Objective This study aimed at exploring the causative genes and summarizing the clinical characteristics in two Chinese families with thoracic aortic aneurysm and dissection ( TAAD ) .Methods The whole exome capture and high throughput sequencing were applied to identify the causative gene.Family members were examined for features of syndromic ge-netic diseases by clinician and geneticist.Results Four known TAAD candidate genes were identified in family TAA01:rs140598(FBN1), rs185661462(MYH11), rs77620762(MYLK3), and rs111426349(TGFBR1).The TGFBR1 mutation (c.1459C>T) had been confirmed to co-segregate with the TAAD phenotype in all affected family members.Early onset of aortic root dilatation was significant in this family , and the average age at diagnosis of aortic root dilatation or aneurysm was23. 2 years.ACTA2(c.445C>T) was proved in family TAA02, and livedo reticularis was confirmed.Conclusion The causa-tive genes were identified via whole exome capture and high throughput sequencing in two TAAD families .Early onset of aortic root aneurysm was proved in TAA01, while livedo reticularis was found in TAA02.

Objective To observe the characteristics of respiratory airflow in healthy adults and stable chronic obstructive pulmonary disease (COPD) patients by analysis of analyzing tidal breathing flow-volume curves (TBFV). Methods Fifteen stable moderate COPD patients (COPD group) and 15 healthy cases without smoking(healthy control group)were enrolled into the study. No bronchodilators were used in patients of COPD group 8 h before test. Pulmonary function test and TBFV in seated position were measured, and the pressure of oral cavity was monitored concomitantly. Results The levels of percentage of vital capacity (VC%), percentage of forced expiratory volume in the first second (FEV 1)/forced vital capacity (FVC) and percentage of maximum mid-expiratory flow (MMEF%) in COPD group were significantly lower than those in healthy control group (P<0.01). The parameters of TBFV showed that the fraction of exhaled volume to achieve PTEF to VTE (VPTEF/VTE) and the fraction of exhaled time to achieve PTEF to TE (TPTEF/TE) in COPD group were 0.18 ± 0.08 and 0.20 ± 0.08, which were lower than those in healthy control group: 0.27 ± 0.04 and 0.29 ± 0.06, and there were significant differences (P<0.01). The level of peak tidal expiratory flow (PTEF) and peak tidal inspiratory flow (PTIF) in two groups had no significant differences (P>0.05). The levels of tidal expiratory flow at 50%of the remaining tidal volume/PTEF (TEF50/PTEF) and tidal expiratory flow at 25%of the remaining tidal volume/PTEF (TEF25/PTEF) in healthy control group were significantly higher than those in COPD group:0.54 ± 0.13 vs. 0.40 ± 0.12, 0.28 ± 0.13 vs. 0.20 ± 0.06, P<0.01 or<0.05. No differences were found in peak inspiratory pressure (PI max) and peak expiratory pressure (PE max) between two groups. Conclusions The degree of airflow limitation and the effect of bronchodilator in critical patients could be evaluated by analysis of TBFV parameters. The measurement of TBFV is simple and don′t need special technique. It is worth of promoting.

Objective To compare the biomechanical properties of Gamma3 and InterTan nails in the fixation of femoral intertrochanteric fractures. Methods Twelve synthetic femora of 4th generation were randomized into 4 equal groups ( n=3 ) for assessment of the 2 constructs of fracture fixation ( Gamma3 versus InterTan nails ) . Groups A and B were made into models of stable femoral intertrochanteric fracture (AO/OTA type 31-A1. 1) and groups C and D into unstable ones(AO/OTA type 31-A2. 3) . The biomechanical properties of Gamma3 and InterTan nails in the 4 models were tested and compared. Results For stable fracture models, the fracture gap movement increased with the increasing axial load and the torque increased with the increasing torsion angle. There were significant differences between groups A and B in fracture gap movement and torque ( P <0. 05 ) . There was no significant difference between groups A and B in failure load ( 5, 855. 5 ± 627. 8 N versus 5, 547. 1 ± 365. 4 N ) ( P > 0. 05 ) . For unstable fracture models, there were no significant differences between groups C and D in fracture gap movement when the axial loads were 500 N, 600 N or 700 N ( P > 0. 05 ) , but there was a significant difference between the 2 groups when the axial load was larger than 800 N ( P <0. 05 ) . With the increasing torsion angle, the torque increased in groups C and D. There was a significant difference between the 2 groups in the torque at the same torsion angle ( P <0. 05 ) . There were a significant difference between groups C and D in failure load ( 2, 781. 5 ± 600. 6 N versus 3, 150. 5 ± 633. 8 N ) ( P=0. 007 ) . Conclusions For stable femoral intertrochanteric fractures, InterTan and Gamma3 nails may exhibit similar biomechanical properties. For unstable femoral intertrochanteric fractures, InterTan nails may provide obviously better biomechanical stability than Gamma3 nails.

