DJ-1 plays a neuroprotective role in SH-SY5Y cells by modulating Nrf2 signaling in response to lidocaine-mediated oxidative stress and apoptosis.

To investigate the effects of DJ-1 on lidocaine-induced cytotoxicity in neurons and the link with Nrf2 signaling, SH-SY5Y cells were treated with 1, 4, 8, and 16 mM lidocaine. Cell viability was measured by MTT assay, and apoptosis was measured by flow cytometry analysis. The mitochondrial membrane potential, reactive oxygen species (ROS) levels, lipid peroxidation (MDA), and GSH/GSSG ratio were determined with specific kits. Expression of DJ-1, Nrf2, and Nrf2 downstream signaling proteins (glutathione peroxidase [GPx], heme oxygenase-1 [HO-1], catalase [CAT], and glutathione reductase [GR]), was determined by western blot and qRT-PCR. The cell viability was dramatically decreased, while levels of apoptosis, ROS and Cys106-oxidized DJ-1 were significantly enhanced following treatment with lidocaine (concentration 4-16 mM), and increases were observed in a dose-dependent manner. After treatment with 8 mM lidocaine, DJ-1, and nuclear Nrf2, as well as antioxidative stress-related proteins, GPx, GR, HO-1, and CAT, were all significantly inhibited. Overexpression of DJ-1 suppressed lidocaine-induced apoptosis and oxidative stress in SH-SY5Y cells and activated Nrf2 signalling at the same time, and these effects were reversed by the inhibition of Nrf2. DJ-1 could protect SH-SY5Y cells from lidocaine-induced apoptosis through inhibition of oxidative stress via Nrf2 signaling.

Optimal effective concentration of ropivacaine for postoperative analgesia by single-shot femoral-sciatic nerve block in outpatient knee arthroscopy.

OBJECTIVE: To compare analgesic and mobility effects of different ropivacaine concentrations in femoral-sciatic nerve block, for postoperative analgesia in knee arthroscopy. METHODS: Outpatients (American Society of Anesthesiologists physical classification status of I or II), scheduled for elective knee arthroscopy, were randomly allocated to one of seven groups, prospectively investigating different concentrations of ropivacaine (0.12%; 0.14%; 0.16%; 0.18%; 0.20%; 0.22% or 0.50%), for ultrasound-guided femoral-sciatic nerve block procedures for postoperative analgesia. Visual analogue scale (VAS) pain scores and motor block evaluation scales were observed at 4, 8, 16 and 24 h postsurgery. RESULTS: In total, 105 patients were enrolled; results were analysed for 103. VAS scores for the 0.12%, 0.14% and 0.16% groups were significantly different from the 0.50% group. There were no significant differences between the 0.18%, 0.20%, 0.22% and 0.50% groups: half maximal effective concentrations and 95% maximal effective concentrations of ropivacaine were 0.158 (95% confidence intervals [CI] 0.149, 0.167) and 0.198 (95% CI 0.186, 0.221), respectively. Rates of motor blockade (Bromage score or hip motor function scale > 0) were significantly different between the 0.50% group and all other ropivacaine doses. CONCLUSION: The 0.20% ropivacaine dose for femoral-sciatic nerve block in knee arthroscopy provided satisfactory postoperative analgesia, while preserving ability of motion.

Percutaneous cardiopulmonary support for catastrophic pulmonary fat embolism in pigs.

