Enlarged multicystic dysplastic kidneys with oligohydramnios during infancy caused by NPHP3 gene mutation / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and genomic abnorm ality of a fetus enlarged multicystic dysplastic kidneys with oligohydramnios caused by NPHP3 gene mutation.@*METHODS@#The fetuse was found to have multicystic dysplastic kidneys with oligohydramnios upon ultrasonography during the second trimester. Following induced abortion, fetal tissue was collected for the extraction of DNA, chromosomal microarray analysis (CMA) and whole exome sequencing (WES). Sanger sequencing was used to verify the suspected variants in the family.@*RESULTS@#Antenatal ultrasound examination at 19 weeks showed "polycystic" kidneys with Oligohydramnios. Delivery was by induced labour because of the critically low amniotic fluid volume. Testing of CMA was normal. WES showed a compound heterozygous mutation of c.1817G>A, p.W606X; c.432dupA, p.E145Rfs*18 mutations are novel mutations in this study.@*CONCLUSION@#The research may further expand the NPHP3 gene mutation spectrum. Enlarged multicystic dysplastic kidneys with oligohydramnios caused by NPHP3 gene mutation at least include one or two splice site mutation, frameshift mutation or nonsense mutation foetal poor prognosis.

Analysis of TUBB2B gene variant in a fetus with complex cortical dysplasia with other brain malformations-7 / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a fetus with dysgenesis of corpus callosum and other brain malformations.@*METHODS@#Whole exome sequencing was carried out for the fetus and its parents. Suspected pathogenic variants were verified by Sanger sequencing.@*RESULTS@#A novel de novo missense variant c.758T>A (p.L253Q) of the TUBB2B gene was identified, which was unreported previously. Based on the guidelines from the American College of Medical Genetics, the c.758T>A variant was predicted to be likely pathogenic. Bioinformatics analysis predicted that the leucine at position 253 was highly conserved among various species, and the c.758T>A variant may impact the formation of hydrogen bonds between Leu253 and Asp249 and Met257 residues, which in turn may affect the combination of GTP/GDP and function of the TUBB2B protein.@*CONCLUSION@#The c.758T>A variant of the TUBB2B gene probably underlay the fetal malformations in this Chinese family. Above discovery has enriched the spectrum of TUBB2B gene variants and provided a basis for genetic counseling and prenatal diagnosis.

Variation analysis of EPG5 gene in a Vici syndrome family / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of Vici syndrome in a Chinese family.@*METHODS@#Whole exome sequencing (WES) technology was used to detect gene variants in a fetus of abnormal ultrasonic structure without abnormalities in routine chromosome karyotype analysis and SNP-array. Sanger sequencing and bioinformatics prediction were performed for the suspected variants of the fetus and parents.@*RESULTS@#The fetus and the elder sister have carried c. 2427delC (p.T809fs) and c.1886A>T (p.E629V) compound heterozygous variants of the EPG5 gene, which were respectively inherited from their mother and father. Neither variant was reported previously. According to ACMG guidelines, the c.2427delC variant was predicted as pathogenic, while the c.1886A>T variant was of uncertain significance. PolyPhen-2 and PROVEAN software indicated that c.1886A>T variant was probably damaging.@*CONCLUSION@#The c.2427delC and c.1886A>T variants of the EPG5 gene probably underlie the pathogenesis of the Vici syndrome in this family. Above finding has enriched the variational spectrum of EPG5 gene and provided a basis for genetic counseling and prenatal diagnosis for the family.

A retrospective analysis of the funding of respiratory projects supported by the National Natural Science Foundation of China from 2009 to 2019 / 中华医学科研管理杂志

Objective:To understand the status quo of basic research projects on respiratory diseases in China.Methods:Descriptive statistical methods were used to review the project number, funding input, funding categories and distribution of National Natural Science Foundation of China (NSFC) respiratory disease funding projects from 2009 to 2019.Results:according to the research, the number of NSFC respiratory projects and funding increased significantly, which promoted the development of respiratory science. However, due to the heavy burden of respiratory diseases, it is still necessary to increase the investment in respiratory diseases.Conclusions:taking into account of the importance of respiratory science, this paper suggests that NSFC should increase investment and support for respiratory diseases projects, strengthen the development of existing respiratory advantages, encourage cross-cutting and frontier research on respiration, cultivate a group of internationally influential scientists and research teams, and promote academic innovation in respiratory science.

