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Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
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Female , Animals , Mice , Humans , Child, Preschool , Intellectual Disability/genetics , Heart Defects, Congenital/genetics , Facies , Cleft Palate , Muscle HypotoniaABSTRACT
@#As the key to regeneration of oral and maxillofacial tissues such as bone, dental pulp and skin, vascularization has always been the focus of tissue engineering. With the development of three-dimensional (3D) printing in tissue engineering, there are increasing ways to construct vascular structures. However, to achieve the objective of highly simulating vascular structure in morphology and function and promote tissue repair, it is still a major difficulty for 3D bioprinting to construct highly precise and biologically functional simulated vascular structures. This paper summarizes new progress of 3D printing vascular structure, expounds frontier biological manufacturing technologies of vascular and vascularized structure such as suspension printing, coaxial printing, 4D printing, and so on, analyzes its advantages and disadvantages, and discusses its development prospect, in order to provide reference for the application of 3D printing blood vessels in regeneration and repair of oral and maxillofacial tissues.
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To analyze the clinical characteristics, diagnosis, treatment and outcome of patients with thrombotic thrombocytopenic purpura (TTP). The clinical data of 69 adult patients with TTP were retrospectively analyzed. There were 19 males and 50 females with a median age of 42 (18-79) years. PLASMIC score 6-7 was recognized in 82.8% (53/64) patients. The activity of von Willebrand factor-cleaving protease (ADAMTS13), which was detected in 21 patients before treatment, was less than 5% in 17 patients and 5%-10% in 3 patients. All 69 patients were treated with plasma exchange (PEX) and/or fresh frozen plasma infusion (PI), 43 of whom were also given glucocorticoid. In addition to PEX/PI and glucocorticoid, rituximab and/or immunosuppressants were administrated in 20 patients. The median follow-up time was 12 (1-57) months. The remission rate was 69.6%, while the relapse rate was 11.6%. The 2-year overall survival (OS) rate was 69.6%±5.5%. The univariate and multivariate analysis showed that relapsed/refractory disease was an independent risk factor for OS. The 2-year OS rate of relapsed/refractory patients was significantly lower than that of the rest patients (41.5%±9.8% vs. 83.7%±5.6%, P<0.001). Regarding the unfavorable prognosis in relapsed/refractory patients, rituximab and/or immunosuppressants are strongly recommended for sake of improving the overall survival.
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Objective:Analyze the drug resistance of Mycobacterium tuberculosis (MTB) to commonly used anti-tuberculosis drugs and its spatial distribution in Dali Bai Autonomous Prefecture from 2017 to 2019, which would provid a reference for the treatment of tuberculosis and the prevention and control of drug-resistant tuberculosis. Methods:A total of 1 013 Mycobacterial strains were isolated from sputum samples in the tuberculosis laboratories of the designated People′s hospital of 12 counties (cities) of Dali Bai Autonomous Prefecture from January 2017 to December 2019. Proportional method was used to conduct drug susceptibility tests and strain identification of 6 anti-tuberculosis drugs. Further used ArcMap10.2 and GeoDa1.14 software to visualize the map display and spatial autocorrelation analysis of the drug resistance of MTB.Results:From 2017 to 2019, the drug resistance rates of MTB in Dali Prefecture were 10.33%(28/271), 10.35%(55/531) and 30.00%(51/170), respectively, showing an rising trend ( χ2=26.62, P<0.05). Among 1 030 samples, 972 strains (95.95%) was MTB and 41 strains (4.05%) was non-tuberculous Mycobacterium (NTM). The total resistance rate of 972 strains of MTB was 13.79% (134/972), of which the single resistance rate was 6.59% (64/972), the multi-drug resistance rate was 4.84% (47/972), and the poly-drug resistance rate was 2.06% (20/972), the rate of extensive drug resistance is 0.31% (3/972). There are 25 combinations of drug resistance patterns. The detection rate of NTM was 4% (41/1 013), among which Midu County had the highest detection rate (0.89%, 9/1 013). The spatial distribution showed that the number of MTB resistant strains among counties and cities had a negative spatial correlation (Moran′s I value was -0.367, P<0.05). It shows that there is no clustering of drug resistance among counties and cities, and the resistance is serious in individual counties and cities. Yongping County and Nanjian Yi Autonomous County had low and high aggregation, and Yunlong County had high and low aggregation. Conclusions:The drug resistance of MTB showed an rising trend in Dali Bai Autonomous Prefecture from 2017 to 2019. The number of drug-resistant strains among regions was not randomly distributed, the regional difference was large, and spatial autocorrelation analysis provided theoretical clues and basis for the formulation of drug resistance prevention and control measures for tuberculosis in the whole state.
