Comprehensive landscape of the T and B-cell repertoires of newly diagnosed gestational diabetes mellitus.

This study conducted a high-throughput sequencing analysis of the T- and B- repertoires in the newly diagnosed GDM patients and evaluated the association between abnormal adaptive immunity and GDM. The unique TCR CDR3 clonotypes were mildly decreased in GDM patients, and the similarity of TCR V-J distributions was higher in the GDM group. Moreover, the usages of the V gene and V-J pair and the frequency distributions of some CDR3 amino acids (AAs) both in BCR and TCR were significantly different between groups. Moreover, the cytokines including IL-4, IL-6, IFN-γ and IL-17A were synchronously elevated in the GDM cases. Our findings provide a comprehensive view of BCR and TCR repertoires at newly diagnosed GDM patients, revealing the mild reduction in unique TCRB CDR3 sequences and slight alteration of the V gene, V-J combination and CDR3 (AA) usages of BCR and TCR. This work provides deep insight into the mechanism of maternal adaptive immunity in GDM and provides novel diagnostic biomarkers and potential immunotherapy targets for GDM.

Ambient air pollution and gestational diabetes mellitus: An updated systematic review and meta-analysis.

OBJECTIVE: We aimed to evaluate the relationship between the composition of particulate matter (PM) and gestational diabetes mellitus (GDM) by a comprehensively review of epidemiological studies. METHODS: We systematically identified cohort studies related to air pollution and GDM risk before February 8, 2023 from six databases (PubMed, Embase, Web of Science Core Collection, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform and Chongqing VIP Chinese Science and Technology Periodical databases). We calculated the relative risk (RR) and its 95% confidence intervals (CIs) to assess the overall effect by using a random effects model. RESULTS: This meta-analysis of 31 eligible cohort studies showed that exposure to PM2.5, PM10, SO2, and NO2 was associated with a significantly increased risk of GDM, especially in preconception and first trimester. Analysis of the components of PM2.5 found that the risk of GDM was strongly linked to black carbon (BC) and nitrates (NO3-). Specifically, BC exposure in the second trimester and NO3- exposure in the first trimester elevated the risk of GDM, with the RR of 1.128 (1.032-1.231) and 1.128 (1.032-1.231), respectively. The stratified analysis showed stronger correlations of GDM risk with higher levels of pollutants in Asia, except for PM2.5 and BC, which suggested that the specific composition of particulate pollutants had a greater effect on the exposure-outcome association than the concentration. CONCLUSIONS: Our study found that ambient air pollutant is a critical factor for GDM and further studies on specific particulate matter components should be considered in the future.

The irreplaceable role of medical massive open online courses in China during the COVID-19 pandemic.

BACKGROUND: Massive open online courses (MOOCs) have become innovative open-learning approach in medical education. This study aimed to evaluate the dynamic changes in the construction and application of medical MOOCs before and after the coronavirus disease 2019 (COVID-19) pandemic in China. METHODS: The dynamic changes of usages about medical MOOCs before and after 2020 were mainly searched on the Smart Education of China Higher Education platform, and the detailed learning profiles and outcome indicators were further analyzed using 40 national first-class medical MOOCs from 'zhihuishu' platform. RESULTS: A total of 2,405 medical MOOCs were exported from the Smart Education of China Higher Education platform, of which 1,313 (54.6%) were launched since 2020. The total and average numbers of participants of 141 national first-class medical MOOCs peaked during the initial spread of COVID-19 in 2020. We further analyzed the dynamic usage of MOOCs from 2018 to 2022 based on 40 national first-class medical MOOCs launched on the 'Zhihuishu' platform. The findings revealed that the number of registered learners (3,240 versus 2,654), questions and answers (27,005 versus 5,116) and students taking the final examination (2,782 versus 1,995) per semester were significantly higher since 2020 compared to these before 2020. Especially, the number of registered learners, registered schools, questions and answers, and students participating in online discussion, taking the unit quiz, taking final examinations and passing final examinations all peaked in the 2020 spring-summer semester. Pearson's correlation analysis found that the number of questions and answers and the number of learners who participated in online discussion were both positively correlated with the number of students who passed the final examination, and the correlation was especially strong since 2020. Moreover, the number of publications on medical MOOC research has soared since 2020 and has maintained a continuous upward trend. CONCLUSIONS: High-quality medical MOOCs have been launched rapidly since the COVID-19 pandemic in China. The number of participants and online interactions of medical MOOCs peaked during the initial spread of COVID-19 in 2020. MOOCs are reliable and valid digital sources that facilitate medical higher education and play irreplaceable roles in emergency management.