OBJECTIVE: The purpose of this study was to evaluate the effect of percutaneous cardiopulmonary support (PCPS) for fatal fat embolism. METHODS: Twelve piglets were randomly assigned into either a conventional treatment group (CT group, n = 6) or a PCPS group (n = 6) after receiving 0.3 mL/kg of fat intravenously. The piglets in the CT group received conventional treatments including mechanical ventilation with 100% oxygen, steroid, fluids, anticoagulant, and positive inotropic agents. In addition to conventional treatments, the piglets in the PCPS group received PCPS after fat injection. Mean arterial pressure, central venous pressure, pressure of end tidal carbon dioxide, oxygen saturation, partial pressure of oxygen in arterial blood, arterial carbon dioxide pressure or tension, plasmic lactic acid, and free fatty acid were monitored. The survival rate and the consumption of positive inotropic agents were also recorded. RESULTS: The survival rate of piglets 10 hours after fat injection was much higher in the PCPS group than that in the CT group (100% vs. 0%, p < 0.01). The dosages of positive inotropic agents in the PCPS group were much lower than that in the CT group (p < 0.01). Oxygen saturation, partial pressure of oxygen in arterial blood, and arterial carbon dioxide pressure or tension were significantly improved in the PCPS group in the first 3 hours after fat injection when compared with those in the CT group (p < 0.05 or 0.01), but there were no statistical differences between the two groups in mean arterial pressure, central venous pressure, free fatty acid, and lactic acid at the period. CONCLUSION: PCPS can increase the survival rate of piglets with fatal fat embolism by providing effective cardiopulmonary support. This study suggests that PCPS might be an effective treatment for a patient with severe fat embolism if conventional treatments have not worked.

Sex-related differences in DNA copy number alterations in hepatitis B virus-associated hepatocellular carcinoma.

BACKGROUND: Males have a higher prevalence of hepatocellular carcinoma (HCC) than females in general, but the reasons for the sex disparity are still obscure. DNA copy number alteration (CNA) is a major feature of solid tumors including HCC, but whether CNA plays a role in sex-related differences in HCC development has never been evaluated. METHODS: High-resolution array comparative genomic hybridization (CGH) was used to examine 17 female and 46 male HCC patients with chronic hepatitis B virus (HBV) infection in Shanghai, China. Two-tailed Fisher's exact or chi2 tests was used to compare CNAs between females and males. RESULTS: The overall frequencies and patterns of CNAs in female and male cases were similar. However, female HCC tumors presented more copy number gains compared to those in males on 1q21.3-q22 (76.5% vs. 37.0%, P = 0.009), 11q11 (35.3% vs. 0.0%, P = 0.0002) and 19q13.31-q13.32 (23.5% vs. 0.0%, P = 0.004), and loss on 16p11.2 (35.3% vs. 6.5%, P = 0.009). Relative to females, male cases had greater copy number loss on 11q11 (63.0% vs. 17.6%, P = 0.002). Further analyses showed that 11q11 gain correlated with 19q13.31-q13.32 gain (P = 0.042), 11q11 loss (P = 0.011) and 16p11.2 loss (P = 0.033), while 1q21.3-q22 gain correlated with 19q13.31-q13.32 gain (P = 0.046). CONCLUSIONS: These findings suggest that CNAs may play a role in sex-related differences in HBV-associated HCC development.

Association of genetic polymorphisms in STAT1 gene with increased risk of hepatocellular carcinoma.

OBJECTIVE: Although signal transducer and activator of transcription 1 (STAT1), a transcription factor, plays a critical role in carcinogenesis and has been implicated as a tumor suppressor, few studies have investigated the associations between polymorphisms of this gene and the risk of cancer development. The aim of this study was to examine whether STAT1 gene polymorphisms are associated with the risk of hepatocellular carcinoma (HCC). METHODS: Ten single nucleotide polymorphisms in the STAT1 gene were genotyped by TaqMan assays in 469 HCC cases and 558 age-, sex- and HBsAg-matched controls in a Chinese population. RESULTS: Minor allele homozygous genotypes at rs867637 (9,046 bp 3' of STP A>G), rs3771300 (IVS24-153T>G), and rs2280235 (IVS20-103G>A), compared with their homozygote genotypes of common alleles, were associated with 1.6- (95% CI 1.1-2.3), 1.6- (95% CI 1.1-2.4), and 1.4-fold (95% CI 0.95-1.9) increased risk of HCC, respectively. The GGA haplotype, comprised of risk alleles at rs867637, rs3771300 and rs2280235, conferred a 1.2-fold (95% CI 1.0-1.5) increased risk of HCC, as compared to the most common haplotype of ATG. Diplotype GGA/GGA conferred a 1.6-fold (95% CI 1.0-2.5) increased risk of HCC compared with diplotype ATG/ATG. CONCLUSION: Our results demonstrate for the first time that polymorphisms in the STAT1 gene are associated with HCC susceptibility.

