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1.  Stress-induced intestinal necrosis resulting from severe trauma of an earthquake 
AIM: To investigate the possible reasons and suggest therapeutic plan of stress-induced intestinal necrosis resulting from the severe trauma.
METHODS: Three patients in our study were trapped inside collapsed structures for 22, 21 and 37 h, respectively. The patients underwent 3-4 operations after sustaining their injuries. Mechanical ventilation, intermittent hemodialysis and other treatments were also provided. The patients showed signs of peritoneal irritation on postoperative days 10-38. Small intestinal necrosis was confirmed by emergency laparotomy, and for each patient, part of the small bowel was removed.
RESULTS: Two patients who all performed 3 operations died of respiratory complications on the first and second postoperative days respectively. The third patient who performed 4 operations was discharged and made a full recovery. Three patients had the following common characteristics: (1) Multiple severe trauma events with no direct penetrating gastrointestinal injury; (2) Multiple surgeries with impaired renal function and intermittent hemodialysis treatment; (3) Progressive abdominal pain and tenderness, and peritoneal irritation was present on post-traumatic days 10-38; (4) Abdominal operations confirmed segment ulcer, necrosis of the small intestine, hyperplasia and stiffness of the intestinal wall; and (5) Pathological examinations suggested submucosal hemorrhage, necrosis, fibrosis and hyalinization of the vascular wall. Pathological examinations of all 3 patients suggested intestinal necrosis with fistulas.
CONCLUSION: Intestinal necrosis is strongly asso-ciated with stress from trauma and post-traumatic complications; timely exploratory laparotomy maybe an effective method for preventing and treating stress-induced intestinal necrosis.
doi:10.3748/wjg.v18.i17.2127
PMCID: PMC3342613  PMID: 22563202
Intestinal necrosis; Stress; Trauma; Earthquake; Exploratory laparotomy; Fatty acid binding protein
2.  A Novel Cold-Active Lipase from Candida albicans: Cloning, Expression and Characterization of the Recombinant Enzyme 
A novel lipase gene lip5 from the yeast Candida albicans was cloned and sequenced. Alignment of amino acid sequences revealed that 86–34% identity exists with lipases from other Candida species. The lipase and its mutants were expressed in the yeast Pichia pastoris, where alternative codon usage caused the mistranslation of 154-Ser and 293-Ser as leucine. 154-Ser to leucine resulted in loss of expression of Lip5, and 293-Ser to leucine caused a marked reduction in the lipase activity. Lip5-DM, which has double mutations that revert 154 and 293 to serine residues, showed good lipase activity, and was overexpressed and purified by (NH4)2SO4 precipitation and ion-exchange chromatography. The pure Lip5-DM was stable at low temperatures ranging from 15–35 °C and pH 5–9, with the optimal conditions being 15–25 °C and pH 5–6. The activation energy of recombinant lipase was 8.5 Kcal/mol between 5 and 25 °C, suggesting that Lip5-DM was a cold–active lipase. Its activity was found to increase in the presence of Zn2+, but it was strongly inhibited by Fe2+, Fe3+, Hg2+ and some surfactants. In addition, the Lip5-DM could not tolerate water-miscible organic solvents. Lip5-DM exhibited a preference for the short-and medium-chain length p-nitrophenyl (C4 and C8 acyl group) esters rather than the long chain length p-nitrophenyl esters (C12, C16 and C18 acyl group) with highest activity observed with the C8 derivatives. The recombinant enzyme displayed activity toward triacylglycerols, such as olive oil and safflower oil.
doi:10.3390/ijms12063950
PMCID: PMC3131601  PMID: 21747717
Candida albicans; cold-active lipase; Pichia pastoris expression; enzyme purification
3.  Investigation on Quantitative Structure Activity Relationships and Pharmacophore Modeling of a Series of mGluR2 Antagonists 
MGluR2 is G protein-coupled receptor that is targeted for diseases like anxiety, depression, Parkinson’s disease and schizophrenia. Herein, we report the three-dimensional quantitative structure–activity relationship (3D-QSAR) studies of a series of 1,3-dihydrobenzo[ b][1,4]diazepin-2-one derivatives as mGluR2 antagonists. Two series of models using two different activities of the antagonists against rat mGluR2, which has been shown to be very similar to the human mGluR2, (activity I: inhibition of [3H]-LY354740; activity II: mGluR2 (1S,3R)-ACPD inhibition of forskolin stimulated cAMP.) were derived from datasets composed of 137 and 69 molecules respectively. For activity I study, the best predictive model obtained from CoMFA analysis yielded a Q2 of 0.513, R2 ncv of 0.868, R2 pred = 0.876, while the CoMSIA model yielded a Q2 of 0.450, R2 ncv = 0.899, R2 pred = 0.735. For activity II study, CoMFA model yielded statistics of Q2 = 0.5, R2 ncv = 0.715, R2 pred = 0.723. These results prove the high predictability of the models. Furthermore, a combined analysis between the CoMFA, CoMSIA contour maps shows that: (1) Bulky substituents in R7, R3 and position A benefit activity I of the antagonists, but decrease it when projected in R8 and position B; (2) Hydrophilic groups at position A and B increase both antagonistic activity I and II; (3) Electrostatic field plays an essential rule in the variance of activity II. In search for more potent mGluR2 antagonists, two pharmacophore models were developed separately for the two activities. The first model reveals six pharmacophoric features, namely an aromatic center, two hydrophobic centers, an H-donor atom, an H-acceptor atom and an H-donor site. The second model shares all features of the first one and has an additional acceptor site, a positive N and an aromatic center. These models can be used as guidance for the development of new mGluR2 antagonists of high activity and selectivity. This work is the first report on 3D-QSAR modeling of these mGluR2 antagonists. All the conclusions may lead to a better understanding of the mechanism of antagonism and be helpful in the design of new potent mGluR2 antagonists.
doi:10.3390/ijms12095999
PMCID: PMC3189765  PMID: 22016641
3D-QSAR; mGluR2 antagonist; CoMFA; CoMSIA; pharmacophore modeling
4.  Orthochina.org: Case-based Orthopaedic Wiki Project in China 
Traditional continuing medical education (CME) depended primarily on periodic courses and conferences. The cost-effectiveness of these courses has not been established, and often the content is not tailored to best meet the needs of the students. Internet training has the potential to accomplish these goals. Over the last 10 years, we have developed a Web site entitled “Orthochina.org,” based upon the wiki concept, which uses an interactive, case-based format. We describe the development of online case discussions, and various technical and administrative requirements. As of December 31, 2007, there were 33,984 registered users, 9,759 of which passed the confirmation procedures. In 2007, an average of 211 registrants visited daily. The average number of first page clicks was 4,248 per day, and the average number of posts was 70 per day. All cases submitted for discussion include the patient’s complaint, physical examination findings, and relevant images based on specific criteria for case discussion. The case discussions develop well professionally. No spam posting or unauthorized personal advertisement is permitted. In conclusion, online academic discussions proceed well when the orthopaedic surgeons who participate have established their identities.
doi:10.1007/s11999-008-0396-z
PMCID: PMC2584280  PMID: 18685911

Results 1-4 (4)