Genomic analysis of 9 infants with hypermethioninemia by whole-exome sequencing among in Henan, China.

BACKGROUND: Hypermethioninemia is an inborn error of metabolism with elevated plasma methionine (Met) caused by methionine adenosyltransferase deficiency. Methionine adenosyltransferase (MAT) I/III deficiency is the most common cause of hypermethioninemia. Except for increased blood Met, most patients have no symptoms, but a small number have nervous system complications, including cognitive impairment and mental retardation. OBJECTIVE: To investigate the gene variation of patients with hypermethioninemia in newborns in Henan province. METHODS: 9 cases of hypermethioninemia were screened for amino acids profile and acyl carnitine by tandem mass spectrometric (MS/MS) among 245 054 newborns. We performed whole-exome sequencing on 9 families of infants with hypermethioninemia. We identified mutated genes under different models of inheritance and further assessed these mutations through Sanger sequencing and association analysis. RESULTS: The incidence of neonatal hypermethioninemia was 1:27 228 in Henan province. A total of ten mutations in the MAT1A gene in the 9 patients were identified, including nine reported mutations (c.1070C > T, c.895C > T, c.100 T > A, c.315C > A, c.529C > T, c.623A > C, c.407G > T, c.1066C > T, 867G > T) and one novel mutations (c.772G > C). c.772G > C was detected in 2 families and is the most common variant. 7 infants (7/9) with hypermethioninemia were genetically autosomal dominant, and 2 infants (2/9) with hypermethioninemia were genetically autosomal recessive. CONCLUSION: Our findings expand the mutational spectrum of hypermethioninemia, with the description of one new mutation. They improve the understanding of the genetic background and clinical manifestation of MAT1A in Chinese patients.

Diagnostic value of a single ß-hCG test in predicting reproductive outcomes in women undergoing cleavage embryo transfer: a retrospective analysis from a single center.

PURPOSE: The present study investigated the role of ß-hCG in predicting reproductive outcomes and established optimal ß-hCG cutoff values in women undergoing cleavage embryo transfer. METHODS: The patients were transferred with fresh or frozen-thawed embryos and had serum ß-hCG levels tested on the 14th day post-embryo transfer. Serum ß-hCG levels were compared between different groups. Different cutoff values of ß-hCG were established and used to divide the patients into different groups. Reproductive outcomes between groups based on ß-hCG levels were compared. RESULTS: Significant discrepancies in general characteristics were observed in the subgroups. The cutoff values of ß-hCG for predicting the presence/absence of pregnancy, biochemical pregnancy/clinical pregnancy, presence/absence of adverse pregnancy outcomes, and singleton/twin live birth in the cleavage groups were 89.6, 241.1, 585.9, and 981.1 mIU/L, respectively. Biochemical pregnancy rates and adverse pregnancy outcome rates significantly decreased from the low ß-hCG group to the higher ß-hCG group in sequence. Significantly higher full-term live birth rates were observed in the highest ß-hCG group (P < 0.001). CONCLUSION: Serum ß-hCG levels were strongly associated with reproductive outcomes. However, the interpretation of ß-hCG levels must consider the number and quality of embryos and transfer protocols. When ß-hCG was tested on a fixed day post-ET, different cutoff values were required for the prediction of early clinical outcomes. The association between ß-hCG and obstetric outcomes must be investigated.

To investigate the association between ß-hCG and reproductive and obstetrical outcomes in women with cleavage ET and to establish different ß-hCG cutoff values for the prediction of reproductive outcomes, this study retrospectively included 6909 infertile women who were divided into different groups based on the number and quality of transferred embryos, age, and transfer protocols. The cutoff values of ß-hCG for predicting the presence/absence of pregnancy, biochemical pregnancy/clinical pregnancy, presence/absence of adverse pregnancy outcomes, singleton/twin live birth in the cleavage groups were 89.6, 241.1, 585.9, and 981.1 mIU/L, respectively. Biochemical pregnancy rates and adverse pregnancy outcome rates decreased significantly in the higher ß-hCG groups. In conclusion, the interpretation of ß-hCG levels must consider the number and quality of embryos and transfer protocols. When ß-hCG was tested on a fixed day post-ET, different cutoff values were required for the prediction of early clinical outcomes.

