Mendelian randomization study of circulating lipids and biliary tract cancer among East Asians.

BACKGROUND: Associations of High-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol (CHL), and triglyceride (TRG) concentrations with risk of biliary tract cancer (BtC) were conflicting in observational studies. We aim to investigate the causal link between circulating lipids and BtC using genetic information. METHODS: Single nucleotide polymorphisms of the four circulating lipids (n = 34,421) and BtC (418 cases and 159,201 controls) were retrieved from two independent GWAS studies performed in East Asian populations. Two-sample univariate and multivariate Mendelian Randomization (MR) analyses were conducted to determine the causal link between circulating lipids and BtC. RESULTS: No significant horizontal pleiotropy was detected for all circulating lipids according to the MR-PRESSO global test (P = 0.458, 0.368, 0.522, and 0.587 for HDL, LDL, CHL, and TRG, respectively). No significant evidence of heterogeneity and directional pleiotropy was detected by the Cochran's Q test and MR-Egger regression. Univariate MR estimates from inverse variance weighting method suggested that one standard deviation (1-SD) increase of inverse-normal transformed HDL (OR = 1.38, 95% CI 0.98-1.94), LDL (OR = 1.46, 95% CI 0.96-2.23), and CHL (OR = 1.34, 95% CI 0.83-2.16) were not significantly associated with BtC risk. Whereas 1-SD increase of inverse-normal transformed TRG showed a significantly negative association with BtC risk (OR = 0.48, 95% CI 0.31-0.74). In multivariate MR analyses including all the four lipid traits, we found that 1-SD increase of LDL and TRG was significantly associated with elevated (OR = 1.32, 95% CI 1.04-2.01) and decreased (OR = 0.54, 95% CI 0.42-0.68) risk of BtC, respectively. CONCLUSION: Circulating lipids, particularly LDL and TRG, may have roles in the development of BtC. However, the results of this study should be replicated in MR with larger GWAS sample sizes for BtC.

Single-nucleotide polymorphisms responsible for pseudo-albinism and hypermelanosis in Japanese flounder (Paralichthys olivaceus) and reveal two genes related to malpigmentation.

Paralichthys olivaceus is the kind of cold-water benthic marine fish. In the early stages of development, the symmetrical juveniles transform into an asymmetrical body shape through metamorphosis for adapting benthic life. After that, one side of the fish body is attached to the ground, and the eyes turn to the opposite side which is called ocular side. The body color also appears asymmetry. The skin on the ocular side is dark brown, and the skin on the blind side is white without pigmentation. Pseudo-albinism and hypermelanosis have been considered distinct body color disorders in flatfish. Pseudo-albinism and hypermelanosis in Paralichthys olivaceus are due to abnormal or uneven pigment distribution, due to the interaction of hereditary and environmental factors, rather than a single-nucleotide mutation of a specific gene. Here, we report three single-nucleotide polymorphisms (SNPs) responsible for both pseudo-albinism and hypermelanosis, which are located on two body color-related genes involved in melanogenesis-related pathways. c.2440C>A (P. V605I) and c.2271-96T>C are located on the Inositol 1,4,5-trisphosphate receptor type 2-like (ITPR2) (Gene ID: 109624047), they are located in exon 16 and the non-coding region, respectively, and c.2406C>A (P.H798N) is located in exon 13 of the adenylate cyclase type 6-like (AC6) gene(Gene ID: 109630770). ITPR2 and AC6 expression, which both participate in the thyroid hormone synthesis pathway associated with pseudo-albinism and hypermelanosis in P. olivaceus, were also investigated using qRT-PCR. In hypermelanotic fish, there were relatively higher levels of expression in ITPR2 and AC6 mRNA of hyper-pigmented skin of blind side than that of non-pigmented skin on the blind side and pigmented skin on the ocular side, while in pseudo-albino fish, expression level of ITPR2 and AC6 mRNA in pigmented skin of ocular side was significantly higher than that in non-pigmented skin both ocular and blind side. The results indicated that the expression of the two genes in abnormal parts of body color is positively correlated with pigmentation, suggesting that the influence of abnormal expression of two genes on the pigmentation in abnormal parts of body color deserves further study.

