Differences Between Sorafenib and Lenvatinib Treatment from Genetic and Clinical Perspectives for Patients with Hepatocellular Carcinoma.

BACKGROUND The aim of this work was to systematically compare the differences between sorafenib and lenvatinib for patients with hepatocellular carcinoma (HCC) from genetic and clinical perspectives. MATERIAL AND METHODS The mRNA and miRNA sequencing information of patients with HCC treated with either sorafenib or lenvatinib was analyzed using differential expression and a protein-protein interaction assay. The clinical manifestations and adverse events of the 2 drugs were also investigated. RESULTS Compared with patients with HCC treated with sorafenib, patients treated with lenvatinib developed 8 differentially expressed genes (DEGs, FGF4, FGF23, UNC13C, RIMBP2, STXBP5L, PHOX2B, NEUROD4, and POU4F2) and 3 miRNAs (DEMs, has-miR-548ah, has-miR-888, and has-miR-196a-1), of which hsa-miR-548 regulated 4 target genes, the largest number among the 3 miRNAs. The functions of these DEMs and DEGs were verified by external experiments in the HCC cell line Hep3B2.1-7. We further investigated the adverse events of the drugs for patients with advanced HCC in clinical treatment. The patients in the sorafenib group developed less frequent symptoms of hypertension and diarrhea. Also, the frequency of hand-foot skin reactions in patients treated with lenvatinib was lower than that of patients treated with sorafenib (P<0.05). There were no significant differences in nausea, fatigue, frequent urination, and dizziness (P>0.05). CONCLUSIONS In a time of increasing interest in chemotherapy drug treatments for patients with HCC, this study provided a better understanding of the clinical evaluations of sorafenib and lenvatinib.

Effect of Carbohydrate-Restricted Dietary Pattern on Insulin Treatment Rate, Lipid Metabolism and Nutritional Status in Pregnant Women with Gestational Diabetes in Beijing, China.

Carbohydrates play an important role in blood glucose control in pregnant women with GDM. Carbohydrate-restricted dietary (CRD) pattern for gestational diabetes mellitus (GDM) has been widely used in clinics, but the change in insulin utilization rate beyond CRD intervention in GDM remains unclear. The aim of the present study was to explore the application of insulin in pregnancy with GDM, as well as the influence of CRD pattern on lipid metabolism and nutritional state. A retrospective study of 265 women with GDM who delivered in Peking University People's Hospital from July 2018 to January 2020 was conducted using a questionnaire survey. Women were divided into a CRD group or a control group according to whether they had received CRD intervention during pregnancy. There was no statistically significant difference in the rate of insulin therapy between the two groups (p > 0.05), the initial gestational week of the CRD group combined with insulin treatment was significantly higher than that of the control group (p < 0.05), and the risk of insulin therapy was positively correlated with fasting plasma glucose (FPG) in early pregnancy (p < 0.05). The incidence of abnormal low-density lipoprotein cholesterol levels in the CRD group was significantly lower than that in the control group (p < 0.05). There were no significant differences in nutritional indexes between the two groups. The results indicate that CRD intervention may be effective in delaying the use of insulin and improving the blood lipids metabolism during GDM pregnancy, while nutritional status may not be significantly affected under CRD intervention, and a high FPG in early pregnancy with GDM may be a risk factor for combined insulin therapy with CRD intervention.

Impact of maternal nutrition during early pregnancy and diet during lactation on lactoferrin in mature breast milk.

OBJECTIVE: Lactoferrin supplementation is a promising strategy to prevent infections in neonates. Exploring whether maternal nutritional status in early pregnancy and maternal diet during lactation are associated with lactoferrin concentrations in mature human milk can provide early warning and allow timely adjustment. METHODS: In this follow-up cohort study, 206 participants were recruited at Peking University People's Hospital from June 2018 to June 2019. The levels of albumin and thyroid-stimulating hormones (TSH) were determined as nutritional indicators during early pregnancy. Information on maternal diet during lactation was collected with a semiquantitative food frequency questionnaire, and the lactoferrin concentrations in breast milk were examined at around 42 d postpartum. RESULTS: The median level (interquartile range) of lactoferrin in breast milk was 2844.2 (2568.1, 3103.1) µg/mL. Overall, 5.5% of participants had lower albumin (<40 g/L), and 21.6% had elevated TSH (>2.5 mIU/L), respectively. The concentration of lactoferrin was higher (216.8 [13.4, 420.2] µg/mL) in women with lower albumin levels than in those with normal levels, and elevated TSH had no effect. A 1 g increase in egg intake led to a 0.3 (0.0, 0.6) µg/mL increase in lactoferrin concentration. Lactoferrin levels were also affected by intake of energy, protein, cholesterol, and vitamin A. CONCLUSIONS: Women with lower albumin levels in early pregnancy had higher levels of lactoferrin in mature breast milk. TSH was not related to lactoferrin levels. Intake of energy, protein, cholesterol, and vitamin A may have contributed to lactoferrin concentrations in milk, and egg intake was positively associated with lactoferrin.

Pulsatile GnRH Therapy May Restore Hypothalamus-Pituitary-Testis Axis Function in Patients With Congenital Combined Pituitary Hormone Deficiency: A Prospective, Self-Controlled Trial.

Context: The effectiveness of pulsatile gonadotropin-releasing hormone (GnRH) therapy in patients with congenital combined pituitary hormone deficiency (CCPHD) has not been investigated because of the limited number of patients, as well as these patients' presumed pituitary hypoplasia, poor gonadotrophic cell reserve, and impaired gonadotrophic response to GnRH. Objective: To assess the pituitary response to pulsatile GnRH therapy in men with CCPHD. Design: Prospective, self-controlled, 3-month clinical trial. Settings: University endocrine clinic. Patients: Men with hypogonadotropic hypogonadism caused by CCPHD. Intervention: Pulsatile GnRH was administered subcutaneously for 3 months. Main outcome measures: Primary endpoints were total serum testosterone, testicular volume, and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Secondary endpoints included occurrence of spermatogenesis. Results: A total of 40 men with CCPHD completed the study. Of these, 60% (24 of 40) showed a good response to pulsatile GnRH treatment (response group). At 3 months, their LH and FSH levels increased to within the normal range and their testosterone levels increased to 8.67 ± 4.83 nmol/L. Of the patients in the response group, 33.3% (8 of 24) of them achieved spermatogenesis. The remaining 40% (16 of 40) of patients had a poor response to pulsatile GnRH treatment. Magnetic resonance imaging (MRI) did not reveal any correlation between pituitary response and pituitary height and/or integrity of the pituitary stalk. Conclusions: This study suggests that gonadotrophs in patients with CCPHD can exist and be functional-even with MRI evidence of pituitary hypoplasia or dysplasia. Pulsatile GnRH therapy restored pituitary-testis axis function in 60% of patients with CCPHD. These results may directly guide the clinical therapeutic choice.