The Relationship between Human Embryo Parameters and De Novo Chromosomal Abnormalities in Preimplantation Genetic Testing Cycles.

Design: In total, 456 PGT cycles, including 283 PGT-SR cycles and 173 PGT-A cycles, were assessed through comprehensive chromosome screening (CCS) from January 2017 to June 2020 at the Department of Reproductive Medicine of the Third Affiliated Hospital of Zhengzhou University. Trophectoderm (TE) biopsies were sequenced using next-generation sequencing (NGS). The incidence of de novo chromosome abnormalities was calculated, and the relationships between de novo chromosome abnormality rates and maternal age, number of oocytes retrieved, and parameters of cleavage-stage embryos and blastocyst-stage embryos were investigated. Results: The incidence of de novo chromosome abnormalities was 28.0% (318/1,135) in the PGT-SR cycles and 36.3% (214/590) in the PGT-A cycles, which increased with maternal age in both PGT-SR cycles (P = 0.018) and PGT-A cycles (P < 0.001). The incidence of de novo chromosome abnormalities was related to TE grade (P < 0.001), internal cell mass grade (P = 0.002), and development speed (day 5 vs. day 7: P < 0.001) of blastocyst-stage embryos. The incidence of de novo chromosomal abnormalities was irrelevant to the number of oocytes retrieved and the parameters of the embryo at the cleavage stage. Conclusion: Blastocysts with higher morphology scores and faster progression had a lower incidence of de novo chromosome abnormalities, especially complex chromosome abnormalities. De novo chromosome abnormalities may negatively affect the morphological grading of blastocysts. Our findings will provide valuable information to the fertility doctor for embryo selection in non-PGT cycles.

CtBP1 Mediates Hypoxia-Induced Sarcomatoid Transformation in Hepatocellular Carcinoma.

BACKGROUND: Sarcomatoid hepatocellular carcinoma (sHCC), a highly aggressive subtype of hepatocellular carcinoma (HCC), mostly transforms from classical hepatocellular carcinoma (cHCC). The study intended to explore the role of C-terminal binding protein 1 (CtBP1) in sarcomatoid transformation of hepatocellular carcinoma. METHODS: Western blotting and/or immunohistochemistry were used to confirm the expression of CtBP1 and other proteins in HCC cells, xenografts and clinical tissue samples. CtBP1 shRNA-expressing lentivirus was used to infect HepG2 cells to construct CtBP1 knockdown cells. Cell migration was determined by scratch wound assays and Transwell assays. Immunofluorescence was used to label the a-tubulin cytoskeleton to evaluate cell morphology. HepG2 cells were inoculated subcutaneously in nude mice to construct xenografts and beneath the liver capsule to evaluate in vivo metastasis. RESULTS: Compared to that in the cHCC area, CtBP1 expression was significantly upregulated in the sHCC area, as shown by immunohistochemistry. HE staining showed that cells in the sHCC area were spindle-shaped, while those in the cHCC area were polygonal. Immunohistochemically, the epithelial markers pancytokeratin (CK) and E-cadherin were partially or completely lost, while the expression of the mesenchymal marker vimentin was upregulated in the sHCC area. Moreover, HepG2, an HCC cell line with high expression of CtBP1, autonomously underwent sarcomatoid transformation, showing a sarcomatoid morphology and phenotype. HIF1a expression was upregulated in epithelial cells adjacent to the sHCC area. Hypoxia upregulated CtBP1 protein expression and induced an EMT phenotype with increased migration and a spindle-shaped morphology in HepG2 cells. Knockdown of CtBP1 partially reversed the EMT phenotype induced by hypoxia. Silencing CtBP1 completely blocked the sarcomatoid transformation of subcutaneous xenografts and decreased lung metastasis in subcapsular xenografts of the liver in nude mice. CONCLUSION: CtBP1 plays a key role in hypoxia-induced EMT and sarcomatoid transformation in HCC and could be a candidate target for the management of sHCC.

