Profiles of alternative splicing events in the diagnosis and prognosis of Gastric Cancer.

Background: Gastric cancer (GC) is a heterogeneous disease, and alternative splicing (AS) is a powerful universal transcriptional regulatory mechanism that contributes to the occurrence and development of cancer. However, the systematic analysis of AS events in GC is lacking; therefore, further studies are needed. Methods: Genome-wide analysis of AS events was performed using RNA-Seq data to evaluate the difference between GC and adjacent tissues at the AS level. Prognostic signatures based on differentially expressed alternative splicing (DEAS) events and a correlation network between DEAS and genes were built. Results: We identified 48,141 AS events, of which 2325 showed differential expression patterns. The parental genes before DEAS events play an essential role in regulating GC-related processes such as ribosome (FDR < 0.0001) and thermogenesis (FDR = 0.0002). There were 76 survival-associated DEAS cases. Stratifying patients according to the percent spliced in index value of six types of splicing patterns formed significant Kaplan-Meier curves in the overall survival analysis. A prognostic feature based on DEAS performed well for stratification in patients with GC. Conclusion: The present study will enrich our understanding regarding the distinction of GC and provide a generous amount of biomarkers and potential targets for the treatment of GC.

Systematic profiling of alternative splicing events and splicing factors in left- and right-sided colon cancer.

Left- and right-sided colon cancer (LC and RC) differ substantially in their molecular characteristics and prognoses, and are thus treated using different strategies. We systematically analyzed alternative splicing (AS) events and splicing factors in LC and RC. RNA-seq data were used for genome-wide profiling of AS events that could distinguish LC from RC. The Exon Skip splicing pattern was more common in RC, while the Retained Intron pattern was more common in LC. The AS events that were upregulated in RC were enriched for genes in the axon guidance pathway, while those that were upregulated in LC were enriched for genes in immune-related pathways. Prognostic models based on differentially expressed AS events were built, and a prognostic signature based on these AS events performed well for risk stratification in colon cancer patients. A correlation network of differentially expressed AS events and differentially expressed splicing factors was constructed, and RBM25 was identified as the hub gene in the network. In conclusion, large differences in AS events may contribute to the phenotypic differences between LC and RC. The differentially expressed AS events reported herein could be used as biomarkers and treatment targets for colon cancer.

Single-molecule long-read sequencing reveals the chromatin basis of gene expression.

Genome-wide chromatin accessibility and nucleosome occupancy profiles have been widely investigated, while the long-range dynamics remain poorly studied at the single-cell level. Here, we present a new experimental approach, methyltransferase treatment followed by single-molecule long-read sequencing (MeSMLR-seq), for long-range mapping of nucleosomes and chromatin accessibility at single DNA molecules and thus achieve comprehensive-coverage characterization of the corresponding heterogeneity. MeSMLR-seq offers direct measurements of both nucleosome-occupied and nucleosome-evicted regions on a single DNA molecule, which is challenging for many existing methods. We applied MeSMLR-seq to haploid yeast, where single DNA molecules represent single cells, and thus we could investigate the combinatorics of many (up to 356) nucleosomes at long range in single cells. We illustrated the differential organization principles of nucleosomes surrounding the transcription start site for silent and actively transcribed genes, at the single-cell level and in the long-range scale. The heterogeneous patterns of chromatin status spanning multiple genes were phased. Together with single-cell RNA-seq data, we quantitatively revealed how chromatin accessibility correlated with gene transcription positively in a highly heterogeneous scenario. Moreover, we quantified the openness of promoters and investigated the coupled chromatin changes of adjacent genes at single DNA molecules during transcription reprogramming. In addition, we revealed the coupled changes of chromatin accessibility for two neighboring glucose transporter genes in response to changes in glucose concentration.

[Laparoscope hepatectomy for hepatic hemangioma: a report of 18 cases].

OBJECTIVE: To evaluate the feasibility and practicality of laparoscopic hepatectomy for hepatic hemangioma. METHODS: Candidate for laparoscopic liver resection were 18 cases of hepatic hemangioma from January 2002 to October 2006. The portal bloods stream was blocked by the laparoscope portal blood blocker. The Electric-cautery and ultracision were used for liver transection. Operative procedures included anatomical left hepatectomy in 2 cases, non-anatomical left hepatectomy 1 case, left lobectomy 5 cases, local liver resection 10 cases. Two cases of hepatic hemangioma associated with gallbladder stone were performed cholecystectomy synchronously, 1 case associated with chronic appendicitis were performed appendectomy synchronously. RESULTS: Laparoscopic left liver resection was successfully performed in all 18 cases. The operative duration was (185.4 +/- 55.7) min. The quantity of blood lost during the operation was (416.2 +/- 128.8) ml. The postoperative recovery was smooth and good. No critical complications occurred. The duration for hospitalization was (6.2 +/- 1.0) d. CONCLUSION: Laparoscope hepatectomy for hepatic hemangioma is safe and feasible.

A novel method for reconstruction in laparoscopic pancreaticoduodenectomy: an experience of 13 cases.

Laparoscopic pancreaticoduodenectomy (LPD) is a challenging operation to general surgeon. Up to date, only about 135 cases have been reported, 16 cases in China, 119 cases outside China. The reconstruction of alimentary system is a key procedure to ensure success of the whole surgery. It is worth investigating the methods of reconstruction in LPD. A retrospective study is made to investigate the methods of reconstruction in LPD. We analyze 13 cases of LPD performed in our center. Child's or modified Child's method was used to make the reconstruction in our practice. We tried three methods to make the anastomosis of pancreaticojejunostomy, including end-to-end dunking binding pancreaticojejunostomy in two cases, end-to-end dunking pancreaticojejunostomy using interrupted suture in two cases, and duct-to-jejunal end-to-side embedding pancreaticojejunostomy in nine cases. The clinical data was collected and analyzed. Three of four patients, who underwent end-to-end pancreaticojejunostomy, had a little pancreatic leakage, especially in the first case. None of other nine patients, who underwent duct-to-jejunal end-to-side embedding pancreaticojejunostomy, was detected to have pancreatic leakage, and the operating time of these nine cases was less than other four cases. Duct-to-jejunal end-to-side embedding pancreaticojejunostomy is a safe and efficient method of reconstruction in LPD.