The rotation center of traditional hip disarticulation prosthesis is often placed in the front and lower part of the socket, which is asymmetric with the rotation center of the healthy hip joint, resulting in poor symmetry between the prosthesis movement and the healthy lower limb movement. Besides, most of the prosthesis are passive joints, which need to rely on the amputee’s compensatory hip lifting movement to realize the prosthesis movement, and the same walking movement needs to consume 2–3 times of energy compared with normal people. This paper presents a dynamic hip disarticulation prosthesis (HDPs) based on remote center of mechanism (RCM). Using the double parallelogram design method, taking the minimum size of the mechanism as the objective, the genetic algorithm was used to optimize the size, and the rotation center of the prosthesis was symmetrical with the rotation center of the healthy lower limb. By analyzing the relationship between the torque and angle of hip joint in the process of human walking, the control system mirrored the motion parameters of the lower on the healthy side, and used the parallel drive system to provide assistance for the prosthesis. Based on the established virtual prototype simulation platform of solid works and Adams, the motion simulation of hip disarticulation prosthesis was carried out and the change curve was obtained. Through quantitative comparison with healthy lower limb and traditional prosthesis, the scientificity of the design scheme was analyzed. The results show that the design can achieve the desired effect, and the design scheme is feasible.
Objective To analyze the correlation between HLA-A and B genotypes and maculopapular exanthema (MPE) caused by Carbamazepine (CBZ) and Oxcarbazepine (OXC), and to explore the genetic risk factors of MPE. Methods Patients with MPE (rash group) and patients without MPE (non-rash group) after taking CBZ or OXC were retrospectively collected from January 2016 to October 2021 in the Second Affiliated Hospital of Guangzhou Medical University. DNA was extracted from peripheral blood. HLA-A and HLA-B alleles were sequenced by high resolution sequencing, and a case-control study was conducted to analysis the correlations between MPE and HLA genotypes. Results A total of 100 patients with CBZ-MPE, 100 patients with CBZ-tolerant, 50 patients with OXC-MPE, and 50 patients with OXC-tolerant were collected. There was no significant difference in age and sex between CBZ, OXC rash groups and non-rash groups The average latency of CBZ-rash group was (11.31±11.00) days and their average dosage was (348.46±174.10) mg; the average latency of OXC-rash group was (11.67±10.34) days and their average dosage was (433.52±209.22) mg [equivalent to CBZ (289.01±139.48 mg)], showing no significant difference in latency and dosage between CBZ and OXC (P>0.05). The positive rates of HLA-A*24:02 and A*30:01 in CBZ-rash group were 28% and 6%, respectively, which were significantly higher than those in CBZ-non rash group (16% and 0%, both P=0.04). The positive rate of HLA-B*40:01 in CBZ-rash group was 18%, which was significantly lower than that in CBZ-non rash group (40%, P<0.001). No association between HLA-A or B genotype and OXC-rash was found yet. When pooled, it was still found that the positive rates of HLA-A*24:02 and A*30:01 in the rash group were higher than those in the non-rash group, while the positive rate of HLA-B*40:01 in the rash group was lower than that in the non-rash group, and the difference was statistically significant (P<0.05). Conclusions HLA-A*24:02 and A*30:01 were associated with MPE caused by CBZ, and may be common risk factors for aromatic antiepileptic drugs.