The Impact of High-Normal TSH Levels on Reproductive Outcomes in Women Undergoing ART Treatment: a Systematic Review and Meta-analysis.

The role of high-normal thyroid-stimulating hormone levels has been of great concern recently. However, the conclusions of different studies are inconsistent. To assess whether high-normal conditions have an impact on reproductive and obstetric outcomes in euthyroid women undergoing ART treatment, a systematic review and meta-analysis was performed. Eligible studies published up to December 30, 2020, were searched from the PubMed, EMBASE, COCHRANE, and CNKI databases. Quality assessment of the included studies, data extraction, and synthesis were performed separately. RevMan 5.2 was used to carry out the meta-analysis. A total of 23 studies that included 25,143 patients were included. We observed similar clinical pregnancy rates (RR = 1.01, 95% CI: 0.99-1.05), miscarriage rates (RR = 0.95, 95% CI: 0.84-1.08), live birth rates (RR = 1.04, 95% CI: 0.99-1.09), birth weights (SMD = 0.07, 95% CI: -0.02 to 0.16), and gestational ages (SMD = 0.07, 95% CI: -0.02 to 0.16) between the high-normal TSH group and low TSH group. Subgroup analysis showed similar results. High-normal TSH levels were associated with similar clinical pregnancy rates, live birth rates, and miscarriage rates to those of women with low TSH levels. The results suggested that preconceptional TSH levels, regardless of potentially being affected by the controlled ovarian stimulation process, had little impact on reproductive and obstetric outcomes and should not be of great concern.

Analysis of basal serum TSH, FT3, and FT4 levels based on age, sampling time in women with infertility.

BACKGROUND: To analyze the characteristics of basal thyroid hormone levels in infertile women consulting for assisted reproductive technology (ART) treatment. METHODS: This was a retrospective study. Serum TSH, FT3 and FT4 levels of women seeking ART consultation were tested routinely. Analyses were performed based on age and sampling time. One-way ANOVA or Kruskal-Wallis rank sum test was used to compare the continuous data among the groups, and the chi-square test or Fisher's exact test was used to compare categorical data where appropriate. RESULTS: A total of 6426 women were initially included in the study. After exclusion criteria were applied, the remaining 4126 women were categorized into different groups. The prevalence of subclinical hypothyroidism significantly decreased with age and sampling time, from 21.09 to 11.91% and from 28.57 to 10.67%, respectively (P < 0.001, respectively). Mean serum TSH, FT3, and FT4 levels decreased significantly with age (P = 0.017, < 0.001, < 0.001, respectively). In the context of sampling time, TSH levels from early in the morning were significantly higher (P < 0.001), while FT4 and FT3 levels were similar in different groups (P = 0.258, 0.300, respectively). CONCLUSIONS: The prevalence of subclinical hypothyroidism significantly decreased with increasing age and sampling time, as did the serum TSH levels. Even though, the establishment of reference interval of TSH level based on age or sampling time was not recommended. Full consideration of age and sampling time should be carefully taken before initiation of treatment.

Bioactive peptides from foods: production, function, and application.

Bioactive peptides are a class of peptides with special physiological functions and have potential applications in human health and disease prevention. Bioactive peptides have gained much research attention because they affect the cardiovascular, endocrine, immune, and nervous systems. Recent research has reported that bioactive peptides are of great value for physiological function regulation, including antioxidation, anti-hypertension, antithrombosis, antibacterial properties, anti-cancer, anti-inflammation, anti-diabetic, anti-obesity, cholesterol-lowering, immunoregulation, mineral binding and opioid activities. The production of food-derived bioactive peptides is mainly through the hydrolysis of digestive enzymes and proteolytic enzymes or microbial fermentation. The purpose of this review is to introduce the production, function, application, challenges, and prospects of food-derived bioactive peptides.

