Objective To explore the callsal association between intrahepatic cholestasis of pregnancy(ICP)and offspring attention-deficit hyperactivity disorder(ADHD)and Tourette's syndrome(TS)and its potential mechanisms.Methods Genome wide association study(GWAS)in public datasets was used to extract data.Among them,exposure was ICP(n=123 579),which stems from FinnGen dataset.Outcome was defined as ADHD,TS and other tic disorders(n=23 918),which is extracted from GWAS Catalog.Among mediators,total cholesterol in high-density lipoprotein(TC in HDL)were from the genetic map of the human plasma proteinome(n=21 558),and Obg-like ATPase 1 was from whole-genome study of circulating metabolites(n=3 301).In this study,we chose instrumental variables(IVs)that meets the Mendelian randomization(MR)hypothesis.When using two-sample MR,inverse variance weighted(IVW)was adopted as the primary method,and MR-Egger regression,weighted median,weighted mode,and simple mode were also utilized to analyse the robustness.Cochran's Q test,MR-Egger intercept test and leave-one-out sensitivity analysis were performed to verify the reliability.Significant threshold was set up as P<0.05.When using two-step MR,the first step is two-sample MR from exposure to mediator,and the second step is multivariable MR(MVMR),which is from mediator to outcome.At this time,conditional F-statistic was adopted to test the strength of IVs.At last,product distribution test was applied to determine the significance of mediation effects.Results ICP was significantly related to ADHD and TS as well as other tic disorders in offspring(IVW:OR=1.003,95%CI:1.000～1.006,P=0.035),and sensitivity analysis verified the robustness of the results.The potential positive mediators included TC in HDL[total effect(TE)=2.855×10-3;mediated effect(ME)=8.628×10-4;mediated proportion(MP)=30.217%,95%CI:0.878%～73.954%],and Obg-like ATPase 1(TE=2.855×10-3;ME=1.216×10-3;MP=42.572%,95%CI:6.356%～90.195%).Conclusion ICP is possible to elevate the incidence rate of ADHD and TS and other tic disorders via reducing TC in HDL and Obg-like ATPase 1.

Objective:To investigate the application value of a new clinical probation log designed based on the subjective-objective-assessment-plan (SOAP) structured medical record.Methods:Quantitative and qualitative studies were conducted among 97 students in the autumn semester to evaluate the effect of the new clinical probation log based on the SOAP structured medical record on their academic performance and clinical thinking. SPSS 26.0 was used to perform the t-test and ANOVA. Results:The students using the new version had a significantly better score (96.29±1.38) than those using the old version (93.53±1.60) ( P<0.001), while the multivariate analysis showed that the students who first used the old version and then switched to the new version had a significantly better improvement in the score compared with those who first used the new version and then switched to the old version ( P<0.001). The qualitative interview showed that it was necessary to use handwritten internship log, and compared with the old version, the new version could better promote the ordered clinical thinking of students. The teacher comments could give feedbacks, and all the students interviewed thought that the new version held promise for clinical application. Conclusions:The clinical probation log based on the SOAP structured medical record can help to improve the effectiveness of probation and cultivate clinical thinking ability, and thus it holds promise for application in clinical probation teaching.

Objective:To explore the genetic basis of a Chinese patient with Bardet-Biedl syndrome (BBS).Methods:Clinical data of the patient was analyzed. Next-generation sequencing was carry out to screen pathogenic variants, and candidate variants were verified by Sanger sequencing and subjected to bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics.Results:Next-generation sequencing revealed that the proband has harbored two pathogenic variants of the MKKS gene (c.635C>T and c. 1664C>G) and one likely pathogenic variant of the TMEM67 gene (c.2498T>C). Sanger sequencing of the proband and her mother confirmed that the proband has harbored two compound heterozygous MKKS variants and a heterozygous TMEM67 variant. Both of the MKKS variants were previously unreported and located in a highly conserved domain and predicted to be disease-causing by bioinformatic analysis. Conclusion:The two novel MKKS/BBS6 variants probably underlay the BBS in the proband. The TMEM67 variant may have an epistatic effect on mutations of BBS-associated loci.

Objective To detect variant of APOE gene in a Chinese Tibetan patient with lipoprotein glomerulopathy (LPG) confirmed by renal biopsy and to explore its pathogenesis.Methods Clinical and pathological data was collected.DNA was extracted from peripheral blood sample of the patient and subjected to PCR and Sanger sequencing.Pathogenicity of the variant was analyzed by bioinformatics software.Results Renal biopsy of the patient has confirmed the diagnosis of LPG.DNA sequencing suggested that the patient has carried a heterozygous c.527G＞C (p.R176P) variant of the APOE gene (APOE Osaka/Kurashiki).Four cases of LPG have been found to carry the same variant,and the encoded amino acid (p.176R) is highly conserved during evolution.Bioinformatic analysis using SIFT,PolyPhen2 and PANTHER software all predicted the variant to be pathogenic.Conclusion The discovery of author's patient provided further evidence for the pathogenicity of APOE Osaka/Kurashiki and,more importantly,provide new evidence for the multiracial origin of LPG-related APOE variants.

OBJECTIVETo analyze the clinicopathologic features and genetic mutation in a patient diagnosed with focal segmental glomerulosclerosis (FSGS).