ObjectiveTo study SCN1A gene mutations and their inheritance in patients with Dravet syndrome (DS), and to analyze the phenotypes of their family members. MethodsGenomic DNA was extracted from peripheral blood samples from DS patients and their parents. SCN1A gene mutations were screened using PCR-DNA sequencing and multiplex ligation-dependent probe amplification (MLPA). Results547 DS patients were collected, SCN1A gene mutations were identified in 379 patients (69.3%), which included 179 missense mutations (47.2%), 78 nonsense mutations (20.6%), 77 frameshift mutations (20.3%), 37 splice site mutations (9.8%), and 8 cases with SCN1A gene fragment deletions or duplications (2.1%). Of 379 DS patients, the parents of 354 DS patients were further analyzed, the de novo mutations accounted for 92.9%, inherited mutations accounted for 7.1%, and in 5 of the latter families, the SCN1A-positive parent carried a somatic mutations mosaicism. For the 25 parents carrying SCN1A mutations, 1 had DS, 11 had febrile seizures plus, 9 had febrile seizures, whilst 4 were normal. ConclusionsThe mutation rate of SCN1A in DS patients is high. Most mutations are of missense and truncation mutations (including nonsense mutation and frameshift mutation). Only a few patients have carried fragment deletions or duplications. Most SCN1A mutations are de novo, only a few are inherited from the parents. SCN1A mutations carried by the parents can be in the form of mosaicism. The phenotypes of parents with SCN1A mutations can be severe, mild or normal, and a mosaic transmitting parent always shows mild or normal.
Objective To observe the mutation frequency and the characteristics of rentinitis pigmentosa (RP)1 gene in the Chinese patients with autosomal dominant (AD) RP or sporadic RP (SRP), and to evaluate their potential effects on the pathogenesis of RP. Methods Fifty-five members from 7 Chinese families with ADRP, 30 patients with SRP, and 75 healthy adults were recruited. Polymerase chain reaction (PCR) and direct DNA sequencing were used to detect the sequence mutation in the entire coding region and splice sites of RP1 gene. Univariate analysis and multivariate analysis were used to detect the effect of RP1 gene mutation sites on RP. Results Four coding sequence variants were detected in the codes of 852，872，921 and 939 at the exon 4 of RP1 gene. The R872H alteration, which was found in both ADRP families and patients with SRP, showed positive correlation with RP confirmed by the multivariate logistic regression analysis. The P903L alteration was only found in ADRP families but not in the patients with SRP or the healthy adults. Conclusions The R872H alteration in the RP1 gene is likely to increase the risk of RP, and may be a susceptible gene of RP. Whether the P903L alteration is a diseasecausing factor needs to be further studied.
OCT angiography (OCTA) is a fast, noninvasive and quantifiable new technique, which is especially suitable for long-term follow-up in patients with hereditary retinochoroidal degeneration, such as retinitis pigmentosa, Best vitelliform macular dystrophy, adult onset foveomacular vitelliform dystrophy, doyne honeycomb retinal dystrophy, choroideremia and Stargardt disease. During the follow-up, clinicians can find the subtle signs that explain disease development from the blood flow imaging, quantitatively describe the vascular density, timely detect and treat choroidal neovascularization. It is significant to explore the etiology and monitor the course of these diseases. With the development of more treatments for these diseases, OCTA parameters can also be used as indicators to evaluate and compare different therapeutic effects. In the future, more quantitative indicators of OCTA will be applied to evaluate the course of hereditary retinochoroidal degeneration, and provide valuable basis for early diagnosis and treatment.
Epilepsy is a chronic brain dysfunction disease with complex and diverse causes, but 70%-80% of patients do not have obvious characteristic phenotypic symptoms. In order to provide precise treatment for epilepsy patients, research on the genetic pathogenic factors and pathogenesis of epilepsy has attracted much attention. Different types of epilepsy are constantly found to be closely related to mutations in specific genes, such as SCN1A, KCNA2, KCNT1, GABRA1, TSCs, CDKL5, and so on. Therefore, the development of broad-spectrum antiepileptic drugs is very difficult. However, plant-based drugs or functional ingredients derived from traditional medicinal herbs, such as cannabinol, aconitine, and dodecenal, will expand the development of safer and more effective anti epileptic drugs.
