Objective To find the new mutations of Leber's hereditary optic neuropathy (LHON). Methods Two LHON families were enrolled in this study. The probands and all maternal members in this two families were underwent ophthalmologic examinations. The ages of probands were seven and 14 years old respectively. A total of 358 healthy adults were enrolled in this study as control group. The genomic DNA from whole blood of participants were extracted. The entire mitochondrial genome of probands were PCR amplified and sequenced in 24 overlapping fragments using primers as designed. At the same time, the mtDNA of maternal relatives and 358 controls were also detected. Fourteen primate species were selected from GenBank to analyzed the phylogenetics of mitochondrial sequence. Results There was no ND4 G11778A, ND1 G3460A, ND6 T14484C mutational site in all maternal members. Molecular analysis of mtDNA in this two families identified the homoplasmic tRNAGluA14683G mutation and distinct set of variants belonging to the Asian haplogroup F1a1 and G2. The site was at theTpsi;C stem oftRNAGlu and extremely conserved among 14 primate species. It was anticipated that the A14683G increased the highly conserved C-G basepairing. Furthermore, the A14683G was absence in control group. Conclusion The tRNAGluA14683G mutation is likely a new mutation associated with LHON.
Objective To screen mitochondrial DNA mutations in 3 Chinese pedigrees with Leberprime;s hereditary optic neuropathy (LHON) carrying the ND1 G3635A mutation. Methods 88 members（53 maternal relatives and 35 paternal relatives）in 3 pedigrees were enrolled. The ophthalmologic examinations were performed for all members, including visual acuity (standard logarithmic visual acuity charts), fundus photography (Canon fundus camera),visual field (Humphrey Visual Field Analyzer), color vision (Yu zhiping color vision plate), and visual evoked potentials (Roland Consult RETI port gamma, flash VEP). 16 members had LHON, 72 members did not have LHON. 135 healthy people from Wenzhou were included as the control group. Genomic DNA was extracted from peripheral blood leukocytes of all subjects. G3635A mutation was screened by PCR mplification of mitochondrial DNA for all subjects. Mitochondrial haplotypes and other mutations in the entire mitochondrial genome were also determined by PCR using 24 pairs of primers for the probands. Results Analysis of mitochondrial DNA (mtDNA) in 3 pedigrees revealed the presence of ND1 G3635A mutation in 3 probands and all maternal relatives, but not in paternal relatives and healthy controls. Probandprime;s haplogroup belong to East Asia group N9a3, D4, and R11a. In addition to the G3635A mutation, probands also had other variants including 12 variants in D-loop region, 6 variants in RNA gene, and 36 variants in protein-encoding gene. Conclusions G3635A mutation was identified in probands and maternal relatives of 3 pedigrees of LHON. It showed that G3635A mutation was the pathogenic molecular basis for those patients.
Lower limb ankle exoskeletons have been used to improve walking efficiency and assist the elderly and patients with motor dysfunction in daily activities or rehabilitation training, while the assistance patterns may influence the wearer’s lower limb muscle activities and coordination patterns. In this paper, we aim to evaluate the effects of different ankle exoskeleton assistance patterns on wearer’s lower limb muscle activities and coordination patterns. A tethered ankle exoskeleton with nine assistance patterns that combined with differenet actuation timing values and torque magnitude levels was used to assist human walking. Lower limb muscle surface electromyography signals were collected from 7 participants walking on a treadmill at a speed of 1.25 m/s. Results showed that the soleus muscle activities were significantly reduced during assisted walking. In one assistance pattern with peak time in 49% of stride and peak torque at 0.7 N·m/kg, the soleus muscle activity was decreased by (38.5 ± 10.8)%. Compared with actuation timing, the assistance torque magnitude had a more significant influence on soleus muscle activity. In all assistance patterns, the eight lower limb muscle activities could be decomposed to five basic muscle synergies. The muscle synergies changed little under assistance with appropriate actuation timing and torque magnitude. Besides, co-contraction indexs of soleus and tibialis anterior, rectus femoris and semitendinosus under exoskeleton assistance were higher than normal walking. Our results are expected to help to understand how healthy wearers adjust their neuromuscular control mechanisms to adapt to different exoskeleton assistance patterns, and provide reference to select appropriate assistance to improve walking efficiency.