Objective The purpose of this study was to investigate the anti-inflammatory effects on acute and chronic inflammation ofHuamoyan Granules(HMYG).Methods KM mice and SD rats were randomly divided into model group, ibuprofen group and HMYG high, middle and low three dosages groups. The Ibuprofen group was administrated drug by gavage, mice 0.13 g/kg and rats 0.093 g/kg. The HMYG groups were administrated orally, mice 12, 6 and 3g/kg, rats 4, 4.2 and 2.1 g/kg. The model group was given the same volume distilled water, once a day, 3 or 10 continuous days. The increased permeability of mice abdominal capillary was induced by acetic acid, edema of rat hind paw was induced by albumen and carrageenin, which both were adopted to observe the acute anti-inflammatory effects; and cotton pellet granuloma was to observe the chronic anti- inflammation effects of HMYG.Results Compared with the model group, the ibuprofen group, the HMYG high and middle group showed anti-inflammatory actions of mice induced by acetic acid (0.185 ± 0.046, 0.177 ± 0.055, 0.190 ± 0.052vs. 0.246 ± 0.050,P<0.05 orP<0.01); after 0.5, 1, 2, 4 and 6 hrs inflammation, HMYG high dosage group had significant inhibition for the edema of rats hind paw induced byalbumen model, the inhibitory rate was 22.46%, 19.20% and 24.32%, 33.75%, 24.19%; 4 and 6 hrs after inflammation, HMYG high dosage group could reduce rats paw edema induced by carrageenin, the inhibitory rate was 32.05%, 30.56% and 19.23%, 20.83%.Conclusion HMYG has evident anti-inflammatory effects on acute inflammation.

Objective To compare the effectiveness of surgical procedures (devascularization,shunt and combined shunt and devascularization) in treating recurrent variceal bleeding and other complications in patients with portal hypertension.Methods A systematic literature search was carried out on patients with portal hypertension,and a Meta-analysis was conducted using Revman 5.3 software to evaluate the effectiveness of different surgical procedures on recurrent esophageal variceal bleeding,hepatic encephalopathy,operative mortality and survival rates.Results A total of 24 trials were finally selected using predetermined inclusion criteria.Meta-analysis showed there was no significant difference among the three operations on operative mortality (P ＞ 0.05).The rebleeding rate of the combined group was significantly lower than the devascularization group (P ＜ 0.05).The encephalopathy rate of the combined group was significantly lower than the shunt group (P ＜ 0.05),and the 1-year and 3-year survival rates of the combined group were better than the devascularization group (both P ＜ 0.05),but there were no significant difference in the 5-year survival rates between these two groups (P ＞ 0.18).The 1-year and 3-year survival rates were not significantly different between the combined and the shunt groups (both P ＞ 0.05).Conclusions Combined shunt and devascularization had better therapeutic effectiveness than either devascularization alone or shunt alone in patients with portal hypertension with a high rebleeding risk.There were no significant difference among the three surgical procedures in operative mortality.The survival rates of combined surgery were significantly better than devascrlarization alone.

Objective To study the anti-rheumatoid arthritis mechanism of Ermiao powder by high-throughput urine metabolomics.Methods The rats were randomly divided into control group,model group and administration group with 8 rats in each group.The rat model of rheumatoid arthritis was established by intradermal injection of complete Freund's adjuvant.Rats in control group were given Ermiao power solution 0.108 g/ml by gavage.The degree of joint swelling in rats was observed and scored.On this basis,metabolic data of rat urine samples were collected for metabolomic analysis.Unsupervised and supervised pattern recognition technology was used to analyze the high-throughput biological information data and reduce the dimension.Metabolic information related to rheumatoid arthritis was screened and focused to clarify the pathogenesis of rheumatoid arthritis and the therapeutic mechanism of Ermiao power.Results Compared with the model group,the swelling degree of the foot (1.93 ± 0.11 vs.2.36 ± 0.19) in Ermiao power group significantly decreased (P＜0.01).Metabolic profiles showed that the metabolic distribution of healthy rats was significantly separated from that of model rats,and the treatment group was in the middle of the two groups.From the macro-metabolic point of view,the metabolism of model rats changed dramatically.The Ermiao power had a good intervention effect on rheumatoid arthritis.Thirteen biomarkers related to rheumatoid arthritis were identified by database matching,including linolenic acid,arachidonic acid,5,6-EET,alpha-lactose,sucrose,trehalose,prostaglandins and leukotriene C4.It involved linoleic acid metabolism,arachidonic acid metabolism,starch and galactose metabolism and sphingolipid metabolism.Conclusions The Ermiao power has significant therapeutic effect on rheumatoid arthritis rats.Regulation of the linoleic acid metabolism,arachidonic acid metabolism,starch and galactose metabolism may be the mechanism of its treatment of rheumatoid arthritis.

