Objective To examine the effect and mechanism of Duhuo Jisheng Decoction on lumbar intervertebral disc degeneration.Methods In total,105 Sprague-Dawley(SD)rats were randomly assigned to seven groups:sham operation group,model group,Duhuo Jisheng Decoction 1,rapamycin group,rapamycin+Duhuo Jisheng Decoction group,MHY1485 group,and MHY1485+Duhuo Jisheng Decoction group.Except for the sham operation group,the other groups underwent annulus fibrosus puncture to establish a lumbar intervertebral disc degeneration(IDD)animal model.After successful model establishment,a six-week drug intervention was performed,followed by MRI evaluation of the degree of disc degeneration.Samples of the L5-6 intervertebral disc were collected for HE and Alcian blue-nuclear fast red staining,and the degeneration of the nucleus pulposus and changes in the extracellular matrix were observed using light microscopy.Simultaneously,the expression levels of the downstream proteins of the mTOR pathway,p70S6K and 4E-BP1,along with the autophagy-related genes Beclin-1 and LC3,were assessed at both the protein and mRNA levels.Autolysosomes in nucleus pulposus cells were visualized using transmission electron microscopy(TEM).Results ①MRI showed disc Pfirrmann grade I in the sham group,and disc Pfirrmann grade Ⅲ-Ⅳ in the remaining 6 groups in L5-6 segments.②The degree of lumbar disc degeneration with histomorphological observation:MHY1485 group>model group>MHY1485 group+Duhuo Jisheng Decoction group>rapamycin group>Duhuo Jisheng Decoction group>rapamycin+Duhuo Jisheng Decoction group>sham group.Allan-nuclear red staining extracellular matrix proteoglycan content:sham group>rapamycin+Duhuo Jisheng Decoction group>rapamycin group>MHY1485 group+Duhuo Jisheng Decoction group>model group>MHY1485 group.③Relative expression of p-mTOR,p70S6K and 4E-BP1 downstream of mTOR signaling pathway:MHY1485 group>MHY1485 group+Duhuo Jisheng Decoction group>model group>rapamycin group>Duhuo Jisheng Decoction group>rapamycin+Duhuo Jisheng Decoction group>sham group,each experimental group varied significantly from the model group(P<0.01).④Autophagy-related protein Beclin-1 and LC3 expression levels:rapamycin+Duhuo Jisheng Decoction group>Duhuo Jisheng Decoction group>rapamycin>MHY1485 group+Duhuo Jisheng Decoction group>model group>MHY1485>sham group,and the content of each group was significantly(P<0.01).⑤TEM observation of autophagy levels in the cells of each group showed the formation of autolysosomes in Duhuo Jisheng Decoction group,rapamycin group andrapamycin+Duhuo Jisheng Decoction group.Conclusion Duhuo Jisheng Decoction can slow down the degenerative process of lumbar intervertebral discs in rats,and its effect may be linked to the suppression of the mTOR signaling pathway and the promotion of autophagy in nucleus pulposus cells.

Objective To examine the effect and mechanism of Duhuo Jisheng Decoction on lumbar intervertebral disc degeneration.Methods In total,105 Sprague-Dawley(SD)rats were randomly assigned to seven groups:sham operation group,model group,Duhuo Jisheng Decoction 1,rapamycin group,rapamycin+Duhuo Jisheng Decoction group,MHY1485 group,and MHY1485+Duhuo Jisheng Decoction group.Except for the sham operation group,the other groups underwent annulus fibrosus puncture to establish a lumbar intervertebral disc degeneration(IDD)animal model.After successful model establishment,a six-week drug intervention was performed,followed by MRI evaluation of the degree of disc degeneration.Samples of the L5-6 intervertebral disc were collected for HE and Alcian blue-nuclear fast red staining,and the degeneration of the nucleus pulposus and changes in the extracellular matrix were observed using light microscopy.Simultaneously,the expression levels of the downstream proteins of the mTOR pathway,p70S6K and 4E-BP1,along with the autophagy-related genes Beclin-1 and LC3,were assessed at both the protein and mRNA levels.Autolysosomes in nucleus pulposus cells were visualized using transmission electron microscopy(TEM).Results ①MRI showed disc Pfirrmann grade I in the sham group,and disc Pfirrmann grade Ⅲ-Ⅳ in the remaining 6 groups in L5-6 segments.②The degree of lumbar disc degeneration with histomorphological observation:MHY1485 group>model group>MHY1485 group+Duhuo Jisheng Decoction group>rapamycin group>Duhuo Jisheng Decoction group>rapamycin+Duhuo Jisheng Decoction group>sham group.Allan-nuclear red staining extracellular matrix proteoglycan content:sham group>rapamycin+Duhuo Jisheng Decoction group>rapamycin group>MHY1485 group+Duhuo Jisheng Decoction group>model group>MHY1485 group.③Relative expression of p-mTOR,p70S6K and 4E-BP1 downstream of mTOR signaling pathway:MHY1485 group>MHY1485 group+Duhuo Jisheng Decoction group>model group>rapamycin group>Duhuo Jisheng Decoction group>rapamycin+Duhuo Jisheng Decoction group>sham group,each experimental group varied significantly from the model group(P<0.01).④Autophagy-related protein Beclin-1 and LC3 expression levels:rapamycin+Duhuo Jisheng Decoction group>Duhuo Jisheng Decoction group>rapamycin>MHY1485 group+Duhuo Jisheng Decoction group>model group>MHY1485>sham group,and the content of each group was significantly(P<0.01).⑤TEM observation of autophagy levels in the cells of each group showed the formation of autolysosomes in Duhuo Jisheng Decoction group,rapamycin group andrapamycin+Duhuo Jisheng Decoction group.Conclusion Duhuo Jisheng Decoction can slow down the degenerative process of lumbar intervertebral discs in rats,and its effect may be linked to the suppression of the mTOR signaling pathway and the promotion of autophagy in nucleus pulposus cells.