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Objective To investigate the effects of pregnancy on long-term outcomes of pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD).Methods Women with PAH-CHD who had undergone pregnancy under the care of Beijing Anzhen Hospital from 2004 to 2013 were retrospectively identified and 1∶1 matched to nulliparous PAH-CHD females (controls).Functional status and other clinical data were recorded for each group at baseline and follow-up.Results We successfully matched 40 pairs of pregnant and non-pregnant women with PAH-CHD.The patients were followed up for a mean of (6.5 ± 1.9) years,the outcomes of patients were documented during April 2016 to October 2016.No deaths occurred in either group during the study period.There were no statistically significant differences in long-term cardiac function between the two groups (Z =-1.41,P =0.16).After adjusting age,timing of follow-up,specific drug therapy and Eisenmenger's syndrome,pregnancy didn't have significant effect on the long-term deterioration of cardiac function in PAH-CHD patients (OR =1.32,95％ CI:0.33-5.37,P =0.70).Conclusion Pregnancy may not have significant effect on long-term cardiac function in PAH-CHD patients,but this conclusion needs to be confirmed by further studies.
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Objective To investigate the perinatal outcome , risk factors and long-term outcome of pregnancy complicated with pulmonary arterial hypertension (PAH) and congenital heart diseases (CHD). Methods Clinical data of 110 pregnant women who were diagnosed as PAH-CHD were retrospectively analyzed in the Department of Obstetrics and Gynecology and Surgical Intensive Care Unit at Beijing Anzhen Hospital from 2004 to 2013.The survival and treatment status were followed up .Results 110 subjects consisted of 11 mild PAH, 33 moderate and 66 severe ones .The incidences of deterioration in New York Heart Association ( NYHA ) classes (≥2 ) during pregnancy , respiratory failure , pulmonary hypertension crisis and arrhythmia were 25.5% (28/110),7.3% (8/110),10.0% (11/110),10.0% (11/110) respectively.Among them, the difference of deterioration in NYHA classes (≥2) during pregnancy among the three groups was statistically significant .A total of 8 ( 7.3%) maternal deaths occurred during hospitalization , all of whom were severe PAH cases .Multivariate analysis showed that pulmonary artery systolic pressure was a risk factor of perioperative death (OR=1.042, P=0.005).There were 55 cases (50.0%) of term delivery, and 35 cases (31.8%) of iatrogenic abortion.The proportion of term delivery in the severe PAH group was significantly lower . The proportion of iatrogenic abortion and small for gestational age infant ( SGA ) were higher in severe group .The incidence of neonatal malformations was 8.0%(6/75).The follow-up rate was 61.8%(63/102).Sudden death was reported in a parturient a few days after discharge .The remaining 62 patients survived during follow-up, while 53 patients (85.5%) were functional class ( FC ) Ⅰ -Ⅱ, 9 ( 14.5%) were FC Ⅲ -Ⅳ at follow-up.The cardiac function deterioration during pregnancy was not significantly correlated with long-term deterioration (P =0.767). Conclusions Perinatal mortality and the incidence of maternal and fetal adverse events were high in pregnancy with PAH-CHD.Pulmonary artery systolic pressure is a major risk factor for perioperative mortality in pregnant women .PAH-CHD woman had good overall outcome after puerperium .