Objective To investigate the expression and clinicopathological features of fumarate hydratase (FH) in multiple leiomyoma of the uterus. Methods Relevant clinicopathological data of patients with multiple leiomyoma of the uterus diagnosed pathologically between September 1, 2018 and August 31, 2019 were collected from the Department of Pathology of West China Second University Hospital. The morphology, FH protein expression and prognosis of FH negative patients were observed. Results A total of 900 patients were included. Among them, there were 825 cases of nonatypical leiomyomas, 36 cases of leiomyoma with bizarre nuclei, 34 cases of cellular leiomyoma and 5 cases of mitotically active leiomyoma. A total of 69 patients with negative FH expression were included, with an average age of (37.28±8.22) years. Among them, there were 43 cases of nonatypical leiomyomas, 19 cases of leiomyoma with bizarre nuclei, 6 cases of cellular leiomyoma, and 1 cases of mitotically active leiomyoma. At low magnification, staghorn shaped blood vessels, alveolar pattern edema, palisade distribution of smooth muscle cells and bizarre nuclei smooth muscle cells could be seen in patients with negative FH expression. At high magnification, cytoplasmic eosinophilicglobules andeosinophilic nucleolus surrounded by a halo could be seen in patients with negative FH expression. Among the 69 cases with negative FH expression, 60 cases (86.96%, 60/69) were followed up. All patients survived, of which 24 cases (40%, 24/60) recurred. Conclusion Immunohistochemically, the marker FH for multiple leiomyoma of the uterus is helpful to improve the identification of FH deficient leiomyoma in clinical work as well as early diagnosis in hereditary leiomyomatosis renal cell cancer syndrome.
ObjectiveTo systematically review the association between angiotension-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and osteoarthritis (OA) by using meta-analysis and trial sequential analysis (TSA). MethodsThe PubMed, EMbase, CNKI, CBM, VIP, and WanFang Data were searched up to October 12th, 2016 for case-control or cohort studies on the correlation between ACE I/D polymorphism and OA risk. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis and TSA analysis were performed using Stata 13.1 software and TSA v0.9 soft ware. ResultsA total of six case-control studies involving 1 165 OA patients and 1 029 controls were included. The results of meta-analysis showed that the ACE I/D was associated with OA risk (DD+DI vs. II: OR=1.72, 95%CI 1.02 to 2.90, P=0.04; DI vs. II: OR=1.65, 95%CI 1.06 to 2.56, P=0.03). Subgroup analysis of ethnicity showed that, in Caucasians, the ACE I/D was associated with OA risk (DD vs. DI+II: OR=2.10, 95%CI 1.54 to 2.85, P<0.01; DD+DI vs. II: OR=3.11, 95%CI 2.20 to 4.39, P<0.01; DD vs. II: OR=4.01, 95%CI 2.68 to 6.00, P<0.01; DI vs. II: OR=2.65, 95%CI 1.06 to 2.56, P<0.01; D vs. I: OR=2.11, 95%CI 1.72 to 2.58, P=0.73). And TSA showed that all of the cumulative Z-curve strode the conventional and TSA threshold value which suggested the result of the association between ACE I/D polymorphism and OA in Caucasians was very reliable. However, the association did not exist in Asians (DD vs. DI+II: OR=0.80, 95%CI 0.60 to 1.07, P=0.13; DD+DI vs. II: OR=1.08, 95%CI 0.87 to 1.35, P=0.49; DD vs. II: OR=0.86, 95%CI 0.62 to 1.20, P=0.38; DI vs. II: OR=1.18, 95%CI 0.93 to 1.50, P=0.19; D vs. I: OR=0.93, 95%CI 0.83 to 1.14, P=0.73). And the results of TSA displayed that all of the cumulative Z-curve did not strode both TSA threshold value and required information size line excepting for DD vs. DI+II genetic model which suggested that the sample-size in Asians was insufficient. ConclusionsThe ACE D allele maybe a risk factor for OA in Caucasians. However, the association between ACE I/D polymorphism and OA risk in Asians still need more studies to prove.