Identifying the molecular basis of Jinhong tablets against chronic superficial gastritis via chemical profile identification and symptom-guided network pharmacology analysis / 药物分析学报

Chronic superficial gastritis(CSG)is a common disease of the digestive system that possesses a serious pathogenesis.Jinhong tablet(JHT),a traditional Chinese medicine(TCM)prescription,exerts therapeutic effects against CSG.However,the molecular basis of its therapeutic effect has not been clarified.Herein,we employed ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC-Q/TOF-MS)based chemical profile identification to determine the chemical components in JHT.Further,we applied network pharmacology to illustrate its molecular mechanisms.A total of 96 chemical constituents were identified in JHT,31 of which were confirmed using reference standards.Based on the bioinformatics analysis using the symptom-guided pharmacological networks of"chi,""blood,""pain,"and"inflammation,"and target screening through the interaction probabilities between compounds and targets,matrix metalloproteinase 2(MMP2),dopamine d2 receptor(DRD2),and Aldo-keto reductase family 1 member B1(AKR1B1)were identified as key targets in the therapeutic effect exhibited by JHT against CSG.Moreover,according to the inhibitory activities presented in the literature and binding mode analysis,the structural types of alkaloids,flavonoids,organic acids,including chlorogenic acid(10),caffeic acid(13),(-)-corydalmine(33),(-)-isocorypalmine(36),isochlorogenic acid C(38),isochlorogenic acid A(41),quercetin-3-O-α-L-rhamnoside(42),isochlorogenic acid B(47),quercetin(63),and kaempferol(70)tended to show remarkable activities against CSG.Owing to the above findings,we systematically identified the chemical components of JHT and revealed its molecular mechanisms based on the symptoms associated with CSG.

Genetic analysis of a rare fetus with mandibulofacial dysostosis Guion-Almeida type / 中华医学遗传学杂志

OBJECTIVE@#To delineate the clinical and genetic features of a fetus with micrognathia, low-set ears, microtia, polyhydramnios and anechoic stomach by ultrasonography.@*METHODS@#Whole exome sequencing (WES) was carried out to detect genetic variant in the fetus, for which routine chromosomal karyotyping and chromosomal microarray analysis (CMA) yielded no positive finding. Candidate variants were verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#WES revealed that the fetus has carried a de novo nonsense c.2302C>T (p.Q768X) variant in exon 23 of the EFTUD2 gene, which was detected in neither parent. The variant was unreported previously and may lead to premature termination of the translation of EFTUD2 protein at the 768th amino acid. Bioinformatic analysis predicted the amino acid to be highly conserved and may alter the structure and function of the EFTUD2 protein.@*CONCLUSION@#The c.2302C>T variant of the EFTUD2 gene probably underlay the mandibulofacial dysostosis Guion-Almeida type in the fetus. Discovery of the novel variant has enriched variant spectrum of the EFTUD2 gene and provided a basis for genetic counseling and prenatal diagnosis for the family.