Exosomal miRNAs as potential biomarkers for acute myocardial infarction.

microRNAs (miRNAs) can be used as biomarkers for acute myocardial infarction (AMI). However, few reports have focused on the value of exosomal miRNAs in the mechanism of the pathophysiological process from stable coronary artery disease (SCAD) to AMI. Exosomes were isolated via ultracentrifugation after serum samples were collected. The exosomes were then identified by transmission electron microscopy, western blotting, and nanoparticle tracking analysis. The differential expression of miRNAs in exosomes from six AMI and six matching SCAD patients was screened using the Agilent Human miRNA Microarray Kit. Target genes of the candidate miRNAs were predicted via an online miRNA database, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses. Further validation was conducted through quantitative real-time polymerase chain reaction with 60 exosome samples. The expression of 13 miRNAs was significantly downregulated in the AMI samples compared with the SCAD samples. In addition, we identified various target genes that are mainly involved in the pathways of cardiac rehabilitation and remodelling. Validation of the expression of candidate miRNAs indicated that exosomal miR-1915-3p, miR-4,507, and miR-3,656 were significantly less expressed in AMI samples than in SCAD samples, and area under the receiver-operating-characteristic curve (AUC) analysis showed that the expression of these miRNAs resulted in good predictive accuracy [miR-1915-3p (AUC: 0.772); miR-4,507 (AUC: 0.684); and miR-3,656 (AUC: 0.771)], suggesting that these serum exosomal miRNAs might be predictive for AMI at an early stage. Hence, exosomal miRNAs might play an important role in the pathophysiology of AMI and could serve as diagnostic biomarkers.

Microarray Analysis of Long Noncoding RNAs in Female Diabetic Peripheral Neuropathy Patients.

BACKGROUND/AIMS: Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus (DM). Because of its controversial pathogenesis, DPN is still not diagnosed or managed properly in most patients. METHODS: In this study, human lncRNA microarrays were used to identify the differentially expressed lncRNAs in DM and DPN patients, and some of the discovered lncRNAs were further validated in additional 78 samples by quantitative realtime PCR (qRT-PCR). RESULTS: The microarray analysis identified 446 and 1327 differentially expressed lncRNAs in DM and DPN, respectively. The KEGG pathway analysis further revealed that the differentially expressed lncRNA-coexpressed mRNAs between DPN and DM groups were significantly enriched in the MAPK signaling pathway. The lncRNA/mRNA coexpression network indicated that BDNF and TRAF2 correlated with 6 lncRNAs. The qRT-PCR confirmed the initial microarray results. CONCLUSION: These findings demonstrated that the interplay between lncRNAs and mRNA may be involved in the pathogenesis of DPN, especially the neurotrophin-MAPK signaling pathway, thus providing relevant information for future studies.

Tributyltin induces disruption of microfilament in HL7702 cells via MAPK-mediated hyperphosphorylation of VASP.

Tributyltin (TBT) has been widely used for various industrial purposes, and it has toxic effects on multiple organs and tissues. Previous studies have found that TBT could induce cytoskeletal disruption, especially of the actin filaments. However, the underlying mechanisms remain unclear. The aim of the present study was to determine whether TBT could induce microfilament disruption using HL7702 cells and then to assess for the total levels of various microfilament-associated proteins; finally, the involvement of the MAPK pathway was investigated. The results showed that after TBT treatment, F-actin began to depolymerize and lost its characteristic filamentous structure. The protein levels of Ezrin and Cofilin remained unchanged, the actin-related protein (ARP) 2/3 levels decreased slightly, and the vasodilator-stimulated phosphoprotein (VASP) decreased dramatically. However, the phosphorylation levels of VASP increased 2.5-fold, and the ratio of phosphorylated-VASP/unphosphorylated-VASP increased 31-fold. The mitogen-activated protein kinases (MAPKs) ERK and JNK were discovered to be activated. Inhibition of ERK and JNK not only largely diminished the TBT-induced hyperphosphorylation of VASP but also recovered the cellular morphology and rescued the cells from death. In summary, this study demonstrates that TBT-induced disruption of actin filaments is caused by the hyperphosphorylation of VASP through MAPK pathways. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1530-1538, 2016.