ObjectiveTo compare the similarities and differences in procedures between Western medicine (WM) and traditional Chinese medicine (TCM) guidelines. MethodsWe systematically searched China National Knowledge Infrastructure, WanFang Data, China Biology Medicine disc and PubMed from inception to May 17, 2022. Supplementary search of reputable medical institutions and organizations, as well as retrospective references were conducted and screened. We extracted and analyzed the basic information and guideline development procedure of the included handbooks. ResultsA total of 10 handbooks published from 2013 to 2022 were included, with four WM handbooks and six TCM handbooks. The median completeness of handbooks was 53.3%, with a maximum of 93.3% and a minimum of 43.3%. There are six handbooks with less than 60.0% completeness. The median reporting rate of the key steps was 65.0%, and the reporting rate of 5/8 of the key steps was more than 80.0%. Among the key reporting steps, role of funders, update methods, and conflict of interest management were reported at a low rate. Compared with WM handbooks, TCM handbooks reflected TCM characteristics in the procedure of topic selection, working groups, conflict of interest declaration and management, clinical questions, evidence, recommendations, report guideline, and external review. ConclusionThe completeness and reporting rate of the key steps need to be improved. TCM characteristics need to be further integrated when developing TCM guideline handbooks. We highly recommend that guideline stakeholders actively participate in handbook development to promote the quality of handbooks.
Objective To observe the molecular genetic characteristics of seven Chinese families with Leberprime;s hereditary optic neuropathy (LHON). Methods Ophthalmologic examinations were performed on seven probands, maternal members from seven Chinese families and 134 healthy controls. There were two LHON patients in seven Chinese families except probands. The entire mitochondrial genome was amplified using 24 pairs of oligonucleotide primers with overlapping fragments.The mutational site was analyzed through comparison of the Results and Cambridge reference sequence. The penetrance of mutation site was calculated and the haplotype was analyzed. Results Molecular analysis of mitochondrial DNA (mtDNA) in these pedigrees revealed the absence of three common LHON associated with ND4 G11778A, ND1 G3460A and ND6 T14484C mutations. The ND1 T3394C mutation in probands and other matrilineal relatives was present in four out of 134 Chinese healthy controls. Strikingly, these families exhibited very low penetrance of visual impairment. The penetrance was 12.50%, 22.22%, 16.76%, 6.25%, 9.09%, 11.11% and 28.57%. The Results of phylogenetic tree analysis of submitochondrial haplotype showed that these mtDNA polymorphism sites belong to the Asian haplogroups M9, M9, M, D4, M, M9 and M9. Conclusions T3394C mutation exists in seven Chinese LHON pedigrees, and the penetrance was ranged from 6.25% to 28.57%. The patients have different clinical manifestations.
Technology in traditional Chinese medicine (TCM), which has a long history, provides excellent traditional culture and valuable spiritual wealth in China. TCM standardization technology will provide an important basis for guiding and evaluating the professional level and service quality of technicians in TCM. And it is also conducive to the sustainable development of TCM technology. However, at present, there is no relevant research on the development process of technical specifications for TCM. So, the urgent need is how to develop standardized technical specifications, and apply them to patients in practice. Therefore, this study first convened relevant experts, including TCM clinical experts, epidemiologists, methodology experts, etc., to form the core expert group, implementation group and quality assurance task group. According to the personnel functions, they are divided into technical specification steering committee, consensus expert group, secretariat group, external review group, evidence evaluation group, etc. Then, the initial entries are collected by systematically searching the current TCM technical guidelines, consensus and specifications and referring to the existing technical specifications. Finally, expert opinions were collected based on the Delphi survey, and the final reporting checklist of technical specifications for TCM was formed after consensus discussion. The study can provide evidence-based methodological guidance for the development of TCM technical specifications, and promote the standardization and internationalization of TCM technical specifications.