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)=1.05~4.83) increased risk of liver metastases. On the stratification analysis, 72R-carrying genotype conferred a 3.46-fold (95% CI=1.02~11.72) and a 1.05-fold (95% CI=0.36~3.08) 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.

Objective: To assess the occurrence of stressful life events in the year before the initiation of systemic sclerosis. Methods: A consecutive series of 40 patients with systemic sclerosis (mean age (56.3±11.9) years, mean disease duration (4.3±3.1) years; 32 females and 8 males), including 28 with diffuse cutaneous scleroderma and 12 with limited cutaneous scleroderma, were evaluated. A control group of 40 healthy subjects free of systemic sclerosis also was included. Socioeconomic status was investigated and Paykel’s interview for recent life events (a semi-structured research interview covering 64 life events) was conducted. Results: Patients with systemic sclerosis showed higher percentages of lower education (72.5%) and working class (82.5%), and reported more stressful life events (P<0.05), such as exits (P<0.05), undesirable events (P<0.01), and uncontrolled events (P<0.001), when compared with the control. More events that had an objective negative impact (P<0.001) were also reported in systemic sclerosis patients than in the control. These results are in accordance with a multifactorial model of pathogenesis in systemic sclerosis. Conclusion: We reported a strong relationship between stressful life events and the initiation of systemic sclerosis. Our findings are consistent with current understanding of the extensive links of behavioral responses to stress with neurophysiological and biochemical processes.

Objective: To assess the diagnostic efficiency of OMOM capsule endoscopy (CE) in a group of patients with different indications. Methods: Data from 89 consecutive patients (49 males, 40 females) with suspected small bowel disease who underwent OMOM CE (Jinshan Science and Technology Company, Chongqing, China) examination were obtained by retrospective review. The patients’ indications of the disease consisted of the following: obscure gastrointestinal bleeding (OGIB), abdominal pain or diarrhea, partial intestinal obstruction, suspected inflammatory bowel disease, tumor of unknown origin, hypoproteinemia, constipation, weight loss, and elevated tumor markers. Results: CE failed in one patient. Visualization of the entire small bowel was achieved in 75.0%. Capsules were naturally excreted by all patients. The detection rate of abnormalities was 70.5% for patients with suspected small bowel disease, and the diagnostic yield for patients with OGIB was higher than that for patients with abdominal pain or diarrhea (85.7% vs 53.3%, P<0.005). Angiodysplasia was the most common small bowel finding. Active bleeding sites were noted in the small intestine in 11 cases. Conclusion: OMOM CE is a useful diagnostic tool for the diagnosis of variably suspected small bowel disease, whose diagnostic efficiency is similar to that of the Pillcam SB (small bowel) CE (Given Imaging, Yoqneam, Israel).

Objective: To develop a new bioinformatic tool based on a data-mining approach for extraction of the most informative proteins that could be used to find the potential biomarkers for the detection of cancer. Methods: Two independent datasets from serum samples of 253 ovarian cancer and 167 breast cancer patients were used. The samples were examined by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). The datasets were used to extract the informative proteins using a data-mining method in the discrete stationary wavelet transform domain. As a dimensionality reduction procedure, the hard thresholding method was applied to reduce the number of wavelet coefficients. Also, a distance measure was used to select the most discriminative coefficients. To find the potential biomarkers using the selected wavelet coefficients, we applied the inverse discrete stationary wavelet transform combined with a two-sided t-test. Results: From the ovarian cancer dataset, a set of five proteins were detected as potential biomarkers that could be used to identify the cancer patients from the healthy cases with accuracy, sensitivity, and specificity of 100%. Also, from the breast cancer dataset, a set of eight proteins were found as the potential biomarkers that could separate the healthy cases from the cancer patients with accuracy of 98.26%, sensitivity of 100%, and specificity of 95.6%. Conclusion: The results have shown that the new bioinformatic tool can be used in combination with the high-throughput proteomic data such as SELDI-TOF MS to find the potential biomarkers with high discriminative power.