The Impact of Preconception TSH on the Reproductive Outcomes of Infertile Women Undergoing the First Fresh D3 Embryo Transfer Cycle.

PURPOSE: To investigate the association between high-normal preconception TSH levels and reproductive outcomes in infertile women undergoing the first fresh D3 embryo transfer. METHODS: This was a retrospective study. Euthyroid patients undergoing the first fresh D3 embryo transfer from January 2018 to May 2019 were initially included. The patients were divided into a low-TSH (0.27-2.5 mIU/L) group and a high-normal TSH (2.5-4.2 Miu) group. The reproductive outcomes were compared between the groups. RESULTS: A total of 1786 women were ultimately included, in which 1008 of whom had serum TSH levels between 0.27 and 2.5 mIU/L and 778 of whom had serum TSH levels between 2.5 and 4.2 mIU/L. The patients were highly homogeneous in terms of general characteristics. High-normal TSH levels had no adverse impact on the clinical pregnancy rate, miscarriage rate, or live birth rate (respectively, aOR = 0.92, 1.30, and 0.88 and P = 0.416, 0.163, and 0.219). No significant differences were observed in terms of gestational age, single live birth rates, and birth weight, or birth length. CONCLUSION: High-normal TSH levels did not significantly influence reproductive outcomes in infertile women undergoing the first fresh D3 embryo transfer. Further studies are needed to test whether the results might be applicable to a wider population.

The impact of TSH levels on clinical outcomes 14 days after frozen-thawed embryo transfer.

BACKGROUND: The aim of this study was to investigate the impact of TSH levels on clinical outcomes 14 days after frozen-thawed embryo transfer. METHODS: Blood samples were collected on the first visit to our department and 14 days after embryo transfer. Women were divided into three groups based on D14 TSH levels, which were compared to basal TSH levels in groups with different clinical outcomes. TSH levels between pregnant and nonpregnant women were also compared. RESULTS: The clinical pregnancy rate in women with lower TSH levels 14 days after transfer was slightly but significantly lower (56%, P = 0.05) compared to those with higher TSH levels. Furthermore, TSH levels were significantly elevated 14 days after transfer compared to basal TSH levels in pregnant women and in women who successfully became pregnant (P < 0.001, respectively). CONCLUSIONS: Elevated TSH levels 14 days after embryo transfer compared to basal TSH levels seem to play a protective role and predict favorable clinical outcomes under specific conditions.

High-Normal Preconception TSH Levels Have No Adverse Effects on Reproductive Outcomes in Infertile Women Undergoing the First Single Fresh D5 Blastocyst Transfer.

PURPOSE: To investigate the association between high-normal preconception TSH levels and reproductive outcomes in infertile women undergoing the first single fresh D5 blastocyst transfer. METHODS: This was a retrospective study. Euthyroid patients undergoing the first single fresh D5 blastocyst transfer from January 2018 to May 2019 were initially included. The patients were divided into a low TSH (0.27-2.5 mIU/L) group and a high-normal TSH (2.5-4.2 mIU/L) group. The reproductive outcomes were compared between the groups. RESULTS: A total of 824 women were ultimately included, 460 of whom had serum TSH levels less than 2.5 mIU/L and 364 of whom had serum TSH levels between 2.5 and 4.2 mIU/L. The patients were highly homogeneous in terms of general characteristics. High-normal TSH levels had no adverse impact on the clinical pregnancy rate, miscarriage rate, or live birth rate (respectively, aOR = 0.84, 0.65, 0.61, and P=0.234, 0.145, 0.083). No significant differences were observed in terms of gestational age, single live birth rates, birth weight, or birth length. CONCLUSION: High-normal TSH levels did not significantly influence reproductive outcomes in infertile women undergoing the first single fresh D5 blastocyst transfer. Further studies are needed to test whether the results might be applicable to a wider population.

Variant analysis of HPD genes from two families showing elevated tyrosine upon newborn screening by tandem mass spectrometry (MS/MS).

