Status and progress of school screening for adolescent scoliosis / 中华骨科杂志

Scoliosis is one of the common diseases in adolescents. It can rapidly progress during the peak growth period. Scoliosis school screening (SSS) is the main way for early detection and treatment of this disease. The SSS project began in the 1960s and was gradually promoted from the United States to the world. However, some problems were gradually exposed during the implementation of the project, such as the high false positive rate of screening methods, potential radiation damage, the uncertainty of the potency ratio of screening and the lack of evidence-based medical evidence of the effectiveness of high-level conservative treatment, which led to many European and American countries stopping the implementation of SSS. However, with the progress of research related to diagnosis and treatment of scoliosis, based on the latest evidence-based medical evidence assessment, the United States Preventive Medicine Task Force again adjusted the recommendation level of SSS to "no recommendation, no objection" in 2018. In recent years, SSS has gradually received extensive attention from the Chinese government and society. Five national ministries and commissions also issued a document in 2021 to include scoliosis in the monitoring of common diseases among students. However, the implementation of the project should also refer to the effectiveness criteria of disease screening recommended by the World Health Organization. In the future, with the improvement of the accuracy of scoliosis screening methods, the development of multi-mode screening such as artificial intelligence, the emergence of non-radiation detection technology and the improvement of the effectiveness of conservative treatment of mild and moderate scoliosis, the long-term and large-scale implementation of SSS project and the early prevention and control of scoliosis will be possible to truly achieve.

Copy number variant sequencing for chromosome analysis in 487 fetuses with increased nuchal translucency / 中华围产医学杂志

Objective:To analyze the genetic etiology of 487 fetuses with increased nuchal translucency (NT) using copy number variant sequencing (CNV-seq) and explore the relationship between increased NT and chromosomal abnormality.Methods:A retrospective study was performed on 487 fetuses with increased NT who received CNV-seq in the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2020. These fetuses either had NT of ≥3.0-<3.5 mm (Group A, n=129) or ≥3.5 mm (Group B, n=358), the distribution and incidence of chromosomal abnormalities in the two sets of fetuses were analyzed using Chi square test or Fisher's exact test. Results:Fetuses with abnormal chromosomes accounted for 25.9%(126/487) of cases, including 107 with chromosome aneuploidy (22.0%) and 19 with pathogenic or likely pathogenic copy number variation (CNV, 3.9%). The detection rate of fetal aneuploidy in Group B was higher than that in Group A [14.0% (18/129) vs 24.9% (89/358), χ2=6.58, P=0.010]. However, no significant difference was observed regarding the detection rate of pathogenic or likely pathogenic CNV between the two groups ( χ2=0.30, P=0.584). Conclusions:The risk of fetal chromosome aneuploidy increased with NT thickness, but not with pathogenic or likely pathogenic CNV, which needed further verification due to the small sample size. CNV-seq is an option to detect the conventional detection methods for the genetic etiology of NT thickening fetuses.

Application of CNV-seq and chromosomal karyotyping in the prenatal diagnosis for carriers of balanced translocations / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of copy number variation sequencing (CNV-seq) and karyotyping in the prenatal diagnosis for carriers of balanced translocations.@*METHODS@#Clinical records of 135 amniocentesis samples of balanced translocation carriers undergoing simultaneous CNV-seq and karyotyping were analyzed. Chromosomal aberrations were defined as those can definitely lead to birth defects definitely, which included chromosomal numerical abnormality, large deletion/duplication and pathogenic copy number variations (pCNVs).@*RESULTS@#The detection rates for karyotyping and CNV-seq were 4.44% (6/135) and 5.93% (8/135) respectively, and the latter had a detection rate of 1.48(2/135) higher than the former. A total of 68 fetal chromosomal translocations were detected by karyotying analysis.@*CONCLUSION@#For couples carrying a balanced translocation, simultaneous CNV-seq and karyotyping is conducive to the detection of fetal chromosomal abnormalities and genetic counseling.

