Newborn genetic screening for Fabry disease: Insights from a retrospective analysis in Nanjing, China.

Fabry disease (FD), an X-linked disorder resulting from dysfunction of α-galactosidase A, can result in significant complications. Early intervention yields better outcomes, but misdiagnosis or delayed diagnosis is common, impacting prognosis. Thus, early detection is crucial in the clinical diagnosis and treatment of FD. While newborn screening for FD has been implemented in certain regions, challenges persist in enzyme activity detection techniques, particularly for female and late-onset patients. Further exploration of improved screening strategies is warranted. This study retrospectively analyzed genetic screening results for pathogenic GLA variants in 17,171 newborns. The results indicated an estimated incidence of FD in the Nanjing region of China of approximately 1 in 1321. The most prevalent pathogenic variant among potential FD patients was c.640-801G > A (46.15 %). Furthermore, the residual enzyme activity of the pathogenic variant c.911G > C was marginally higher than that of other variants, and suggesting that genetic screening may be more effective in identifying potential female and late-onset patients compared to enzyme activity testing. This research offers initial insights into the effectiveness of GLA genetic screening and serves as a reference for early diagnosis, treatment, and genetic counseling in FD.

The prevalence and risk factors of rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis.

BACKGROUND: Interstitial lung disease (ILD) is the most widespread and fatal pulmonary complication of rheumatoid arthritis (RA). Existing knowledge on the prevalence and risk factors of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is inconclusive. Therefore, we designed this review to address this gap. MATERIALS AND METHODS: To find relevant observational studies discussing the prevalence and/or risk factors of RA-ILD, EMBASE, Web of Science, PubMed, and the Cochrane Library were explored. The pooled odds ratios (ORs) / hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated with a fixed/ random effects model. While subgroup analysis, meta-regression analysis and sensitivity analysis were carried out to determine the sources of heterogeneity, the I2 statistic was utilized to assess between-studies heterogeneity. Funnel plots and Egger's test were employed to assess publication bias. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, our review was conducted. RESULTS: A total of 56 studies with 11,851 RA-ILD patients were included in this meta-analysis. The pooled prevalence of RA-ILD was 18.7% (95% CI 15.8-21.6) with significant heterogeneity (I2 = 96.4%). The prevalence of RA-ILD was found to be more likely as a result of several identified factors, including male sex (ORs = 1.92 95% CI 1.70-2.16), older age (WMDs = 6.89, 95% CI 3.10-10.67), having a smoking history (ORs =1.91, 95% CI 1.48-2.47), pulmonary comorbidities predicted (HRs = 2.08, 95% CI 1.89-2.30), longer RA duration (ORs = 1.03, 95% CI 1.01-1.05), older age of RA onset (WMDs =4.46, 95% CI 0.63-8.29), positive RF (HRs = 1.15, 95%CI 0.75-1.77; ORs = 2.11, 95%CI 1.65-2.68), positive ACPA (ORs = 2.11, 95%CI 1.65-2.68), higher ESR (ORs = 1.008, 95%CI 1.002-1.014), moderate and high DAS28 (≥3.2) (ORs = 1.87, 95%CI 1.36-2.58), rheumatoid nodules (ORs = 1.87, 95% CI 1.18-2.98), LEF use (ORs = 1.42, 95%CI 1.08-1.87) and steroid use (HRs= 1.70, 1.13-2.55). The use of biological agents was a protective factor (HRs = 0.77, 95% CI 0.69-0.87). CONCLUSION(S): The pooled prevalence of RA-ILD in our study was approximately 18.7%. Furthermore, we identified 13 risk factors for RA-ILD, including male sex, older age, having a smoking history, pulmonary comorbidities, older age of RA onset, longer RA duration, positive RF, positive ACPA, higher ESR, moderate and high DAS28 (≥3.2), rheumatoid nodules, LEF use and steroid use. Additionally, biological agents use was a protective factor.

Utility, benefits, and risks of newborn genetic screening carrier reports for families.

