Objective:To investigate the relationship between the virulence and the carbapenem resistance phenotype of Klebsiella pneumoniae from blood infection,and to identify carbapenem-resistant and hypervirulent Klebsiella pneumoniae(CR-HVKP)strains.Methods:A total of 192 Klebsiella pneumoniae strains were isolated from blood culture of patients with bloodstream infections from 2016 to 2019,of which 96 isolates were carbapenem-resistant Klebsiella pneumoniae(CRKP)and 96 were carbapenem-sensitive Klebsiella pneumoniae(CSKP).The drug susceptibility was detected by VITEK-2 automatic microbial analyzer;carbapenemase genes,virulence genes and capsule typing were detected by polymerase chain reaction;the high viscosity phenotype of strains was detected by string test,and the genome characteristics of CR-HVKP were detected by whole genome sequencing.Serum killing and biofilm formation test were used to further verify the virulence of CR-HVKP.Results:There were significant differences in drug resistance to common antibiotics,except for minocycline between CSKP and CRKP isolates(all P<0.05).92 out of 96 CRKP isolates carried carbapenemase genes,mainly blaKPC-2.The string tests were positive in 4 isolates of CRKP and 36 isolates of CSKP(P<0.05).The detection rates of virulence genes Kfu,aerobictin,iutA,ybtS,rmpA,magA,allS,and capsule antigen K1 and K2 in CSKP group were significantly higher than those in CRKP group(all P<0.05).One HVKP strain was detected in the CRKP group(CR-HVKP)and 36 HVKP was detected in the CSKP group(P<0.05).The CR-HVKP strain belonged to the MLST412,serotype K57,expressed iutA,entB,mrkD,fimH,and rmpA virulence genes,and showed strong biofilm formation and significantly increased serum resistance.Whole genome sequencing results showed that this CR-HVKP isolate carried blaSHV-145,blaTEM-1,blaCTX-M-3,fosA6,oqxA5,oqxB26,and aac(3)-Ⅱd resistance genes,accompanied by abnormalities in outer membrane protein K(OmpK)35 and OmpK36.Conclusions:The drug resistance of CRKP is significantly higher than that of CSKP,while CRKP carrying fewer virulence genes in both number and types compared to CSKP.A new MLST type of carbapenem-resistant and hypervirulent Klebsiella pneumoniae strain has been detected,which requires clinical awareness and epidemiological monitoring.

【Objective】 To investigate the predictive value of non-invasive parameters in assessing detrusor function in patients with benign prostatic hyperplasia (BPH). 【Methods】 Clinical data of 384 BPH patients to undergo surgery were enrolled and retrospectively analyzed. The patients’ age and medical history time (MHT) were recorded. The free urinary flow rate was measured and maximum flow rate (Qmax) was recorded. Post-void residual (PVR) and voiding volume (VV) were measured with Bladder Scan, and bladder voiding efficiency (BVE) was calculated. Parameters including detrusor pressure (Pdet@Qmax) and Watts factor (WFmax) were collected in invasive urodynamic examination. Patients were grouped as detrusor underactivity (DU) group and non detrusor underactivity (NDU) group according to the results of WFmax, and the factors influencing detrusor function were analyzed with Logistic regression. The optimal cut-off values were confirmed with receiver operating characteristic (ROC) curve. 【Results】 Significant differences were observed in patients’ age, MHT, Qmax, PVR, BVE, Pdet@Qmax between the DU and NDU groups. Logistic regression showed that the overall prediction accuracy was higher when MHT, Qmax and BVE were included. The model prediction formula was Y=6.020-0.451XMHT+0.554XQmax-0.074XBVE. ROC curve showed when age ≥70.5 years and MHT≥ 7.5 years, there was a greater possibility of DU. When Qmax ≥5.7 mL/s and BVE ≥75.5%, the contractile function of detrusor was normal. Model prediction formula Y≥0.72 showed that detrusor contractility was normal. 【Conclusion】 Age, MHT, Qmax and BVE have certain predictive value for assessing detrusor function in BPH patients.

In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.

Objective: To analysis the pathogenic mutation and the clinical characteristics of a three generation family with congenital pulverulent cataract. Methods: A congenital cataract family was chosen from the First Affiliated Hospital of AnHui Medical University, 5 ml peripheral blood was obtained from each family member to extract genomic DNA.Next generation sequencing was used to detect the mutation in proband (Ⅱ5), Ⅱ6 and Ⅲ8, and Sanger sequencing was applied to verify pathogenic mutation in the whole family members.The mutation site was compared with the gene sequence of 10 000 normal Chinese.PolyPhen-2 and SIFT were applied to analysis the alteration on the protein structure and function and its possible pathogenesis.This study followed the Declaration of Helsinki and was approved by the Ethics Committee of AnHui Medical University (NO.PJ2017-5-17). All patients signed informed consent. Results: The pedigree consisted of 19 members of three generations, including 10 patients and 9 normal family members.Heterozygous mutation of GJA3 gene c. 427G>A (p.G143R) was detected in all patients of the pedigree, but was not found in normal members of the pedigree and 10 000 normal Chinese.The score calculated from SIFT and PolyPhen-2 indicated that the mutation probably had malignant effect on normal protein structure, Swiss-model website analysis showed that the mutation likely altered the secondary structure of the protein CX 46 by reducing an α-helix between 107-115 amino acids.Meanwhile, c.1325-1G>T mutation of HSF4 gene were detected in Ⅱ5 and Ⅲ8, which was not found in other family members and 10 000 normal Chinese.HSF and MaxEntScan results showed that the mutation probably had serious effect on the splicing of mRNA.The cataract development rates of Ⅱ5 and Ⅲ8 were faster than that of the same age in the same generation of the pedigree, and the morphology of lens opacity was changed. Conclusions The heterozygous c. 427G>A mutation in GJA3 gene is responsible for pulverulent cataract in this family, meanwhile the c. 1325-1G>T mutation in HSF4 gene may change the type of phacoscotasmus and accelerate the progress of disease.

