A meta-analysis was performed to assess the benefits and safety profile of approved immune checkpoint inhibitors in hepatocellular carcinoma patients. Eligible studies were searched from Cochrane, Embase, and PubMed databases based on a well-established strategy. Following the exclusion of ineligible studies, 12 studies were included in this meta-analysis. Compared with control group, immune checkpoint inhibitors were associated with improved ORR (OR 3.03, 95% CI 2.26–4.05, P < 0.00001), SD (OR 0.77, 95% CI 0.62–0.95, P = 0.02), OS (HR 0.75, 95% CI 0.68–0.83, P < 0.00001), and PFS (HR 0.74, 95% CI 0.63–0.87, P < 0.0003). However, no significant differences were observed in DCR (OR 1.33, 95% CI 0.97–1.81, P = 0.07), PD (OR 0.90, 95% CI 0.67–1.21, P = 0.48), and all caused any-grade adverse events (OR 1.22, 95% CI 0.62–2.39, P = 0. 57), all caused ≥ grade 3 adverse events (OR 1.10, 95% CI 0.97–1.25, P = 0.14), treatment-related any-grade adverse events (OR 1.13, 95% CI 0.55–2.32, P = 0.73), and treatment-related ≥ grade 3 events (OR 0.82, 95% CI 0.34–1.97, P = 0.65) between the two groups. After subgroup analysis conducted, patients in the immune checkpoint inhibitor group compared with targeted drug group showed significant improvements in OS (HR 0.74, 95% CI 0.66–0.84, P < 0.00001) and PFS (HR 0.75, 95% CI 0.61–0.91, P = 0.004). Immune checkpoint inhibitors have demonstrated peculiar benefits in the treatment of HCC with an acceptable safety profile. Compared to targeted drugs, immune checkpoint inhibitors still offer advantages in the treatment of hepatocellular carcinoma. However, there is still considerable room for further improvement.

Microplastics (MPs), as persistent environmental pollutants, have been detected in various human tissues, yet their distribution and bioaccumulation in fetal organs remain uninvestigated. Given that fetal development is highly vulnerable to environmental disturbances, assessing microplastic exposure during gestation is of critical importance. Using Raman spectroscopy, we analyzed MPs in major organs-including the placenta, cerebrum, heart, lung, liver, kidney, and intestine-from 6 fetuses with a mean gestational age of 22 + weeks, encompassing cases of intrauterine fetal death and congenital defects. MPs were detected in all cases, with polyethylene (PE) being the predominant type (98.4%). The highest particle counts were observed on the maternal surface of placenta (300 particles), followed by the heart (233) and liver (230). The largest particle, measuring 897 μm, was found in the liver. This study confirmed the widespread presence of MPs in fetal organs.

Currently, there are still many challenges in prenatal diagnosis, such as limited or uncertain fetal phenotyping, variant interpretation, and rapid turnaround times. The aim of this study was to illustrate the value of a comprehensive genomic evaluation in prenatal diagnosis. We retrospectively reviewed 20 fetuses with clinically significant copy number variants (CNVs) detected by chromosomal microarray analysis (CMA) and no further exome sequencing testing in our tertiary center between 2019 and 2020. The residual DNA from the prenatal cases was used for the parallel implementation of CNV sequencing (CNV-seq) and trio-based clinical exome sequencing (trio-CES). CMA revealed 26 clinically significant CNVs (18 deletions and eight duplications) in 20 fetuses, in which five fetuses had two or more CNVs. There were eight fetuses with pathogenic CNVs (e.g., del 1p36), nine fetuses with likely pathogenic CNVs (e.g., dup 22q11.21), and three fetuses with variants of unknown significance (VOUS, e.g., dup 1q21.1q21.2). Trio-CES identified four fetuses with likely pathogenic mutations (SNV/InDels). Of note, a fetus was detected with a maternally inherited hemizygous variant in the SLX4 gene due to a 16p13.3 deletion on the paternal chromosome. The sizes of CNVs detected by CNV-seq were slightly larger than that of the SNP array, and four cases with mosaic CNVs were all identified by CNV-seq. In conclusion, microdeletion/duplication syndromes and monogenic disorders may co-exist in a subject, and CNV deletion may contribute to uncovering additional recessive disease alleles. The application of a comprehensive genomic evaluation (CNVs and SNV/InDels) has great value in the prenatal diagnosis arena. CNV-seq based on NGS technology is a reliable and a cost-effective technique for identifying CNVs.

Purpose A meta-analysis was performed to assess the benefits and safety profile of approved immune checkpoint inhibitors in hepatocellular carcinoma patients.Methods Eligible studies were searched from Cochrane, Embase, and PubMed databases based on a well-established strategy. Review manager version 5.4 was employed for data analysis.Results Following the exclusion of ineligible studies, eight studies were included in this meta-analysis. Compared with control group, immune checkpoint inhibitors were associated with improved ORR (OR 3.65, 95% CI 2.82–4.73, P < 0.00001), DCR (OR 1.17, 95% CI 1.02–1.35, P = 0.02), SD (OR 0.72, 95% CI 0.58–0.89, P = 0.002), and more risk of all caused any-grade adverse events (OR 1.64, 95% CI 1.03–2.60, P = 0.004). However, no significant differences were observed in PD (OR 0.96, 95% CI 0.82–1.12, P = 0.59), OS (HR 0.76, 95% CI 0.66–0.87, P = 0.25), PFS (HR 0.74, 95% CI 0.63–0.87, P = 0.24) and all caused grade 3 or 4 adverse events (OR 1.22, 95% CI 0.98–1.52, P = 0.07), treatment-related any grade adverse events (OR 0.99, 95% CI 0.48–2.07, P = 0.98), treatment-related grade 3 or 4 events (OR 1.05, 95% CI 0.81–1.35, P = 0.72) between the two groups. After studies with nivolumab as a monotherapy excluded, patients in the immune checkpoint inhibitor group showed significant improvements in OS (HR 0.67, 95% CI 0.58–0.77, P < 0.00001) and PFS (HR 0.62, 95% CI 0.54–0.71, P < 0.00001).Conclusion Immune checkpoint inhibitors have demonstrated peculiar benefits in the treatment of HCC with an acceptable safety profile. Combining immune checkpoint inhibitors with other medications may be more beneficial for patients with hepatocellular carcinoma.

MiRNAs are critical regulators of target gene expression in many biological processes. In this study, we developed a simple, specific, and sensitive miRNA detection method based on proximity ligation reaction of AuNPs-immobilized DNA probes, which is easy to operate.