Background: Newborn genetic screening (NBGS) based on next-generation sequencing offers enhanced disease detection and better detection rates than traditional newborn screening. However, challenges remain, especially around reporting the NBGS carrier results. Therefore, we aimed to investigate the NBGS carrier parents' views on NBGS and NBGS reports in China. Methods: We distributed a survey querying demographic information, knowledge and perceptions of NBGS, the impact of NBGS on a total of 2930 parents, and their decision-making to parents of newborns reported as carriers in NBGS in Nanjing, China in 2022. Results: The average age of the survey respondents was 30.7 years (standard deviation = 3.6). Most (68.38%) felt informed about NBGS, especially women, the highly educated, and high earners. Nearly all (98.74%) saw NBGS as crucial for early disease detection, with 73.18% believing it positively impacts their future. However, 19.16% felt it might cause anxiety, especially among the less educated. Concerns included potential discrimination due to exposed genetic data and strained family ties. Many suggested NBGS coverage by medical insurance to ease financial burdens. Conclusions: Through our study, we gained insights into parents' perspectives and concerns regarding the NBGS carrier result reporting, thus providing relevant information for further refinement and clinical promotion of the NBGS project.

Normal sperm head morphometric reference values in fertile Asian males.

ABSTRACT: Sperm head morphology is crucial for male factor infertility diagnosis and assessment of male reproductive potential. Several criteria are available to analyze sperm head morphology, but they are limited by poor methodology comparability and population applicability. This study aimed to explore comprehensive and new normal morphometric reference values for spermatozoa heads in fertile Asian males. An automated sperm morphology analysis system captured 23 152 stained spermatozoa from confirmed fertile males. Of these samples, 1856 sperm head images were annotated by three experienced laboratory technicians as "normal". We employed 14 novel morphometric features to describe sperm head size (head length, head width, length/width ratio, and girth), shape (ellipse intersection over union, girth intersection over union, short-axis symmetry, and long-axis symmetry), area (head, acrosome, postacrosomal areas, and acrosome area ratio), and degrees of acrosome and nuclear uniformity. This straight-forward method for the morphometric analysis of sperm by accurate visual measurements is clinically applicable. The measured parameters present valuable information to establish morphometric reference intervals for normal sperm heads in fertile Asian males. The presented detailed measurement data will be valuable for interlaboratory comparisons and technician training. In vitro fertilization and andrology laboratory technicians can use these parameters to perform objective morphology evaluation when assessing male fertilization potential.

Newborn genetic screening is highly effective for high-risk infants: A single-centre study in China.

Background: Newborn genetic screening (NBGS) is promising for early detection of genetic diseases in newborns. However, little is known about its clinical effectiveness in special groups like high-risk infants. To address this gap, we aimed to investigate the impact of NBGS on high-risk infants. Methods: We screened 10 334 healthy newborns from the general maternity unit and 886 high-risk infants from the neonatal ward using both traditional newborn screening (tNBS) and NBGS, and collected clinical data from electronic medical records. Results: We found that high-risk infants had a higher proportion of eutocia (P < 0.01) and prematurity (P < 0.01). For high-risk infants vs healthy newborns screened by tNBS, the primary screening positive rate was 3.84% vs 1.31%, the false positive rate (FPR) was 3.62% vs 1.18% (P < 0.001), and the positive predictive value (PPV) was 5.88% vs 8.27%. For NBGS vs tNBS in high-risk infants, the primary screening positive rate was 0.54% vs 3.68%, the FPR was 0.22% vs 3.47%, and the PPV was 60.00% vs 5.88%. Conclusions: We found that combined newborn screening can effectively reduce the FPR caused by the high-risk symptoms and improve the PPV in high-risk infants, sufficient for more accurately showing the true status of the disease.

Current attitudes and preconceptions on newborn genetic screening in the Chinese reproductive-aged population.