Objective To investigate the clinical features of patients with bronchiectasis of different types.Methods One hundred and twenty two patients with bronchiectasis at stable stage were recruited from January 2014 to July 2015.The patients were typed as cystic bronchiectasis (n =45) or non-cystic bronchiectasis (n =77) by high resolution CT (HRCT),expectoration bronchiectasis (n =80) or dry brochiectasis (n =42) by clinical symptoms,bacterial colonization (n =42) or non-bacterial colonization (n =80) by sputum culture.The modified British Medical Research Council (mMRC) dyspnea scale,Leicester Cough Questionnaire (LCQ),St George's Respiratory Questionnaire (SGRQ) and pulmonary function test were used to assess the clinical features,and the episodes of exacerbations and hospitalization,and mortality during 1-year follow-up were documented.Results mMRC dyspnea scale (1.90 ± 0.94 vs.2.90±1.09,t=-5.040),LCQ (16.20±4.60 vs.11.20±2.20,t=8.114),SGRQ (36.80±13.10 vs.52.06±22.10,t=-4.780),FEV1％ pred (68.45 ±26.50 vs.52.22 ±20.60,t=3.458),FVC％ pred (72.20 ±26.32 vs.63.10 ±21.42,t =2.058),FEV1/FVC (75.14 ±20.52 vs.58.12 ± 19.82,t =4.546),diffusing capacity of the lung for carbon monoxide (DLCO) (76.24 ± 28.40 vs.54.32 ± 21.20,t =4.400),episodes of exacerbations (Z =-8.272) and hospitalization during 1-year follow-up [6(14.29％) vs.29(36.25％),x2 =6.495] in patients with dry bronchiectasis were significantly better than those in patients with expectoration bronchiectasis (all P ＜ 0.05).mMRC dyspnea scale (3.20 ± 2.10vs.2.10±1.40,t=3.131),LCQ (10.12±2.63vs.16.22 ±3.22,t=11.365),SGRQ (54.80± 18.12 vs.34.06 ± 12.10,t =6.839) and FEV1％ pred (46.52 ± 22.55 vs.58.22 ± 24.62,t=-2.611),FVC％ pred (60.24± 18.22 vs.70.10±24.20,t =-2.547),FEV1/FVC (62.54± 19.02vs.73.12 ±18.42,t=-3.025),DLCO (62.24 ±22.40 vs.74.52 ±26.26,t=-2.627),episodes of exacerbations (Z =10.213) and hospitalizations during 1-year follow-up [21 (46.67 ％) vs.14 (18.18％),x2 =1 1.260] in patients with cystic bronchiectasis were significantly more severe than those in patients with non-cystic bronchiectasis (all P ＜ 0.05).mMRC dyspnea scale (2.38 ± 1.45 vs.1.92 ± 1.14,t =2.175),LCQ (12.82 ±2.12 vs.16.20 ±3.96,t =-6.140),SGRQ (54.22±21.50 vs.41.20 ± 14.60,t =3.521) and FEV1 ％ pred (54.20 ± 21.60 vs.66.45 ± 28.24,t =-2.668),FVC％ pred (63.10 ±24.32 vs.73.46 ±25.30,t =-2.177),FEV1/FVC (62.22 ±20.80 vs.72.14 ±24.36,t =-2.243),DLCO (58.52 ± 20.42 vs.69.22 ± 25.60,t =-2.344),episodes of exacerbation (Z =19.352) and hospitalization during 1-year follow-up [19 (45.24％) vs.16 (20.00％),x2 =8.575] in patients with bacterial colonization bronchiectasis were significantly more severe than those in patients with non-bacterial colonization bronchiectasis (all P ＜ 0.05).However,there was no significant difference in mortality during 1-year follow-up (all P ＞ 0.05) among patients with different types of bronchiectasis.Conclusion Patients with cystic,bacterial colonization and expectoration types of bronchiectasis seem to have more severe symptoms,more episodes of exacerbations and hospitalizations than those of non-cystic,non-bacteria colonization and dry types of bronchiectasis.

OBJECTIVETo detect potential mutation of the WAS gene in a Chinese family affected with Wiskott-Aldrich syndrome.

