Association between maternal metabolic profiles in pregnancy, dietary patterns during lactation and breast milk leptin: a retrospective cohort study.

Breast milk leptin plays a potential role in preventing childhood obesity. However, the associations of breast milk leptin with maternal metabolism in pregnancy and dietary patterns during lactation are still unclear. We aimed to explore associations of breast milk leptin with maternal metabolic profiles in pregnancy and dietary patterns during lactation. A total of 332 participants were recruited for this retrospective cohort study. Breast milk samples were collected at approximately 6 weeks postpartum. Breast milk leptin and twenty-three metabolic profiles in pregnancy were measured in this study. A semi-quantitative FFQ was used to gather dietary information during lactation. Both principal component analysis and the diet balance index were used to derive dietary patterns. Among twenty-three maternal metabolic profiles, maternal serum glucose (ß = 1·61, P = 0·009), γ-glutamyl transferase (ß = 0·32, P = 0·047) and albumin (ß = -2·96, P = 0·044) in pregnancy were correlated with breast milk leptin. All dietary patterns were associated with breast milk leptin. Given the joint effects of maternal metabolism in pregnancy and dietary patterns during lactation, only diet quality distance was significantly associated with leptin concentrations in breast milk (low level v. almost no diet problem: ß = -0·46, P = 0·011; moderate/high level v. almost no diet problem: ß = -0·43, P = 0·035). In conclusion, both maternal metabolism in pregnancy and dietary patterns during lactation were associated with breast milk leptin. Maternal diet balance during lactation was helpful to improve breast milk leptin concentration.

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.

Establishment of a Ciliogenesis-Associated Signaling Model for Polycystic Kidney Disease.

BACKGROUND: Polycystic kidney disease (PKD) represents the most prevalent inherited progressive kidney disorder in humans. Due to complexity of the genetic network behind the disease, the molecular mechanisms of PKD are still poorly understood yet. OBJECTIVES: This study aimed to develop a ciliogenesis-associated gene network for PKD patients and comprehensively understand the molecular mechanisms underlying the disease. METHOD: The potential hub genes were selected based on the differential expression analysis from the GEO database. Meanwhile, the primary hub genes were further elucidated by both in vivo and in vitro experiments. RESULTS: In this study, we established a comprehensive differentially expressed genes profile (including GNAS, PI4KB, UMOD, SLC7A13, and MIOX) for PKD patients compared with the control specimen. At the same time, enrichment analysis was utilized to demonstrate that the G-protein-related signaling and cilia assembling signaling pathways were closely associated with PKD development. The further investigations of the interaction between 2 genes (GNAS and PI4KB) with in vivo and in vitro analyses revealed that PI4KB functioned as a downstream factor for GNAS and spontaneously activated the phosphorylation of Akt into p-Akt for ciliogenesis in PKD formation. The PI4KB depletion mutant zebrafish model displayed a PKD phenotype as well as absence of primary cilia in the kidney. CONCLUSIONS: Collectively, our work discovered an innovative potential signaling pathway model for PKD formation, which provided a valuable insight for future study of the mechanism of this disease.

A large-scale screening and functional sorting of tumour microenvironment prognostic genes for breast cancer patients.

Purpose: The aim of this study was to systematically establish a comprehensive tumour microenvironment (TME)-relevant prognostic gene and target miRNA network for breast cancer patients. Methods: Based on a large-scale screening of TME-relevant prognostic genes (760 genes) for breast cancer patients, the prognostic model was established. The primary TME prognostic genes were selected from the constructing database and verified in the testing database. The internal relationships between the potential TME prognostic genes and the prognosis of breast cancer patients were explored in depth. The associated miRNAs for the TME prognostic genes were generated, and the functions of each primary TME member were investigated in the breast cancer cell line. Results: Compared with sibling controls, breast cancer patients showed 55 differentially expressed TME prognostic genes, of which 31 were considered as protective genes, while the remaining 24 genes were considered as risk genes. According to the lambda values of the LASSO Cox analysis, the 15 potential TME prognostic genes were as follows: ENPEP, CCDC102B, FEZ1, NOS2, SCG2, RPLP2, RELB, RGS3, EMP1, PDLIM4, EPHA3, PCDH9, VIM, GFI1, and IRF1. Among these, there was a remarkable linear internal relationship for CCDC102B but non-linear relationships for others with breast cancer patient prognosis. Using the siRNA technique, we silenced the expression of each TME prognostic gene. Seven of the 15 TME prognostic genes (NOS2, SCG2, RGS3, EMP1, PDLIM4, PCDH9, and GFI1) were involved in enhancing cell proliferation, destroying cell apoptosis, promoting cell invasion, or migration in breast cancer. Six of them (CCDC102B, RPLP2, RELB, EPHA3, VIM, and IRF1) were favourable for maintaining cell invasion or migration. Only two of them (ENPEP and FEZ1) were favourable for the processes of cell proliferation and apoptosis. Conclusions: This integrated study hypothesised an innovative TME-associated genetic functional network for breast cancer patients. The external relationships between these TME prognostic genes and the disease were measured. Meanwhile, the internal molecular mechanisms were also investigated.

