Clinical and biomarker analyses of sintilimab plus gemcitabine and cisplatin as first-line treatment for patients with advanced biliary tract cancer.

The prognosis of biliary tract cancer (BTC) remains unsatisfactory. This single-arm, phase II clinical trial (ChiCTR2000036652) investigated the efficacy, safety, and predictive biomarkers of sintilimab plus gemcitabine and cisplatin as the first-line treatment for patients with advanced BTCs. The primary endpoint was overall survival (OS). Secondary endpoints included toxicities, progression-free survival (PFS), and objective response rate (ORR); multi-omics biomarkers were assessed as exploratory objective. Thirty patients were enrolled and received treatment, the median OS and PFS were 15.9 months and 5.1 months, the ORR was 36.7%. The most common grade 3 or 4 treatment-related adverse events were thrombocytopenia (33.3%), with no reported deaths nor unexpected safety events. Predefined biomarker analysis indicated that patients with homologous recombination repair pathway gene alterations or loss-of-function mutations in chromatin remodeling genes presented better tumor response and survival outcomes. Furthermore, transcriptome analysis revealed a markedly longer PFS and tumor response were associated with higher expression of a 3-gene effector T cell signature or an 18-gene inflamed T cell signature. Sintilimab plus gemcitabine and cisplatin meets pre-specified endpoints and displays acceptable safety profile, multiomics potential predictive biomarkers are identified and warrant further verification.

[Source Apportionment and Spatial Distribution Simulation of Heavy Metals in a Typical Petrochemical Industrial City].

Identifying the quantitative source and hazardous areas of heavy metals in soils plays a pivotal role in soil pollution research, and can provide a basis for regional soil risk monitoring and environmental management. For this purpose, a total of 175 samples were collected in topsoils from Linzi, a typical petrochemical industrial city in Shandong Province. Positive matrix factorization (PMF) and factor analysis with non-negative constraints (FA-NNC) receptor models were applied to analyze the sources of the heavy metals. Based on the multivariate statistical simulation methods of min/max autocorrelation factors (MAF) and sequential Gaussian simulation (SGS), the distribution of heavy metal and potential pollution areas were determined. As, Co, Cr, and Mn were mainly affected by natural sources, their concentrations were dominated by the parent materials, and the high-value areas were distributed in the south of the study area. Hg was the most serious pollution element among the 10 heavy metals analyzed in Linzi and originated from atmosphere deposition from industrial emissions and coal combustion, and the highest values were distributed in the northeast of the study area. Cd, Cu, Ni, Pb, and Zn were dominated by natural sources and human activities. The hot-spot areas were mainly concentrated in the middle of the study area. The potentially contaminated areas of Cd and Hg were 580.80 km2 and 666.60 km2, about 85.04% and 97.59% of the total area, and should require more attention. The potential pollution area of most elements was small and scattered across the study area, accounting for less than 1%.

The complete mitochondrial genome of Rhodeus lighti (Cypriniformes: Cyprinidae): sequencing and analysis.

Phylogenetic placement of Rhodeus lighti (R. lighti) remains unresolved. We determined the first complete mitochondrial genome of R. lighti (Cypriniformes: Cyprinidae). The genome is 16,597 bp in length. It consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and 2 non-coding regions. The gene composition and order were similar to most of the other vertebrates. The complete mitochondrial genome sequence of R. lighti should contribute towards clarifying the systematics of Rhodeus fishes. The phylogenetic relationships using partitioned Neighbor-Joining tree indicated that (((((Pseudorasbora, Rhodeus) Ctenopharyngodon) (Acheilognathus, Tanakia) Carassius)) Danio rerio). This study will contribute to confirm the phylogenetic status of Rhodeus within family Cyprinidae.

[Spatial Characteristics and Environmental Risk of Heavy Metals in Typical Gold Mining Area of Shandong Province].

In order to reveal the influence of anthropogenic factors on soil environment quality, a total of seventy-seven samples in topsoils were collected from Jiaojia gold mining area in Shandong province and were determined for Cu, Pb, Zn, Cr contents. Spatial structure, spatial distributions of concentrations and risk probability of heavy metals were analyzed using spatial statistic analysis. The average concentrations of Cu, Pb, Zn and Cr were 19.41 mg·kg-1, 27.32 mg·kg-1, 49.81 mg·kg-1 and 39.27 mg·kg-1, respectively. Pb, Zn and Cr were distributed normally and Cu was distributed normally after logarithm transformation. Semivariance analysis demostrated that Pb could be fitted to exponential model, and Cu, Zn and Cr were fit for spherical model. Nugget coefficents of Cu and Pb were between 0.25 and 0.75, which illustrated middle spatial autocorrelation; Zn and Cr showed the structural variation with nugget values below 0.25. Cu and Pb in the topsoils were distributed dispersedly due to effects of some human factors, whereas contents of Zn and Cr indicated relatively regular distributions and were mainly affected by natural factors. Spatial distributions of the 4 heavy metals were approximately consisitent and the high value areas appeared in the gold mines band. The result of hot spot analysis and indicator kriging interpolation revealed that the relatively high risk areas were located in Jincheng town, the boundary zone of Xinzhuang town and Canzhuang town, while the safe zone was situated in south part of the study area. Pb had higher probability exceeding the threshold and the middle or high environmental risk areas of Pb were distributed widely, which should be paid more attentions.

