BACKGROUND:Previous studies of the research group have found that icariin-containing serum can delay the progression of knee osteoarthritis,promote chondrocyte proliferation and stem cell cartilage differentiation in rats,but there is still a lack of sufficient basis for clinical application.OBJECTIVE:To investigate the repair effect of icariin-containing serum on lipopolysaccharide-induced inflammatory damage of human chondrocytes.METHODS:The effect of icariin-containing serum on chondrocyte viability was detected by cell counting kit-8 method,and the optimal volume fraction and time of icariin-containing serum were screened.The cells were then divided into blank group,lipopolysaccharide group,icariin-containing serum group and lipopolysaccharide+icariin-containing serum group.After grouping,immunofluorescence was used to detect the secretion of type Ⅱ collagen in chondrocytes in each group.Real-time PCR was used to detect the expression of related genes.RESULTS AND CONCLUSION:(1)Icariin-containing serum showed good biosafety characteristics for human chondrocytes,and the cell viability reached the highest level after 48 hours of intervention when the icariin-containing serum volume fraction was 15％,and the follow-up experiments were carried out according to the conditions.(2)Compared with the blank group,lipopolysaccharide significantly inhibited the expression of type Ⅱ collagen in chondrocytes,while icariin-containing serum showed a positive mobilization effect,which could effectively promote the secretion of type Ⅱ collagen in chondrocytes under normal and inflammatory conditions.(3)The mRNA expression of type Ⅱ collagen and Aggrecan in chondrocytes decreased significantly under lipopolysaccharide stimulation,and the mRNA expression levels of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 increased significantly.Icariin-containing serum promoted the mRNA expression of type Ⅱ collagen in human chondrocytes under inflammatory conditions and reduced the mRNA expression of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 in chondrocytes after lipopolysaccharide intervention.Therefore,these findings indicate that the icariin-containing serum has good safety for human chondrocytes and plays an important role in maintaining the normal physiological functions of chondrocytes,promoting the synthesis of extracellular matrix,and inhibiting the secretion of inflammatory factors.

BACKGROUND:Previous studies of the research group have found that icariin-containing serum can delay the progression of knee osteoarthritis,promote chondrocyte proliferation and stem cell cartilage differentiation in rats,but there is still a lack of sufficient basis for clinical application.OBJECTIVE:To investigate the repair effect of icariin-containing serum on lipopolysaccharide-induced inflammatory damage of human chondrocytes.METHODS:The effect of icariin-containing serum on chondrocyte viability was detected by cell counting kit-8 method,and the optimal volume fraction and time of icariin-containing serum were screened.The cells were then divided into blank group,lipopolysaccharide group,icariin-containing serum group and lipopolysaccharide+icariin-containing serum group.After grouping,immunofluorescence was used to detect the secretion of type Ⅱ collagen in chondrocytes in each group.Real-time PCR was used to detect the expression of related genes.RESULTS AND CONCLUSION:(1)Icariin-containing serum showed good biosafety characteristics for human chondrocytes,and the cell viability reached the highest level after 48 hours of intervention when the icariin-containing serum volume fraction was 15％,and the follow-up experiments were carried out according to the conditions.(2)Compared with the blank group,lipopolysaccharide significantly inhibited the expression of type Ⅱ collagen in chondrocytes,while icariin-containing serum showed a positive mobilization effect,which could effectively promote the secretion of type Ⅱ collagen in chondrocytes under normal and inflammatory conditions.(3)The mRNA expression of type Ⅱ collagen and Aggrecan in chondrocytes decreased significantly under lipopolysaccharide stimulation,and the mRNA expression levels of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 increased significantly.Icariin-containing serum promoted the mRNA expression of type Ⅱ collagen in human chondrocytes under inflammatory conditions and reduced the mRNA expression of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 in chondrocytes after lipopolysaccharide intervention.Therefore,these findings indicate that the icariin-containing serum has good safety for human chondrocytes and plays an important role in maintaining the normal physiological functions of chondrocytes,promoting the synthesis of extracellular matrix,and inhibiting the secretion of inflammatory factors.