Background Alterations in the structure and activity of 4-hydroxyphenylpyruvate dioxygenase (HPD) are causally related to two different metabolic disorders: recessively inherited tyrosinemia type III and dominantly inherited hawkinsinuria. The aim of this study was to provide a new perspective for the clinical understanding of the pathogenesis of tyrosinemia type III or hawkinsinuria. Case presentation A full-term newborn baby born after a safe pregnancy and childbirth with a birth weight of 3200 g and another full-term baby born after a safe pregnancy and childbirth with a birth weight of 2800 g are reported and analysed. DNA extraction, next-generation sequencing, bioinformatics analysis, Sanger sequencing and biochemical analysis were performed. One patient with a heterozygous HPD gene (NM_002150.2) c.460G > A mutation and one patient with a heterozygous HPD gene (NM_002150.2) c.248delG mutation showing elevated tyrosine levels upon newborn screening by tandem mass spectrometry (MS/MS) are reported. Conclusions The HPD gene may not be a strictly autosomal recessive pathogenic gene, which provides a new perspective for the clinical understanding of the pathogenesis of tyrosinemia type III or hawkinsinuria.

Variant analysis of PEX11B gene from a family with peroxisome biogenesis disorder 14B by whole exome sequencing.

BACKGROUND: Peroxisome biogenesis disorder 14B (PBD14B) is an autosomal recessive peroxisome biogenesis disorder characterized clinically by mild intellectual disability, congenital cataracts, progressive hearing loss, and polyneuropathy peroxisome biogenesis disorders are genetically heterogeneous group of disorders caused by biallelic mutations in peroxin (PEX) genes. METHODOLOGY/LABORATORY EXAMINATION: DNA of the family was extracted and sequenced by whole exome sequencing. The results were validated with Sanger sequencing analyzed with Bioinformatics software. RESULTS: Sequencing result showed that the patient has carried a homozygous variant of c.277C>T of the PEX11B gene. The patient's brother has carried a homozygous variant of c.277C>T of the PEX11B gene and their variants of c.277C>T of the PEX11B gene were inherited, respectively, from his mother and father. DISCUSSION AND CONCLUSION: The homozygous variant of c.277C>T of the PEX11B gene probably underlie the disease in this child and her brother.

Molecular characterization of three intestinal protozoans in hospitalized children with different disease backgrounds in Zhengzhou, central China.

BACKGROUND: Cryptosporidium spp. and Giardia duodenalis are major intestinal pathogens that can cause diarrheal diseases in humans, especially children. Enterocytozoon bieneusi is another parasite which can cause gastrointestinal tract disorders, with diarrhea being the main clinical symptom. However, few genetic studies of these parasites in pediatric inpatients in China have been published. METHODS: To assess the genetic characteristics and epidemiological status of these parasites, a total of 2284 fecal samples were collected from children in the pediatric departments of three hospitals in Zhengzhou, central China, and screened for these protozoans with PCR, based on the small subunit ribosomal RNA (SSU rRNA) genes of Cryptosporidium spp. and G. duodenalis and the internal transcribed spacer (ITS) of E. bieneusi. RESULTS: Six (0.26%), 14 (0.61%), and 27 (1.18%) of the samples were positive for Cryptosporidium spp., G. duodenalis and E. bieneusi, respectively. Of the 12 successfully sequenced G. duodenalis isolates, four were identified as assemblage A and eight as assemblage B. In subtype and multilocus genotype (MLG) analyses, C. parvum IIdA19G1 (n = 4) and two novel G. duodenalis MLGs belonging to subassemblage AII (n = 3) and BIV (n = 5) were successfully identified. The E. bieneusi isolates included genotypes D (n = 17), J (n = 2), PigEBITS7 (n = 1), BEB6 (n = 1), and CM8 (n = 1). This is the first report of C. parvum subtype IIdA19G1 in HIV-negative children and E. bieneusi genotype CM8 in humans. CONCLUSIONS: The dominance of zoonotic C. parvum subtype IIdA19G1 indicates that this parasite is turning into zoonotic origin from human-to-human transmission. The phylogenetic analysis also revealed the zoonotic origins and anthroponotic transmission potential of G. duodenalis and E. bieneusi, suggesting more efforts must be made to minimize the threat these pathogens pose to public health.

