[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.

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.

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.

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.

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.

[Study on protective and haemodynamic effects of Danshen Tongluo capsule on rats with myocardial infarction].

To study the protective effect of Danshen Tongluo capsule on rat hearts in the myocardial infarction (MI) model. After being fed with high fat diets for one month, the SD rats were randomly divided into the sham group and the model group according to the left ventricular ejection fraction (EF). The MI model group was duplicated by ligating coronary artery and then divided into five groups: the model group, the positive control group (model + captopril), the small dose group (model + Danshen Tongluo), the medium dose group (model + Danshen Tongluo) and the high dose group (model + Danshen Tongluo). Four weeks later, changes in myocardium ultra-structure were observed by hemodynamics, cardiac ultrasound and electron microscope. The results showed: (1) All doses of Danshen Tongluo capsule could significantly reduce the left ventricular end diastolic pressure (LVEDP) (P <0.01), increase the maximum internal pressure of the left ventricle (+ dp/dtmax), and lower the drop rate of left ventricular pressure (- dp/dtmax), with statistical significances in medium and high dose groups; (2) The B ultrasound results showed increase in EF and left ventricular shortening fraction (FS) in all dose groups of Danshen Tongluo capsule; (3) The medium dose group showed significant decrease in myocardial infarction index (P <0.01) and injured and fractured myofilament and sarcomere of ischemic myocardium in myocardial ultra-structure; All of Danshen Tongluo capsule-treated groups revealed reduction in myocardial injury and myocardial infraction area. The study preliminarily proves that Danshen Tongluo capsule can improve hemodynamic function, and has a protective effect on myocardial ischemia.

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.

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.

Toxoplasma gondii: enzyme-linked immunosorbent assay based on a recombinant multi-epitope peptide for distinguishing recent from past infection in human sera.

Enzyme-linked immunosorbent assays (ELISAs) based on a recombinant multi-epitope peptide (rMEP) were used in an attempt to differentiate pregnant women with Toxoplasma serologic profiles (TSPs) indicative of recently acquired infections (acute profile) from those with TSPs indicative of infections acquired in the distant past (chronic profile). The recombinant expression vector pET-32c-MEP encoding MEP constructed previously was expressed in Escherichia coli and the rMEP was purified as a bioactive fusion protein. The IgG-ELISA and IgM-ELISA based on the purified rMEP were developed, and used to detect IgG and IgM antibodies against Toxoplasma gondii in human sera. Immunoblot assays showed that the purified rMEP could be strongly recognized by IgM antibodies in the pooled sera from women with acute profiles, and by IgG antibodies in the pooled sera from women with chronic profiles. ELISA results also proved that the reactivities of IgG and IgM antibodies differed significantly in sera from women with acute and chronic profiles. Compared with two commercial ELISA tests for seradiagnosis of toxoplasmosis, the total concordance (including positive and negative sera) of this rMEP-based assay was 93.2% and 95.7% for the detection of IgG and IgM antibodies, respectively. Our study suggests that the rMEP protein could be used as the diagnostic antigen to differentiate recent from past infections in human toxoplasmosis.

[Expression of SSB following early myocardial ischemia in rats].

OBJECTIVE: To investigate the expression of Sjögren's syndrome antigen B (SSB) gene and SSB protein in the early ischemic myocardium in rats. METHODS: Adult healthy Sprague-Dawley rats were randomly divided into groups of operation [myocardial ischemia (MI) and non-ischemia (NI)], non-operation (NO) and sham-operation (SO) (n = 6 for MI and NI; n = 4 for NO and SO). According to time of ischemia, it was then divided into groups of 0 min, 15 min, 30 min, 60 min, 120 min, and 240 min. The expression of SSB gene in the myocardium was examined by real-time PCR, and the expression of SSB protein was examined by Western blot and immunofluorescence staining. RESULTS: The expressions of SSB gene was down-regulated at early stage of ischemia. There was significant difference between 0 min and 120 min at the level of expression of SSB gene in MI group, so did that between 120 min group and NO group (P < 0.05). The expression of SSB protein at 60 min after ischemia was significantly decreased compared with that in the group of 0 min (P < 0.05). The expression of SSB protein in NI groups was significantly higher than that in MI groups at the time of 60 min and 120 min after myocardial ischemia (P < 0.05). Additionally, the expression of SSB protein was mainly located in the myocardial nucleus, myocardial plasma, and plasma membrane of partial myocardiocytes according to the result of immunofluorescence staining. CONCLUSION: SSB may participate in pathophysiologic regulation process in myocardial cells at the early stage of myocardial ischemia in rats.