Objective To investigate the differences of brain imaging changes in patients with mesial temporal lobe epilepsy(mTLE)based on individual structural covariance networks of gray matter volume.Methods A total of 74 mTLE patients,including 39 patients in the left mTLE group and 35 patients in the right mTLE group,along with 46 healthy controls(control group),had completed 3D T1WI structural imaging scans.The network template perturbation approach was used to analyze the individualized structural covariance networks in patients with mTLE.Results Compared with the control group,the left and right mTLE groups showed decreased structural covariance connections for the ipsilateral hippocampus to the contralateral hippocampus and parahippocampal gyrus,orbitofrontal gyrus,middle frontal gyrus,superior parietal gyrus,amygdala and fusiform gyrus.In addition,increased structural covariation connections was mainly distributed in the bilateral frontal lobe,parietal lobe,temporal lobe,occipital lobe and paralimbic system in the right mTLE group,whereas increased structural covariation connections was mainly located within the left frontal lobe,parietal lobe and occipital lobe in the left mTLE group(P＜0.05).Compared with the left mTLE group,the right mTLE group showed decreased structural covariance connections with the ipsilateral hippocampus as a core node(P＜0.05).Conclusion Compared with the left mTLE group,the right mTLE group showed more pronounced decreased structural covariance connections centered around the ipsilateral hippocampus,as well as a more intricate compensatory mechanism.The pattern of the individual structural covariance networks in mTLE patients not only contribute to understanding of its pathogenesis but also served as a potential biomarker for clinical diagnosis.

Objective To investigate the differences of brain imaging changes in patients with mesial temporal lobe epilepsy(mTLE)based on individual structural covariance networks of gray matter volume.Methods A total of 74 mTLE patients,including 39 patients in the left mTLE group and 35 patients in the right mTLE group,along with 46 healthy controls(control group),had completed 3D T1WI structural imaging scans.The network template perturbation approach was used to analyze the individualized structural covariance networks in patients with mTLE.Results Compared with the control group,the left and right mTLE groups showed decreased structural covariance connections for the ipsilateral hippocampus to the contralateral hippocampus and parahippocampal gyrus,orbitofrontal gyrus,middle frontal gyrus,superior parietal gyrus,amygdala and fusiform gyrus.In addition,increased structural covariation connections was mainly distributed in the bilateral frontal lobe,parietal lobe,temporal lobe,occipital lobe and paralimbic system in the right mTLE group,whereas increased structural covariation connections was mainly located within the left frontal lobe,parietal lobe and occipital lobe in the left mTLE group(P＜0.05).Compared with the left mTLE group,the right mTLE group showed decreased structural covariance connections with the ipsilateral hippocampus as a core node(P＜0.05).Conclusion Compared with the left mTLE group,the right mTLE group showed more pronounced decreased structural covariance connections centered around the ipsilateral hippocampus,as well as a more intricate compensatory mechanism.The pattern of the individual structural covariance networks in mTLE patients not only contribute to understanding of its pathogenesis but also served as a potential biomarker for clinical diagnosis.

Liposomes have made remarkable achievements as drug delivery vehicles in the clinic. Liposomal products mostly benefited from remote drug loading techniques that succeeded in amphipathic and/or ionizable drugs, but seemed impracticable for nonionizable and poorly water-soluble therapeutic agents, thereby impeding extensive promising drugs to hitchhike liposomal vehicles for disease therapy. In this study, a series of weak acid drug derivatives were designed by a simplistic one step synthesis, which could be remotely loaded into liposomes by pH gradient method. Cabazitaxel (CTX) weak acid derivatives were selected to evaluate regarding its safety profiles, pharmacodynamics, and pharmacokinetics. CTX weak acid derivative liposomes were superior to Jevtana® in terms of safety profiles, including systemic toxicity, hematological toxicity, and potential central nerve toxicity. Specifically, it was demonstrated that liposomes had capacity to weaken potential toxicity of CTX on cortex and hippocampus neurons. Significant advantages of CTX weak acid derivative-loaded liposomes were achieved in prostate cancer and metastatic cancer therapy resulting from higher safety and elevated tolerated doses.

OBJECTIVETo identify potential disease-causing mutation in the COL2A1 gene in a Chinese family affected with autosomal dominant spondyloepiphyseal dysplasia congenita (SEDC; OMIM 183900) and to analyze the phenotype-genotype correlation.