Analysis of three families with recurrence of non-immune hydrops fetalis by trio whole exome sequencing / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis of three families with recurrence of non-immune hydrops fetalis (NIHF) but negative result by copy number variation sequencing (CNV-seq).@*METHODS@#Amniotic fluid sample and/or abortive tissues of the fetuses were collected and subjected to CNV-seq analysis. Peripheral blood samples of the parents were also taken for trio whole exome sequencing (trio WES).@*RESULTS@#Fetus 1 was found to harbor heterozygous c.976G>T(p.Glu326*) variant of the SOX18 gene in addition with compound heterozygous variants c.844C>T(p.Arg282Trp) and c.9472+1G>A of the RYR1 gene. The three variants were all inherited from its parents and have been associated with the etiology of NIHF. Based on the American College of Medical Genetics and Genomics (ACMG) standards and guidelines, the c.976G>T variant of SOX18 gene and c.9472+1G>A of RYR1 gene were predicted to be pathogenic (PVS1+PM2+PP3+PP4, PVS1+PM2+PP3), and c.844C>T variant of RYR1 gene to be likely pathogenic (PM1+PM2+PP3). Fetus 2 was found to harbor compound heterozygous variants c.6682C>T(p.Gln2228*) and c.4373_4383del(p.Val1458Alafs*63) of the PIEZO1 gene. Both variants were also inherited from its parents and are associated with the etiology of NIHF. Based on ACMG standards and guidelines, both c.6682C>T and c.4373_4383del variants of PIEZO1 gene were predicted to be pathogenic (PVS1+PM2+PP4, PVS1+PM2). Fetus 3 was found to harbor compound heterozygous variants of the TTN gene c.29860G>C(p.Asp9954His) and c.21107A>T(p.Asp7036Val), which were respectively inherited from its parents. Both variants have been strongly associated with the phenotype, though the connection between the etiology of NIHF and variants of the TTN gene remains elusive. Based on ACMG standards and guidelines, the c.29860G>C and c.21107A>T variants of TTN gene were predicted to be likely pathogenic (PM1+PM2+PP3).@*CONCLUSION@#Trio WES can improve the diagnosis rate of NIHF with a negative result by CNV-seq. Considering the urgency of prenatal diagnosis, CNV-seq and trio WES should be carried out at the same time for fetuses with NIHF.

Progress of research on induced pluripotent stem cell models for Down syndrome / 中华医学遗传学杂志

With an incidence of 1/800 - 1/600, Down syndrome (DS) is the most common chromosomal disorder in humans. Whilst most DS patients has trisomy 21, a small proportion may carry translocations or mosaicisms involving chromosome 21. The main characteristics of DS include mental retardation, peculiar facies, growth retardation, congenital heart disease, duodenal stenosis, Alzheimer's disease, leukemia, and immunodeficiency, which may be due to increased dosage of critical genes. Recent studies also showed that epigenetic changes may also occur in DS. For research on patients with DS or other trisomies have been restricted by ethical considerations, and commonly used mouse models cannot fully replicate the characteristic features of DS, pluripotent stem cells induced from fetal samples or biopsy tissues from DS patients may generate models with the same genetic content, which may provide idea materials for studying the pathogenesis of DS and customized cell and/or gene therapies.

Progress on utilizing mesenchymal stem cells as cellular delivery system for targeting delivery of as drug/gene for anti-tumor therapy / 浙江大学学报·医学版

Mesenchymal stem cells (MSCs) have the inherent tumor-homing ability with the attraction of multiple chemokines released by tumor tissues or tumor microenvironments, which can be utilized as promising cellular carriers for targeted delivery of anti-tumor drugs and genes. In most circumstances, large amount of systemicly administrated MSCs will be firstly trapped by lungs, following with re-distribution and homing to tumor tissues after lung clearance. Several approaches like enhanced interactions between chemokines and receptors on MSCs or reducing the retention of MSCs by changes of administration methods are firstly reviewed for improving the homing of MSCs towards tumor tissues. Additionally, the potentials and gains of utilizing MSCs to carry several chemotherapeutics, such as doxorubicin, paclitaxel and gemcitabine are summarized, showing the advantages of overcoming the short half-life and poor tumor targeting of these chemotherapeutics. Moreover, the applications of MSCs to protect and deliver therapeutic genes to tumor sites for selectively tumor cells eliminating or promoting immune system are highlighted. In addition, the potentials of using MSCs for tumor-targeting delivery of diagnostic and therapeutic agents are addressed. We believed that the continuous improvement and optimization of this stem cells-based cellular delivery system will provide a novel delivery strategy and option for tumor treatment.

