Objective:To observe therapeutic effect and influence of rosuvastatin on levels of interleukin (IL)-35 and nu- clear factor-κB (NF-κB)in patients with coronary heart disease (CHD).Methods:A total of 85 CHD patients were randomly divided into rosuvastatin group (n=43,received rosuvastatin calcium therapy based on routine treatment)and atorvastatin group (n=42,received atorvastatin calcium therapy based on routine treatment),both groups were treated for eight weeks all.Cardiac index (CI),cardiac output (CO),left ventricular ejection fraction (LVEF),left ventricular end-diastolic dimension (LVEDd),serum levels of IL-35 and NF-κB,and total effective rate were measured and compared be- tween two groups before and after treatment.Results:Compared with before treatment,there were significant rise in CI, CO,LVEF and IL-35 level,and significant reductions in LVEDd and NF-κB level in both groups after treatment (P<0.05 or<0.01).Compared with atorvastatin group after treatment,there were significant rise in CI [(3.54±0.72)L· min-1 ·m-2 vs.(3.88±0.83)L·min-1 ·m-2 ],CO [(3.78±0.89)L/min vs.(4.94±0.96)L/min],LVEF [(56.20 ±9.71)% vs.(63.48±14.15)%]and serum IL-35 level [(96.26±24.33)pg/ml vs.(106.92±27.26)pg/ml],and sig- nificant reductions in LVEDd [(4.71±0.89)cm vs.(4.36±0.75)cm]and NF-κB level [(21.51±5.01)ng/ml vs. (18.32± 5.17)ng/ml]in rosuvastatin group,P<0.05 all.Total effective rate of rosuvastatin group (95.35% vs. 76.19%)was significantly higher than that of atorvastatin group,P<0.05. Conclusion:Rosuvastatin possesses more sig- nificant therapeutic effect than that of atorvastatin on coronary heart disease,and its heart protection effect besides lipid lowering may be related to regulating levels of interleukin-35 and nuclear factor-κB.

Objective:To explore the genetic etiology of a fetus with cryptophthalmos detected by prenatal ultrasonography.Methods:A fetus undergoing induced labor at 32nd gestational week due to absence of bilateral eye fissures detected by prenatal ultrasonography in January 2017 was selected as the study subject. Umbilical cord blood sample from the fetus and peripheral blood samples from its parents were collected for the extraction of genomic DNA. Pathogenic variants were screened through whole exome sequencing (WES) and verified by Sanger sequencing. Pathogenicity of candidate variants was verified by bioinformatic analysis and protein structure simulation. Based on the results of genetic testing, prenatal diagnosis was provided to the couple upon their subsequent pregnancy.Results:The couple had four adverse pregnancies previously. The aborted fetus was the fifth, with fused bilateral upper and lower eyelids, poorly developed eyeballs, adhesion of the cornea with the upper eyelid, low-set ears, and abnormal plantar creases, and was diagnosed with cryptophthalmos. WES and Sanger sequencing revealed that the fetus has harbored compound heterozygous variants of the FREM2 gene, namely c. 4537G>A (p.D1513N) and c.7292C>T (p.T2431M). Both variants were unreported associated with cryptophthalmos previously. Protein structure simulation showed that they may lead to loss of hydrogen bonds in the protein product. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be likely pathogenic (PM1_Supporting+ PM2_Supporting+ PM5+ PP3+ PP4; PM2_Supporting+ PM3+ PP3+ PP4). The mother was performed prenatal diagnosis in her sixth pregnancy based on the variants detected in this family, and delivered a daughter with normal phenotype. Conclusion:The FREM2: c. 4537G>A and c. 7292C>T compound heterozygous variants probably underlay the pathogenesis of cryptophthalmos in this fetus. Above finding has enriched the mutational spectrum of the FREM2 gene.

Objective To identify the clinical features and pathogenic variants in two unrelated families with gna-thodiaphyseal dysplasia(GDD),a rare genetic bone disorder.Methods Facial and limb deformities and skeletal morphology were observed in the probands and their family members.Peripheral blood samples(3-4 mL)were col-lected from the probands and their parents.Genomic DNA was extracted by standard phenol-chloroform method.Whole exome sequencing(WES)was performed to screen for candidate pathogenic gene variants of the probands.PCR-Sanger sequencing was used to validate the candidate pathogenic variants in the probands and their family members.The pathogenic variants responsible for GDD in the target families were determined through co-segregation of the pathogenic variants in the affected families,evolutionary conservation at the mutation sites,population allele frequency analysis and bioinformatics analysis.Results Heterozygous missense variants in the ANO5 gene were identified in both GDD probands.In family 1,the pathogenic variant was c.1 066T＞G located in the exon 11 of the ANO5 gene,while in family 2,the pathogenic variant was c.1 553G＞A located in the exon 15 of the ANO5.These two variants resulted in the substitutions of amino acid cysteine with glycine at position 356(p.Cys356Gly)and amino acid glycine with glutamic acid at position 518(p.Gly518Glu)in the ANO5 protein,respectively.Conclusions This study first identified the pathogenic variant c.1 066T＞G(p.Cys356Gly)in Chinese population,provided important evidence for prediction of disease prognosis and development of potential prenatal genetic diagnosis.