Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

The current status of exoskeletons was introduced in enhancing individual soldier's battlefield rescue capabilities,promoting the integrated use of battlefield rescue equipment,protecting medical personnel on the battlefield and assisting injured soldiers in rehabilitation training.The challenges of exoskeletons faced in human-machine interaction,power supply endurance,heavy overall structure,restricted movement and high cost were analyzed when applied to medical service support,and some suggestions were proposed accordingly including enhancing technology research and development,integrated application,communication and cooperation and personnel training.References were provided for the application of exoskeletons in China's medical service support.[Chinese Medical Equipment Journal,2024,45(3):71-75]

Immune checkpoint inhibitor(ICI)-based combination therapies have achieved great breakthroughs in the treatment of advanced non-small cell lung cancer(NSCLC)with negative driver genes;however,challenges persist owing to unmet clinical needs.Recent advances in fundamental and translational research on radioimmunotherapy offer hope for addressing these challenges.Adaptive immunotherapy ra-diotherapy(AIRT)is a promising treatment modality with potential applicability and universality that can provide accessibility and potentially superior clinical outcomes to most patients undergoing chemoimmunotherapy.However,extensive fundamental research and clinical trials in radiation oncology is required to substantiate the efficacy of this approach.

Objective To study the stability of plate-assisted intramedullary nailing for fixing proximal third tibiafractures, compare and observe biomechanical characteristics of anterolateral or posteromedial plate-assisted intramedullary nailing after fixation of proximal third tibia fractures. Methods Eight artificial tibia of 4th-generation sawbones were divided into two groups based on location of the assisted plate, namely, anterolateral plate group and posteromedial plate group, with 4 specimens in each group. Each two locking bolts were fixed to theintramedullary nail proximally and distally, and each three bicortical screws were fixed to the plate proximally and distally. The specimens were osteotomized with a 10-mm defect which located 0. 5 cm to the proximal locking bolt of intramedullary nail or 5-6 cm distally to the knee joint line, in order to simulate an AO/ OTA 41-A2 type proximal third tibia fracture after fixation of intramedullary nail. After osteotomy was finished, axial compression test, three point bending test, cyclic loading and overstress test were conducted by mechanical testing machine. The results of axial stiffness and three-point stiffness between two groups were compared and analyzed. Results Axial compression test showed that the average axial stiffness in posteromedial plate group was lower than that in anterolateral plate group, but no significantly statistical differences were found between the two groups. Three point bending test showed that the average bending stiffness in posteromedial plate group was significantly higher than that in anterolateral plate group when stimulating either varus stress (plate located at pressure side of the fracture, t = 3. 679, P<0. 05) or valgus stress (plate located at tension side of the fracture, t = 8. 975, P<0. 05). Conclusions Plate-assisted intramedullary nailing for fixation of proximal third tibia fractures can minimize the angulation malalignment, improve the stability of nailed proximal tibial fragment and allow the early weight bearing. Both anterolateral and posteromedial plate-assisted intramedullary nail can provide satisfactory axial stability for proximal third tibia fractures, while posteromedial plate-assisted intramedullary nail shows better bending stability than anterolateral plate in countering varus or valgus stress deformity. This study provides an essential basis for clinical decision making about plate-assisted intramedullary nailing for fixing proximal third tibia fractures.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems

Objective To observe the electromyography characteristics of children's handwriting with attention deficit hyperactivity disorder(ADHD),and explore its electrophysiological mechanism,so as to provide an objective basis for developing non-pharmacological treatment for such children.Methods Between September 2021 and April 2022,29 ADHD children were recruited from an ordinary public primary school and the psychiatric clinic of a class-3 grade-A hospital in Beijing.Among them,25 were boys and 4 were girls,with an average age of 8.21±1.78 years.Meanwhile,23 male and 5 fe-male healthy counterparts were selected with the age gap no more than 6 months.The Delsys wireless surface EMG system was used to collect the electromyographic signals of the abductor pollicis breve,the first dorsal interosseous muscle,the flexor radial carpi motor and the extensor finger muscles dur-ing their writing tasks such as tracing trajectories,writing Arabic numerals 0-9,26 small and capital English letters,Chinese characters one to ten and"Yong".The percentage of the averaged electromyog-raphy(AEMG)of a muscle in the sum value of all measured muscles,and the coefficient of differ-ence were selected to evaluate the muscle contribution rate and the consistency of exertion,respective-ly.Moreover,the independent sample t-test was employed to compare the two different groups with the significance set at α=0.05.Results There was a significant difference in the muscle contribution of abductor pollicis breve and first dorsal interosseous muscles when writing Arabic numerals and that of abductor pollicis breve muscles when writing Chinese characters between ADHD children(27.29%,25.58%and 27.53%)and their healthy counterparts(42.87%,19.96%and 37.13%)(P<0.05).Most muscle differentiation coefficients of ADHD children were higher than 100%,with that of the domi-nant hand radial wrist flexor muscle reaching 270%in the trajectory tracing task.Conclusion Accord-ing to the characteristics of EMG signals,school-age ADHD children show an immature writing pat-tern,including poor stability of writing-related muscles,insufficient control of small finger muscle groups,poor control of hand coordination,and insufficient muscle inhibition of non-dominant hand.It is recommended to conduct the electromyoelectric assessment of handwriting movements in ADHD chil-dren,so as to carry out targeted intervention at an early stage.