Sedative efficacy of remimazolam in outpatients undergoing curettage / 中华麻醉学杂志

Objective:To evaluate the sedative efficacy of remimazolam in outpatients undergoing curettage.Methods:Eighty outpatients, of American Society of Anesthesiologists physical status Ⅰor Ⅱ, aged ≥18 yr, undergoing curettage, were divided into 2 groups according to the random number table method: remimazolam group (group R, n=41) and propofol group (group P, n=39). Anesthesia was induced with alfentanil 10 μg/kg injected intravenously in two groups, and in addition remimazolam 7 mg was intravenously injected in group R, and propofol 1.5 mg/kg was intravenously injected in group P. If the Modified Observer′s Assessment of Alertness/Sedation score ≥3 or the patient could not tolerate the surgical procedure, remimazolam 2.5 mg was given for rescue sedation in group R and propofol 0.5 mg/kg was given for rescue sedation in group P, and alfentanil 1 μg/kg was given as rescue analgesic.The onset time of sedatives, time to eye opening, emergence time and time to discharge were recorded.The success of sedation, intraoperative BIS value, requirement for rescue medications, and occurrence of adverse reactions were recorded. Results:The intraoperative BIS values were maintained at 61-72 and 40-64 in group R and group P, respectively.The success rate of sedation was 95% in group R and 100% in group P, and there was no significant difference between the two groups ( P>0.05). Compared with group P, the rate of rescue sedative agents used and rate of rescue alfentanil given were significantly increased, the onset time of sedative agents was significantly prolonged, the incidence of postoperative nausea and vomiting was increased, and the incidence of respiratory depression and injection pain was decreased in group R ( P<0.05 ). Conclusion:Remimazolam (given according to the instructions) is safer when used for outpatient curettage, but it can only maintain a light sedation status, and the sedative efficacy is inferior to propofol.

Summary of the research frontiers of liver transplantation in 2020 ATC / 器官移植

The American Transplant Congress (ATC) is an influential academic congress in the field of organ transplantation. In this article, the hotspots of liver transplantation in 2020 ATC were summarized, including the latest research progress in donor liver procurement and quality assessment, donor liver preservation and ischemia-reperfusion injury (IRI), liver transplantation for hepatocellular carcinoma and other hepatic malignancies, complications after liver transplantation, transplantation immunology, perioperative management and donor-derived infection, pediatric liver transplantation and cell therapy, etc.

Effect of electroacupuncture on pyroptosis in renal tubular epithelial cells of rats with acute kidney injury induced by endotoxin / 中华麻醉学杂志

Objective:To evaluate the effect of electroacupuncture (EA) on pyroptosis in renal tubular epithelial cells of rats with acute kidney injury (AKI) induced by endotoxin.Methods:Twenty-four healthy clean-grade Sprague-Dawley rats of either gender, aged 6-8 weeks, weighing 160-182 g, were divided into 4 groups ( n=6 each) using a random number table method: control group (group C), group AKI, EA plus AKI group (group EA), sham EA at non-acupoint plus AKI group (group SEA). The model of endotoxemia was established by intraperitoneally injecting 10 mg/kg lipopolysaccharide.Bilateral 30 min EA stimulation of Zusanli and Shenyu (according to atlas of animal acupoint) was performed starting from 5 days before establishing the model (once a day) and at 30 min before lipopolysaccharide administration on the day of establishing the model, with disperse-dense waves, frequency of 15 Hz, and the needle was kept until 6 h after injection of LPS in group EA.EA was performed at the points 0.5 cm lateral to the acupoints of Zusanli and Shenyu in group SEA.At 6 h after LPS injection, blood was taken from the heart, and the concentrations of serum blood urea nitrogen (BUN) and creatinine (Cr) were detected by an automatic biochemical analyzer, and the serum concentrations of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) by enzyme-linked immunosorbent assay.The rats were then sacrificed, and the left renal cortex was obtained for determination of pyroptosis rate of renal tubular epithelial cells (by TUNEL). The right renal cortex was obtained to detect the expression of caspase-1 and IL-1β by Western blot, and the expression of caspase-1 mRNA and IL-1β mRNA was detected by real-time polymerase chain reaction. Results:Compared with group C, the concentrations of BUN, Cr, NGAL, KIM-1, TNF-α, and IL-6 were significantly increased, the pyroptosis rate of renal tubular epithelial cells was increased, the expression of caspase-1 and IL-1β protein and mRNA in the renal cortex was up-regulated in group AKI ( P<0.05). Compared with group AKI, the concentrations of BUN, Cr, NGAL, KIM-1, TNF-α, and IL-6 were significantly decreased, the pyroptosis rate of renal tubular epithelial cells was decreased, the expression of caspase-1 and IL-1β protein and mRNA in the renal cortex was down-regulated in group SEA ( P>0.05). Conclusion:The mechanism by which EA reduces AKI may be related to inhibiting pyroptosis in renal tubular epithelial cells of rats.