Characteristics of intestinal microbiota in infants with late-onset breast milk jaundice.

Introduction: In this paper, microbiota analysis was determined to analyze the structure and difference of intestinal microbiota between LBMJ (late-onset breast milk jaundice) infants and healthy individuals. Methods: We collected fresh fecal samples from 13 infants with LBMJ and 13 healthy individuals, then determined the intestinal microbiota by 16 s rRNA sequencing. The differences of microbiota structure, diversity and functional characteristics between the two groups were analyzed, and the correlation between dominant genus and TcB (transcutaneous bilirubin) value was calculated. Results: In this study, there were no significant differences in maternal demographic characteristics, neonatal status and macronutrients in breast milk between the two groups (p > 0.05). There are differences in the structure of intestinal microbiota between LBMJ and the control group. At the genus level, the relative abundance of Klebsiella in the case group is high (p < 0.05). At the same time, correlation analysis indicates that the abundance of Klebsiella is positively correlated with TcB value. The intestinal microbiota richness and diversity (Alpha diversity and Beta diversity) of the two groups were significantly different (p < 0.05). LEfSe analysis showed that 25 genera including Klebsiella was significantly enriched in the LBMJ infants, and the other 17 species are enriched in the control group. Functional prediction analysis indicated that 42 metabolic pathways may be related to the occurrence of LBMJ. Conclusion: In conclusion, characteristic changes are seen in intestinal microbiota compositions between LBMJ infants and the healthy controls. Klebsiella is closely associated with the severity of the disease, which may be due to enhanced ß-glucuronidase activity.

The role of inflammatory biomarkers in the development and progression of pre-eclampsia: a systematic review and meta-analysis.

Background: Pre-eclampsia (PE) is a pregnancy complication associated with maternal and fetal morbidity and mortality. Among the potential pathogenesis discussed, inflammation is considered an essential initiator of PE. Previous studies have compared the levels of various inflammatory biomarkers that indicate the existence of PE; however, the relative levels of pro-inflammatory and anti-inflammatory biomarkers and their dynamic changes during PE progression remain unclear. This knowledge is essential to explain the occurrence and progression of the disease. Objective: We aimed to identify the relationship between inflammatory status and PE using inflammatory biomarkers as indicators. We also discussed the underlying mechanism by which inflammatory imbalance contributes to PE by comparing the relative levels of pro-inflammatory and anti-inflammatory biomarkers. Furthermore, we identified additional risk factors for PE. Methods: We reviewed PubMed, Embase, and the Cochrane Library for articles published until 15th September 2022. Original articles that investigated inflammatory biomarkers in PE and normal pregnancy were included. We selected healthy pregnant women as controls. The inflammatory biomarkers in the case and control groups were expressed as standardized mean differences and 95% confidence intervals using a random-effects model. Study quality was assessed using the Newcastle-Ottawa Scale. Publication bias was assessed using Egger's test. Results: Thirteen articles that investigated 2,549 participants were included in this meta-analysis. Patients with PE had significantly higher levels of C-reactive protein (CRP), interleukin (IL)-4, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF) than the controls. CRP and pro-inflammatory cytokine levels were higher than those of anti-inflammatory cytokines. Patients with gestational age > 34 weeks had significantly higher IL-6 and TNF levels. Patients with higher systolic blood pressure had significantly higher IL-8, IL-10, and CRP levels. Conclusion: Inflammatory imbalance is an independent risk factor for PE development. Impairment of the anti-inflammatory system is a crucial initiating factor for PE development. Failed autoregulation, manifested as prolonged exposure to pro-inflammatory cytokines, leads to PE progression. Higher levels of inflammatory biomarkers suggest more severe symptoms, and pregnant women after 34 weeks of gestation are more susceptible to PE.