Ultrasound-guided continuous femoral nerve block for analgesia after total knee arthroplasty: catheter perpendicular to the nerve versus catheter parallel to the nerve.

BACKGROUND AND OBJECTIVES: This study tested the hypothesis that, in continuous femoral nerve block (CFNB) under ultrasound guidance, placing a catheter perpendicular to the nerve can shorten the time of catheter insertion while providing a similar quality of analgesia compared with placing a catheter parallel to the nerve. METHODS: Fifty patients undergoing total knee arthroplasty were randomly assigned to receive ultrasound-guided CFNB either with the catheter parallel to the nerve technique (parallel group, n = 25) or with the catheter perpendicular to the nerve technique (perpendicular group, n = 25). Patient-controlled morphine analgesia pumps were available to all the patients after surgery. The time of catheter insertion, failure rates, pain scores, morphine consumption, nausea and vomiting, and maximal degree of knee flexion were recorded. RESULTS: The time of catheter insertion was shorter in the perpendicular group than in the parallel group (12 +/- 3 versus 22 +/- 6 mins, P < 0.01). Failed catheter insertion occurred in 3 (12%) of 25 patients in the parallel group and in none of 25 patients in the perpendicular group (P = 0.2347). There were no significant differences in pain scores, opioid consumption, incidence of nausea and vomiting, and maximal degree of knee flexion between the 2 groups. CONCLUSIONS: In CFNB under ultrasound guidance, using the catheter perpendicular to the nerve technique can shorten the time of catheter insertion while providing a similar quality of analgesia after total knee arthroplasty as compared with the catheter parallel to the nerve technique.

Association of p53 codon 72 polymorphism with liver metastases of colorectal cancers positive for p53 overexpression.

OBJECTIVE: To evaluate the association between p53 codon 72 polymorphism (R72P) and the risk of colorectal liver metastases. METHODS: The p53 R72P genotype was identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 78 consecutive colorectal cancer patients with liver metastases and 214 age- and sex-matched cases with nonmetastatic colorectal cancer. RESULTS: The R allele of the p53 R72P polymorphism was more frequently found in metastatic cases than in nonmetastatic cases (P=0.075). Carriers of the 72R allele had a 2.25-fold (95% CI (confidence interval)=1.05 to approximately 4.83) increased risk of liver metastases. On the stratification analysis, 72R-carrying genotype conferred a 3.46-fold (95% CI=1.02 to approximately 11.72) and a 1.05-fold (95% CI=0.36 to approximately 3.08) increased risk of liver metastases for p53 overexpression-positive and negative colorectal cancers, respectively. CONCLUSION: These results demonstrate for the first time that the 72R allele of the p53 polymorphism has an increased risk for liver metastases in colorectal cancers positive for p53 overexpression.

[Association of TP53 gene polymorphisms with genetic susceptibility to liver metastases of colorectal cancer].

OBJECTIVE: To investigate the possible association between the single nucleotide polymorphisms (SNPs) (C-8343G, C-1863T and R72P) in TP53 gene and susceptibility to liver metastases of colorectal cancer (CRC) in a Chinese population. METHODS: The genotypes of each SNP in TP53 gene were determined by either TaqMan assays or PCR-based restriction fragment length polymorphism (RFLP) method in 121 colorectal cancer patients with liver metastases and sex-, age-matched 280 cases with nonmetastatic CRC as a control. Immunohistochemical staining for P53 was performed on paraffin-embedded sections. Odds ratios (ORs) for colorectal liver metastases and 95% confidence intervals (CIs) from unconditional logistic regression models were used to evaluate relative risks. RESULTS: No significant association of C-8343G or C-1863T with colorectal liver metastases risk was observed. However, the R allele of the TP53 R72P polymorphism was more frequently found in metastatic cases than in nonmetastatic cases (P= 0.037). When compared with PP homozygotes, the ORs of metastases for RP heterozygotes was 2.21 (95% CI: 1.13-4.33), for RR homozygotes was 2.26 (95% CI: 1.03-4.94), and for carriers of the 72R allele (RP or RR genotype) was 2.22 (95% CI: 1.16-4.26). Stratified analysis indicated that carrying the 72R allele had a more pronounced increase in colorectal liver metastases risk among patients with positive P53 expression tumors (OR= 3.28, 95% CI: 1.21-8.88), whereas no significantly increased metastases risk was found in patients with negative P53 expression tumors (OR= 1.37, 95% CI: 0.52-3.62). CONCLUSION: The R allele of the TP53 R72P polymorphism may contribute to the etiology of liver metastases in CRC patients, particularly among those with positive P53 expression tumors. Both TP53 C-8343G and C-1863T may be not associated with colorectal liver metastases risk.