Genetic testing and clinical phenotypic analysis of familial vitreous amyloidosis in two Han Chinese families / 中华实验眼科杂志

Objective:To investigate the clinical characteristics of two Han families with familial vitreous amyloidosis (FVA) and the gene mutation.Methods:A pedigree investigation was performed.Two Han Chinese families with FVA treated in Xiangya Hospital of Central South University from January 2015 to December 2018 were collected.General examination and ophthalmic examination were performed among 112 members of the two families.Peripheral blood samples were collected from 32 family members (15 patients in MZ001 pedigree, 7 patients in MZ002 pedigree, and 5 persons with normal clinical phenotype from each pedigree) for DNA extraction, polymerase chain reaction (PCR) amplification, transthyretin ( TTR) gene screening and sequencing.Vitreous biopsy following three-channel 23-gauge pars plana vitrectomy was performed on the two probands in the two families.Vitreous specimens were sent for pathological examination.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of Xiangya Hospital of Central South University (No.201412463), and written informed consent was obtained from all subjects before any medical examination. Results:In MZ001, there were 15 cases of the 63 members presented bilateral vitreous opacity at an average age of (43.6±5.8) years.No lesion was found in nervous system, cardiovascular system, kidney or liver in general inspection.The vitreous of the proband (Ⅲ13) was so sticky that could not be totally removed during vitrectomy.The vitreous specimen showed positive Congo red staining.Ⅲ13 had elevated intraocular pressure after vitrectomy and was diagnosed as open-angle glaucoma.Gene sequencing revealed Gly83Arg mutation in the exon 3 of TTR gene.In MZ002, 7 cases of 49 members had bilateral vitreous opacity at an average age of (50.4±5.5) years, among which, 3 cases appeared symptoms of limb numbness and decreased muscle strength.The vitreous body of the proband (Ⅱ11) in MZ002 pedigree was looser and easier to remove during vitrectomy than that of Ⅲ13 in MZ001 pedigree.Vitreous specimen of Ⅱ11 was positive with Congo red staining.Gene sequencing revealed an Ala36Pro variant in the exon 3 of TTR gene. Conclusions:Gly83Arg or Ala36Pro mutation of TTR gene can cause FVA.Different mutations can lead to different clinical phenotypes such as age of onset, clinical symptoms and complications of other systems.

Inhibiting effect of retinal Sigma-1 receptor antagonist on the form deprivation myopia in guinea pigs and its mechanism / 中华实验眼科杂志