Evaluation of the benefit of post-mastectomy radiotherapy in patients with early-stage breast cancer: A propensity score matching study.

The present study aimed to evaluate the significance of post-mastectomy radiotherapy (PMRT) in patients with early stage (T1-2) breast cancer. The Surveillance, Epidemiology, and End Results database was searched, and data on female patients with early stage (T1-2) breast cancer with 1-3 positive axillary lymph nodes (LNs) were extracted. Patients were subdivided into two groups: Those who had received PMRT and those who had not (no PMRT). Data from the two groups were analyzed in order to identify associations between PMRT status, breast cancer-specific survival (BCSS) probability and overall survival (OS) probability using multivariate Cox proportional hazards regression and propensity score matching models. A total of 7,316 patients were included in the analysis. Prior to propensity score matching, outcome probabilities were increased in the PMRT group, compared with the no PMRT group (BCSS probabilities: 92.0 vs. 90.1%, respectively, P=0.015; OS probabilities: 89.8 vs. 86.0%, respectively, P<0.001). In multivariate analyses, tumor location was not identified as being a risk factor for BCSS (hazard ratio, 0.917; 95% confidence interval, 0.772-1.090; P=0.326). Following propensity score matching, differences between the two treatment groups (PMRT and no PMRT) in terms of their BCSS scores remained significant (93.7 vs. 90.1%, respectively; P=0.007). Compared with the no PMRT group, the OS probabilities of the PMRT group were increased (89.4 vs. 86.0%; P=0.025). In conclusion, the present results indicated that PMRT may benefit the prognosis of patients with breast cancer with early stage disease (T1-2), and those with one to three positive axillary LNs.

The application of Compont gel in chronic obstructive jaundice rats model.

PURPOSE: To establish a new rat model, the pathogenesis of which is closer to the clinical occurrence of chronic obstructive jaundice with liver fibrosis. METHODS: 90 SD rats were randomly divided into 3 groups. Group A common bile duct ligation, group B common bile duct injection compont and group C injection saline. The serum of three groups was extracted, and the liver function was detected by ELISA. HE staining, Masson staining and immunohistochemistry were used to detect liver pathology. RESULTS: Group B showed a fluctuant development of jaundice, obstructive degree reached a peak at 2 weeks, and decreased from 3 weeks. HA, LA and PCIII were significantly higher than control group. 3 weeks after surgery, liver tissue fibrosis occurred in group B, and a wide range of fiber spacing was formed at 5 weeks. Immunohistochemistry showed that hepatic stellate cells were more active than the control group. CONCLUSION: Intra-biliary injection of Compont gel is different from the classic obstructive jaundice animal model caused by classic bile duct ligation, which can provide an ideal rat model of chronic obstructive jaundice with liver fibrosis.

The application of Compont gel in chronic obstructive jaundice rats model

Abstract Purpose: To establish a new rat model, the pathogenesis of which is closer to the clinical occurrence of chronic obstructive jaundice with liver fibrosis. Methods: 90 SD rats were randomly divided into 3 groups. Group A common bile duct ligation, group B common bile duct injection compont and group C injection saline. The serum of three groups was extracted, and the liver function was detected by ELISA. HE staining, Masson staining and immunohistochemistry were used to detect liver pathology. Results: Group B showed a fluctuant development of jaundice, obstructive degree reached a peak at 2 weeks, and decreased from 3 weeks. HA, LA and PCIII were significantly higher than control group. 3 weeks after surgery, liver tissue fibrosis occurred in group B, and a wide range of fiber spacing was formed at 5 weeks. Immunohistochemistry showed that hepatic stellate cells were more active than the control group. Conclusion: Intra-biliary injection of Compont gel is different from the classic obstructive jaundice animal model caused by classic bile duct ligation, which can provide an ideal rat model of chronic obstructive jaundice with liver fibrosis.