Objective:By studying the gait changes of patients with knee osteoarthritis (KOA), the study provided a theoretical basis for the quantitative indicators obtained from gait analysis to the diagnosis of KOA. And it provided a gait reference for the clinical diagnosis, treatment, rehabilitation, prevention and efficacy evaluation of KOA.Methods:A total of 30 patients (KOA group) with KOA hospitalized in our hospital from May 2021 to October 2021 and 30 healthy people (control group) were compared for gait changes. The t test, Mann-Whitney U test and Fisher′s exact test were used to compare differences between groups. Results:The KOA group were greater than the control group in terms of step time [(642±81) ms and (548±62) ms, t=-5.01, P<0.001], gait cycle [(1 284±168) ms and (1 076±114) ms, t=-5.61, P<0.001], double support time [(531±125) ms and (331±51) ms, t=-8.10, P<0.001], double support time period proportion (0.417±0.063 and 0.309±0.023, t=-8.50, P<0.001), total support time [(914±135) ms and (678±107) ms, t=-7.52, P<0.001], total support time period proportion (0.711±0.027 and 0.627±0.044, t=-8.87, P<0.001), and left static standing time (55.7±8.4 and 51.5±2.2, t=-2.65, P=0.012), for which the differences were statistically significant. The KOA group were lower than the control group in terms of single support time period proportion (0.287±0.030 and 0.334±0.013, t=7.80, P<0.001), right static standing time (44.3±8.4 and 48.5±2.3, t=2.65, P=0.012), step length [(36±8) cm and (52±5) cm, t=9.97, P<0.001], stride length [(70±16) cm and (103±8) cm, t=10.00, P<0.001], velocity [(0.60±0.18) m/s and (1.05±0.19) m/s, t=9.54, P<0.001], left knee range of motion [(42±17)° and (63±4) °, t=6.49, P<0.001], and right knee range of motion [(37±18) ° and (62±3)°, t=7.54, P<0.001], for which the differences were statistically significant. Conclusion:Gait analysis can quantitatively evaluate the condition of patients with KOA, making it possible to transform the diagnostic criteria of KOA from qualitative to quantitative.

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with non-syndromic cleft lip and cleft palate (NSCLP). METHODS: With informed consent obtained, members of the pedigree were subjected to clinical examination and history taking to exclude syndromic cleft lip and palate. One affected member was subjected to whole-exome sequencing and bioinformatics analysis. Candidate variant was verified by Sanger sequencing and co-segregation analysis of her family members and 100 unrelated healthy individuals. RESULTS: Whole-exome sequencing and co-segregation analysis showed that all affected members of this pedigree have carried a heterozygous missense c.253A>G (p.Cys85Arg) variant in exon 4 of the IRF6 gene, which has co-segregated with the phenotype and was not found among the 100 unrelated healthy individuals. CONCLUSION The missense c.253A>G variant in exon 4 of the IRF6 gene probably underlay the NSCLP in this pedigree.
Brain/abnormalities* ; China ; Cleft Lip/genetics* ; Cleft Palate/genetics* ; Female ; Humans ; Interferon Regulatory Factors/genetics* ; Mutation, Missense ; Pedigree ; Whole Exome Sequencing

Objective: To explore the association between dietary inflammatory index (DII) and metabolic syndrome (MetS) and its components among children aged 6-14 years in Beijing, so as to provide a reference for preventing MetS. Methods: A cross sectional study was carried out in 2 086 records of 1 832 children from the 2017 and 2019 Nutrition and Health Surveillance in Primary and Secondary school students of Beijing (NHSPSB). Three day consecutive 24 hour dietary recalls combined with weighing household cooking oils and condiments were used to collect dietary intake and calculate DII. MetS was diagnosed according to "Definition and Suggestion on the Metabolic Syndrome of Chinese Children and Adolescent". The Generalized estimating equations (GEEs) models were used to analyze the association between DII and the presence of MetS and its components (abdominal obesity, high triglyceride, low high density lipoprotein cholesterol, hypertension, and hyperglycemia). Results: The mean DII score was (1.64±1.07) for the included children. No significant association was found between DII scores and the likelihood of MetS (per 1 point increment: OR =1.16, 95% CI =0.92-1.48, P >0.05). In terms of the components of MetS, DII scores were positively associated with the odds of high triglyceride (per 1 point increment: OR =1.17, 95% CI =1.01-1.36, P <0.05). There was no statistically significant difference in the association among different age groups ( P >0.05). No significant associations were observed between DII and other MetS components( P >0.05). Conclusion DII scores may not be correlated with the risk of MetS, but proinflammatory diet might increase the risk of high triglyceride. DII score in childhood should be emphasized to identify and prevent MetS as soon as possible.

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.‍T260A, p.‍R422W, and p.‍R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‍‒‍49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‍‒‍17.9%, which was significantly higher than that (6.9%‍‒‍7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.
Humans ; Apoptosis Inducing Factor/metabolism* ; NAD/metabolism* ; Dimerization ; Apoptosis