Objective:To investigate the role and mechanism of retinal Sigma-1 receptor antagonist N, N-diethyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethanaminehydrochloride (NE-100) in the formation of form deprivation myopia (FDM) in guinea pigs.Methods:Eighty-five 21-day-old guinea pigs were selected, and 36 of them were randomly divided into normal control group, occluded 14-day group and occluded 11-day group, with 12 in each group.The right eyes of guinea pigs in the occluded 14-day group were covered with translucent eye shield for consecutive 14 days, and guinea pigs in the occluded 11-day group were treated in the same way for consecutive 11 days plus 3 days without cover, and guinea pigs in the normal control group were not covered.The other 49 guinea pigs were randomly divided into FDM group ( n=10), FDM+ NE-100 6 μg group ( n=12), FDM+ NE-100 60 μg group ( n=10), FDM+ NE-100 600 μg group ( n=9), and FDM+ saline group ( n=8). The right eyes in each group received 100 μl peribulbar injection of NE-100 6 μg, 60 μg and 600 μg or saline once a day according to grouping.Ocular refraction and axial dimensions were measured using eccentric infrared photorefractor and A-scan ultrasonography, respectively.Corneal curvature was measured with keratometer.Immunohistochemical staining and Western blot were used to detect the expression levels of Sigma-1 receptor protein, and retinal dopamine content was evaluated by high-performance liquid chromatography with electrochemical detection.This study was approved by an Ethics Committee of the Department of Laboratory Animal Science of Central South University (No.2020sydw0084). The use and care of experimental animals followed the Regulations for the Administration of Affairs Concerning Experimental Animals in China. Results:There were statistical significant differences in diopter and axial length among the normal control group, occluded 14-day group and occluded 11-day group ( F=147.81, 160.10; both at P<0.01). Compared with the normal control group, the relative myopia was the deepest and the axial length was the longest in the occluded 14-day group, then the occluded 11-day group, showing significant differences between them (all at P<0.05). In the normal control group, Sigma-1 protein was mainly expressed in retinal ganglion cells (RGCs), photoreceptor inner segment and the inner nuclear layer.In the occluded 14-day group, Sigma-1 protein staining was enhanced in RGCs and photoreceptor inner segment.Sigma-1 staining positive cells in the inner nuclear layer were increased significantly and were also seen in the inner and outer plexiform layers, especially in Müller cells, in which the expression levels of Sigma-1 receptor protein were significantly increased.Compared with the occluded 14-day group, the Sigma-1 receptor protein expression levels in the retina of the occluded 11-day group was significantly decreased ( P<0.01). The diopters of guinea pigs in the FDM+ NE-100 6 μg, 60 μg and 600 μg groups were lower than those in the FDM group, and the diopters of FDM+ NE-100 60 μg and 600 μg guinea pigs were lower than those in the FDM+ NE-100 6 μg group, and the differences were statistically significant (all at P<0.05). The dopamine content in the retina of the FDM+ NE-100 60 μg group was (0.74±0.09) ng/mg, which was significantly higher than (0.57±0.10) ng/mg in the FDM group, with a significant difference between them ( t=15.18, P<0.01). Conclusions:Sigma-1 receptor antagonist inhibits FDM formation, which may be associated with the elevation of dopamine content in retina.

Establishment of a blood concentration detection system for everolimus in recipients after liver transplantation / 器官移植

Objective To establish a detection system of ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for everolimus concentration in whole blood of liver transplant recipients. Methods The proteins of samples were precipitated with methanol and zinc sulfate, and everolimus-D4 was used as the internal standard. Phenomenex Kinetex PFP column was used. The mobile phase A was water (containing 2 mmol/Lammonium formate and 0.1% formic acid), and the mobile phase B was methanol (containing 2 mmol/L ammonium formate and 0.1% formic acid). The gradient elution was performed with the flow rate of 1 mL/min, the column temperature of 50 ℃ and the injection volume of 1 μL. The multi-reaction monitoring mode was used to quantitatively analyze with electrospray positive ionization. The UPLC-MS/MS detection system required only 100 μL of whole blood, and could achieve a sufficient lower limit of quantification without complicated sample preparation. The total running time was within 4.5 min. Linear regression (1/x2) analysis was performed using peak area of everolimus / peak area of everolimus-D4 (y) and concentration of everolimus/concentration of everolimus-D4 (x) to calculate the calibration function and analyze its accuracy and linear relationship. UPLC-MS/MS was used to detect the trough blood concentration of everolimus in blood samples of 5 recipients after liver transplantation. Results The accuracy of quality control was within 15%, and the linear relationship of everolimus was good in the blood concentration range of 1-100 ng /mL(R2 > 0.990). Trough blood concentration of everolimus measured in blood samples of 5 liver transplant recipients ranged from 3.77 to 9.27 ng/mL. Conclusions The detection system of UPLC-MS/MS in this study is suitable for monitoring the concentration of everolimus in whole blood of liver transplant recipients because of its high accuracy, simple sample processing method and short detection time.

Predictive value of bioelectrical impedance analysis-measured body fat to abnormal lipid profiles in children and adolescents: the optimal cut-off values of body fat / 中华实用儿科临床杂志

