No effective drug and definitive “gold standard” treatment for Toxoplasma gondii (T. gondii) infection has been available so far, though some medicines have been commonly used in the treatment of T. gondii infection, such as spiramycin, azithromycin, traditional Chinese medicine (TCM), pyrimethamine- sulfadiazine (P-S), trimethoprim-sulfamethoxazole (TMP-SMX), and pyrimethamine-clindamycin (P-C). A systematic review and meta-analysis were performed to compare the efficacies of these conventional medicines in the treatment. Cohort studies for the treatment of acute T. gondii infection were searched from PubMed, Google Scholar, ect. All the cases number for different group extracted from each included literature were input to meta-analysis 3.13 software to calculate the pooled negative conversion rate (NCR), cure rate (CR) or vertical transmission rate based on their sample size and weight. The pooled NCR with 95% confidence intervals (CI) was used to evaluate the overall rate of a diagnosis positive result conversion to a negative result after treatment, which of spiramycin, azithromycin and TCM were 83.4% (95%CI, 72.1%-90.8%), 82.5% (95%CI, 75.9%-87.6%), and 85.5% (95%CI, 71.3%-93.3%) respectively, with no statistical difference between them. The pooled CR with 95% CI was used to evaluate the overall rate of complete disappearance of clinical symptoms for toxoplasmic encephalitis after therapy, which of P-S, TMP-SMX, and P-C were 49.8% (95%CI, 38. 8% -60.8%), 59.9% (95%CI, 48.9%-70.0%), and 47.6% (95%CI, 24.8%-71.4%) respectively, with no statistical difference between them. Primary T. gondii infection in pregnancy was treated mainly with spiramycin alone or combined with other drugs, and the pooled rate of vertical transmission was about 9.9% (95%CI, 5.9%-16.2%) after therapy. Toxoplasmic encephalitis in AIDS patients was usually treated with sulfonamides combined with other drugs and the pooled CR was 49.4% (95%CI, 37.9%-60.9%).

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Compared with the high-protein diet, the NAFLD-inducing effects of high-fat and high-sugar diets are independent from calories, and may be associated with changed intestinal microbiota.

Background LncRNA MIR4435-2HG is observed in a variety of cancers, while its role in colorectal cancer is unknown. We aimed to demonstrate the relationship between MIR4435-2HG and colorectal cancer based on The Cancer Genome Atlas (TCGA) database. Materials and Methods Patients with colorectal cancer were collected from TCGA. We compared the expression of MIR4435-2HG in colorectal cancer and normal tissues with Wilcoxon rank sum test, and logistic regression was used to evaluate the relationship between MIR4435-2HG and clinicopathological characters. Moreover, Kaplan–Meier and Cox regression was performed to evaluate the correlation between MIR4435-2HG and survival rate. Gene set enrichment analysis (GSEA) was also conducted to annotate biological function of MIR4435-2HG. Results MIR4435-2HG level was elevated in colorectal cancer tissues. Increased level of MIR4435-2HG was significantly correlated with TNM stage (OR = 1.66 for T1/T2 vs. T3/T4; OR = 1.68 for N0 vs. N1/N2), stage (OR = 1.66 for stage 1/2 vs. stage 3/4), and carcinoembryonic antigen level before treatment (OR = 1.70 for <5 vs. ≥5) (all P-value <0.05). High MIR4435-2HG expression had a poorer progression-free survival (p = 0.048), and overall survival (OS) (P = 0.028), which were validated in the GSE92921 and GSE29621 datasets. MIR4435-2HG expression (P = 0.040, HR = 1.955 (95% CI [1.031–3.710])) was independently correlated with OS. GSEA demonstrated that the P38/MAPK pathway, the VEGF pathway, the cell adhesion molecules cams, the NOD-like receptor signaling pathway, the cell surface interactions at the vascular wall, and integrin cell surface interactions were differentially enriched in MIR4435-2HG high expression phenotype. Conclusions Increased MIR4435-2HG might be a potential biomarker for the diagnosis and prognosis of colorectal cancer. Moreover, MIR4435-2HG might participate in the development of colorectal cancer via the P38/MAPK and VEGF pathway.

During meiosis, telomere attachment to the inner nuclear envelope is required for proper pairing of homologous chromosomes and recombination. Here, we identified F-box protein 47 (FBXO47) as a regulator of the telomeric shelterin complex that is specifically expressed during meiotic prophase I. Knockout of Fbxo47 in mice leads to infertility in males. We found that the Fbxo47 deficient spermatocytes are unable to form a complete synaptonemal complex. FBXO47 interacts with TRF1/2, and the disruption of Fbxo47 destabilizes TRF2, leading to unstable telomere attachment and slow traversing through the bouquet stage. Our findings uncover a novel mechanism of FBXO47 in telomeric shelterin subunit stabilization during meiosis.