Analysis of a family with recurrent fetal copy number variations in 1p31.1 / 中华医学遗传学杂志

Objective@#To analyze a family with recurrent fetal copy number variations (microdeletion and microduplication, respectively) of 1p31.1 using single nucleotide polymorphism-based array (SNP-array) and G banding chromosomal karyotyping.@*Methods@#Amniocentesis and chorionic villus sampling were performed for a woman during the two pregnancies. Whole genome SNP-array was used to detect genomic imbalance of the fetus. The couple was also subjected to G-banding chromosomal analysis and SNP-array analysis.@*Results@#SNP-array showed a 1p31.1 (70 164 686-83 474 843)×1 and a 1p31.1 (70 164 686-83 479 747) × 3 in the fetuses during the two pregnancies, respectively. SNP array results of the couple appeared to be normal. The mother of the fetuses had a 46, XX, inv(1)(p31.1p32.1) karyotype.@*Conclusion@#The paracentric inversion in chromosome 1 in the gravida probably underlies the recurrent 1p31.1 copy number variations in the fetuses. SNP-array combined with G banding chromosomal analysis are suitable for prenatal diagnosis for recurrent microdeletion and microduplication in the same chromosomal region, and can provide detailed information for genetic counseling.

Analysis of a family with recurrent fetal copy number variations in 1p31.1 / 中华医学遗传学杂志

OBJECTIVE@#To analyze a family with recurrent fetal copy number variations (microdeletion and microduplication, respectively) of 1p31.1 using single nucleotide polymorphism-based array (SNP-array) and G banding chromosomal karyotyping.@*METHODS@#Amniocentesis and chorionic villus sampling were performed for a woman during the two pregnancies. Whole genome SNP-array was used to detect genomic imbalance of the fetus. The couple was also subjected to G-banding chromosomal analysis and SNP-array analysis.@*RESULTS@#SNP-array showed a 1p31.1 (70 164 686-83 474 843) ×1 and a 1p31.1 (70 164 686-83 479 747) ×3 in the fetuses during the two pregnancies, respectively. SNP array results of the couple appeared to be normal. The mother of the fetuses had a 46,XX,inv(1)(p31.1p32.1) karyotype.@*CONCLUSION@#The paracentric inversion in chromosome 1 in the gravida probably underlies the recurrent 1p31.1 copy number variations in the fetuses. SNP-array combined with G banding chromosomal analysis are suitable for prenatal diagnosis for recurrent microdeletion and microduplication in the same chromosomal region, and can provide detailed information for genetic counseling.

Therapeutic effect of fibroblast growth factor 21 on NAFLD in MSG-iR mice and its mechanism / 药学学报

This study is to evaluate the therapeutic effect of fibroblast growth factor 21 (FGF21) on NAFLD in MSG-IR mice and to provide mechanism insights into its therapeutic effect. The MSG-IR mice with insulin resistance were treated with high dose (0.1 micromol.kg-1d-1) and low dose (0.025 micromol.kg-1d-1) of FGF21 once a day for 5 weeks. Body weight was measured weekly. At the end of the experiment, serum lipids, insulin and aminotransferases were measured. Hepatic steatosis was observed. The expression of key genes regulating energy metabolism were detected by real-time PCR. The results showed that after 5 weeks treatment, both doses of FGF21 reduced body weight (P<0.01), corrected dyslipidemia (P<0.01), reversed steatosis and restored the liver morphology in the MSG model mice and significantly ameliorated insulin resistance. Additionally, real-time PCR showed that FGF21 significantly reduced transcription levels of fat synthetic genes, decreased fat synthesis and promoted lipolysis and energy metabolism by up-regulating key genes of lipolysis, thereby liver fat accumulation was reduced and liver function was restored to normal levels. In conclusion, FGF21 significantly reduces body weight of the MSG-IR mice, ameliorates insulin resistance, reverses hepatic steatosis. These findings provide a theoretical support for clinical application of FGF21 as a novel therapeutics for treatment of NAFLD.

Research progress of gene recombinant mesenchymal stem cells as tumor targeting delivery vehicles / 药学学报

The applications of targeting gene delivery systems in tumor therapy have attracted extensive attention of researchers in recent years, as they can selectively deliver the therapeutic gene to tumor sites, improve the success rate of gene therapy and reduce the side effects. Therefore, design and development of novel gene delivery vehicles have been a hot area of current research. Recent studies have shown that mesenchymal stem cells (MSCs) have the ability to migrate towards and engraft into the tumor sites. Therefore, these properties make them a great hope for efficient targeted-delivery vehicles in cancer gene therapy. In this review, we examine the promising of utilization of MSCs as a targeted-delivery vehicle for cancer gene therapy, and summarize various challenges and concerns regarding this therapy.