METHODSPeripheral blood samples were collected from the proband and his family members. All exons and flanking regions of the WAS gene were subjected to PCR amplification - Sanger sequencing as well as restriction endonuclease analysis. Plasma level of B-cell activating factor (BAFF) was also determined for all family members.

RESULTSA hemizygous mutation (c.257G>A) of the WAS gene was identified in all patients from the family, for which the patient's mother was heterozygous. The same mutation was not found among healthy members of the family. Compared with unaffected members, all patients had a higher level of BAFF.

CONCLUSIONThe c.257G>A mutation of the WAS gene probably underlies the Wiskott-Aldrich syndrome in this family.

B-Cell Activating Factor ; blood ; Child, Preschool ; Heterozygote ; Humans ; Male ; Mutation ; Wiskott-Aldrich Syndrome ; genetics ; Wiskott-Aldrich Syndrome Protein ; genetics

OBJECTIVETo determine the origin of chromosomal aberration in a boy with mental retardation and multiple congenital malformations.

METHODSThe karotypes of the proband and his parents were analyzed with conventional G-banding. Their genomic DNA was analyzed with array comparative genomic hybridization (aCGH).

RESULTSNo karyotypic abnormality was detected in the proband and his parents. aCGH has identified a de novo 405 kb deletion at 9q34.3 in the proband, which encompassed the EHMT1 gene and part of CACNA1B gene.

CONCLUSIONThe de novo 9q34.3 deletion probably underlies the mental retardation and development delay in the boy. EHMT1 may be one of the key genes responsible for 9q34.3 microdeletion syndrome.

Child ; Chromosome Banding ; Chromosome Deletion ; Chromosomes, Human, Pair 9 ; genetics ; Comparative Genomic Hybridization ; Craniofacial Abnormalities ; genetics ; Heart Defects, Congenital ; genetics ; Histone-Lysine N-Methyltransferase ; genetics ; Humans ; Intellectual Disability ; genetics ; Karyotyping ; Male

OBJECTIVETo determine the origin and pathogenicity of a chromosomal aberration for a fetus and analyze the possible mechanism.

METHODSThe karotypes of the fetus and its parents were analyzed with routine G-banding. Their genomic DNA was also analyzed with array comparative genomic hybridization (aCGH).

RESULTSNo karyotypic abnormality was detected at cytogenetic level for the fetus and its parents. aCGH has identified a de novo 2.04 Mb deletion at 6q27 in the fetus. The region involves candidate genes responsible for structural brain abnormalities. The area flanking the chromosomal breakpoint contains a 2410 bp sequence rich in palindromes which can form stable secondary structures.

CONCLUSIONThe de novo 6q27 deletion is pathogenic. The 6q27 deletion may be responsible for the structural brain abnormalities in the fetus. The palindrome sequence flanking the chromosomal breakpoint may be involved the formation of the 6q27 deletion.

Adult ; Chromosome Deletion ; Chromosomes, Human, Pair 6 ; Comparative Genomic Hybridization ; Female ; Genetic Testing ; Humans ; Pregnancy ; Prenatal Diagnosis

OBJECTIVETo screen potential mutations of PRRT2 gene in a Chinese family affected with paroxysmal kinesigenic dyskinesia (PKD).

METHODSPolymerase chain reaction, DNA sequencing and restriction endonuclaese analysis were used to analyze all members of the family.

RESULTSA heterozygous mutation c.649dupC was identified in the PRRT2 gene in all patients, while no similar mutation was found in healthy members from the family.

CONCLUSIONThe c.649dupC mutation of the PRRT2 gene probably underlies the PKD in this family. Prenatal diagnosis can reduce the risk for further birth of affected children for this family.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; Child, Preschool ; China ; DNA Mutational Analysis ; Dystonia ; genetics ; Female ; Frameshift Mutation ; Humans ; Male ; Membrane Proteins ; genetics ; Middle Aged ; Molecular Sequence Data ; Nerve Tissue Proteins ; genetics ; Young Adult

Objective To study the gene mutation of a Chinese family with Alport syndrome and to perform preimplantation genetic diagnosis before embryo implantation.Methods Next generation sequence analysis was done for checking COL4A3,COL4A4 and COL4A5 genes in the Alport syndrome family members.Array comparative genomic hybridization(CGH) was used to detect the embryos.Results A mutation c.2605G ＞ A was found and identified in COL4A5 gene of all of the Alport syndrome patients in the family,but COL4A3 and COL4A3 genes were normal in all of the detected people.After searching for the mutation database,the mutation c.2605G ＞ A of COL4A5 gene was related to the X-linked dominant Alport syndrome.Three embryos were detected by using the preimplantation genetic diagnosis.Among these embryos,there were two male and one female.One of the male embryos was chromosomal aneuploidy,which was 45,XY,-16 and the other was normal.This normal embryo was implanted,and after 20 weeks the prenatal amniocentesis diagnosis approved that the fetus was normal.Conclusions The mutation of COL4A5 gene (c.2605 G ＞ A) is the cause of Alport syndrome in this family,which indicates that next generation sequence analysis proves to be an accurate and rapid method to detect Alport syndrome disease.Meanwhile array CGH can be used to reduce birth rates as a useful preimplantation genetic diagnosis method.