PURPOSE: Newborn screening (NBS) applications are limited as they can only cover a few genetic diseases and may have false positive or false negative rates. A new detection program called newborn genetic screening (NBGS) has been designed to address the potential defects of NBS. This study aimed to investigate the perceptions, acceptance, and expectations of childbearing people related to NBGS to provide the basis for the targeted improvement in the NBGS program carried out in Hospitals. METHODS: A questionnaire with 20 items was designed on www.wjx.cn . Individuals who came to the Nanjing maternity and child health care Hospital for consultation from June 2021 to August 2021 participated in the survey. The data of the study was arranged properly and analyzed after the investigation. RESULTS: A total of 1141 valid questionnaires were collected in the survey, in which the average age of the participants was 31 (± 4) years, and a 1:4 ratio of males to females. Additionally, 65.12% of the participants possessed a bachelor's degree or above qualification. Overall, 50.57% of participants had an annual household income of 100,000-250,000 RMB, while about 86.68% of the participants supported the development of NBGS. The participation cost to pay for NBGS depended on the family incomes; about 59.42% of them were willing to pay a participation fee of 1000-2000 RMB. CONCLUSION: Our research provisionally demonstrated that the residents generally supported the use of NBGS, especially those with higher educational degrees, but the understanding of the genetic diseases and NBGS among the low-educated population still needs to be strengthened.

Unveiling of brain transcriptome of masked palm civet (Paguma larvata) with chronic infection of Toxoplasma gondii.

BACKGROUND: The aim of this study was to gain an understanding of the transcriptomic changes that occur in a wild species when infected with Toxoplasma gondii. The masked palm civet, an artifically domesticated animal, was used as the model of a wild species. Transcriptome analysis was used to study alterations in gene expression in the domesticated masked palm civet after chronic infection with T. gondii. METHODS: Masked palm civets were infected with 105 T. gondii cysts and their brain tissue collected after 4 months of infection. RNA sequencing (RNA-Seq) was used to gain insight into the spectrum of genes that were differentially expressed due to infection. Quantitative reverse-transcription PCR (qRT-PCR) was also used to validate the level of expression of a set of differentially expressed genes (DEGs) obtained by sequencing. RESULTS: DEGs were screened from the sequencing results and analyzed. A total of 2808 DEGs were detected, of which 860 were upregulated and 1948 were downregulated. RNA-Seq results were confirmed by qRT-PCR. DEGs were mainly enriched in cellular process and metabolic process based on gene ontology enrichment analysis. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that transcriptional changes in the brain of infected masked palm civets evolved over the course of infection and that DEGs were mainly enriched in the signal transduction, immune system processes, transport and catabolic pathways. Finally, 10 essential driving genes were identified from the immune signaling pathway. CONCLUSIONS: This study revealed novel host genes which may provide target genes for the development of new therapeutics and detection methods for T. gondii infection in wild animals.

[Association Between TAB2 Gene Polymorphisms and Susceptibility to Cryptorchidism in Han Chinese Population in Southwest China].

Objective: To conduct preliminary investigation into the correlation between transforming growth factor beta-activated protein kinase 1-binding protein 2 ( TAB2) gene and the incidence of cryptorchidism in Han Chinese population in Southwest China. Methods: A total of 259 patients with cryptorchidism and 355 healthy controls from Southwest China were enrolled for the study. Polymerase chain reaction-restriction fragment length polymorphism method was used to analyze the genotype of the 3 tag single nucleotide polymorphisms (SNPs) of TAB2 gene, i.e., rs237028, rs521845 and rs652921. The Chi-square test was used to analyze the relationship between the genotype frequency of the three tag SNPs and the incidence of cryptorchidism. Results: The distribution of the 3 tag SNPs' alleles and genotypes were in agreement with the Hardy-Weinberg equilibrium, and the genotype results of polymerase chain reaction-restriction fragment length polymorphism assay were consistent with those of Sanger sequencing. The frequency of the G allele at TAB 2 rs237028 was significantly higher in the cryptorchidism group than that in the control group (30.9% vs. 25.6%, P=0.04, OR=1.31, 95% CI: 1.01-1.70). In the dominant model, the risk of cryptorchidism was significantly higher in AG/GG genotype carriers ( P=0.006, OR=1.57, 95% CI: 1.14-2.17). In the cryptorchidism group, the TC/CC genotype frequency of the rs652921 locus were significantly higher than that of the control group (75.3% vs. 67.0%, P=0.03, OR=1.50, 95% CI: 1.05-2.14). Correlation between rs521845 and susceptibility to cryptorchidism was not observed in the Han Chinese population. Conclusion: The AG/GG genotype of rs237028 locus and the TC/CC genotype of rs652921 locus of the TAB2 gene may be associated with increased risks of cryptorchidism in Han Chinese population in southwest China.

