OBJECTIVE: To explore the genetic variants and phenotypic characteristics of patients with Neurofibromatosis type I (NF1). METHODS: Twenty two NF1 patients who presented at Enze Medical (Center) Group in Taizhou between 2018 and 2024 were selected as the study subjects. Clinical phenotype and family history were collected for the patients. Whole exome sequencing (WES) was carried out for the 22 probands to screen the variants of NF1 gene. Candidate variants were verified by Sanger sequencing of their family members. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: K20230902). RESULTS: The 22 probands were diagnosed between the age of 5 months to 47 years old, and have all shown cafe au lait spots on their skin. Seventeen patients exhibited the phenotype at birth, and 11 had various degrees of neurofibromatosis. Among them, probands 1 and 13 underwent surgical resection of the tumor but had recurred, while proband 12 had amputation due to the huge size and serious impact of the neurofibroma and had no recurrence. Five patients had various degrees of scoliosis. In total 22 germline mutations and one somatic mutation were identified among the 22 families, with 5 variants unreported previously, including 1 nonsense mutation c.1603C>T (Q535*), 3 frameshift mutations [c.7268_7269delCA (Thr2423fs), c.2293del (Arg765Alafs*26), and c.5433_5438delinsGC (Phe1812ArgfsTer50)], and 1 deletion involving exons 41-44 of the NF1 gene and adjacent introns. Proband 13 was found to harbor germline mutation c.6796C>T (Gln2266Ter) and somatic mutation c.1019_1020del (Ser340Cysfs Ter12) in the peripheral blood and tumor tissue, respectively. Among the 22 NF1 probands, 6 had received treatment due to severe illness. Proband 1 had tumor resection in the right upper limb, but was found to have malignant lung tumor and died during follow-up. Proband 12 had multiple recurrence of neurofibroma in the left ring finger. Proband 4 underwent spinal correction surgery due to severe scoliosis. Proband 11 had died due to a central nervous system disease. Among the 22 germline mutations, 6 had led to the occurrence of truncated proteins, which may have a more severe impact on the phenotype. CONCLUSION This study investigated the genetic variants and clinical phenotypes of 22 NF1 families and identified 5 novel variants of the NF1 gene, which has expanded the genotypic and phenotypic spectra of the NF1. Preliminary studies have identified an association between truncated mutations, young age, and severe phenotypes, which may provide important clues for prognosis evaluation. For the clinical diagnosis and treatment of NF1, it is necessary to consider the phenotypic characteristics and genetic testing in combination with genetic counseling and long-term follow-up.
Humans ; Neurofibromatosis 1/pathology* ; Male ; Female ; Pedigree ; Adult ; Child ; Child, Preschool ; Middle Aged ; Adolescent ; Infant ; Young Adult ; Neurofibromin 1/genetics* ; Phenotype ; Asian People/genetics* ; Mutation ; Exome Sequencing ; East Asian People

BACKGROUND:Basketball shoes are one of the most important pieces of athletic equipment in basketball,helping to improve players'performance and reduce the risk of injury.With the development of basketball,the demand for basketball shoe performance is getting higher and higher.OBJECTIVE:To systematically review and summarize the effects of different functional parameters of basketball shoes on the wearer's biomechanical performance,and to investigate the effects of each functional parameter of basketball shoes on athletic performance and injury risk.METHODS:Relevant literature addressing the effect of basketball shoes'functional parameters on human biomechanics from CNKI,WanFang,Web of Science,ScienceDirect and other databases was searched by computer,with the search terms of"basketball,basketball shoe,shoes,footwear,sports biomechanics,kinematics,kinetics"in Chinese and English.All the retrieved literature was evaluated and screened,and finally 61 articles were included for literature review.RESULTS AND CONCLUSION:Existing studies on functional parameters of basketball shoes include shoe collar height and heel counter-stiffness,midsole hardness,midsole cushioning,midsole thickness,forefoot flexural stiffness,whole shoe mass,and outsole traction.The functional parameters of basketball shoes play a role in improving sports performance and reducing the risk of sports injuries:(1)Compared with low-top shoes,high shoe collars can reduce the risk of ankle sprains,but may affect sports performance,ankle proprioception,and increase the load on the knee.(2)Better midsole cushioning or softer midsoles can effectively reduce vertical impact,and the forefoot cushioning structure can effectively improve the athletic performance of lateral movement.(3)The midsole thickness of 11 mm in the forefoot and 20 mm in the rearfoot can obtain the best ankle stability and sprinting performance.(4)Improving the outsole traction and forefoot bending stiffness can significantly improve the performance of jumping,sprinting,and side-cutting.There are diminishing returns to the improvement of athletic performance by improving outsole traction.(5)Lighter basketball shoes can improve athletic performance,but this effect only occurs when the wearer is aware of the shoes'weight.