METHODSClinicopathologic data of the patient, who was diagnosed with primary FSGS by renal biopsy, was collected. Mutations of FSGS-related genes were screened with next-generation sequencing. Suspected pathogenic mutation was verified with Sanger sequencing.

RESULTSNext-generation sequencing detected a missense mutation (c.2215C to G, p.P739A) in exon 28 of the COL4A5 gene in the patient. The same mutation was also detected in his mother who was asymptomatic. Another missense mutation (c.2215C to T, p.P739S) in the same codon has been related with Alport syndrome.

CONCLUSIONThe c.2215C to G (p.P739A) mutation may be one of pathogenic mutations underlying FSGS. This has provided further evidence for the phenotypic heterogeneity of COL4A5 gene mutations.

Adult ; Base Sequence ; Collagen Type IV ; genetics ; Exons ; Female ; Glomerulosclerosis, Focal Segmental ; genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Young Adult

Objective To explore the assessment value of serum albumin(ALB) to the severity and prognosis of very low birth weight(VLBW).Methods The quality of birth weight,gestational age,serum albumin,critically ill scores and prognosis were analyzed retrospectively from October 2015 to September 2016 in this hospital.Results The mean birth weight was(1.32±0.15) kg,the overall survival rate was 80.21 ％ and the serum albumin was (27.39±3.80)g/L in 96 cases of patients.The occurrence rate of neonatal respiratory distress syndrome,sepsis,mechanical ventilation and critical cases were higher in albumin＜28 g/L group than that of albumin≥28 g/L group,and the survival rate was lower,the difference were statistically significant(P＜0.05).The area under ROC curve(AUC)showed that ALB and neonatal critical illness score(NCIS) had a predictive value for the survival of VLBW(AUC=0.848,0.917,P＜0.5),but the predicted value of ALB was less than NCIS.According to Logistic analysis,ALB was the risk factors for survival rate in VLBW.Conclusion Serum ALB has a certain predictive value for the severity and prognosis of VLBW,but subgroups of NCIS.

Objective To explore the correlation between maternal serum total bile acid (TBA) of pregnant women with intrahepatic cholestasis of pregnancy (ICP) and varying degrees of neonatal lung injury.Methods A total of 52 cases of pregnant women with ICP and their corresponding newborns were enrolled into the ICP group from March 2014 to December 2015 in the People's Hospital of Shapingba District.Other 52 cases of pregnant women received cesarean delivery whose gestational age and birth weight of newborns were close to the ICP group and their corresponding newborns were selected as the control group.The conditions of neonatal lung injury were recorded,and the correlations of maternal serum level of TBA and exposure time of high serum level of TBA to degrees of lung injury were analyzed as well.Results The incidence rate of neonatal lung injury in the ICP group (67.3 ％) was higher than that in the control group (17.3 ％),there was statistically significant difference (P＜0.05).The degree of lung injury was positively correlated with maternal serum level of TBA and exposure time of high serum level of TBA (r=0.687,P=0.000;r=0.523,P=0.001).Conclusion The probability of neonatal lung injury of corresponding pregnant women with ICP is significantly increased,and the extent of lung injury is positively correlated with concentration of maternal serum TBA and exposure time of high serum level of TBA.

On May 12,2008,a disastrous earthquake scaled 8.0 Richter hit Wenchuan,Sichuan province in China.Treating the acute kidney injury caused by crush syndrome in survivals of the earthquake has been a big challenge to the nephrologists.In this paper,we shared our experiences on the multi-disciplinary collaboration in management of acute kidney injury caused by crush syndrome.In addition to surgical therapy for crush injury and compartment syndrome and the renal replacement therapy for acute renal injury and its related complications,the early multi-disciplinary collaboration including rehabilitation,mental health care,infection control and ICU also contributed greatly to the successful treatment of the victims of the earthquake.

Objective To explore the effects of intra-jugular vein dual lumen catheter lock heparin in different concentrations on the coagulation function,hemorrhagic tendency and catheter thrombosis risk in hemodialysis patients,and to investigate the reasonable lock heparin cuncentration. Method Ninety end stage renal disease (ESRD)patients receiving regular hemodialysis were enrolled and randomly assigned into 3 groups(n=30):Group A(pure heparin lock solution,6250 U/m1),GrouP B(medium heparin lock solution,1040 U/ml)and Group C(low hepafin lock solution,625 U/ml).The coagulation indexes were determined in short term.Complications such as bleeding,thrombosis,infection and thrombocytopenia were monitored.Results Prothrombin time(PT),actiwtted partial thromboplastin time(APTT)and thrombin time (TT)were significantly prolonged in Group A(P＜0.01);only APTT was signifieanlly prolonged in Group B:however,no significant changes were observed in Group C.Hemorrhage risk was much higher in Group A than that in Group B and C (26.7%vs 10%and 0.P＜0.05).Catheter thrombosis incidence was significantly higher in Group C than that in Group A and B(23.3%vs 0and 10%,P＜0.05).Only 1 suspected catheter related infection was found in Group C,and 2cases of moderated thrombocytopenia in Group A. Concltrsion Moderate concentration of lock heparin solution has the best balance of hemorrhagic and thrombotic risk,and should be recommended to most of regular hemodialysis patients.