Purpose To evaluate the effect of PCSK9 gene knockout on myocardial function in obese mice via ultrasound strain technology,and to discuss the related mechanisms.Materials and Methods Twenty six-week-old wild-type C57BL/6 male mice were selected and randomly divided into a normal group(n=10)and an obese group(n=10).Additionally,ten six-week-old PCSK9-/-C57BL/6 male mice were selected as the PCSK9-/-group.Mice in the obese group and PCSK9-/-group were fed with high-fat feed to create models,while those in the normal group were fed with regular feed.After 12 weeks,mice that were successfully modeled were selected from the obese group and PCSK9-/-group.Then,the three groups of mice were subjected to cardiac ultrasound,transmission electron microscopy and immunofluorescence staining to observe relevant indicators.Results The interventricular septal end-diastolic thickness of mice in obese group,normal group,and PCSK9-/-group were(0.98±0.13)mm,(0.77±0.07)mm,(0.78±0.13)mm,respectively,with statistically significant difference(F=5.10,P=0.02).The obese group was thicker than the normal group(t=2.73,P＜0.05),while the PCSK9-/-group was thinner than the obese group(t=-2.92,P＜0.05).There were statistically significant differences in global longitudinal strain and global circumferential strain of the left ventricle among the three groups(F=7.44,15.40,P＜0.05),with the obese group showing a decrease in global longitudinal strain and global circumferential strain compared to the normal group(t=3.79,5.50,P＜0.05).The PCSK9-/-group showed an increase in global longitudinal strain and global circumferential strain compared to the obese group(t=-2.53,-3.37,P＜0.05).Electron microscopy and immunofluorescence results showed that the myocardial ultrastructure of the obese group was damaged,and the expression of NLRP3 and Caspase-1 were higher than that of the normal group(t=12.53,-4.73,P＜0.05),the myocardial ultrastructure damage in the PCSK9-/-group was significantly improved,the expression of NLRP3 and Caspase-1 were lower than that in the obese group(t=-6.23,2.05,P＜0.05).Conclusion Ultrasound strain can more sensitively detect changes in myocardial function in obese mice with PCSK9 gene knockout compared with conventional cardiac ultrasound parameters.Knockout of the PCSK9 gene may improve myocardial function in obese mice by inhibiting the expression of NLRP3 and Caspase-1.

Novel coronavirus has brought great threats to the people and challenges to the health systems around the world. Compared with general population, lymphoma patients are more vulnerable to novel coronavirus infection(COVID-19) and have poorer prognosis. So the clinical management of COVID-19 in lymphoma patients in more difficult and the great importance should be attached. This article reviews the clinical characteristics and current management strategies of lymphoma patients with COVID-19, to provide reference for the clinical treatment of lymphoma patients with COVID-19.

Metastasis is crucial for the mortality of non-small cell lung carcinoma (NSCLC) patients. The epithelial-mesenchymal transition (EMT) plays a critical role in regulating tumor metastasis. Glioma-associated oncogene 1 (Gli1) is aberrantly active in a series of tumor tissues. However, the molecular regulatory relationships between Gli1 and NSCLC metastasis have not yet been identified. Herein, we reported Gli1 promoted NSCLC metastasis. High Gli1 expression was associated with poor survival of NSCLC patients. Ectopic expression of Gli1 in low metastatic A549 and NCI-H460 cells enhanced their migration, invasion abilities and facilitated EMT process, whereas knock-down of Gli1 in high metastatic NCI-H1299 and NCI-H1703 cells showed an opposite effect. Notably, Gli1 overexpression accelerated the lung and liver metastasis of NSCLC in the intravenously injected metastasis model. Further research showed that Gli1 positively regulated Snail expression by binding to its promoter and enhancing its protein stability, thereby facilitating the migration, invasion and EMT of NSCLC. In addition, administration of GANT-61, a Gli1 inhibitor, obviously suppressed the metastasis of NSCLC. Collectively, our study reveals that Gli1 is a critical regulator for NSCLC metastasis and suggests that targeting Gli1 is a prospective therapy strategy for metastatic NSCLC.

Objective:To explore the genetic basis for a child with mental retardation.Methods:The child was subjected to chromosomal microarray analysis (CMA) and targeted capture next-generation sequencing for the exons of genes related to genetic and metabolic diseases. Candidate variants were verified by Sanger sequencing of the child and his parents.Results:CMA suggested that the child has a 47, XYY karyotype. Next-generation sequencing revealed that the child has harbored compound heterozygous variants of the AUH gene, including c. 677G>A (p.R226H) and c. 373C>T (p.R125W), which were respectively inherited from his parents. Based on the American college of Medical Genetics and Genomics (ACMG) standards and guidelines, the c. 677G>A (P.r226h) variant was predicted as variant of uncertain significance (PM2+ PP4+ PP3), whilst the c. 373C>T (P.R125W) variant was predicted as likely pathogenic (PM1+ PM2+ PP3+ PP4). Conclusion:The child had XYY syndrome in conjunct with 3-methylglutaenedioic aciduria type I due to biallelic pathogenic variants of the AUH gene.

Medical information registration of rare disease cases serves as scientific basis for development of population intervention strategy, improvement of medical service system, better patient medical support level, and higher medicine accessibility. Based on their hospital work, the authors introduced the development practice of an all-dimensional management system for such information registration, in terms of formulating policies, establishing organizational structure, organizing and publicizing policies for the medical service of rare diseases, maintaining registration data and so on, so as to provide the reference for the management of registration work of rare diseases.

