1 g/100 g of cholesterol (Chol diet), a chow diet with 1 g/100 g of cholesterol and 14 g/100 g of safflower oil (Chol + PUFA diet), a chow diet with 1 g/100 g of cholesterol and olive oil (Chol + MUFA diet), or a chow diet with 1 g/100 g of cholesterol and myristic acid (Chol + SFA diet) for 6 wk. The results showed that the Chol + SFA diet decreased CYP7alpha1 gene expression and bile acid pool size, resulting in increased blood and liver cholesterol levels. Addition of PUFA and MUFA to a 1% cholesterol diet increased the bile acid pool production or bile acid excretion and simultaneously decreased liver cholesterol accumulation despite decreased CYP7alpha1 mRNA expression. The results indicate that the decreased bile acid pool size induced by the SFA diet is related to inhibition of the liver CYP7alpha1 gene expression, but an increased bile acid pool size and improved cholesterol homeostasis are disassociated from the liver CYP7alpha1 gene expression.