Combined genetic screening and traditional biochemical screening to optimize newborn screening systems.

Newborn screening can detect around 40 different diseases based on biochemical indicators and has resulted in the improved quality of life for children suffering from genetic diseases. However, NBS is limited as it does not cover all genetic diseases in newborns and has high rates of false positives and negatives. Genetic screening can be used to address the shortcomings of traditional biochemical screening, however, the comprehensive clinical value of genetic screening is yet to be systematically studied. In this study, we used two different genetic screening methods to examine 200 cases of NBS. We found that genetic screening can be used to identify a broader spectrum of diseases and is not limited to traditional biochemical screening diseases; it can identify positive cases of disease and can eliminate false positives caused by multiple factors such as pathogenic variants carrier or the mode of childbirth. Genetic screening has shortened the time to diagnosis and reduced the costs of testing. Furthermore, we found that the biochemical detection results were limited when patients simultaneously carried multiple pathogenic mutations. Our research provisionally demonstrates the necessity, feasibility and significance of clinical genetic screening in newborns and provides a solid basis for future clinical developments.

RIP1 promotes proliferation through G2/M checkpoint progression and mediates cisplatin-induced apoptosis and necroptosis in human ovarian cancer cells.

Receptor-interacting protein 1 (RIP1, also known as RIPK1) is not only a tumor-promoting factor in several cancers but also mediates either apoptosis or necroptosis in certain circumstances. In this study we investigated what role RIP1 plays in human ovarian cancer cells. We showed that knockout (KO) of RIP1 substantially suppressed cell proliferation, accompanied by the G2/M checkpoint arrest in two human ovarian cancer cell lines SKOV3 and A2780. On the other hand, RIP1 KO remarkably attenuated cisplatin-induced cytotoxicity, which was associated with reduction of the apoptosis markers PARP cleavage and the necroptosis marker phospho-MLKL. We found that RIP1 KO suppressed cisplatin-induced ROS accumulation in both SKOV3 and A2780 cells. ROS scavenger BHA, apoptosis inhibitor Z-VAD or necroptosis inhibitor NSA could effectively suppress cisplatin's cytotoxicity in the control cells, suggesting that ROS-mediated apoptosis and necroptosis were involved in cisplatin-induced cell death. In addition, blocking necroptosis with MLKL siRNA effectively attenuated cisplatin-induced cytotoxicity. In human ovarian cancer A2780 cell line xenograft nude mice, RIP1 KO not only significantly suppressed the tumor growth but also greatly attenuated cisplatin's anticancer activity. Our results demonstrate a dual role of RIP1 in human ovarian cancer: it acts as either a tumor-promoting factor to promote cancer cell proliferation or a tumor-suppressing factor to facilitate anticancer effects of chemotherapeutics such as cisplatin.

Transcriptome changes induced by RUNX3 in cervical cancer cells in vitro.

Runt-related transcription factor 3 (RUNX3) is a member of Runt domain family that is known to play key roles in various different types of tumor. It was recently demonstrated that RUNX3 may also be associated with cervical cancer. The aim of the present study was to investigate the potential association between transcriptome changes and RUNX3 expression in cervical cancer. A RUNX3 overexpression model was constructed using cervical cancer cell lines by RUNX3 plasmid transfection. It was demonstrated that the upregulated expression of RUNX3 inhibited proliferation of cervical cancer cell lines, particularly SiHa cells, and was associated with the expression of the IL-6, PTGS2, FOSL1 and TNF genes. In addition, it was revealed that the TNF and FoxO pathways may also be affected by RUNX3. Therefore, the expression of the RUNX3 gene may be involved in the occurrence and progression of cervical cancer.

A Novel Approach of Urinary Monohydroxyphenyl Metabolites Assay in Cancer Screening.