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.

Effect of Epidermal Growth Factor in Human Milk and Maternal Diet on Late-Onset Breast Milk Jaundice: A Case-Control Study in Beijing.

Breast milk is crucial in the development of late-onset breast milk jaundice (BMJ), possibly due to the composition of breast milk and the lactating mother's diet. To explore the possible nutritional pathogenesis of late-onset BMJ, we investigated the lactation diet and collected breast milk by following the 42-day postpartum mother−infants pairs in Beijing and a total of 94 pairs were enrolled. The macronutrient content of breast milk was measured, and the epidermal growth factor (EGF) content in breast milk was determined by ELISA. Data on in-hospital and out-of-hospital breastfeeding, infant growth, jaundice-related vaccination, and puerperium diet were collected. The BMJ group received the second dose of hepatitis B vaccine later than the control group, and the difference was statistically significant (p < 0.001). The EGF concentration in breast milk was lower in the BMJ group than in the control group (p = 0.03). When EGF increased by 1 ng/mL, the transcutaneous bilirubin (TcB) value decreased by 0.33 ng/mL and 0.27 ng/mL before and after the adjustment, respectively. A 1 g increase in oil intake led to a 0.38 ng/mL increase in EGF concentration before the adjustment. With a 1 g increase in oil intake, the TcB value decreased by 0.27 ng/mL before the adjustment, and with a 1 g increase in soybean and soybean product intake, the TcB value decreased by 0.34 ng/mL after the adjustment. Collectively, EGF in breast milk may inhibit the occurrence of late-onset BMJ, and the dietary intake of oil in lactating mothers may affect the level of EGF in breast milk, thus affecting the occurrence of late-onset BMJ. Finally, dietary oil intake may be a protective factor for the occurrence of late-onset BMJ by increasing EGF levels in breast milk.

Intermittent Fasting versus Continuous Calorie Restriction: Which Is Better for Weight Loss?

We conducted a systematic review and meta-analysis of randomized clinical trials and pilot trial studies to compare the effectiveness of intermittent fasting (IF) and continuous calorie restriction (CCR) in overweight and obese people. The parameters included body mass index (BMI), body weight, and other metabolism-related indicators. A systematic search in PubMed, Embase, Cochrane Library, and Web of Science was conducted up to January 2022. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to measure the effectiveness. Publication bias was assessed using Egger's test. The stability of the results was evaluated using sensitivity analyses. The significance of body weight change (SMD = -0.21, 95% CI (-0.40, -0.02) p = 0.028) was more significant after IF than CCR. There was no significant difference in BMI (SMD = 0.02, 95% CI (-0.16, 0.20) p = 0.848) between IF and CCR. These findings suggest that IF may be superior to CCR for weight loss in some respects.

Development and validation of LRP1B mutation-associated prognostic model for hepatocellular carcinoma.

PURPOSE: To develop a lipoprotein receptor-related protein 1B (LRP1B) gene mutation-based prognostic model for hepatocellular carcinoma (HCC) patients risk prediction. METHODS: The LRP1B gene mutation rate was calculated from HCC patient samples. Meanwhile, differentially expressed genes according to LRP1B mutant were screened out for prognostic model establishment. Based on this innovative model, HCC patients were categorized into high- and low-risk groups. The immune status including immune cell infiltration ratio and checkpoints have been explored in two groups. The functions of LRP1B and risk factors in the model were verified using both in vivo and in vitro experiments. RESULTS: It could be demonstrated that LRP1B was a potential negative predictor for HCC patients prognosis with high mutation frequency. The functions of LRP1B were verified with ELISA and Quantitative Real-time PCR method based on clinic-recruited HCC participants. Eleven genes displayed significant differences according to LRP1B status, which could better predict HCC patient prognosis. The functions of these genes were examined using HCC cell line HCCLM3, suggesting they played a pivotal role in determining HCC cell proliferation and apoptosis. From the immune cell infiltration ratio analysis, there was a significant difference in the infiltration degree of seven types of immune cells and two immune checkpoints between high- and low-risk HCC patients. CONCLUSION: The present study hypothesized a potential prognostic biomarker and developed a novel LRP1B mutation-associated prognostic model for HCC, which provided a systematic reference for future understanding of clinical research.