METHODSComplete physical, and radiographic examinations of 4 affected individuals from the family were conducted. Genomic DNA was isolated from peripheral blood leukocytes. Whole-exome sequencing was performed using a HiSeq2000 sequencer. All 54 exons and exon-intron boundaries of the COL2A1 gene were amplified by polymerase chain reaction (PCR) and bidirectionally sequenced.

RESULTSAll of the 4 individuals were found to carry a novel missense mutation of c.2224G>A (p.Gly687Ser) in the COL2A1 gene, while the same mutation was not found in the normal members of the family and 50 healthy controls. Protein prediction of missense mutation by Polyphen-2 and SIFT software indicated severe damage to the function.

CONCLUSIONThe mutation c.2224G>A (p.Gly687Ser) of the COL2A1 gene is responsible for this family. There are heterozygous of phenotype for the mutation.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; Collagen Type II ; genetics ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation, Missense ; Osteochondrodysplasias ; congenital ; genetics ; Pedigree ; Point Mutation ; Young Adult

Objective To compare the features of activity and participation difficulty of children with cerebral palsy, intellectual disability and autism. Methods 42 children with cerebral palsy, intellectual disability, and autism aged 3-6 years were evaluated with ICF-CY Questionnaire. Results There were mild barriers in the domains of learning and applying knowledge, communication, mobility, self-care, domestic life and major life areas, and the moderate barriers in the domains of general tasks and demands, interpersonal interactions and relations. There were more barriers in learning and applying knowledge in children with cerebral palsy and intellectual disability than those with autism. Conclusion There are various features in activity and participation difficulty in children with cerebral palsy, intellectual disability or autism, which required diversity of educational rehabilitation strategies.

Objective To investigate the changes of brain tissue in bilateral temporal lobes at different stages after nasopharyngeal carcinoma radiotherapy by diffusion tensor imaging(DTI)and 1H-MR spectroscopy(1H-MRS).Methods DTI and 1H-MRS were performed in 48 patients with nasopharyngeal carcinoma.in which conventional MRI revealed normal findings after radiotherapy.Twenty-four healthy controls were enrolled in this study and underwent the galne MR scanning.After the image processing and spectral analysis,apparent diffusion coefficient(ADC),fractional anisotropy(FA) and 3 eigenvalue λ1,λ2,λ3 of DTI and the NAA/Cho,NAA/Cr,Cho/Cr of 1H-MRS were measured in bilateral temporal lobes.Forty-eight NPC patients were divided into 3 groups [ less than 6 months(16 cases),6 to 12 months (6 cases)and more than 12 months(26 cases)after radiotherapy]according to different stages of radiationinduced injury of brain.each group's DTI and 1H-MRS data were measured respectively and one-way ANOVA was applied to analyze each parameter. Results The FA value of each test group(less than 6 months.6 to 12 months and more than 12 months)and the control group were 0.445±0.017,0.460±0.016,0.461±0.025,0.473±0.023 respectively.The ADC values of each group were(8.51±0.43)×10-4.(8.48±0.34)×10-4,(8.40±0.33)×10-4,(8.68±0.57)×10-4mm2/s respectively.And the maximum eigenvalue λ1 of each group were(1.251±0.065)× 10-3,(1.293±0.051)×10-3,(1.317±0.074)×10-3,(1.350±0.091)× 10-3mm2/s.The three indicators were significantly difrerent among groups(F=10.873,3.399,9.750 respectively,P<0.05).λ2,λ3 values showed no significant difference among the groups.The NAA/Cho of 1H-MRS of each groups were0.910±0.112,0.972±0.101,1.060±0.095,1.261±0.105 respectively,and the NAA/Cr were 1.212±0.236,1.208±0.183,1.228±0.236,1.435±0.225 respectively.Both of them had significant differences among groups(F=52.840,8.176 respectively,P<0.01).Cho/Cr showed no significant difference among the groups.Conclusions DTI combining with 1H-MRS play a certain guiding role on monitoring and evaluating of radiation injury of brain tissue in nasopharyngeal carcinoma after radiotherapy.It Can provide a scientific basis for the dynamic monitoring of radiation brain injury.