Head-to-Tail Cross-Linking to Generate Bicyclic Helical Peptides with Enhanced Helicity and Proteolytic Stability.

We report a new pattern of a bicyclic helical peptide constructed through head-to-tail cross-linking. The described bicyclic helical peptide has a head-to-tail cross-linking arm and a C-terminal i, i + 4 cross-linking arm. This scaffold will provide a promising scaffold for designing a proteolytically resistant helix-constrained peptide.

Helix-Constrained Peptides Constructed by Head-to-Side Chain Cross-Linking Strategies.

Facile head-to-side chain cross-linking strategies are developed to generate helix-constrained peptides. In our strategies, a covalent cross-linker is incorporated at N, i+7 or N, i+1 positions to lock the peptide into a helical conformation. The described patterns of head-to-side chain cross-linking will provide new frameworks for constrained helical peptide.

Application of POSSUM and P-POSSUM in Surgical Risk Assessment of Elderly Patients Undergoing Hepatobiliary and Pancreatic Surgery.

PURPOSE: To investigate the efficacy and accuracy of the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) and Portsmouth-POSSUM (P-POSSUM) scoring systems in the risk assessment of postoperative complications and death in elderly patients undergoing hepatobiliary and pancreatic surgery. PATIENTS AND METHODS: Using POSSUM and P-POSSUM, 274 elderly patients undergoing hepatobiliary and pancreatic surgery were evaluated, and the complications and deaths predicted by the systems were compared with the actual situation. The accuracy and predictive ability of POSSUM and P-POSSUM were evaluated using chi-squared and t-tests, consistency of predicted and actual complication rates (observed/expected, OE ratio), and receiver operating characteristic (ROC) curve. RESULTS: The complication rate predicted by POSSUM (R1) was 22.57%, while the actual postoperative complication rate was 17.88% (P>0.05). The mortality rate predicted by POSSUM (R2) was 4.61%, while the actual rate was 1.09% (P<0.05). The mortality rate predicted by P-POSSUM (R) was 1.42%, while the actual rate was 1.09% (P>0.05). Patients with complications had higher physiology scores (PS), operative severity scores (OS), and POSSUM scores than those without complications (P<0.05). Furthermore, PS, OS, and POSSUM scores were higher in the mortality group than in the survival group. However, the number of individuals in the mortality group was too small to accurately reflect the overall situation. Stratified analysis showed that consistency of the OE ratio in different subgroups was close to 1. The ROC curve showed that the area under the curve for the complication rate predicted by POSSUM was 0.76. CONCLUSION: Although the postoperative mortality rate was higher than the actual value, POSSUM could accurately predict the postoperative complication rate in elderly patients undergoing hepatobiliary and pancreatic surgery. The P-POSSUM accurately predicted the postoperative mortality rate in this population. Patients with complications had higher POSSUM scores.

Maternal Serum Angiogenic Factor sFlt-1 to PlGF Ratio in Preeclampsia: A Useful Marker for Differential Diagnosis and Prognosis Evaluation in Chinese Women.

The ratio of soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF) is elevated and proved to be useful in preeclampsia (PE) diagnosis. Its value in differential diagnosis with other pregnancy complications and prediction of pregnancy duration has yet to be clarified in Chinese population. We retrospectively analyzed 118 singleton pregnancies with suspected or diagnosed PE at the Peking Union Medical College Hospital (PUMCH) in China. Among these, 62 pregnancies were diagnosed as PE (48 early onsets and 14 late onsets, with 39 and 5 severe PE, respectively), 12 gestational hypertension (GH), 15 chronic hypertension (chrHTN), 16 autoimmune diseases, and 13 pregnancies with uncomplicated proteinuria. And 76 normal pregnancies were included as control. The results showed (1) the sFlt-1/PlGF ratio in early onset PE subgroup was significantly higher than that in GH, chrHTN, and control groups; the sFlt-1/PlGF ratio in late onset PE subgroup was significantly higher than that in chrHTN and control groups, but similar as GH group; the sFlt-1/PlGF ratio was similar among GH, chrHTN, and control groups. (2) The sFlt-1/PlGF ratio was significantly increased in the PE group compared with autoimmune disease and uncomplicated proteinuria pregnancies. (3) By ROC curve analysis, the cutoff value of the sFlt-1/PlGF ratio was less than 21.5 to rule out PE and higher than 97.2 to confirm the diagnosis of PE. (4) The sFlt-1/PlGF ratio was higher in PE pregnancies delivering within 7 days than those more than 7 days, either in early onset PE or severe PE. In conclusion, we show that maternal sFlt-1/PlGF ratio is an efficient biomarker in the diagnosis and differential diagnosis of PE. This ratio can be used to predict the timing of delivery for PE pregnancies.

Comprehensive expression analysis suggests functional overlapping of human FOX transcription factors in cancer.

Forkhead-box (FOX) transcription factors comprise a large gene family that contains more than 50 members in man. Extensive studies have revealed that they not only have functions in control of growth and development, but also play important roles in different diseases, especially in cancer. However, biological functions for most of the members in the FOX family remain unknown. In the present study, the expression of 39 FOX genes in 48 kinds of cancer was mined from the Gene Expression Atlas database of European Bioinformatics Institute. The analysis results showed that some FOX genes demonstrate overlapping expression in various cancers, which suggests particular biological functions. The pleiotropic features of the FOX genes make them excellent candidates in efforts aimed to give medical treatment for cancers at the genetic level. The results also indicated that different FOX genes may have the synergy or antagonistics effects in the same cancers. The study provides clues for further functional analysis of FOX genes, especially for the pleiotropic biological functions and crosstalk of FOX genes in human cancers.