BACKGROUND: A noninvasive, fast, highly sensitive and simple test is needed for cancer screening in addition to the detection of biomarkers in blood. Recently, the patent (CN102565055A) for the Urinary Monohydroxyphenyl Metabolites Assay (UMM-A) was authorized, and the effectiveness of clinical application has yet to be studied further. METHODS: A retrospective study was conducted consisting of 432 cancer patients, 28 benign tumor patients, 117 non-cancerous diseases patients, and 120 healthy donors to analyze the levels of monohydroxyphenyl metabolites in the urine sample. A logistic regression model was used to study the possible confounding factors affecting the diagnostic performance and to test the probability of a case to be positive for UMM-A. RESULTS: Compared with healthy donors, non-cancerous disease, and benign tumor subjects, the positive rate and MM level of UMM-A in cancer patients have significantly increased. After the 246 retreated cancer patients were excluded, and 186 untreated cancer patients were included, with the same specificity to 77.0%, the sensitivity improved from 66.7 to 89.8%, the negative predictive value improved from 58.6 to 91.4%. CONCLUSIONS: The present study has provided important information on the diagnostic characteristics of UMM-A for untreated cancer and its potential application in cancer screening.

Comparisons between two methods of multifetal pregnancy reduction in women with a dichorionic triamniotic triplet pregnancy.

OBJECTIVE: To compare the different pregnancy outcomes of women with a reduced dichorionic triamniotic (DCTA) triplet managed with radiofrequency ablation (RFA) or potassium chloride (KCL). MATERIALS AND METHODS: This was a retrospective cohort study. We studied 30 women of DCTA triplets managed with RFA as well as 85 managed with KCL. We compared the mean neonatal birthweight, median gestational age and perinatal mortality of two groups. RESULTS: The mean neonatal birthweight of children in RFA group was 2572.4 g (SD, 407.0), vs 2899.3 g (SD, 554.9) in KCL group (P < 0.001). The rate of low birth weight infants was 23 (42.6%) vs. 16 (18.0%), respectively, (p < 0.005). However, there was no statistically significant difference in the median gestational age of delivery, premature birth before 32&37 weeks' gestation, neonatal brain injury or successful pregnancy between two groups. (We define the successful pregnancy as the condition that at least one child survives for a specific woman, while the failed one as no child survives.) CONCLUSION: What we took it for granted was that pregnancy outcomes in women with a reduced DCTA triplet managed with RFA was riskier than with KCL, however, we proved that it is not accurate. For women with a reduced DCTA triplet, managed with RFA is not much riskier than with KCL. What's more, most women have two children survived in RFA group, while in KCL group, only one child survives for most women. This result may change the management alternative for those women with DCTA triplet pregnancies who choose reduction, especially for women who desire to have two surviving and healthy fetuses.

IgG4-related kidney disease (IgG4-RKD) with membranous nephropathy as its initial manifestation: report of one case and literature review.

BACKGROUND: IgG4-related disease (IgG4-RD) often affects multiple organs and tissues, especially the kidneys, and is characterized by interstitial nephritis, obstructive nephropathy, and in rare cases glomerulopathy (including membranous nephropathy). CASE PRESENTATION: In this article, we report a patient with nephrotic syndrome as the only initial manifestation. Membranous nephropathy was confirmed by renal biopsy, but without any renal interstitial lesions. The nephrotic syndrome completely resolved after treatment with immunosuppressants but recurred after drug withdrawal, which was accompanied by acute kidney injury. Ultimately, IgG4-related interstitial nephritis with membranous nephropathy was confirmed by a second renal biopsy. After routine administration of steroids and cyclophosphamide, renal function returned to normal after 2 months, and nephrotic syndrome was ameliorated after 5 months. CONCLUSION: Special attention should be paid to this rare condition in the clinical setting. In patients with membranous nephropathy (MN) that is accompanied by multi-system damage, impaired renal function, elevated IgG4 levels (absolute or relative value), negative PLA2R, and/or renal interstitial plasma cell infiltration, the possibility of IgG4-related kidney disease (IgG4-RKD) should be carefully assessed.

Circular Ribonucleic Acid Expression Profile in Mouse Cortex after Traumatic Brain Injury.