In recent years, the MYB-related gene family has been found pivotal in plant growth and development. MYB-related gene family in Angelica dahurica var. formosana was systematically investigated based on "Chuanzhi No. 2" through transcriptome database search and bioinformatics and the temporal and spatial expression patterns were analyzed through real-time fluorescence-based quantitative polymerase chain reaction(PCR). The results showed that 122 MYB-related proteins family were identified, mainly including the unstable hydrophilic proteins with good thermal stability. Most of the proteins were located in nuclei. The majority of the proteins had the structures of random coil and α-helix. Five MYB-related proteins family of A. dahurica var. formosana had membrane-binding domains. The conserved domain analysis of MYB-related proteins family of A. dahurica var. formosana showed that the MYB domains of genes in five subgroups, similar to 2 R-, 3 R-, and 4 R-MYB proteins, contained three evenly distributed Trp(W) residues in the MYB repeat sequence. The phylogenetic analysis of MYB-related proteins family in A. dahurica var. formosana and Arabidopsis thaliana showed that the MYB-related members were unevenly distributed in five subgroups, and A. thaliana and A. dahurica var. formosana had almost the same number of genes in the CCA1-like subgroup. There were differences in the number, type, and distribution of motifs contained in 122 encoded proteins. Transcription factors with similar branches had similar domains and motifs. The expression pattern analysis showed that the transcription factors AdMYB53, AdMYB83, and AdMYB89 responded to hormones to varying degrees, and they were highly expressed in leaves and responded quickly in roots. This study lays a foundation for further investigating the function of MYB-related transcription factors of A. dahurica var. formosana and solving the corresponding biological problems such as bolting early.
Angelica/chemistry* ; Animals ; Computational Biology ; Gastropoda ; Phylogeny ; Plant Leaves ; Plant Proteins/genetics* ; Transcription Factors/genetics*

ObjectiveTo study the in vitro anti-hepatocarcinoma HepG2 cell mechanism of Jaranol. MethodThe methyl thiazolyl tetrazolium （MTT） assay was employed to examine the inhibition of Jaranol （0， 5， 10， 25， 50， 100， 150， 300 μmol·L^-1） on HepG2 cell proliferation at different time （24 ， 48 ， 72 h）， annexin V-fluorescein isothiocyante/propidium iodide （Annexin V-FITC/PI） kit to detect the effect of Jaranol （0， 3， 15， 75 μmol·L^-1） on HepG2 cell apoptosis， and Western blot to determine the influence of Jaranol on the expression of B-cell lymphoma 2 （Bcl-2） and Bcl-2-associated X protein （Bax） in HepG2 cells. Transcriptome sequencing was performed to analyze the differential expression of genes and changes of related signaling pathways after the treatment of HepG2 cells with Jaranol （15 μmol·L^-1）. Real-time PCR was carried out to verify the relative mRNA content of differential genes ［TEK， platelet-derived growth factor receptor α （PDGFRA）， spleen tyrosine kinase （SYK）， phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit gamma （PIK3CG）， Janus kinase 3 （JAK3）， membrane-associated guanylate kinase inverted 2 （MAGI2）］. ResultCompared with the blank group， Jaranol decreased HepG2 proliferation （P<0.05， P<0.01）， increased apoptosis rate of HepG2 cells （P<0.05， P<0.01）， raised Bax expression （P<0.05， P<0.01）， and reduced Bcl-2 expression （P<0.05， P<0.01）. Transcriptome sequencing yielded 59 000 regulated genes， 125 of which showed significantly different expression， with 47 up-regulated and 74 down-regulated. Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis showed that the differential genes related to apoptosis in the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway changed significantly after drug addition. The mRNA expression of TEK， PDGFRA， SYK， PIK3CG， JAK3， and MAGI2 decreased in Jaranol （15 μmol·L^-1） group compared with that in the control group （P<0.05）. ConclusionIn vitro cytological experiment verified that Jaranol inhibited the proliferation of HepG2 cells and promoted the apoptosis， possibly by influencing the expression of some differential genes in the PI3K/Akt signaling pathway. The result lays an experimental basis for the follow-up study of the anti-tumor effect of Jaranol， and the further development and utilization of flavonoids.