[TP53 gene polymorphisms and colorectal cancer risk in Chinese population].

OBJECTIVE: To investigate the association between the single nucleotide polymorphisms (SNPs) in TP53 gene and susceptibility to colorectal cancer (CRC) in Chinese population. METHODS: Peripheral blood samples were collected and white cell genomic DNA was extracted from 345 CRC patients, 198 males and 1447 females, aged (58.7 +/- 13.5), and 670 sex, age, smoking and drinking situations-matched controls in Ningbo city, Zhejiang province The genotypes of the SNPs of C-8343G, C-1863T, and R72P in TP53 gene were determined by either TaqMan assays or PCR-based restriction fragment length polymorphism method. Unconditional logistic regression was used to calculate the odds ratio (OR) for CRC after adjustment of the covariates, such as sex, age, cigarette smoking, alcohol drinking, body mass index and first-degree family history of CRC, and 95% confidence intervals (CI) so as to evaluate relative risk. RESULTS: There were not significant differences in the above mentioned covariates between these 2 groups. No significant association of C-8343G or C-1863T polymorphism with CRC risk was observed (both P > 0.05). The CRC risk of the 72P genotype was 50.3%, 1.53 times that of the 72R genotype (39.6%) (95% CI = 1.27 - 1.85, P < 0.01). The CRC risk of the RP heterozygotes was 1.60 times that of the RP homozygote (95% CI = 1.17 - 2.18, P < 0.01), and the CRC risk of the PP homozygotes was 2.37 times that of the RP heterozygotes (95% CI = 1.61 - 3.47, P < 0.01). A dose-response relationship was shown (P < 0.01). Stratified analysis indicated that the 72P allele conferred a more pronounced increase in CRC risk among the alcohol consumers: the CRC risk was 3.01 times for the RP heterozygotes (95% CI = 1.48 - 6.12), and 4.71 times for the PP homozygotes (95% CI = 1.90 - 11.68). CONCLUSION: TP53 C-8343G and C-1863T polymorphisms are not associated with CRC risk. R72P polymorphism contributes to the etiology of CRC in the Chinese population, particularly among the alcohol consumers.

Association of the TP53 codon 72 polymorphism with colorectal cancer in a Chinese population.

A TP53 gene polymorphism, resulting in an arginine (R) to proline (P) at codon 72 (TP53 R72P), has been associated with the susceptibility to various cancers. To better understand the role of this polymorphism in colorectal cancer etiology, we examined the association between TP53 R72P and colorectal cancer risk in 345 patients with colorectal cancer and 670 controls in a Chinese population. We observed that subjects with RP and PP genotypes had a 1.60-fold and a 2.37-fold increased risk for colorectal cancer, respectively. The 72P allele conferred a more pronounced increase in colorectal cancer risk among alcohol consumers (heterozygotes: OR = 3.01; homozygotes: OR = 4.71). The TP53 R72P polymorphism was not linked to tumor location, histologic grade, lymph node metastases, Dukes stage, p53 positivity, or age at diagnosis, but to tumor size. We conclude that the TP53 R72P polymorphism may contribute to the etiology of colorectal cancer in the Chinese population, particularly among alcohol consumers.