Traumatic brain injury (TBI) causes high rates of worldwide death and morbidity because of the complex secondary injury cascade. Circular ribonucleic acid (RNA) (circRNA), a type of RNA that forms a covalently closed continuous loop, may be involved in the regulation of secondary injury because it is expressed widely in the brain and contributes to a large class of post-transcriptional regulators. Deep RNA sequencing (RNA-seq) and bioinformatic analysis were performed to investigate the expression profile and function of circRNAs in the mouse cortex after controlled cortical impact (CCI). A total of 19,794 circRNAs were identified, and 1315 were annotated in circBase. There were 191 filtered differentially expressed circRNAs (98 for up-regulated and 93 for down-regulated). The gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that inflammation, cell death, and repair of damage were the main biological processes and molecular mechanisms related to altered circRNAs. The pathway-circRNA interaction network revealed three core circRNAs and five corepathways related to TBI. The circRNA-messenger RNA (mRNA) interaction network and competitive endogenous RNA (ceRNA) analysis suggested potential microRNA (miRNA) sponges and target mRNAs. In addition to five optimal circRNA-miRNA-mRNA pairs were analyzed, circRNA_16895-miRNA myosin-10 (Myo 10) was predicted to regulate fragment crystallizable gamma receptors (FcγR)-mediated phagocytosis pathway. Four circRNAs were selected for quantitative real-time polymerase chain reaction analysis to validate the sequencing data. Our results provide promising functions of circRNAs aberrantly expressed in TBI to explore molecular mechanisms and potential therapeutic targets for its therapy.

Neuroprotective Effects of Electroacupuncture Preventive Treatment in Senescence-Accelerated Mouse Prone 8 Mice.

OBJECTIVE: To investigate the preventive treatment effects of electroacupuncture (EA) on cognitive changes and brain damage in senescence-accelerated mouse prone 8 (SAMP8) mice. METHODS: The 5-month-old male SAMP8 and age-matched homologous normal aging mice (SAMR1) were adopted in this study. EA stimulation at Baihui (GV 20) and Yintang (EX-HN 3) was performed every other day for 12 weeks, 4 weeks as a course. Morris water maze test and Nissl-stained with cresyl violet were used for cognitive impairments evaluation and brain morphometric analysis. Amyloid-ß (A ß) expression in hippocampus and parietal cortex was detected by immunohistochemistry, and apoptosis was observed by TUNEL staining. RESULTS: After 3 courses of EA preventive treatment, the escape latencies of 8-month-old SAMP8 mice in EA group were significantly shortened than those of un-pretreated SAMP8 mice. Compared with SAMR1 mice, extensive neuronal changes were visualized in the CA1 area of hippocampus in SAMP8 mice, while these pathological changes and attenuate cell loss in hippocampal CA1 area of SAMP8 mice markedly reduced after EA preventive treatment. Furthermore, A ß expression in hippocampus and parietal cortex of SAMP8 mice decreased significantly after EA treatment, and neuronal apoptosis decreased as well. CONCLUSION: EA preventive treatment at GV 20 and EX-HN 3 might improve cognitive deficits and neuropathological changes in SAMP8 mice, which might be, at least in part, due to the effects of reducing brain neuronal damage, decreasing neuronal apoptosis and inhibiting A ß-containing aggregates.

Radiofrequency ablation for selective reduction in complex monochorionic multiple pregnancies: A case series.

OBJECTIVE: To determine the safety and efficacy of radiofrequency ablation (RFA) for selective fetal reduction in complex monochorionic multiple pregnancies. MATERIALS AND METHODS: From July 2011 to January 2015, data on all cases treated with RFA were collected prospectively in our hospital. Indications, procedure details, cause of fetal demise and pregnancy outcomes were analyzed. Sonography and magnetic resonance imaging were performed to detect fetal brain damage. Information regarding development after birth was collected according to the Gesell Development Schedule®. RESULTS: There were 22 cases of twins (6 presenting with twin-twin transfusion syndrome, 10 with malformations, 4 with selective intrauterine growth restriction, and 2 with twin reversed arterial perfusion sequence); and 11 cases of triplets (9 dichorionictriamniotic, 2 monochorionictriamniotic). All surgeries were completed with one puncture. No maternal complications presented during RFA procedure, and the PPROM rate before 32 w was 9% (3/33). There were 3 cases of intrauterine fetal demise and 4 twin cases where pregnancy was terminated. The fetal survival rate was 77% (17/22) in twins, 91% (20/22) in triplets. Total fetal survival rate was 84% (37/44). The neurodevelopmental follow-up investigations showed no abnormalities in any of the survivors. CONCLUSION: RFA for selective fetal reduction in complex monochorionic multiple pregnancies is effective, minimally invasive, and safe.