Psoriasis is a chronic,inflammatory,recurrent,and systemic disease mediated by immune dysregulation,which is often accompanied by psychological issues such as depression and anxiety.Recent research on the gut microbiota and depression and anxiety has made significant progress,with studies demonstrating that the gut microbiota plays a crucial role in the pathogenesis of psoriasis.Dysbiosis of the gut microbiota may be an important comorbidity mechanism linking psoriasis with depression and anxiety.This article summarizes the changes in the abundance of gut microbiota in patients with psoriasis and those with depression and anxiety,as well as how the gut microbiota influences this comorbidity through neural pathways and immune-endocrine pathways.It aims to provide novel perspectives for the study of the comorbidity mechanisms and clinical treatment of psoriasis and depression and anxiety.In the future,targeting the gut microbiota may enable the development of personalized treatments.

ObjectiveTo explore the effect of exercise on anxiety and depression in cancer patients during chemotherapy, as well as the optimal exercise dosage. MethodsA PICO framework was constructed, and randomized controlled trials (RCTs) on the effect of exercise on anxiety and depression in cancer patients during chemotherapy were retrieved from databases of PubMed, Web of Science, Cochrane Library, Embase, Medline, CNKI, VIP and Wanfang data, from the establishment to November, 2023. The quality of the literature was evaluated with Cochrane Risk of Bias Tool and Physiotherapy Evidence Database (PEDro) scale. Data were synthesized and analyzed using RevMan 5.3, and the risk of bias was evaluated using Stata 18.0. ResultsA total of 13 RCTs involving 1 340 subjects were included. The scores of PEDro scale were five to eight. Exercise interventions significantly improved anxiety (SMD = -0.70, 95%CI -1.18 to -0.22, P = 0.004) and depression (SMD = -0.89, 95%CI -1.43 to -0.34, P = 0.002) compared to the control group. Subgroup analyses showed that, the exercise effect on anxiety was less than 45 minutes a time (SMD = -0.26, 95%CI -0.46 to -0.05, P = 0.01), more than three times a week (SMD = -0.26, 95%CI -0.46 to -0.05, P = 0.01), and less than twelve weeks (SMD = -0.21, 95%CI -0.36 to -0.07, P = 0.005). For depression, it was less than 45 minutes a time (SMD = -0.69, 95%CI -1.29 to -0.08, P = 0.03), more than three times a week (SMD = -0.69, 95%CI -1.29 to -0.08, P = 0.03), and less than twelve weeks (SMD = -0.52, 95%CI -0.92 to -0.13, P = 0.01). Moderate to high-intensity exercise interventions significantly outperformed the control group in improving anxiety (SMD = -0.21, 95%CI -0.37 to -0.06, P = 0.007) and depression (SMD = -0.21, 95%CI -0.41 to -0.01, P = 0.04). ConclusionExercise interventions can effectively improve anxiety and depression in cancer patients during chemotherapy, and it suggests for high-intensity exercise, less than 45 minutes a time, more than three times a week, and less than twelve weeks.

BACKGROUND:The use of assistive devices and technologies for blindness is a common intervention for people with visual impairment today,improving participation in activities of daily living and work-learning abilities,and facilitating return to family and society.The forms,technologies and functions of assistive devices for blindness in the age of digital information and intelligence vary,and their classification has not yet been effectively discussed and evaluated in a uniform manner.OBJECTIVE:To classify and evaluate the compensation function of intelligent guide devices for the people with visual impairment in China based on the International Classification of Functioning,Disability and Health(ICF).METHODS:CNKI,CQVIP and WanFang databases were searched for relevant literature.The time frame for the search was from January 1,2013 to December 31,2023.Based on the ICF theoretical model and framework structure,the terminology structure and coding procedure were applied to summarize the relevant visual impairment assessment categories,collate and analyze the research and classification of the compensation function of intelligent assistive devices for the people with visual impairment in China.RESULTS AND CONCLUSION:(1)A total of 197 articles were finally included.There was 1 article on body function,containing b2(b210);1 article on body structure,containing s2(s220);119 articles addressing activity and participation,containing d1(10 articles involving d110,d115,d120,d140,and d166,)d3(4 articles involving d315,d325,d345,and d360),d4(102 articles involving d465,d470),and d8(3 articles involving d820,d825);76 articles addressing environmental factors,including e1(72 articles involving e115,e120,e125,e130,e140,e150,e155,e160)and e2(4 articles involving e210 and e240).(2)The ICF-based research classification of the compensation function of intelligent guide devices for the people with visual impairment contains 4 parts,8 classifications and 25 categories,with areas related to physical compensation,daily necessities,education and learning,traveling and blindness guidance,and layout planning.