A review on hepatocyte nuclear factor-1beta and tumor.

Hepatocyte nuclear factor-1beta (HNF1ß) was initially identified as a liver-specific transcription factor. It is a homeobox transcription factor that functions as a homodimer or heterodimer with HNF1α. HNF1ß plays an important role in organogenesis during embryonic stage, especially of the liver, kidney, and pancreas. Mutations in the HNF1ß gene cause maturity-onset diabetes of the young type 5 (MODY5), renal cysts, genital malformations, and pancreas atrophy. Recently, it has been shown that the expression of HNF1ß is associated with cancer risk in several tumors, including hepatocellular carcinoma, pancreatic carcinoma, renal cancer, ovarian cancer, endometrial cancer, and prostate cancer. HNF1ß also regulates the expression of genes associated with stem/progenitor cells, which indicates that HNF1ß may play an important role in stem cell regulation. In this review, we discuss some of the current developments about HNF1ß and tumor, the relationship between HNF1ß and stem/progenitor cells, and the potential pathogenesis of HNF1ß in various tumors.

Overexpression Of Hepatocyte Nuclear Factor-1beta Predicting Poor Prognosis Is Associated With Biliary Phenotype In Patients With Hepatocellular Carcinoma.

Hepatocyte nuclear factor-1beta (HNF-1B) is involved in the hepatobiliary specification of hepatoblasts to cholangiocytes during liver development, and is strongly expressed throughout adult biliary epithelium. The aim of this study was to examine the expression of HNF-1B in different pathologic subtypes of primary liver cancer, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (ICC), and the relationship between HNF-1B expression, clinicopathological features and prognosis. We retrospectively investigated 2 cohorts of patients, including 183 HCCs and 69 ICCs. The expression of HNF-1B was examined by immunohistochemistry. We found that HNF-1B expression was associated with pathological subtype of primary tumor, and HNF-1B expression in HCC tissue may be associated with the change of phenotype on recurrence. The HNF-1B expression was positively correlated with biliary/HPC (hepatic progenitor cell) markers expression. Further, multivariable analysis showed that HNF-1B expression was an independent prognostic factor for both overall survival and disease-free survival of HCC patients. However, no correlation between HNF-1B expression and survival was found in ICC patients. In summary, HCC with high HNF-1B expression displayed biliary phenotype and tended to show poorer prognosis. HNF-1B-positive malignant cells could be bipotential cells and give rise to both hepatocytic and cholangiocytic lineages during tumorigenesis.

[Effect of the Runoff-sediment Control of the Xiaolangdi Reservoir on DOC Transport].

The sampling was carried out in Sanmenxia hydrological station, Xiaolangdi hydrological station and Huayuankou hydrological station from November 2011 to October 2012. The impact of the runoff-sediment control of the Xiaolangdi reservoir on DOC transport,was analyzed. The results were as follows. DOC contents in Sanmenxia station, Xiaolangdi station and Huayuankou station were 1.97-2.71 mg-L(-1), 1.87-2.76 mg x L(-1) and 2.07-2.93 mg x L(-1), respectively, during the normal operation period of Xiaolangdi Reservoir and Sanmenxia reservoir, and the DOC content in the three reservoirs had obvious seasonal change. DOC contents in the three stations were 2.14-3.32 mg x L(-1), 2.21-2.84 mg x L(-1) and 2.11-2.84 mg x L(-1), respectively, during the runoff-sediment control, and the DOC content in the sediment-releasing period of reservoir was higher than that in the water-releasing period of reservoir. DOC content had no significant correlation with TSS and flow either during the normal operation or during the water-sediment regulation of the reservoir. But the DOC content had significant correlation with water temperature during the normal operation of the reservoir. DOC flux in Sanmenxia station was similar to that in Xiaolangdi station from November to March. DOC flux in Sanmenxia station was obviously less than that in Xiaolangdi station from April to July. And the DOC flux in Sanmenxia station was much higher than that in Xiaolangdi station from August to October. The result showed that DOC was retained from August to October by Xiaolangdi reservoir and discharged from Xiaolangdi reservoir from April to July. The yearly DOC fluxes were 8.6 x 10(10), 9.0 x 10(10) and 9.7 x 10(10) g respectively in Sanmenxia station, Xiaolangdi station and Huayuankou station. The DOC flux of Sanmenxia station was the highest in September, which accounted for 22.0% of the yearly DOC flux, and the DOC flux of Xiaolangdi station was the highest in June, which accounted for 17.6% of the yearly DOC flux. The DOC flux of Huayuankou station was the highest in July, which accounted for 16.7% of the yearly DOC flux. DOC fluxes during the runoff-sediment regulation accounted for 14.7% and 13.8% of the yearly DOC flux respectively in Xiaolangdi station and Huayuankou station, but the DOC fluxes during the runoff-sediment regulation accounted for only 3.6% of the yearly DOC flux in Sanmenxia station.