Another functional frame-shift polymorphism of DEFB126 (rs11467497) associated with male infertility.

DEFB126 rs140685149 mutation was shown to cause sperm dysfunction and subfertility. Indel rs11467497 is another 4-nucleotide frame-shift mutation (151bp upstream of rs140685149) that leads to the premature termination of translation and the expression of peptide truncated at the carboxyl terminus. In the present study, we performed a comprehensive association study to check the contribution of rs140685149 and rs11467497 to male infertility. Our results confirmed the previous findings that there was no association between rs140685149 and sperm motility. In contrast, we found a significant association of another indel rs11467497 with male infertility. Moreover, rs11467497 was shown to be associated with higher number of round cells in the infertile males with low sperm motility. Surprisingly, the two mutations commonly existed in the sperm donors (n = 672), suggesting a potential application of the two indels in the screening for eligible sperm donors. Western blotting assays showed the sperms with rs140685149 2-nt deletion tended to have unstable DEFB126 protein in contrast of no DEFB126 protein expressed in the sperms with rs11467497 4-nt deletion, suggesting a more severe consequence caused by rs11467497 mutation. In conclusion, our study presented a significant contribution of another functional frame-shift polymorphism of DEFB126 (rs11467497) to male infertility.

ABCB1 C3435T polymorphism and the lipid-lowering response in hypercholesterolemic patients on statins: a meta-analysis.

BACKGROUND: A number of researches have evaluated the association between the ABCB1 polymorphism and the lipid-lowering response of statins, but the results have been inconclusive. To examine the lipid-lowering efficacy and safety associated with the ABCB1 C3435T polymorphism in hypercholesterolemic patients receiving statin, all available studies were included in this meta-analysis. METHODS: A systematic search for eligible studies in the Cochrane library database, Scopus and PubMed was performed. Articles meeting the inclusion criteria were comprehensively reviewed, and the available data were accumulated by the meta-analysis. RESULTS: The results indicated that the comparisons of CC+CT vs. TT were associated with a significant elevation of the serum HDL-C levels after statin treatment (CC+CT vs. TT: MD, 2.46; 95 % CI, 0.36 to 4.55; P = 0.02), and the ABCB1 C3435T variant in homozygotes was correlated with decreases in LDL-C (CC vs. TT: MD, 2.29; 95 % CI, 0.37 to 4.20; P = 0.02) as well as TC (CC vs. TT: MD, 3.05; 95 % CI, 0.58 to 5.53; P = 0.02) in patients treated with statin. However, we did not observe a significant association in the TG group or an association between other genetic models serum lipid parameters. In addition, statin treatment more than 5 months led to a higher risk of muscle toxicity. CONCLUSIONS: The evidence from the meta-analysis demonstrated that the ABCB1 C3435T polymorphism may represent a pharmacogenomic biomarker for predicting treatment outcomes in patients on statins and that statin treatment for more than 5 months can increase the risk of myopathy.

A novel PCR-based approach to discover miRNA target genes.

MiRNAs are potent regulators of gene expression, and most miRNAs have from several to several thousands of gene targets. Validating the numerous gene targets of a given miRNA remains challenging despite the existence of various tools and databases that predict candidate gene-miRNA pairs. In the present study, we present a high-throughput but flexible method that applies a PCR-based application to simulate the binding of miRNAs to their gene targets. Using hsa-miR-377 as an illustrative example, our method was able to identify 13 potential targets of hsa-miR-377. Moreover, our results include 2 genes (SOD2 and PPM1A) that have already been verified as targets of hsa-miR-377. Our method may provide an alternative way of identifying the gene targets of miRNAs for future research.

The evolutionary study of susceptibility genes for essential hypertension.

