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BackgroundAlpha-fetoprotein (AFP) is a well-identified biomarker in hepatocellular carcinoma (HCC). However, only limited AFP-related studies have evaluated its early response to systemic therapy. This study was performed with the aim of assessing the value of early AFP response in predicting overall survival (OS) and progression-free survival (PFS) in advanced HCC patients receiving systemic therapy.MethodsThis cohort study included HCC patients with baseline AFP ≥ 200 ng/ml and no prior treatment history. A > 20% decline in the serum AFP level from baseline to the first follow-up (i.e., 4~6 weeks after treatment) was defined as an early AFP response. Patient demographic information, clinical characteristics, radiological response, and survival rates were compared between patients with early AFP response and patients without early AFP response. We further utilized multivariate Cox regression to seek characteristics related to OS and PFS.ResultsAmong 154 patients, 69 patients (44.8%) showed an early AFP response. The disease control rate (76.8 vs. 54.1%; P = 0.003) and objective response rate (38.4 vs. 11.8%; P = 0.001) were significantly higher in patients with an early AFP response. By performing multivariate analysis, early AFP response remained a prognostic factor for longer PFS (HR 0.546; 95% CI 0.371-0.804; P = 0.002) and longer OS (HR 0.529; 95% CI 0.335-0.834; P = 0.006).ConclusionAn early AFP response is correlated with longer overall survival and progression-free survival for advanced HCC patients receiving systemic therapy. Moreover, an early AFP response is an independent prognostic factor for longer OS and PFS.

ObjectiveThis study aimed to explore the associations of genetic variants in the semaphorin 3A (SEMA3A) signaling pathway genes, including SEMA3A, NRP1, PLXNA1, PLXNA2 and PLXNA3 with osteoporosis (OP) risk and bone mineral density (BMD) in a Chinese Han older adult population.Study design and methodA two-stage design was adopted. Total of 47.8kb regions in the 5 genes were sequenced using targeted next-generation sequencing (NGS) technology in the discovery stage, and the discovered OP-related single nucleotide polymorphisms (SNPs) were further genotyped using improved multiple linkage detection reaction technique in the validation stage. Methods of ALP/TRAP staining, real-time fluorescent quantitative PCR, and cell proliferation and apoptosis assays were performed with MC3T3-E1 and RAW 264.7 cell lines to clarify biological effects of observed functional variants in cell lines responsible for bone mass remodeling.ResultsTotal of 400 postmenopausal women (211 OP cases) were involved in the discovery stage, where 6 common and 4 rare genetic variants were found to be associated with OP risk. In the validation stage among another 859 participants (417 women, 270 OP cases), the PLXNA2 rs2274446 T allele was associated with reduced OP risk and increased femoral neck (FN) BMD compared to the C allele. Moreover, significant associations of NRP1 rs2070296 with FN BMD/OP risk and of NRP1 rs180868035 with lumbar spine and FN BMDs were also observed in the combination dataset analysis. Compared to the osteoblasts/osteoclasts transfected with the wild-type NRP1 rs180868035, those transfected with the mutant-type had reduced mRNA expression of osteoblastic genes (i.e., ALP, RUNX2, SP7 and OCN), while elevated mRNA expression of osteoclastic genes (i.e., TRAP, NFATc1 and CTSK). Furthermore, mutant NRP1 rs180868035 transfection inhibited osteoblast proliferation and osteoclast apoptosis, while promoted osteoclast proliferation and osteoblast apoptosis in corresponding cell lines.ConclusionGenetic variants located in NRP1 and PLXNA2 genes were associated with OP risk and BMD. The NRP1 rs180868035 affects bone metabolism by influencing osteoblasts and osteoclasts differentiation, proliferation and apoptosis.

BackgroundFew studies have explored the association between water intake and mortality risk, and the findings were inconsistent.ObjectiveThis study aimed to explore the water intake–mortality association, utilizing the data from the National Health and Nutrition Examination Survey (NHANES) and the 2015 public-linked mortality files released by the National Center for Health Statistics.MethodsWe used the diet- and mortality-linked data of a total of 35,463 adults (17,234 men) aged ≥20 years in the NHANESs 1999–2014 to perform a prospective study. The multivariate-adjusted Cox proportional hazards model was used to explore the associations of the amount of water intake (expressed by total water, plain water, beverage, and food water) and water intake proportion (expressed by the percentage of each kind of water) with mortality risks due to all causes, malignant neoplasms/cancer, and heart disease. The restricted cubic spline plots were adopted to clarify the dose–response relationships among them.ResultsWith a median of 88 months (interquartile range: 49–136 months) follow-up, a total of 4,915 all-cause deaths occurred, including 1,073 and 861 deaths from malignant neoplasms/cancer and heart disease, respectively. The amount of water intake in either type was negatively associated with all-cause mortality risk. Additionally, the negative linear dose–response relationships of water intake and all-cause mortality risk were found for all types of water except for food water, which followed a non-linear pattern. Similarly, compared to the lowest quartile (beverage water intake:

Objective: This study aimed to explore the relationships between the common variants of R-spondin/Wnt signaling genes, gut microbiota composition, and osteoporosis (OP) risk in elderly Chinese Han population.Design: Dual-energy X-ray absorptiometry was used to obtain the OP-associated measurements at multiple skeleton sites among all 1,168 participants. Genotyping data was obtained by using the next-generation sequencing in the discovery stage (n = 400, 228 OP patients) and SNPscan technology in the replication stage (n = 768, 356 OP patients). Bioinformatic analysis was performed to provide more evidence for the genotype-OP associations. The 16S ribosomal RNA gene high-throughput sequencing technology was adopted to explore OP-associated gut microbiota variations.Results: The genetic variants of rs10920362 in the LGR6 gene (P-FDR = 1.19 × 10–6) and rs11178860 in the LGR5 gene (P-FDR = 1.51 × 10–4) were found to associate with OP risk significantly. Several microbial taxa were associated with the BMDs and T-scores at multiple skeleton sites. The associations between rs10920362 and BMD-associated microbiota maintained significance after adjusting confounders. The rs10920362 CT/TT genotype associated with a decreased relative abundance of Actinobacteria (β = −1.32, P < 0.001), Bifidobacteriaceae (β = −1.70, P < 0.001), and Bifidobacterium (β = −1.70, P < 0.001) compared to the CC genotype.Conclusion: Our findings suggested that the variants loci of LGR6 may be associate with OP pathogenesis via gut microbiota modifications. The relationship between host genetics and gut microbiome provides new perspectives about OP prevention and treatment.