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<p><b>BACKGROUND</b>Sepsis-induced myocardial injury (SIMI) is caused by a variety of mechanisms. The aim of the study is to investigate the effects of metalloproteinase-8 (MMP-8) on SIMI and its mechanisms in rats.</p><p><b>METHODS</b>Forty male Sprague Dawley rats were randomly divided into four groups: MMP-8 inhibitor (M8I), dexamethasone (DEX), sepsis, and sham groups. The sepsis model was established by cecal ligation and puncture (CLP). Rats in the M8I group immediately received an intraperitoneal injection of M8I (0.1 mg/kg) after CLP. Rats in the DEX group immediately received an intraperitoneal (IP) injection of DEX (2 mg/kg). Rats in the sepsis and sham groups received intraperitoneal injections of normal saline. Rats were sacrificed 12 hours after CLP. Paraffin sections were stained with hematoxylin and eosin to observe the myocardium. The myocardial ultrastructure was observed with transmission electron microscopy. MMP-8, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were detected by immunohistochemistry. The expression of MMP-8 was measured by Western blotting. TNF-α and IL-1β levels in serum and myocardial tissue were determined by enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>Compared with the sham group, the myocardium in the sepsis group was seriously injured. MMP-8, TNF-α and IL-1β expression was higher in the sepsis group than in the sham group. Treatment with M8I or DEX, however, attenuated sepsis induced histopathological changes in the heart, and was associated with significant reductions in serum and myocardial levels of TNF-α and IL-1β (P < 0.05). M8I significantly inhibited MMP-8 expression in myocardial tissue (P < 0.05). In addition, treatment with DEX was not associated with a change in myocardial levels of MMP-8 (P > 0.05).</p><p><b>CONCLUSION</b>MMP-8 inhibitor attenuated myocardial injury in septic rats, which might be related to reduced expression of TNF-α and IL-1β.</p>
Subject(s)
Animals , Male , Rats , Dexamethasone , Therapeutic Uses , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Heart Diseases , Drug Therapy , Interleukin-1beta , Metabolism , Matrix Metalloproteinase 8 , Metabolism , Matrix Metalloproteinase Inhibitors , Therapeutic Uses , Rats, Sprague-Dawley , Sepsis , Drug Therapy , Tumor Necrosis Factor-alpha , MetabolismABSTRACT
Objective To determine if the cardiac index (CI) measured with arterial pressure-based cardiac output (APCO) agrees with that measured with pulmonary artery catheter (PAC) during cesarean section in parturients with congenital heart disease and severe pulmonary hypertension.Methods Thirty parturients with congenital heart disease and severe pulmonary hypertension,scheduled for elective cesarean section,were enrolled in the study.APCO and PAC were used for cardiac output and other parameters of hemodynamics monitoring during operation in all patients.Continuous epidural anesthesia was performed.CI was recorded immediately before epidural administration (T1),at 5 and 10 min after epidural administration (T2-3),immediately before delivery (T4),and at 2 and 5 min after delivery (T5-6).The correlation was tested by Pearsone correlation analysis.CI derived from APCO and PAC was compared by Bland-Altman analysis for agreement.Results CI measured with PAC was significantly higher than that measured with APCO (P ＜ 0.05).Compared with the baseline value at T1,no significant difference in CI measured with PAC and APCO was found at T11-T4 and T6 (P ＞ 0.05),and CI measured with PAC and APCO was significantly increased at T5 (P ＜ 0.05).Bland-Ahman analysis showed poor agreement between CI measured with the two methods.The correlation analysis showed that there was positive correlation between CI derived from the two methods at T1-6 (the correlation coefficient was 0.93,0.95,0.94,0.89,0.96 and 0.91 at T1-6,respectively,P ＜ 0.05).Conclusion CI value obtained with APCO agrees poorly with that obtained with PAC during cesarean section in parturients with congenital heart disease and severe pulmonary hypertension,but agrees well in monitoring the changing trend of CI.
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BACKGROUND:Distraction osteogenesis applied in patient’s canine distal movement, can greatly improve the speed of tooth movement, and protect the molar anchorage. But the researches on the traction rate, canine pulp vitality, canine periodontal tissue remodeling and the biological mechanisms of the technology are rare recently. OBJECTIVE:To evaluate the feasibility of rapid canine retraction through distraction osteogenesis of the periodontal ligament in adult patients and to monitor the pulp vitality, root resorption and periodontal remodeling of the canine. METHODS:Nine malocclusion patients were selected, and the bilateral maxil ary canine in adult patients were rapidly retracted and moved to the scheduled position using modified distraction devices. The canine distal movement distance, anchorage loss, root resorption and alveolar interval alterations were measured through intraoral radiographs, and lateral cephalograms. The pulp and periodontal of canine were mointrored. RESULTS AND CONCLUSION:The canines could be rapidly retracted to the schedualed position through distraction osteogenesis of the periodontal ligament in 12-16 days, the average amount of retraction was 7.18 mm and the canines tipped distal y (13.24±2.87)°. The anchorage loss was 0.5 mm. There was no obvious root resorption and periodontal tissue loss. The pulp vitality of the canines was decreased significantly right after distraction, but it recovered significantly after 3 months. The results indicated that periodontal ligament distraction osteogenesis can significantly accelerate canine movement speed, shorten treatment time, while protecting the molar anchorage;there was no significant adverse reaction of root resorption, loose teeth, pulp necrosis and loss of periodontal tissue. Indcating that distraction osteogenesis of periodontal ligament can move canines rapidly and effectively.