Objective: To determine the effects of albumin administration on lung injury and apoptosis in traumatic/hemorrhagic shock (T/HS) rats. Methods: Studies were performed on an in vivo model of spontaneously breathing rats with induced T/HS; the rats were subjected to femur fracture, ischemia for 30 min, and reperfusion for 20 min with Ringer’s lactate solution (RS) or 5% (w/v) albumin (ALB), and the left lower lobes of the lungs were resected. Results: Albumin administered during reperfusion markedly attenuated injury of the lung and decreased the concentration of lactic acid and the number of in situ TdT-mediated dUTP nick-end labelling (TUNEL)-positive cells. Moreover, immunohistochemistry performed 24 h after reperfusion revealed increases in the level of nuclear factor κB (NF-κB), and phosphorylated p38 mitogen-activated protein kinase (MAPK) in the albumin-untreated group was down-regulated by albumin treatment when compared with the sham rats. Conclusion: Resuscitation with albumin attenuates tissue injury and inhibits T/HS-induced apoptosis in the lung via the p38 MAPK signal transduction pathway that functions to stimulate the activation of NF-κB.

Objective: To investigate the early effects of hypertonic and isotonic saline solutions on apoptosis of intestinal mucosa in rats with hemorrhagic shock. Methods: A model of rat with severe hemorrhagic shock was established in 21 Sprague-Dawley (SD) rats. The rats were randomly divided into the sham group, normal saline resuscitation (NS) group, and hypertonic saline resuscitation (HTS) group, with 7 in each group. We detected and compared the apoptosis in small intestinal mucosa of rats after hemorrhagic shock and resuscitation by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), FITC (fluorescein-iso-thiocyanate)-Annexin V/PI (propidium iodide) double staining method, and flow cytometry. Results: In the early stage of hemorrhagic shock and resuscitation, marked apoptosis of small intestinal mucosa in the rats of both NS and HTS groups was observed. The numbers of apoptotic cells in these two groups were significantly greater than that in the sham group (P<0.01). In the HTS group, the apoptic cells significantly decreased, compared with the NS group (P<0.01). Conclusion: In this rat model of severe hemorrhagic shock, the HTS resuscitation of small volume is more effective than the NS resuscitation in reducing apoptosis of intestinal mucosa in rats, which may improve the prognosis of trauma.

Total saponins of Panax notoginseng (PNS) have been shown to ameliorate renal interstitial fibrosis. Ginsenoside Rg1, a panaxatriol saponin, is one of the major active molecules from PNS. The present study was undertaken to investigate the effect of ginsenoside Rg1 on renal fibrosis in rats with unilateral ureteral obstruction (UUO). The rats were randomly divided into 3 groups: sham-operation (n=15), UUO (n=15) and UUO with ginsenoside Rg1 treatment (n=15, 50 mg per kg body weight, intraperitoneally (i.p.) injected). The rats were sacrificed on Days 7 and 14 after the surgery. Histological examination demonstrated that ginsenoside Rg1 significantly inhibited interstitial fibrosis including tubular injury as well as collagen deposition. α-smooth muscle actin (α-SMA) and E-cadherin are two markers of tubular epithelial-myofibroblast transition (TEMT). Interestingly, ginsenoside Rg1 notably decreased α-SMA expression and simultaneously enhanced E-cadherin expression. The messenger RNA (mRNA) of transforming growth factor-β1 (TGF-β1), a key mediator to regulate TEMT, in the obstructed kidney increased dramatically, but was found to decrease significantly after administration of ginsenoside Rg1. Further study showed that ginsenoside Rg1 considerably decreased the levels of both active TGF-β1 and phosphorylated Smad2 (pSmad2). Moreover, ginsenoside Rg1 substantially suppressed the expression of thrombospondin-1 (TSP-1), a cytokine which can promote the transcription of TGF-β1 mRNA and the activation of latent TGF-β1. These results suggest that ginsenoside Rg1 inhibits renal interstitial fibrosis in rats with UUO. The mechanism might be partly related to the blocking of TEMT via suppressing the expression of TSP-1.