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.

[Genotypic and clinical features of spinal muscular atrophy type 3].

OBJECTIVE: To explore the genotypic and clinical features and laboratory examinations of spinal muscular atrophy type 3 (SMA III). METHODS: Results of genetic testing and laboratory exams of 18 SMA III patients were collected and analyzed. RESULTS: The average age of onset of patients was 6.1 years, with the course of disease lasting from 13 months to 28 years. All patients became symptomatic with lower extremity muscle weakness. The symptoms gradually aggregated, with proximal lower limb muscle becoming atrophic and proximal upper limb muscle becoming weak. Genetic testing indicated that all subjects possessed homozygous deletions of SMN1 gene. Electromyography (EMG) of 15 subjects indicated neurogenic damage. Whilst younger patients had normal level of creatine kinase (CK), elder patients had higher level of CK, though no linear correlation was found. CONCLUSION: Full understanding of Clinical, especially the growth features of SMA III, in combination with genetic testing, can facilitate diagnosis and early intervention of the disease.

[Dosage compensation mechanism of X chromosome].

Dosage compensation mechanism is crucial for the balance expression of X chromosome genes, which ensures the protein or enzyme encoded by the X chromosome to be equal or almost equal expression amounts between males and females. However, different organisms have evolved distinct dosage compensation strategies, and so far three kinds of dosage compensation strategies among organisms have been reported. The first strategy is that the single male X chromosome expression is doubly activated; the second one is to inactivate one female X chromosome by leaving both sexes with one active allele; and the third one is to reduce the expression to half activity in both X chromosomes of the female. The study of dosage compensation will be useful to reveal the mechanism of regulation of X-linked genes as well as the evolution and the differentiation progress of the sex chromosome, and it can also contribute to illustrate mutation and distortion of sex chromosome. Therefore, this paper briefly reviewed and discussed the progresses and prospects of the important mechanism of dosage compensation.

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.

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.

Characteristics of eight X-STR loci for forensic purposes in the Chinese population.

X-chromosomal short tandem repeats (ChrX STRs) loci are used for forensic practice in recent years. Considering the unique heredity characteristics of ChrX, recombination and linkage disequilibrium (LD) among ChrX STR loci vary between male and female and different populations as well. However, there is a lack of data for analysis of recombination and linkage disequilibrium on ChrX STR loci in the Chinese population. In this work, a total of 303 unrelated individuals (203 males and 100 females) in the Chinese Han population were analyzed with Mentype Argus X-8 PCR amplification kit (DXS10135-DXS8378, DXS7132-DXS10074, HPRTB-DXS10101, and DXS10134-DXS7423). The recombination and linkage disequilibrium of the eight ChrX STR loci were investigated with HapMap LD plots and software ARLEQUIN 3.1. Allele frequencies of the eight loci and further population forensic genetic parameters were obtained. Our results revealed hotspots for recombination, and there was no obvious evidence for LD among the eight loci in the Chinese population. Our work implied that single locus frequencies rather than haplotype frequencies should be applied for forensic practice in the Chinese population.

[Study of dystrophin gene non-deletion/duplication mutations causing Becker muscular dystrophy].

OBJECTIVE: To identify potential mutations in patients featuring Becker muscular dystrophy (BMD) and to enhance the understanding of non-deletion/duplication mutations of the dystrophin gene causing BMD. METHODS: Clinical data of two patients affected with BMD were collected. Potential mutations in the dystrophin gene were screened with multiplex ligation-dependent probe amplification assay (MLPA). Biopsied muscle samples were examined with HE staining, immnostaining with anti-dystrophin antibody, and electronic microscopy. RESULTS: MLPA assay suggested that both cases were probably due to non-deletion/duplication mutations of the dystrophin gene. Light and electronic microcopy of skeletal muscle biopsies confirmed dystrophic changes in both patients. For patient A, immunostaining showed non-contiguous weak staining for most parts of sarcolemma. For patient B, immunostaining showed positive result with N-terminal anti-dystrophin antibody and negative result with C-terminal anti-dystrophin antibody. CONCLUSION: For patients with mild phenotypes but without dystrophin gene deletion/duplication, muscle biopsy and immunochemistry are helpful for diagnosis and prognosis.