Besides single-nucleotide variants in the human genome, large-scale genomic variants, such as copy number variations (CNVs), are being increasingly discovered as a genetic source of human diversity and the pathogenic factors of diseases. Recent experimental findings have shed light on the links between different genome architectures and CNV mutagenesis. In this review, we summarize various genomic features and discuss their contributions to CNV formation. Genomic repeats, including both low-copy and high-copy repeats, play important roles in CNV instability, which was initially known as DNA recombination events. Furthermore, it has been found that human genomic repeats can also induce DNA replication errors and consequently result in CNV mutations. Some recent studies showed that DNA replication timing, which reflects the high-order information of genomic organization, is involved in human CNV mutations. Our review highlights that genome architecture, from DNA sequence to high-order genomic organization, is an important molecular factor in CNV mutagenesis and human genomic instability.
Base Sequence ; DNA ; DNA Copy Number Variations ; DNA Replication ; DNA Replication Timing ; Genome* ; Genome, Human ; Genomic Instability ; Humans ; Mutagenesis ; Recombination, Genetic

Objective To investigate the consistency of fetal gallbladder volume (FGV) during middle-late pregnancy with three-dimensional ultrasonic virtual organ computer-aided analysis (VOCAL) technique at different rotation angles,and to analyze the correlation between FGV and gestation age.Methods A total of 157 healthy pregnant women underwent prenatal screening were included.The reference range of FGV was measured with three-dimensional ultrasonic VOCAL at 30°,18° and 12° rotation angle,respectively.The correlation between FGV and gestation age was observed,and the consistency of FGV values measured with VOCAL at different rotation step angles was compared.Results The correlations between FGV values measured with VOCAL at 30°,18°,12° rotation step angles and gestation age were all excellent (r=0.92,0.88,0.90;all P＜ 0.001).The consistency of FGV values measured with VOCAL at different rotation step angles was very good (30° and 18°,ICC=0.94;30° and 12°,ICC=0.97;18° and 12°,ICC=0.94).Conclusion Three-dimensional ultrasonic VOCAL can be used to establish the reference range of fetal gallbladder volume in middle-late pregnancy.The consistency of FGV values measured with VOCAL at different rotation step angles was very good,and the correlation between FGV and gestation age was excellent.

Objective:To investigate the expression of RASAL3 in intrahepatic cholangiocarcinoma (iCCA) and the mechanism of promoting iCCA development.Methods:Tumor and paracancerous tissues were collected from 185 iCCA patients, the expression of RASAL3 was detected by immunohistochemistry, RT-qPCR and Western blot. The expression of RASAL3 and FXYD6 mRNA and protein in human cholangiocarcinoma cell line and human bile duct epithelial cells were detected with RT-qPCR and Western blot, the cell proliferation was detected with CCK-8 assay, and the activity of Na +-K +-ATPase was also detected. Results:RASAL3 was highly expressed in cholangiocarcinoma tissues and cell lines; Survival analysis showed that RASAL3 overexpression was associated with poor prognosis of cholangiocarcinoma( P<0.05) and knockdown of RASAL3 inhibits the proliferation of cholangiocarcinoma cells; Silencing RASAL3 decreases the expression of FXYD6 inhibiting the activity of Na +-K +-ATPase. Conclusion:RASAL3 is up-regulated in human cholangiocarcinoma, which can promote the occurrence and development of cholangiocarcinoma by activating FXYD6 and affecting Na +-K +-ATPase activity.

Objective:To evaluate the efficacy of bupivacaine pamoate for sciatic nerve block in rats.Methods:Forty-eight SPF healthy male Sprague-Dawley rats, weighing 300-400 g, were divided into 6 groups using a random number table method: bupivacaine pamoate vehicle group (group VE), bupivacaine HCl group (group BH), liposomal bupivacaine group (group BL), low-dose bupivacaine pamoate group (group HL), moderate-dose bupivacaine pamoate group (group HM) and high-dose bupivacaine pamoate group (group HH), with 8 animals in each group.In VE, BH, BL, HL, HM and HH groups, bupivacaine pamoate vehicle 0.4 ml, bupivacaine HCl solution 0.4 ml, liposomal bupivacaine suspension 0.4 ml, and 1, 3 and 10 mg/ml bupivacaine pamoate suspension 0.4 ml were injected around the left sciatic nerve, respectively.The thermal paw withdrawal latency were measured before administration (T 0) and at 0.5, 1.5, 3, 5, 8, 12, 16, 24 and 48 h after injection (T 1-9). The percentage of maximum possible effect (MPE) of thermal paw withdrawal latency was calculated, and motor function score was simultaneously performed to evaluate the efficacy of sensory and motor block.Five and three rats in each group were sacrificed at 2 and 7 days after administration (T 9, 10), respectively, and the sciatic nerve at the injection site and the surrounding muscle tissues were harvested for microscopic examination (with a light microscope) after Luxol fast blue and HE staining.Nerve damage and inflammatory responses were assessed and scored to evaluate neurotoxicity. Results:Compared with group VE, the MPE was significantly increased at T 1-4 in group HL, at T 1-8 in group HM and at T 1-8 in group HH, the motor function scores were decreased at T 1-4 in group HL, at T 1-5 in group HM and at T 1-7 in group HH ( P<0.05), and no significant change was found in inflammatory response scores for the sciatic nerve and surrounding muscles at each time point in HL, HM and HH groups ( P>0.05). Compared with group BH, the MPE was significantly increased at T 3-8, motor function scores were decreased at T 3-5, and inflammatory response scores for the muscles around the sciatic nerve were decreased at T 9 in group HM ( P<0.05). Compared with group BL, the MPE was significantly increased at T 3-7, motor function scores were decreased at T 4, 5, and inflammatory response scores for the sciatic nerve and surrounding muscles were decreased at T 9 in group HM ( P<0.05). The nerve damage score was 0 in the six groups. Conclusion:Bupivacaine pamoate can block the sciatic nerve of rats, the duration of block is prolonged with the increase in the concentration, and the duration of motor block is not longer than that of sensory block; compared with the same concentration and equal volume of bupivacaine HCl and liposomal bupivacaine, bupivacaine pamoate produces longer duration of sciatic nerve block and less neurotoxicity.

Immunotherapy combined with targeted therapy can benefit the survival of patients with unresectable hepatocellular carcinoma. Atezolizumab combined with bevacizumab has achieved remarkable efficacy in patients with advanced hepatocellular carcinoma, but the efficacy of conversion therapy in patients with unresectable hepatocellular carcinoma still needs more evidences. The authors report the clinical efficacy of a case of unresectable hepatocellular carcinoma with hepatitis B virus related liver cirrhosis who was treated with immunotherapy plus targeted therapy combined with local treatment. Results show a good effect in patient without tumor recurrence after postoperative 9 months.