Genetic studies, including familial linkage analysis, candidate gene approach and genome-wide association study, to some extent, have failed in detecting confirmative susceptibility genes/loci for essential hypertension (EH) in the general population. Previous genetic studies have suggested that differential susceptibility to many metabolic diseases is due to different environmental adaptation patterns during the out-of-Africa expansion, which provides a new strategy for the genetic study of EH. In this review, we introduce the principle and the latest progress of evolutionary study of susceptibility genes for EH. Furthermore, our recent evolutionary screening for EH susceptible genes/loci in Chinese Han population is also summarized. This review is expected to provide useful information for future genetic studies of EH and many other diseases.

Trajectories tracking of maternal and neonatal health in eastern China from 2010 to 2021: A multicentre cross-sectional study.

Background: China's fertility policy has dramatically changed in the past decade with the successive promulgation of the partial two-child policy, universal two-child policy and three-child policy. The trajectories of maternal and neonatal health accompanied the changes in fertility policy are unknown. Methods: We obtained data of 280 203 deliveries with six common pregnancy complications and thirteen perinatal outcomes between 2010 and 2021 in eastern China. The average annual percent change (AAPC) was calculated to evaluated the temporal trajectories of obstetric characteristics and adverse outcomes during this period. Then, the autoregressive integrated moving average (ARIMA) models were constructed to project future trend of obstetric characteristics and outcomes until 2027. Results: The proportion of advanced maternal age (AMA), assisted reproduction technology (ART) treatment, gestational diabetes mellitus (GDM), anaemia, thrombocytopenia, thyroid dysfunction, oligohydramnios, placental abruption, small for gestational age (SGA) infants, and congenital malformation significantly increased from 2010 to 2021. However, the placenta previa, large for gestational age (LGA) infants and stillbirth significantly decreased during the same period. The AMA and ART treatment were identified as independent risk factors for the uptrends of pregnancy complications and adverse perinatal outcomes. The overall caesarean section rate remained above 40%. Importantly, among multiparas, a previous caesarean section was found to be associated with a significantly reduced risk of hypertensive disorders of pregnancy (HDP), premature rupture of membranes (PROM), placenta previa, placental abruption, perinatal asphyxia, LGA infants, stillbirths, and preterm births. In addition, the ARIMA time series models predicted increasing trends in the ART treatment, GDM, anaemia, thrombocytopenia, postpartum haemorrhage, congenital malformation, and caesarean section until 2027. Conversely, a decreasing trend was predicted for HDP, PROM, and placental abruption premature, LGA infants, SGA infants, perinatal asphyxia, and stillbirth. Conclusions: Maternal and neonatal adverse outcomes became more prevalent from 2010 to 2021 in China. Maternal age and ART treatment were independent risk factors for adverse obstetric outcomes. The findings offered comprehensive trajectories for monitoring pregnancy complications and perinatal outcomes in China, and provided robust intervention targets in obstetric safety. The development of early prediction models and the implementation of prevention efforts for adverse obstetric events are necessary to enhance obstetric safety.

Corrigendum: Association between napping and type 2 diabetes mellitus.

[This corrects the article DOI: 10.3389/fendo.2024.1294638.].

Association between napping and type 2 diabetes mellitus.

As the incidence of type 2 diabetes mellitus (T2DM) is increasing rapidly and its consequences are severe, effective intervention and prevention, including sleep-related interventions, are urgently needed. As a component of sleep architecture, naps, alone or in combination with nocturnal sleep, may influence the onset and progression of T2DM. Overall, napping is associated with an increased risk of T2DM in women, especially in postmenopausal White women. Our study showed that napping >30 minutes (min) increased the risk of T2DM by 8-21%. In addition, non-optimal nighttime sleep increases T2DM risk, and this effect combines with the effect of napping. For nondiabetic patients, napping >30 min could increase the risks of high HbA1c levels and impaired fasting glucose (IFG), which would increase the risk of developing T2DM later on. For diabetic patients, prolonged napping may further impair glycemic control and increase the risk of developing diabetic complications (e.g., diabetic nephropathy) in the distant future. The following three mechanisms are suggested as interpretations for the association between napping and T2DM. First, napping >30 min increases the levels of important inflammatory factors, including interleukin 6 and C-reactive protein, elevating the risks of inflammation, associated adiposity and T2DM. Second, the interaction between postmenopausal hormonal changes and napping further increases insulin resistance. Third, prolonged napping may also affect melatonin secretion by interfering with nighttime sleep, leading to circadian rhythm disruption and further increasing the risk of T2DM. This review summarizes the existing evidence on the effect of napping on T2DM and provides detailed information for future T2DM intervention and prevention strategies that address napping.