Objective:To assess the predictive values of bioelectrical impedance analysis(BIA)-measured body fat indices to abnormal lipid profiles, and to preliminary propose optimal cut-off values of body fat in children and adolescents.Methods:Children and adolescents, aged 6-16 years, were selected from 30 schools (8 primary schools, 21 middle schools and one 12-year education school) in Dongcheng, Tongzhou, Fangshan and Miyun districts of Beijing by adopting a stratified cluster sampling method from November 2017 to January 2018.Questionnaire survey, body mass index(BMI), body fat mass index (FMI), fat mass percentage (FMP) and four lipid profiles were conducted.Results:A total of 14 309 participants, aged (11.0±3.3) years, were enrolled in the analysis, with 49.9% boys.In boys and girls, the percentile values ( P60- P95) fitted by FMI and FMP with K-median-coefficient of variation(LMS) method were taken as the cutting points, and P75 values were selected as the cut-off points of excessive body fat for their better sensitivity, specificity, predictive value and area under curve (AUC) for identification of abnormal lipid profiles.Boys with FMI above P75 accounted for 28% of the total population, and controlling boys with FMI below P75 could prevent dyslipidemia of 8%-57%.FMI in girl population occupied about 26% of the above, and controlling FMI in girl population below this cut-off point may prevent dyslipidemia from 8%-42%.FMP observed similar results to FMI.Assessed by FMI or FMP with P75 cut-off values, adiposity performed better than BMI for recognizing abnormal lipid profiles in boys (AUC: 52.4%-69.6% vs.50.2%-67.1%, P<0.05) rather than in girls ( P>0.05). In addition, when FMI or FMP beyond P90, the specificity of each abnormal lipid profiles was around 90%. Conclusions:The recommend cut-off points for body fat may be to assess children′s adiposity, and can be applied in preventive activities.

Clinical study of microvascular invasion on prognosis of recipients after liver transplantation for liver cancer / 器官移植

Objective To evaluate the effect of microvascular invasion (MVI) on prognosis of recipients after liver transplantation for primary liver cancer (liver cancer). Methods Clinical data of 177 recipients after liver transplantation for liver cancer were retrospectively analyzed. All patients were divided into the MVI-positive group (n=64) and MVI-negative group (n=113) according to postoperative pathological examination results. Clinical data were statistically compared of all recipients between the negative and positive MVI groups. The prognosis and risk factors of liver transplantation recipients for liver cancer were analyzed. Results Among 177 recipients, 64 cases (36.2%) were positive for MVI and 113 (63.8%) negative for MVI. Compared with the MVI-negative recipients, MVI-positive recipients had significantly lower degree of tumor differentiation, higher preoperative alpha-fetaprotein (AFP) level, larger maximal tumor diameter, a larger quantity of tumors, more satellite lesions and more recipients who did not meet the Milan criteria (all P < 0.05). The 1-, 3- and 5-year overall survival (OS) and recurrence-free survival (RFS) of recipients after liver transplantation for liver cancer were 80.2%, 62.1%, 58.5% and 66.3%, 57.5%, 51.2%, respectively. The 1-, 3- and 5-year OS and RFS of MVI-positive recipients were 70%, 39%, 35% and 53%, 39%, 33%, significantly lower than 86%, 75%, 72% and 73%, 68%, 63% of their counterparts negative for MVI (all P < 0.05). Cox regression analysis showed that the maximal tumor diameter >8 cm, preoperative AFP level ≥20 ng/mL, low degree of tumor differentiation and positive MVI were the independent risk factors for OS of recipients after liver transplantation for liver cancer (all P < 0.05). Positive MVI, low degree of tumor differentiation and preoperative down-staging failure were the independent risk factors for RFS of recipients after liver transplantation for liver cancer (all P < 0.05). Conclusions MVI is of significant clinical value in predicting clinical prognosis of recipients after liver transplantation for liver cancer.

Study on newborn screening for Duchenne muscular dystrophy and diagnostic strategy / 中华医学遗传学杂志