BACKGROUND:Basketball shoes are one of the most important pieces of athletic equipment in basketball,helping to improve players'performance and reduce the risk of injury.With the development of basketball,the demand for basketball shoe performance is getting higher and higher.OBJECTIVE:To systematically review and summarize the effects of different functional parameters of basketball shoes on the wearer's biomechanical performance,and to investigate the effects of each functional parameter of basketball shoes on athletic performance and injury risk.METHODS:Relevant literature addressing the effect of basketball shoes'functional parameters on human biomechanics from CNKI,WanFang,Web of Science,ScienceDirect and other databases was searched by computer,with the search terms of"basketball,basketball shoe,shoes,footwear,sports biomechanics,kinematics,kinetics"in Chinese and English.All the retrieved literature was evaluated and screened,and finally 61 articles were included for literature review.RESULTS AND CONCLUSION:Existing studies on functional parameters of basketball shoes include shoe collar height and heel counter-stiffness,midsole hardness,midsole cushioning,midsole thickness,forefoot flexural stiffness,whole shoe mass,and outsole traction.The functional parameters of basketball shoes play a role in improving sports performance and reducing the risk of sports injuries:(1)Compared with low-top shoes,high shoe collars can reduce the risk of ankle sprains,but may affect sports performance,ankle proprioception,and increase the load on the knee.(2)Better midsole cushioning or softer midsoles can effectively reduce vertical impact,and the forefoot cushioning structure can effectively improve the athletic performance of lateral movement.(3)The midsole thickness of 11 mm in the forefoot and 20 mm in the rearfoot can obtain the best ankle stability and sprinting performance.(4)Improving the outsole traction and forefoot bending stiffness can significantly improve the performance of jumping,sprinting,and side-cutting.There are diminishing returns to the improvement of athletic performance by improving outsole traction.(5)Lighter basketball shoes can improve athletic performance,but this effect only occurs when the wearer is aware of the shoes'weight.

BACKGROUND:The use of assistive devices and technologies for blindness is a common intervention for people with visual impairment today,improving participation in activities of daily living and work-learning abilities,and facilitating return to family and society.The forms,technologies and functions of assistive devices for blindness in the age of digital information and intelligence vary,and their classification has not yet been effectively discussed and evaluated in a uniform manner.OBJECTIVE:To classify and evaluate the compensation function of intelligent guide devices for the people with visual impairment in China based on the International Classification of Functioning,Disability and Health(ICF).METHODS:CNKI,CQVIP and WanFang databases were searched for relevant literature.The time frame for the search was from January 1,2013 to December 31,2023.Based on the ICF theoretical model and framework structure,the terminology structure and coding procedure were applied to summarize the relevant visual impairment assessment categories,collate and analyze the research and classification of the compensation function of intelligent assistive devices for the people with visual impairment in China.RESULTS AND CONCLUSION:(1)A total of 197 articles were finally included.There was 1 article on body function,containing b2(b210);1 article on body structure,containing s2(s220);119 articles addressing activity and participation,containing d1(10 articles involving d110,d115,d120,d140,and d166,)d3(4 articles involving d315,d325,d345,and d360),d4(102 articles involving d465,d470),and d8(3 articles involving d820,d825);76 articles addressing environmental factors,including e1(72 articles involving e115,e120,e125,e130,e140,e150,e155,e160)and e2(4 articles involving e210 and e240).(2)The ICF-based research classification of the compensation function of intelligent guide devices for the people with visual impairment contains 4 parts,8 classifications and 25 categories,with areas related to physical compensation,daily necessities,education and learning,traveling and blindness guidance,and layout planning.