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Objective To investigate the risk factors for postpartum cardiac events in pregnant women with heart diseases and to provide prenatal counseling for them.Methods A retrospective analysis was made in cases of pregnant women with heart diseases admitted to the surgical intensive care unit (SICU) of Anzhen Hospital from May 2004 to May 2012.Data were used to identify univariate and multivariate predictors for postpartum cardiac events.Results A total of 190 patients (≥ 20 weeks gestation) were enrolled in the study with 134 (70.5％) of congenital heart disease,30 (15.8％) of rheumatic heart disease,10 (5.3％) of cardiomyopathy,2 (1.1％) of peripartum cardiomyopathy and 14(7.4％) of hypertensive heart disease.Postpartum cardiac events were observed in 42 cases with the incidence of 22.1％.A total of 7 cases resulted in death with the mortality rate of 3.7％.Among them,5 cases were dead of circulatory collapse and pulmonary hypertensive crisis postpartum,while the other 2 cases with secondary pulmonary infection were died of respiratory and circulatory collapse.The baseline parameters of New York Heart Academy(NYHA) ＞ 1,left ventricular ejection fraction (LVEF) ＜ 50％,use of cardiac drugs and pulmonary artery hypertension(PAH) ＞ 80 mm Hg(1 mm Hg =0.133 kPa) were the independent predictors for postpartum cardiac events by univariate and multivariate logistic regression analysis.Conclusions The incidence of postpartum cardiac events is high in pregnant women with heart diseases.Pulmonary artery hypertension and heart failure are the main causes of death.
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Objective To summarize the experience during early stage of postoperative monitoring and treatment for the patients follwing lung transplantation in surgical intensive care unit,and to improve the patient's outcome of lung transplantation.Methods A retrospective analysis of 9 cases of orthotopic lung transplantation admitted to surgical intensive care unit (SICU) of Beijing Anzhen Hospital from May 2005 to May 2011 was made.Results There 5 male patients and 4 female patients with the age 21 -67 (46.1 ± 14.1 ) years old in present group,and among them 6 patients survived (survival rate:66.7％ ).The etiological indication of admission were idiopathic pulmonary fibrosis (n =4),pulmonary lymphangioleiomyomatosis ( n =3 ),and bronehiectasis ( n =2).Bilateral sequential lung transplantation ( n =5 ),single left lung transplantation ( n =1 ) and single rigbt lung transplantation ( n =3) were performed.The postoperative duration of mechanical ventilation,stay duration in SICU and in hospital were 2 -32 d,3 -42 d,and 3 -60 d respeetively.Postoperative complication taking place after surgery were acute rejection in 2 cases and pneumonia 4 cases (3 cases were treated with extracorporeal membrane oxygenator).Postoperative in hospital death was 3 cases of 9 resulting from severe intection (n =2) and cireulation failure ( n =1 ).Conclusion Well-planned postoperative management stroategy in SICU plays an important role in outcome control after lung transplantation,including monitor and respiratory and cardiacvascular management,reasonable implementation of vasoactive medications and diuretics,protective mechanical ventilation strategy,reducing the time of ventilation.
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Objective To analyze the risk factors for perioperative acute cerebral vascular accident (PACVA) and put forward the corresponding preventive measures.Methods The clinical data of elderly patients in our hospital who suffered from PACVA in recent 5 years were retrospectively studied.The correlation between risk factors and the occurrence of PACVA was analyzed.Results One hundred and fifty cases were enrolled in the study.Seventy eight cases of them suffered from PACVA with the average age of 70 years ranging from 60 to 98 years.Fifty six cases(71.8%)were found PACVA in one week after operation.Multiple regression analysis showed that hypertension, history of cerebrovascular disease, unstable blood pressure and obesity were independent risk factors for PACVA.The newly diagnosed perioperative atrial fibrillation and carotid atheroselerosis were the high risk factors for PACVA.Conclusions PACVA is one of the common perioperative complications.Necessary check, monitor and treat measures should be taken in the perioperative period, especially for patients with risk factors.