Objective: To evaluate the effects of tramadol on the proinflammatory responses in a rat model of incisional pain by investigating its effects on nociceptive thresholds and serum interleukin-6 (IL-6) and IL-2 levels. Methods: Forty-two male Sprague-Dawley (SD) rats scheduled for plantar incision were randomly divided into 7 groups (n=6 in each group). Rats in Group 1 receiving general anesthesia with no incision were served as control; At 30 min before skin incision, Groups 2~5 were given 5 ml normal saline or 1, 10, and 20 mg/kg tramadol, respectively, intraperitoneally (i.p.); Group 6 received 10 mg/kg tramadol after operation; Group 7 received 10 mg/kg tramadol before incision, followed by 200 μg/kg naloxone after operation. Mechanical allodynia was measured by electronic von Frey filament to evaluate the nociceptive thresholds 1 h before incision, and 1 h and 2 h after operation. Serum IL-6 and IL-2 levels were measured by enzyme-linked immunosorbent assay (ELISA) 2 h after operation. Results: Mechanical thresholds decreased significantly and serum IL-6 level increased significantly after operation in Group 2 compared with control (P<0.01), and these changes were reversed respectively by tramadol in a dose-dependent manner (P<0.05 and P<0.01, respectively). IL-2 level remained unchanged after operation in Group 2, but decreased in Group 3 (P<0.05), then gradually returned to the normal level in Groups 4 and 5. The intraperitoneally injected tramadol (10 and 20 mg/kg) produced a potent and dose-dependent antinocicptive effect on the lesioned paw. The antinocicptive effects of tramadol were partially antagonized by naloxone (200 μg/kg), suggesting an additional non-opioid mechanism. Conclusion: The results suggest that tramadol could be a good choice for the treatment of pain under the conditions that immunosuppression may be particularly contraindicated.

Objective: To examine modulations caused by cyclooxygenase-2 (COX-2) inhibitors on altered microenvironments and overbalanced neurotransmitters in pilocarpine-induced epileptic status rats and to investigate possible mechanisms. Methods: Celecoxib (a COX-2 inhibitor) was administered 45 min prior to pilocarpine administration. The effects of COX-2 inhibitors on mIPSCs (miniature GABAergic inhibitory postsynaptic currents) of CA3 pyramidal cells in the hippocampus were recorded. Expressions of COX-2, c-Fos, newly generated neurons, and activated microgliosis were analyzed by immunohistochemistry, and expressions of α-subunit of γ-amino butyric acid (GABA_A) receptors and mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) activity were detected by Western blotting. Results: Pretreatment with celecoxib showed protection against pilocarpine-induced seizures. Celecoxib prevented microglia activation in the hilus and inhibited the abnormal neurogenesis and astrogliosis in the hippocampus by inhibiting MAPK/ERK activity and c-Fos transcription. Celecoxib also up-regulated the expression of GABA_A receptors. NS-398 (N-2-cyclohexyloxy-4-nitrophenyl-methanesulfonamide), another COX-2 inhibitor, enhanced the frequency and decay time of mIPSCs. Conclusion: The COX-2 inhibitor celecoxib decreased neuronal excitability and prevented epileptogenesis in pilocarpine-induced status epilepticus rats. Celecoxib regulates synaptic reorganization by inhibiting astrogliosis and ectopic neurogenesis by attenuating MAPK/ERK signal activity, mediated by a GABAergic mechanism.

Objective: Optimization of combining electroencephalography (EEG), short latency somatosensory evoked potentials (SLSEP) and transcranial Doppler (TCD) techniques to diagnose brain death. Methods: One hundred and eleven patients (69 males, 42 females) from the major hospitals of Zhejiang Province were examined with portable EEG, SLSEP and TCD devices. Re-examinations occurred ≤12 h later. Results: The first examination revealed that the combination of SLSEP and EEG led to more sensitive diagnoses than the combination of SLSEP and TCD. Re-examination confirmed this and also revealed that the combination of TCD and EEG was the most sensitive. Conclusion: The results show that using multiple techniques to diagnose brain death is superior to using single method, and that the combination of SLSEP and EEG is better than other combinations.

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