Flavonoid 3-O-glucosyltransferase (3GT) is a key enzyme in the glucosidation of anthocyanins. To investigate the 3GT gene in rhododendron, we cloned an open reading frame (ORF) of 3GT gene (named Rh3GT) from Rhododendron hybridum Hort (Red cultivar) and then characterized this gene and the deduced protein in terms of the biochemical characteristics, expression level, and enzymatic function. The results showed that Rh3GT had a full length of 993 bp and encoded 330 amino acid residues. The deduced protein was hydrophilic, stable, weak acid, belonging to the glycosyltransferase family (GT-B type), with glutamine (Q) at position 44 in the PSPG box. The phylogenetic analysis showed that Rh3GT was most closely related to Vc3GT from Vaccinium corymbosum and Vm3GT from Vaccinium myrtillus. Rh3GT was expressed in the stems, leaves, and flowers and almost not expressed in the roots, with the highest expression level in petals during full blooming stage. Introduction of pCAMBIAL1302-Rh3GT into petals significantly up-regulated the expression level of Rh3GT and increased the total anthocyanin accumulation. Rh3GT was successfully expressed in Escherichia coli BL21 in the form of inclusion bodies with a size of about 36 kDa. The results of HPLC showed that the recombinant Rh3GT after denaturation, purification, and dilution could catalyze the synthesis of cyanidin and UDP-glucose to synthesize cyanidin 3-O-glucoside, indicating that the expressed protein had 3GT activity. This study provides basic data for further studying the molecular regulation mechanism of anthocyanin biosynthesis and theoretical support for molecular breeding of rhododendron.
Rhododendron/classification* ; Glucosyltransferases/metabolism* ; Cloning, Molecular ; Escherichia coli/metabolism* ; Recombinant Proteins/biosynthesis* ; Anthocyanins/biosynthesis* ; Phylogeny ; Plant Proteins/metabolism* ; Amino Acid Sequence

OBJECTIVE: To determine the types of genetic variants in six Chinese pedigrees affected with Marfan syndrome (MFS) and analyze their clinical characteristics and molecular pathogenesis. METHODS: Six MFS pedigrees presented at the Taizhou Enze Medical Center (Group) between 2017 and 2022 were selected as the study subjects. Clinical data of pedigrees were retrospectively analyzed. Peripheral blood samples were collected from the probands and their family members for the extraction of genomic DNA. Whole exome sequencing (WES) was carried out. Candidate variants of the FBN1 gene were verified by Sanger sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), pathogenicity of the candidate variants was assessed. AlphaFold3 and PyMOL software were used for homology modeling of the FBN1 protein and analysis of its three-dimensional structure and amino acid sequence conservation. This study was approved by the Medical Ethics Committee of Taizhou Enze Medical Center (Group) (Ethics No. 20231002). RESULTS: Cardiovascular system abnormalities were noted in all pedigrees, ocular abnormalities were present in pedigrees 2 and 5, skeletal system abnormalities were presented in pedigrees 1, and 4 to 6. FBN1 gene mutations were identified in all pedigrees, including c.1957_1958dupGT (p.Asp654fs), c.5014T>A (p.Cys1672Ser), c.8135delC (p.Pro2712fs), c.2302G>T (p.Glu768*), c.3473A>G (p.Glu1158Gly) and c.6169C>T (p.Arg2057*), with each involving a different exon. Four variants were rated as pathogenic, one as likely pathogenic, and one as variant of uncertain significance. Among these, c.5014T>A (p.Cys1672Ser), c.1957_1958dupGT (p.Asp654fs), c.8135delC (p.Pro2712fs), and c.2302G>T (p.Glu768*) were unreported previously. Bioinformatic analysis with SIFT and PolyPhen-2 predicted that the c.5014T>A (p.Cys1672Ser) and c.3473A>G (p.Glu1158Gly) variants were deleterious. Protein homologous sequence alignment analysis revealed that the four novel mutation sites are highly conserved across various species. Homology modeling of the FBN1 protein three-dimensional structure indicated that the six variant sites in the amino acid sequence are all close to hydrogen bonds and may alter the secondary and tertiary structures to varying degrees, thereby confirmed the relationship between the variants and MFS. CONCLUSION Four novel variants of the FBN1 gene have been discovered in this study, which has enriched the mutational and phenotypic spectrum of MFS and provided a basis for disease diagnosis and genetic counseling.
Adolescent ; Adult ; Child ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; China ; East Asian People/genetics* ; Exome Sequencing ; Fibrillin-1/genetics* ; Marfan Syndrome/genetics* ; Mutation ; Pedigree ; Retrospective Studies ; Adipokines

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.