HDL-cholesterol concentration in pregnant Chinese Han women of late second trimester associated with genetic variants in CETP, ABCA1, APOC3, and GALNT2.

OBJECTIVE: To investigate whether HDL-C level in pregnant Chinese Han women of late second trimester correlated with loci in high-density lipoprotein-cholesterol (HDL-C)-related genes found in genome-wide association studies (GWAS). METHODS: Seven single-nucleotide polymorphisms (rs3764261 in CETP, rs1532085 in LIPC, rs7241918 in LIPG, rs1883025 in ABCA1, rs4225 in APOC3, rs1059611 in LPL, and rs16851339 in GALNT2) were genotyped using the Sequenom MassArray system for 1,884 pregnant women. RESULTS: The following polymorphisms were statistically associated with HDL-C level after adjusting for age, gestational week, pre-pregnancy BMI and state of GDM or HOMAIR: (i) rs3764261 (b = -0.055 mmol/L, 95% CI -0.101 to -0.008, p = 0.021), (ii) rs1883025 (b = -0.054 mmol/L, 95% CI -0.097 to -0.012, p = 0.013), (iii) rs4225 (b = -0.071 mmol/L, 95% CI -0.116 to -0.027, p = 1.79E-3) and (iv) rs16851339 (b = -0.064 mmol/L, 95% CI -0.120 to -0.008, p = 0.025). The more risk alleles the pregnant women have, the lower the plasma HDL-C levels of the subjects are. CONCLUSIONS: Several risk alleles found to be related to HDL-C in GWAS are also associated with HDL-C levels in pregnant Chinese Han women and these risk loci contribute additively to low HDL-C levels.

Novel FSHß mutation in a male patient with isolated FSH deficiency and infertility.

Isolated follicle stimulating hormone (FSH) deficiency due to mutations in FSHß is an extremely rare autosomal recessive disease that has only been reported in ten patients to date. Symptoms of the disease include amenorrhoea and hypogonadism in women and azoospermia and normal testosterone levels in men. This study describes a Chinese male patient who presented with cryptorchidism and infertility. His serum hormonal profile revealed low FSH, elevated LH and normal testosterone levels. Sequence analysis identified a novel homozygous mutation in the FSHß gene (c.343C > T) predicted to result in a premature termination codon and a truncated FSH protein (p.R115X). Both parents were heterozygous carriers of the mutation with normal pubertal development and fertility. The patient's testicular volume increased after one year of exogenous FSH replacement therapy at which point spermatocytes were detected in seminal samples, indicating potential future spermatogenesis. The expanded spectrum of FSHß mutations and associated clinical manifestations described in this study may improve the diagnosis and treatment of this disease.

Analysis of genetic and clinical characteristics of a Chinese Kallmann syndrome cohort with ANOS1 mutations.

OBJECTIVE: To analyze ANOS1 gene mutations in a large Chinese Kallmann syndrome (KS) cohort and to characterize the clinical presentation of the disease in patients with ANOS1 mutations. PATIENTS AND METHODS: Chinese patients with KS, including 187 sporadic and 23 pedigree cases were recruited. Patients' ANOS1 gene sequences were analyzed by direct sequencing of PCR-amplified products. In silico analysis was used to assess functional relevance of newly identified missense mutations. Patients' clinical characteristics were analyzed retrospectively. RESULTS: Fifteen nonsynonymous rare ANOS1 variants were found in 13 out of 187 sporadic and 8 out of 23 familial IHH probands. Seven novel (C86F, C90Y, C151W, Y379X, c.1062 + 1G > A, Y579L fs 591X, R597X) and eight recurrent ANOS1 mutations (S38X, R257X, R262X, R423X, R424X, V560I, c.1843-1G > A, p.R631X) were identified. All the novel mutations were predicted to be pathogenic. The prevalence of cryptorchidism was high (38.1%) and occurred in patients with different kind of ANOS1 mutations, while the patients with the same mutation did not present with cryptorchidism uniformly. CONCLUSIONS: The prevalence of ANOS1 gene mutations is low in sporadic KS patients, but is much higher in familial KS patients. In the present study, we identify seven novel ANOS1 mutations, including two mutations in the CR domain, which are probably pathogenic. These mutations expand the ANOS1 mutation spectrum and provide a foundation for prenatal diagnosis and genetic counseling.