Genetic adaptation of the hypoxia-inducible factor pathway to oxygen pressure among eurasian human populations.

Research into the mechanisms of human adaptation to the hypoxic environment of high altitude is of great interest to the fields of human physiology and clinical medicine. Recently, the gene EGLN1, from the hypoxia-inducible factor (HIF) pathway, was identified as being involved in the hypoxic adaptation of highland Andeans and Tibetans. Both highland Andeans and Tibetans have adapted to an extremely hypoxic habitat and less attention has been paid to populations living in normoxic conditions at sea level and mild-hypoxic environments of moderate altitude, thus, whether a common adaptive mechanism exists in response to quantitative variations of environmental oxygen pressure over a wide range of residing altitudes is unknown. Here, we first performed a genome-wide association study of 35 populations from the Human Genome Diversity-CEPH Panel who dwell at sea level to moderate altitude in Eurasia (N = 691; 0-2,500 m) to identify the genetic adaptation profile of normoxic and mild-hypoxic inhabitants. In addition, we systematically compared the results from the present study to six previously published genome-wide scans of highland Andeans and Tibetans to identify shared adaptive signals in response to quantitative variations of oxygen pressure. For normoxic and mild-hypoxic populations, the strongest adaptive signal came from the mu opioid receptor-encoding gene (OPRM1, 2.54 × 10(-9)), which has been implicated in the stimulation of respiration, while in the systematic survey the EGLN1-DISC1 locus was identified in all studies. A replication study performed with highland Tibetans (N = 733) and sea level Han Chinese (N = 748) confirmed the association between altitude and SNP allele frequencies in OPRM1 (in Tibetans only, P < 0.01) and in EGLN1-DISC1 (in Tibetans and Han Chinese, P < 0.01). Taken together, identification of the OPRM1 gene suggests that cardiopulmonary adaptation mechanisms are important and should be a focus in future studies of hypoxia adaptation. Furthermore, the identification of the EGLN1 gene from the HIF pathway suggests a common adaptive mechanism for Eurasian human populations residing at different altitudes with different oxygen pressures.

Lack of association between polymorphisms from genome-wide association studies and tuberculosis in the Chinese population.

Genome-wide association studies (GWAS) have identified rs4331426 and rs2057178 as being associated with tuberculosis (TB) in African populations. Both are common single nucleotide polymorphisms (SNPs) in Africans, but they are much rarer in Eurasian populations. In order to corroborate these results, we carried out a case-control study in the Chinese population; these 2 SNPs were genotyped in 600 pulmonary TB patients and 618 healthy controls. The results showed that neither of the SNPs was associated with TB, even after stratification by gender, age, and smear status. Considering the limitation of poor coverage of variations in commercial available genotyping platforms in African populations, further GWAS should be conducted in other populations such as Indian and Chinese. Moreover, future genetic studies on host susceptibility to TB need to take into account all the variables, including host, environment, pathogen, and interactions.

[Advances in genome-wide association study of tuberculosis].

Tuberculosis, caused by Mycobacterium tuberculosis (MTB), is one of the oldest and most influential diseases in the history due to its devastating effect on health and high mortality rate worldwide. Tuberculosis causes more human deaths than any other single infectious disease and the incidence of the tuberculosis is increasing dramatically in recent years. Genome-wide association study (GWAS) has been used to delineate the genetic basis of tuberculosis, and several susceptibility genes and loci were found, which provids important clues to the early intervention and treatment of tuberculosis. However, due to difference in the population structure and host-pathogen interactions, GWAS on tuberculosis faces great challenges. In this review, we introduced the achievements of GWAS on tuberculosis, and illustrated challenges and strategies in the future study.

The status of virtual simulation experiments in medical education in China: based on the national virtual simulation experiment teaching Center (iLAB-X).