Antitumor activity of the recombinant rClone30-CD/5-FC system / 药学学报

5-Flucytosine (5-FC) could be changed to 5-fluorouracil (5-FU) by cytosine deaminase (CD), the latter is able to kill cancer cells. However, there is no efficient method to deliver the CD gene into the tumor cells, which hampers the application of the suicide gene system. In this experiment, for the first time, the NDV has been utilized as a vector to deliver the CD gene into the cancer cells, the virus can infect the cancer cells specifically, replicate and assemble, while the cytosine deaminase is expressed. Then the CD converts the prodrug 5-FC into 5-FU to achieve the purpose of inhibiting tumor. Firstly, the whole genome of E. coli JM109 was extracted, and the CD gene was obtained by cloning method. Then the CD and IRES-EGFP were ligated into the pEE12.4 expression vector to become a recombinant pEE12.4IE-CD eukaryotic expression plasmid. The human liver cancer cells were transfected with the plasmid. The cells were treated with different concentrations of 5-FC, MTT method was used to determine the killing effect of CD/5-FC system on the human liver cancer cells. The cell deaths were 18.07%, 42.98% and 62.20% respectively when the concentrations of prodrug were at 10, 20 and 30 mmol x L(-1). In 5-FC acute toxicity experiment, Kunming mice were injected with different concentrations of 5-FC at intervals of 1:0.5. The LD50 of 5-FC through iv injection was determined by improved Karber's method, the LD50 was 507 mg x kg(-1) and the 95% confidence limit was 374-695 mg x kg(-1). According to the maximum LD0 dose of the LD50, the maximum safe dose was 200 mg x kg(-1). Body weight and clinic symptoms of the experimental animals were observed. These results laid the foundation to verify the antitumor effect and safety of CD/5-FC system in animal models. The CD gene was ligated into the NDV (rClone30) carrier, then the tumor-bearing animal was established to perform the tumor inhibiting experiment. The result showed that the recombinant rClone30-CD/5-FC system has a high antitumor activity in vivo. To summarize, CD gene has been cloned and its bioactivity has been confirmed in the mammalian cells. It is the first time in this study to utilize the recombinant NDV to deliver the CD gene into the tumor cells; our result proves the rClone30-CD/5-FC system is a potential method for cancer therapy.

Observation on ultrasonic examination in abdominal visceral injuries / 中国基层医药

Objective To investigate the role of ultrasonic examination in the diagnosis d abdominal visceral injuries.Methods 263 patients with abdominal visceral injuries were examined with ultrasonic,the ultrasonic findings were comfirmed by surgery for patients underwent opeartion,for patients treated without surgery,the ultrasonic findings were compared with CT,other examinations and follow-up studies.Results The accuracy rate of ultrasonic examination was 87.07％.Conclusion The ultrasonic examination was simple,rapid,accurate and it should be the first-choice in the diagnosis of abdominal visceral injuries.

Expression of kringle 1-3 domain fragment of human plasmihogen in E.coli and the anti-tumor activity of its product / 中国免疫学杂志

Objective:To study the expression of kringle 1-3 domain fragment of human plasmihogen in E.coli and the anti-tumor activity of its product.Methods:The K1-3 domain fragment was cloned in expression vector pBV220,the resulted recombinant plasmid pBV-K13 was transformed into E.coli DH5? and its product was purified and assayed its bioactivity.Results:K1-3 domain fragment was expressed in(E.coli) DH5?.The results showed the expressed product covered 20% of the total bacterial protein on SDS-PAGE and the Western blot analysis showed that the product had immunological specificity with the antiserum of human plasminogen and inhibits the growth of chorioallantoic membrane(CAM) angiogenesis and mouse B16 melanoma.Conclusion:Human plasminogen K1-3 domain fragment was expressed in E.coli;the expressed product has anti-angiogenesis and anti-tumor activity.

Cloning and expression of human plasminogen kringle 5 gene in E.Coli / 中国病理生理杂志

AIM: Constructing plasmid that expresses human plasminogen kringle 5 gene to analyze the gene expression in E.coli. METHODS: The gene of human plasminogen kringle 5 was inserted into plasmid PBV220 EcoRI site by gene manipulation techniques and was transformed to E.coli TGI. The gene expression was observed by SDS-PAGE. RESULTS: Expression vector PBVK5 was constructed, and human plasmingen kringle 5 gene product was obtained at 42℃ induction. CONCLUSLON: Expression product of human plasminogen kringle 5 gene was soluble form of proteins, and the expression amount was 9.8% in E.coli TGI total proteins.