OBJECTIVE@#To establish a newborn screening system for Duchenne muscular dystrophy (DMD) through assessment of MM isoenzyme of creatine kinase (CK-MM) activity.@*METHODS@#The CK-MM level was detected using dry blood spot filter paper from 10 252 male newborns. The results were grouped based on their gestational age, sampling time and intervals between the experiments. The threshold value for CK-MM necessitating genetic testing was determined. Next-generation sequencing (NGS) was carried out for those with a CK-MM value over the threshold, and the result was verified by multiplex ligation-dependent probe amplification (MLPA).@*RESULTS@#Based on the result of non-parametric rank sum test, the median CK-MM concentration has increased with the gestational age, and was inversely correlated with the age of the newborns among unaffected specimens. CK-MM on dry blood spot filter paper can be stable for 14 days at 2-8℃. Statistical analysis of CK-MM value of the 10 252 neonates suggested that the threshold may be set as 700 ng/mL. Exonic deletions were found in 2 confirmed cases, whose CK-MM level was greater than 2000 ng/mL.@*CONCLUSION@#Detection of CK-MM in dry blood spot filter paper has provided an effective method for newborn screening of DMD. This simple and inexpensive method can be used for large-scale screening, which is of great value to the early intervention and treatment of the disease.

Prenatal diagnosis and genetic analysis of two fetuses with paternally derived 17q12 microdeletions / 中华医学遗传学杂志

OBJECTIVE@#To reported on two fetuses diagnosed with 17q12 microdeletion syndrome.@*METHODS@#The two fetuses were respectively found to have renal abnormalities and polyhydramnios upon second and third trimester ultrasonography. Umbilical cord blood of the first fetus and amniotic fluid of the second fetus were subjected to single nucleotide polymorphism array (SNP-array) analysis. After 17q12 microdeletion was found in the first fetus, SNP-array was carried out on peripheral blood samples of the parents to determine its origin. With the medical history of the parents taken into consideration, the father underwent high-throughput sequencing for 565 urinary system-related genes to exclude pathogenic or likely pathogenic variants associated with congenital malformations of the urinary and reproductive systems.@*RESULTS@#In both fetuses, SNP-array has revealed a 1.42 Mb deletion at 17q12, or arr[hg19]17q12 (34 822 465-36 243 365) × 1. In both cases the microdeletion was inherited from the father, in whom no urinary disease-related pathogenic or likely pathogenic variants was identified.@*CONCLUSION@#Paternally derived 17q12 microdeletions probably underlay the genetic etiology of the two fetuses with renal ultrasound abnormalities and polyhydramnios. SNP-array can enable the diagnosis and facilitate genetic counseling and prenatal diagnosis for the families.

Prenatal diagnosis of a fetus with 46,XX (SRY positive) male syndrome / 中华医学遗传学杂志

OBJECTIVE@#To carry out genetic testing for a XXY fetus suggested by non-invasive prenatal testing (NIPT).@*METHODS@#G-banding karyotyping, fluorescence in situ hybridization (FISH) and chromosomal microarray analysis (CMA) were performed on amniocytes from the fetus. The genitalia of the fetus was also examined by Doppler ultrasonography. The result was verified with peripheral blood samples from its parents and a brother.@*RESULTS@#The fetus was found to have a 46,XX karyotype. CMA showed presence of sequences from Yp11.2 (2.635 Mb) and Yp11.31p11.2 (3.706 Mb). FISH assay suggested that the SRY fragment on Yp has translocated to Xpter. No karyotypic or pathogenic CNVs was detected in its parents and brother. The fetus was ultimately diagnosed with 46,XX (SRY positive) male syndrome.@*CONCLUSION@#The combination of G-banding karyotyping, FISH, and CMA is of great significance for attaining accurate prenatal diagnosis for this fetus.

Expert consensus on standardized TORCH laboratory detection and clinical application / 中华检验医学杂志

TORCH, which is considered as a series of pathogens, including the Toxoplasma gondii, Rubella virus, Cytomegalovirus or Herpes simplex virus, often infects the pregnant women to induce the the fetus or newborn infection by transplacental infection or exposure to contaminated genital tract secretions at delivery. Increasing evidence have been confirmed that the infection of TORCH may cause the miscarriage, premature birth, malformed fetus, stillbirth, intrauterine growth retardation, neonatal multiple organ dysfunction and other adverse pregnancy outcomes. For most TORCH-infections cases may lacking the effective treatments during pregnancy, and it is important to achieve the effacing monitoring of TORCH infections before and during pregnancy. The laboratory testing of TORCH has the great significance. However, the consensus opinions still need to improve the the standardization of TORCH testing process and the correct interpretation. Based on the characteristics of the TORCH detection method, this article gives a consensus opinion on the standardized detection and clinical application of TORCH from the laboratory perspective according to the characteristics and types of infection of different pathogens.