BACKGROUND: Virtual simulation experiments have been rapidly applied to medical education curricula in recent years. China constructed a national virtual simulation experimental teaching center (iLAB-X), and this platform covered almost all of the virtual simulation experiment curricula of domestic colleges or universities. We aimed to comprehensively assess the characteristics and usages of virtual simulation experiments in medical education based on iLAB-X. METHODS: A total of 480 virtual simulation experiment courses had been constructed on iLAB-X (https://www.ilab-x.com/) by December 20, 2022, and the curriculum level, type and design were all searched in this platform. We also conducted an evaluation of curriculum usage and online tests, including the page view, frequency of participation, number of participants, duration of experimental learning and passing rate of the experimental test. RESULTS: The national and provincial high-quality virtual simulation experiment curricula accounted for 33.5% (161/480) and 35.8% (172/480), respectively. The curricula were mainly set as basic practice experiments (46.5%) and synthetic designing experiments (48.8%). Significantly, forensic medicine (100%), public health and preventive medicine (83%) and basic medical sciences (66%) focused on synthetic design experiments. In terms of usage experiments, the average duration of experimental learning was 25 minutes per course, and the average number of participants was just 1257. The average passing (score ≥60) rate of online tests was 80.6%, but the average rate of score ≥ 85 was only 58.5%. In particular, the average page views, the number of participants, the duration of learning and the test passing rate of clinical medicine were relatively low. CONCLUSIONS: The curriculum design features, construction level and utilization rate varied in different medical majors. Virtual simulation experiments are particularly underutilized in clinical medicine. There is a long way for virtual simulation experiments to go to become a supplement or alternative for traditional medical education in the future.

Molecular Mechanisms of the Melatonin Receptor Pathway Linking Circadian Rhythm to Type 2 Diabetes Mellitus.

Night-shift work and sleep disorders are associated with type 2 diabetes (T2DM), and circadian rhythm disruption is intrinsically involved. Studies have identified several signaling pathways that separately link two melatonin receptors (MT1 and MT2) to insulin secretion and T2DM occurrence, but a comprehensive explanation of the molecular mechanism to elucidate the association between these receptors to T2DM, reasonably and precisely, has been lacking. This review thoroughly explicates the signaling system, which consists of four important pathways, linking melatonin receptors MT1 or MT2 to insulin secretion. Then, the association of the circadian rhythm with MTNR1B transcription is extensively expounded. Finally, a concrete molecular and evolutionary mechanism underlying the macroscopic association between the circadian rhythm and T2DM is established. This review provides new insights into the pathology, treatment, and prevention of T2DM.

The melatonin receptor 1B gene links circadian rhythms and type 2 diabetes mellitus: an evolutionary story.

Disturbed circadian rhythms have been a risk factor for type 2 diabetes mellitus (T2DM). Melatonin is the major chronobiotic hormone regulating both circadian rhythm and glucose homeostasis. The rs10830963 (G allele) of the melatonin receptor 1B (MTNR1B) gene has the strongest genetic associations with T2DM according to several genome-wide association studies. The MTNR1B rs10830963 G allele is also associated with disturbed circadian phenotypes and altered melatonin secretion, both factors that can elevate the risk of diabetes. Furthermore, evolutionary studies implied the presence of selection pressure and ethnic diversity in MTNR1B, which was consistent with the "thrifty gene" hypothesis in T2DM. The rs10830963 G risk allele is associated with delayed melatonin secretion onset in dim-light and prolonged duration of peak melatonin. This delayed melatonin secretion may help human ancestors adapt to famine or food shortages during long nights and early mornings and avoid nocturnal hypoglycemia but confers susceptibility to T2DM due to adequate energy intake in modern society. We provide new insight into the role of MTNR1B variants in T2DM via disturbed circadian rhythms from the perspective of the "thrifty gene" hypothesis; these data indicate a novel target for the prevention and treatment of susceptible populations with the thrifty genotype.

[Application of SNPstream for medical genetics research].

OBJECTIVE: To introduce the principle, procedure, efficacy and application of SNPstream genotyping technology. METHODS: Genotyping results of 152 SNPs were used to analyze the feasibility, call rate and accuracy of SNPstream technology. RESULTS: For the 152 selected SNPs, 122 SNPs can be genotyped with SNPstream, for which 116 SNPs were successfully genotyped. Replication study showed that the repeatability of genotyping is 99%. When the allele cluster was clear, the accuracy can reach 100%. But when the allele cluster was obscure, the accuracy was only 93.8%. CONCLUSION: SNPstream technology has the advantages of high accuracy, flexible throughput, and high cost performance, and may have a wide application for medical genetics research.