[A case of maternal 45,X/46,XX mosaicism detected by non-invasive prenatal testing].

OBJECTIVE: To report on a case of maternally derived 45,X mosaicism detected by non-invasive prenatal testing (NIPT). METHODS: Fetal sex chromosomal abnormality was detected by NIPT. Maternally derived 45,X mosaicism was confirmed by chromosome karyotype analysis. Fetal sex chromosome aneuploidy was detected by amniotic fluid chromosome microarray analysis. RESULTS: A maternal 45,X mosaicism was diagnosed. The fetus was confirmed to be normal. CONCLUSION: Maternal 45,X masaicism can be diagnosed by NIPT.

The Impact of Preconceptional Serum TSH Levels between 2.5 and 4.0 mIU/L on Infertile Women Going through Their First IUI Treatment Cycle.

OBJECTIVE: To evaluate the impact of preconceptional serum TSH levels on the clinical outcomes of infertile patients undergoing their first IUI treatment cycle. METHOD: This was a retrospective study. Euthyroid patients undergoing the first cycle of IUI treatment from Jan 2017 to Aug 2018 were included. The patients were divided into a normal high TSH level (2.5-4.0 mIU/L) group and a low TSH level (0.4-2.5 mIU/L) group. Then, different factors were included separately to compare the outcomes between normal high and low TSH levels. The primary outcomes were clinical pregnancy rates, implantation rates, and miscarriage rates. The secondary outcomes were obstetric outcomes such as single live birth rates, birth length, birth weight, and duration of gestation. RESULTS: Initially, 1856 patients were included, and 371 patients were excluded for different reasons. A total of 1485 patients were finally included in the analysis. The general parameters between normal high and low TSH levels were similar except for infertile duration and female BMI, which were, however, significantly different between AID-IUI patients and AIH-IUI patients (P=0.005 and P=0016). No significant differences were found in terms of either primary outcomes or secondary outcomes. CONCLUSION: Normal high-serum TSH levels within the reference range (0.4-4.0 mIU/L) measured before treatment seemed to have no adverse impact on the clinical outcomes of patients undergoing their first IUI treatment cycle.

Analysis of the accuracy of Z-scores of non-invasive prenatal testing for fetal Trisomies 13, 18, and 21 that employs the ion proton semiconductor sequencing platform.

BACKGROUND: Non-invasive prenatal testing (NIPT) is frequently being used to screen for trisomies 13, 18 and 21 for prenatal diagnosis. However, NIPT performs poorly when compared with invasive testing and thus should not be used to diagnose trisomies. The result of NIPT for an individual woman in most genome-wide methods is calculated as a Z-score. The aim of this study was to assess the correlation between Z-scores of NIPT results and the accuracy of non-invasive prenatal testing. RESULTS: We evaluated 108 pregnant women with positive NIPT results, which were validated through karyotype analysis of amniotic fluid puncture by means of sequencing, bioinformatics analysis, and follow-up. Utilizing the ion proton semiconductor sequencing platform, we report a performance evaluation of NIPT-positive results at Third Affiliated Hospital of Zhengzhou University of Henan Province, China, by classifying Z-scores as 3 ≤ Z<5, 5 ≤ Z < 9 and Z ≥ 9. The findings indicate that positive NIPT results at Z ≥ 9 have a higher accuracy compared with positive NIPT results at 5 ≤ Z < 9 and 3 ≤ Z<5. CONCLUSIONS: The findings show that Z-scores of NIPT results are closely related to the accuracy of non-invasive prenatal testing. However, false-positive NIPT results at 3 ≤ Z<5 may occur due to confined placental mosaicism (CPM).

Gestational age-specific reference intervals for 15 biochemical measurands during normal pregnancy in China.