Effect of sufentanil on activation of Schwann cells after peripheral nerve injury in mice / 中华麻醉学杂志

Objective:To evaluate the effect of sufentanil on activation of Schwann cells after peripheral nerve injury in mice.Methods:Eighty healthy pathogen-free male Balb/c mice, aged 6-8 weeks, weighing 18-22 g, were divided into 4 groups ( n=20 each) using a random number table method: peripheral nerve injury group (group PNI), high dose sufentanil group (group H), medium dose sufentanil group (group M) and low dose sufentanil group (group L). The model of unilateral sciatic nerve transaction was established in ketamine-anesthetized mice.Immediately after establishment of the model, sufentanil 10, 5 and 2.5 μg/kg was injected intraperitoneally once a day for 3 consecutive days in H, M and L groups, respectively, while the equal volume of normal saline was given instead in group PNI.Sciatic function index (SFI) was calculated at 4, 8 and 12 weeks after establishment of the model.At 2, 4, 8 and 12 weeks, 5 mice in each group were sacrificed, and segments of the injuried ipsilateral sciatic nerve were removed for examination of the ultrastructure of the sciatic nerve (with a transmission electron microscope) and for detection of the expression of glial fibrillary acidic protein (GFAP) of sciatic nerve (by immunohistochemistry). Results:Compared with group PNI, SFI was significantly increased, and the expression of GFAP was up-regluated at each time point after establishment of the model in H and M groups ( P<0.05) and no significant change was found in SFI and GFAP expression after establishment of the model in group L ( P>0.05). Compared with group L, SFI was significantly increased, and GFAP expression was up-regluated in H and M groups ( P<0.05). There was no significant difference in SFI and GFAP expression between group H and group M ( P>0.05). The thickness of myelin lamellae was dense, and the proliferation of Schwann cells was not marked in H and M groups.The thickness of myelin lamellae was thin, and the proliferation of Schwann cells was marked in L and MO groups. Conclusion:The mechanism by which sufentanil improves repair after peripheral nerve injury may be related to promoting activation of Schwann cells in mice.

Clinical value of routine non-invasive prenatal testing for the screening of non-target chromosomal abnormalities / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of non-invasive prenatal testing (NIPT) for the identification of sex chromosome aneuploidies (SCAs), copy number variants (CNVs) and rare autosomal trisomies (RATs).@*METHODS@#A total of 11 429 women with singleton pregnancy in Ningbo area were screened by NIPT. 106 women were subjected to invasive prenatal diagnosis due to high risk of chromosomal abnormalities other than 21, 18 and 13 aneuploidies. All cases were followed up for pregnancy outcome and postnatal status.@*RESULTS@#Sixty-six women were signaled by NIPT for fetal SCAs, among whom 54 were willing to undergo prenatal diagnosis. Eighteen cases of fetal SCAs were verified as true positives and 4 were suspected positives, which yielded a positive predictive value (PPV) of 33.3%. Half of the women decided to continue their pregnancy. Forty women were signaled by NIPT for fetal CNVs, among which 32 underwent prenatal diagnosis. 19 cases of fetal CNVs were verified as true positives and 3 cases were suspected positives, which yielded a PPV of 46.8%. All women with pathological or possibly pathological CNVs decided to terminate their pregnancies. Thirty-one women were signaled for with fetal RATs. Two fetuses were confirmed to harbor mosaicism trisomies by prenatal diagnosis, and 1 case was suspected to be positive, which yielded a PPV of 9.7%. All of the three women have decided to terminate their pregnancy.@*CONCLUSION@#In addition to aneuploidies of target chromosomes, NIPT also has important value for the detection of SCAs and CNVs. The results can help to further reduce birth defects. Nevertheless, in view of its low PPV, pregnant women with positive result still need appropriate genetic counseling and prenatal diagnosis to avoid unnecessary induced labor.