Objective:To compare the early clinical efficacy between reaming after distal tibia cortical fenestration combined with antibiotic-loaded calcium sulphate and trench grooving combined with polymethyl methacrylate (PMMA) for the treatment of chronic tibial osteomyelitis after intramedullary nail fixation.Methods:A retrospective analysis was conducted in the 20 patients who had been surgically treated for chronic tibial osteomyelitis after intramedullary nail fixation at Department of Trauma Orthopaedics, Honghui Hospital from January 2019 to January 2021. According to the surgical methods, they were divided into a reaming group and a grooving group. In the reaming group, there were 6 males and 3 females with an age of (47.6±11.4) years; in the grooving group, there were 9 males and 2 females with an age of (49.2±13.9) years. The 2 groups were compared in terms of duration of infection, operation time, intraoperative blood loss, bacterial culture results, total hospital stay, time for inflammatory indexes to return to normal, time for weight-bearing, complication rate, infection control rate, and good to excellent rate by Johner-Wruhs joint function scoring.Results:There was no significant difference in the preoperative general data between the 2 groups, showing they were comparable ( P > 0.05). All patients were followed up for 12 to 25 months after operation. There were no significant differences in the duration of infection, operation time, intraoperative blood loss, bacterial culture results, time for inflammatory indexes to return to normal, complication rate, infection control rate, or Johner-Wruhs scoring between the 2 groups ( P > 0.05). The total hospital stay [(11.7 ± 4.7) d] and weight-bearing time [(5.8 ± 1.6) weeks] for the reaming group were significantly shorter than those for the grooving group [(16.8 ± 4.6) d and (8.1 ± 2.9) weeks] ( P < 0.05). Conclusion:In the treatment of chronic tibial osteomyelitis after intramedullary nail fixation, compared with conventional trench grooving combined with PMMA, reaming after distal tibia cortical fenestration combined with antibiotic-loaded calcium sulphate can not only obtain satisfactory outcomes by infection control but also shorten the treatment cycle by allowing the patients to start early weight bearing.

Objective To investigate the effectiveness of a new health education pathway for echinococcosis control among primary school students in regions highly prevalent for echinococcosis in China. Methods Six primary schools were randomly selected from echinococcosis hyper-endemic regions, with 13 classes assigned to the intervention group and 9 to the control group, and all students in these 21 classes were recruited as the study subjects. Echinococcosis health education was performed through the pathway of assessing the current status-strengthening the building of teaching resources-focusing on practices in the intervention group, while routine health education was given in the control group. A questionnaire survey was performed to assess the score of echinococcosis control knowledge (including theoretical knowledge score and mean daily practical capability score) before and after the health education interventions to evaluate the effectiveness of this new health education pathway for echinococcosis control. Results The mean score of echinococcosis control knowledge was 68.86 ± 18.70 points at baseline, with the mean theoretical knowledge score of 40.97 ± 10.75 points, and the mean daily practical capability score of 27.89 ± 12.50 points. Clustering analysis showed three types of populations, including “unsatisfactory”, “learn and apply creatively”, and “rote learning”, which accounted for 24.62% (240/975), 45.74% (446/975) and 29.64% (289/975), respectively. The mean score of echinococcosis control knowledge was 81.08 ± 18.15 points in the intervention group during the final assessment, with the mean theoretical knowledge score of 43.65 ± 9.40 points, and the mean daily practical capability score of 37.43 ± 12.22 points, and both were significantly higher relative to baseline (t = −4.201 and −15.202, both P values < 0.01). The mean score of echinococcosis control knowledge was comparable between at baseline (70.55 ± 19.46 points) and final assessment (71.74 ± 19.37 points) in the control group (t = −0.87, P > 0.05). Conclusions The awareness of echinococcosis control knowledge is fair among primary school students in echinococcosis hyper-endemic regions; however, the capability of combining theoretical learning and practices requires to be improved. The health education mode based on the pathway of assessing the current status-strengthening the building of teaching resources-focusing on practices seems to remarkably improve the understanding of echinococcosis control knowledge among primary school students in echinococcosis hyper-endemic regions.