Aims Physiological changes that occur during pregnancy can influence biochemical parameters. Therefore, using reference intervals based on specimens from non-pregnant women to interpret laboratory results during pregnancy may be inappropriate. This study aimed to establish the essential reference intervals for a range of analytes during pregnancy. Methods A cross-sectional study was performed in 13,656 healthy pregnant and 2634 non-pregnant women. Fifteen biochemical measurands relating to renal and hepatic function were analysed using an Olympus AU5400 analyzer (Olympus, Tokyo, Japan). All the laboratory results were checked for outliers using Dixon's test. Reference intervals were established using a non-parametric method. Results Alanine aminotransferase, aspartate aminotransferase, albumin, cholinesterase, creatinine, direct bilirubin, gamma-glutamyl transpeptidase, total bilirubin, total bile acid and total protein showed a decrease during the whole gestational period, while alkaline phosphatase and uric acid increased. Urea nitrogen, ß2-microglobulin and cystatin-C fell significantly during the first trimester and then remained relatively stable until third trimester. Reference intervals of all the measurands during normal pregnancy have been established. Conclusions The reference intervals established here can be adopted in other clinical laboratories after appropriate validation. We verified the importance, for some measurands, of partitioning by gestational age when establishing reference intervals during pregnancy.

Multilocus sequence typing and clonal population genetic structure of Cyclospora cayetanensis in humans.

To investigate the prevalence of Cyclospora cayetanensis in a longitudinal study and to conduct a population genetic analysis, fecal specimens from 6579 patients were collected during the cyclosporiasis - prevalent seasons in two urban areas of central China in 2011-2015. The overall incidence of C. cayetanensis infection was 1·2% (76/6579): 1·6% (50/3173) in Zhengzhou and 0·8% (26/3406) in Kaifeng (P 0·05). All the isolates clustered in the C. cayetanensis clade based on the small subunit ribosomal RNA gene sequence phylogenetic analysis. There were 45 specimens positive for all the five C. cayetanensis microsatellite loci, and formed 29 multilocus genotypes (MLGs). The phylogenetic relationships of 54 distinct MLGs (including 25 known reference MLGs), based on the concatenated multilocus sequences, formed three main clusters. A population structure analysis showed that the 79 isolates (including 34 known reference isolates) of C. cayetanensis produced three distinct subpopulations based on allelic profile data. In conclusion, we determined the frequency of C. cayetanensis infection in humans in Henan Province. The clonal population structure of the human C. cayetanensis isolates showed linkage disequilibrium and three distinct subpopulations.

MiRNAs Predict the Prognosis of Patients with Triple Negative Breast Cancer: A Meta-Analysis.

PURPOSE: miRNAs are stable and can be extracted from tissues, blood and other body fluid without degradation. miRNAs are abnormally expressed in the presence of a pathological status, including cancer. Therefore, miRNAs are ideal biomarkers for cancer diagnosis and prognosis. Patients with triple negative breast cancer (TNBC) suffer the worst prognosis, although great efforts have been made. Many studies have investigated the role of miRNAs in predicting the outcomes of TNBC patients for better adjustment of treatment. However, results were inconsistent. Thus, we performed a meta-analysis to summarize the published studies for conclusive results. METHODS: Eligible studies from different database were retrieved from the online databases, and we used STSTA 12.0 to analysis the prognostic role of miRNAs in triple negative breast cancer. RESULTS: Overall high miRNA expression indicated a worse survival with HR value of 1.78 (95% CI: 0.97-3.25). However, subtotal HRs of oncogenic miRNAs and tumor suppressive miRNAs were 2.73 (95% CI: 2.08-3.57; P<0.001) and 0.44 (95% CI: 0.21-0.90; P = 0.024), respectively, and no heterogeneity was observed within the subgroups. CONCLUSIONS: The miRNAs showed a slightly stronger prognostic value for disease-free survival, relapse-free survival and distant metastasis-free survival compared to the overall survival of TNBC patients. Circulating miRNAs could serve as potential biomarkers for the prognosis of TNBC patients and need further investigation.