Clinical features and genotyping of patients with primary carnitine deficiency identified by newborn screening.

BACKGROUND: The objective of the study was to investigate clinical and gene mutation characteristics of primary carnitine deficiency (PCD) patients identified by newborn screening using tandem mass spectrometry (MS/MS). METHODS: Tandem mass spectrometry (MS/MS) was applied to screen inherited metabolic disease and seven patients with PCD were diagnosed among 62,568 samples. The SLC22A5 gene was detected by using diagnosis panel of genetic and metabolic diseases based on Ion Torrent Semiconductor Sequencing Technology. RESULTS: The initial free carnitine (C0) concentrations of the patients were 6.43±1.36 µmol/L, and the recall screening concentrations were 5.59±0.89 µmol/L. The patients were treated with oral carnitine, so the levels after treatment were 20.24±3.88 µmol/L. All patients had two pathogenic mutation alleles. CONCLUSIONS: The combined application of MS/MS and a next generation sequencing panel could be used for the accurate diagnosis of PCD. The results of genetic diagnosis can guide the assisted reproductive treatment. The prognosis of PCD patients is good after early treatment.

Response of Soil Fungi Community Structure to Salt Vegetation Succession in the Yellow River Delta.

High-throughput sequencing technology was used to reveal the composition and distribution of fungal community structure in the Yellow River Delta under bare land and four kinds of halophyte vegetation (saline seepweed, Angiospermae, Imperata and Apocynum venetum [A. venetum]). The results showed that the soil quality continuously improved with the succession of salt vegetation types. The soil fungi richness of mild-salt communities (Imperata and A. venetum) was relatively higher, with Shannon index values of 5.21 and 5.84, respectively. The soil fungi richness of severe-salt-tolerant communities (saline seepweed, Angiospermae) was relatively lower, with Shannon index values of 4.64 and 4.66, respectively. The UniFrac metric values ranged from 0.48 to 0.67 when the vegetation was in different succession stages. A total of 60,174 valid sequences were obtained for the five vegetation types, and they were classified into Ascomycota, Basidiomycota, Chytridiomycota, Glomeromycota and Mucoromycotina. Ascomycota had the greatest advantage among plant communities of Imperata and A. venetum, as indicated by relative abundances of 2.69 and 69.97 %, respectively. Basidiomycota had the greatest advantage among mild-salt communities of saline seepweed and Angiospermae, with relative abundances of 9.43 and 6.64 %, respectively. Soil physical and chemical properties were correlated with the distribution of the fungi, and Mucor was significantly correlated with soil moisture (r = 0.985; P < 0.01). Soil quality, salt vegetation and soil fungi were influenced by each other.

Clinical Significance of Serum Interleukin-31 and Interleukin-33 Levels in Patients of Endometrial Cancer: A Case Control Study.

Aims. Previous evidence has proved that interleukin-31 (IL-31) and interleukin-33 (IL-33) can be potential markers in some cancers' formulation. We aimed to determine the potential role of IL-31 and IL-33 in prognosis of endometrial cancer patients. Methods. Serum samples were collected from 160 patients with endometrial cancer and 160 healthy controls. The ELISA kits (Raybio® Systems) specific for human IL-31 and human IL-33 were used. Serum levels of tumor markers (CEA, CA-125, and CA19-9) were measured by chemiluminescence immunoassay. A two-side P value < 0.05 was indicated to be significant. Results. Serum levels of IL-31 and IL-33 in patients were significantly elevated compared to those of healthy controls. The interleukin levels were also related to clinical characteristics, including tumor stages, depth of invasion, and existence of node metastases and distant metastases. The sensitivity and specificity of IL-31 and IL-33 were higher than the counterparts of tumor markers, both separately and in combination of IL-31, IL-33, and the clinical markers. Conclusions. This report is the first one mentioning the possible association between serum IL-31 and IL-33 and endometrial cancer. With their sensitivity and specificity, the interleukins may be useful biomarkers for endometrial cancer's prognosis.