Novel mutations of HSD17B3 in three Chinese patients with 46,XY Disorders of Sex Development.

17ß-Hydroxysteroid dehydrogenase type 3 (17ß-HSD3) converts the inactive Δ4-androstenedione (A) to testosterone (T). Its deficiency is the most common testosterone biosynthesis defect that results in 46,XY Disorders Of Sex Development (DSD). However, the disease is difficult to distinguish from other 46,XY DSD for similar clinical phenotypes. Therefore, genetic testing provides good criteria for the diagnosis of the disease. In this study, HSD17B3 gene was examined in 3 unrelated Chinese patients with 46,XY DSD. Direct sequencing and quantitative PCR of HSD17B3 gene revealed the presence of a compound heterozygous mutation (p.I60T/exon1 deletion) in Patient 1, a homozygous (p.I60T) mutation in Patient 2 and a frameshift mutation (p.V25Efs∗54) and an exon1 deletion in Patient 3. All of the mutations have not been reported previously. These novel mutations may expand the mutation database of HSD17B3 gene and provide us new insights into the molecular mechanism of 17ß-HSD3 deficiency. It is noteworthy that when direct sequence analysis showed a rare homozygous mutation in patients with non-consanguineous parents, "apparent homozygosity" should be taken into an account and the intragenic deletion should be screened. In addition, when single mutation was found in patients with disease in recessive heredity mode, the intragenic deletion should also be screened.

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.

T2DM Self-Management via Smartphone Applications: A Systematic Review and Meta-Analysis.

BACKGROUND: Mobile health interventions (mHealth) based on smartphone applications (apps) are promising tools to help improve diabetes care and self-management; however, more evidence on the efficacy of mHealth in diabetes care is needed. The objective of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effect of mHealth apps on changes in hemoglobin A1c (HbA1c), blood glucose, blood pressure, serum lipids, and body weight in type 2 diabetes mellitus (T2DM) patients. METHODS: Two independent reviewers searched three online databases (PubMed, the Cochrane Library, and EMBASE) to identify relevant studies published between January 2005 and June 2016. Of the 2,596 articles retrieved, 13 RCTs were included. We used random effects model to estimate the pooled results. RESULTS: Thirteen studies were selected for the systematic review, six of which with data available containing 1,022 patients were included for the meta-analysis. There was a moderate effect on glycemic control after the mHealth app-based interventions. The overall effect on HbA1c shown as mean difference (MD) was -0.40% (-4.37 mmol/mol) (95% confidence interval [CI] -0.69 to -0.11% [-7.54 to -1.20 mmol/mol]; p = 0.007) and standardized mean differences (SMD) was -0.40% (-4.37 mmol/mol) (95% confidence interval [CI] -0.69 to -0.10% [-7.54 to -1.09 mmol/mol]; p = 0.008). A subgroup analysis showed a similar effect with -0.33% (-3.61 mmol/mol) (95% CI -0.59 to -0.06% [-6.45 to -0.66 mmol/mol]; p = 0.02) in MD and -0.38% (-4.15 mmol/mol) (95% CI -0.71 to -0.05% [-7.76 to -0.55 mmol/mol]; p = 0.02) in SMD in studies where patients' baseline HbA1c levels were less than 8.0%. No effects of mHealth app interventions were found on blood pressure, serum lipids, or weight. Assessment of overall study quality and publication bias demonstrated a low risk of bias among the six studies. CONCLUSIONS: Smartphone apps offered moderate benefits for T2DM self-management. However, more research with valid study designs and longer follow-up is needed to evaluate the impact of mHealth apps for diabetes care and self-management.