Objective: To explore the clinical features and molecular basis for a child featuring infantile epilepsy and developmental disorders. Methods: Clinical data and peripheral blood samples of the child and his parents were collected. The coding regions of genes associated with nervous system development were subjected to target region capture sequencing. Results: The child developed generalized spasm at 3 months and was diagnosed with epilepsy at 6 months of age. He was treated with Depakin but was diagnosed with mental retardation and developmental retardation at 3 years of age. A novel heterozygous c. 3842T>G variant of the SYNE1 gene was detected. His father was found to carry the same variant and had a history of convulsions in infancy but with no mental or developmental anomalies. Conclusion A novel variant of SYNE1 gene was identified in this child, and the prognosis may be poor.

The core of standardized training for residents is the cultivation of clinical practice ability,which is also the main content of the professional degree graduate training.With the integration of professional degree graduate training and standardized training of residents,the evaluation system of professional degree graduate tutors should be included in the quality index of graduate clinical skills training.Through the methods of document retrieval and expert consultation,the index structure,the examination content and the weight were set up,and the detailed rules for the evaluation of the professional degree graduate tutors were established to guide them strengthen the training of clinical skills for graduates and improve the cultivation quality of professional degree graduates.

Objective To evaluate the safety and efficacy of botulinum toxin type A for injection in the treatment of post-stroke upper limb spasticity (dosage was 200 U,or 240 U if combined with thumb spasticity).Methods The study was a multi-center,stratified block randomized,double-blind,placebocontrolled trial.All the qualificd subjects were from 15 clinical centers from September 2014 to February 2016.They were randomized (2∶1) to injections of botulinum toxin type A made in China (200-240 U;n =118) or placebo (n =60) in pivotal phase after informed consent signed.The study was divided into two stages.The pivotal trial phase included a one-week screening,12-week double-blind treatment,followed by an expanded phase which included six-week open-label treatment.The tone of the wrist,finger,thumb flexors was assessed at baseline and at weeks 0,1,4,6,8,12,16 and 18 using Modified Ashworth Scale (MAS),disability in activities of daily living was rated using the Disability Assessment Scale and impaction on pain,muscle tone and deformity was assessed using the Global Assessment Scale.The primary endpoint was the score difference between botulinum toxin type A and placebo groups in the tone of the wrist flexor using MAS at six weeks compared to baseline.Results Muscle tone MAS score in the wrist flexor of botulinum toxin type A and placebo groups at six weeks changed-1.00 (-2.00,-1.00) and 0.00 (-0.50,0.00) respectively from baseline.Botulinum toxin type A was significantly superior to placebo for the primary endpoint (Z =6.618,P ＜ 0.01).The safety measurement showed 10 subjects who received botulinum toxin type A had 13 adverse reactions,with an incidence of 8.47％ (10/118),and three subjects who received placebo had three adverse reactions,with an incidence of 5.00％ (3/60) during the pivotal trial phase.All adverse reactions were mild to moderate,none serious.There was no significant difference in adverse reactions incidence between the botulinum toxin type A and the placebo groups.During the expanded phase three subjects had four adverse reactions and the incidence was 1.95％.All adverse reactions were mild,none serious.Conclusion Botulinum toxin type A was found to be safe and efficacious for the treatment of post-stroke upper limb spasticity.Clinical Trial Registration:China Drug Trials,CTR20131191

Objective To observe the effect of PIF1 knockdown on cell growth and cell cycle arrest induced by ionizing radiation.Methods HeLa cell lines that consistently down-regulated PIF1 were prepared by the lentivirus granules interfering technology and confirmed by real-time PCR and Western blotting.The effect of down-regulation of PIF1 on cell growth and cell cycle arrest induced by ionizing radiation was evaluated by cell counting and flow cytometry.Results HeLa cell lines consistently down-regulating PIF1 were established.The growth of HeLa that down-regulated PIF1 was inhibited greatly after 4 Gy of γ-ray irradiation.There was little cell proliferation until the 5th day post 4 Gy γ-ray.Moreover, the S phase block and G2/M phase block of PIF1 knock-downed cell lines were significantly delayed after 8 Gy γ-ray irradiation.Conclusion Knockdown of PIF1 can significantly enhance the radiation sensitivity and delayes the S phase block and G 2 /M phase block induced by ionizing radiation.

Objective To investigate serum total prostate special antigen(tPSA),complexed prostate special antigen(cPSA)and cPSA/tPSA ratio(C/T) in the differential diagnosis of benign prostate hyperplasia(BPH)and prostate cancer(PCa).Methods A total of 184 serum samples from hospital outpatient and inpatient were collected from May 2009 to December 2015,and which were divided into three groups including other diseases 68 patients,benign prostate hyperplasia(BPH group)80 patients,prostate cancer (PCa group)36 patients.Chemiluminescence immunoassay was used to detect the concentration of tPSA and cPSA,and the C/T ratio were calculated in the study.Results The tPSA,ePSA levels and C/T ratio were significant different from patients with PCa,BPH and other diseases group(P＜0.01).Compared with BPH group(r=0.661),the tPSA and cPSA levels have a higher relativity in PCa group(cPSA=0.708 × tPSA-0.219,r=0.956).While when tPSA level ranges 4.0-10.0 ng/mL),no significant difference of tPSA,cPSA levels and C/T ratio were found in these 3 groups(P＞0.05).Conclusion Combined detection of serum tPSA,cPSA and C/T,making importance in the differential diagnosis of BPH and PCa.