BACKGROUND:The incidence of fragility fractures caused by osteoporosis is increasing year by year,and it is urgent to explore its pathophysiology,potential biomarkers,therapeutic targets and effective drugs.There are multiple cells in the bone microenvironment,which are crucial for maintaining bone metabolism.In recent years,single-cell RNA sequencing technology has been developed to characterize the transcriptome of single cells,and has been gradually applied to the study of osteoporosis prevention and treatment.OBJECTIVE:To review the application and progress of single-cell transcriptome sequencing technology in osteoporosis research.METHODS:The first author used a computer search of Web of Science,PubMed database,and CNKI from 2009 to 2023.Chinese and English search terms were "single-cell RNA sequencing,bone marrow derived stromal cells,osteoblasts,osteocytes,osteoclasts,immune cells,bone marrow vascular endothelial cells." Through reading and screening of relevant literature,89 articles were finally included in the review analysis.RESULTS AND CONCLUSION:(1) Single-cell transcriptome sequencing technology can gain an in-depth understanding of the trajectory and regulatory mechanism of cell development,proliferation,differentiation.(2) Candidate genes affecting bone mineral density are mainly concentrated in bone marrow mesenchymal stem cell subpopulation,in which Sox9 is a key transcription factor.(3) The differential expression of Runx2 in different subsets of osteoblasts controls the differentiation of bone marrow mesenchymal stem cells into osteoblasts.(4) RAB38 is related to histone modification and transcriptional regulation during osteoclast differentiation.(5) Studies at the single-cell level have confirmed that there are many kinds of intercellular communication in the bone microenvironment,and osteoclast may conduct intercellular communication through CD160-TNFRSF14 ligand-receptor binding.The neutrocyte/monocyte may interact with osteoblasts through the RESISTIN pathway.Plasma dendritic cells communicate with osteoblast cell lines through the epidermal growth factor pathway.Both can provide directions for target prediction and drug development.(6) An unrecognized capillary subset is called S-type endothelial cells,which originates entirely from the secondary ossification center of the epiphysis,and is even more malleable than H-type blood vessels.(7) This paper reviews the progress of single-cell transcriptome sequencing in characterizing the differentiation fate and differentiation trajectory of different bone tissue cells,identifying new cell subsets,identifying cell regulatory factors,and clarifying intercellular communication from a cellular perspective,so as to provide cell-level information for exploring the pathogenesis of osteoporosis,screening potential diagnostic markers,predicting therapeutic targets,and exploring the mechanism of drug action.(8) In the future,single-cell sequencing technology will provide more valuable information for changes in the bone microenvironment in the direction of single-cell multiomics (genomics,proteomics,and metabolomics) and other technologies such as spatial transcriptome technology.

BACKGROUND:The incidence of fragility fractures caused by osteoporosis is increasing year by year,and it is urgent to explore its pathophysiology,potential biomarkers,therapeutic targets and effective drugs.There are multiple cells in the bone microenvironment,which are crucial for maintaining bone metabolism.In recent years,single-cell RNA sequencing technology has been developed to characterize the transcriptome of single cells,and has been gradually applied to the study of osteoporosis prevention and treatment.OBJECTIVE:To review the application and progress of single-cell transcriptome sequencing technology in osteoporosis research.METHODS:The first author used a computer search of Web of Science,PubMed database,and CNKI from 2009 to 2023.Chinese and English search terms were "single-cell RNA sequencing,bone marrow derived stromal cells,osteoblasts,osteocytes,osteoclasts,immune cells,bone marrow vascular endothelial cells." Through reading and screening of relevant literature,89 articles were finally included in the review analysis.RESULTS AND CONCLUSION:(1) Single-cell transcriptome sequencing technology can gain an in-depth understanding of the trajectory and regulatory mechanism of cell development,proliferation,differentiation.(2) Candidate genes affecting bone mineral density are mainly concentrated in bone marrow mesenchymal stem cell subpopulation,in which Sox9 is a key transcription factor.(3) The differential expression of Runx2 in different subsets of osteoblasts controls the differentiation of bone marrow mesenchymal stem cells into osteoblasts.(4) RAB38 is related to histone modification and transcriptional regulation during osteoclast differentiation.(5) Studies at the single-cell level have confirmed that there are many kinds of intercellular communication in the bone microenvironment,and osteoclast may conduct intercellular communication through CD160-TNFRSF14 ligand-receptor binding.The neutrocyte/monocyte may interact with osteoblasts through the RESISTIN pathway.Plasma dendritic cells communicate with osteoblast cell lines through the epidermal growth factor pathway.Both can provide directions for target prediction and drug development.(6) An unrecognized capillary subset is called S-type endothelial cells,which originates entirely from the secondary ossification center of the epiphysis,and is even more malleable than H-type blood vessels.(7) This paper reviews the progress of single-cell transcriptome sequencing in characterizing the differentiation fate and differentiation trajectory of different bone tissue cells,identifying new cell subsets,identifying cell regulatory factors,and clarifying intercellular communication from a cellular perspective,so as to provide cell-level information for exploring the pathogenesis of osteoporosis,screening potential diagnostic markers,predicting therapeutic targets,and exploring the mechanism of drug action.(8) In the future,single-cell sequencing technology will provide more valuable information for changes in the bone microenvironment in the direction of single-cell multiomics (genomics,proteomics,and metabolomics) and other technologies such as spatial transcriptome technology.

Objective To analyze the clinical characteristics and survival prognosis of patients with AIDS-related malignant tumor. Methods We retrospectively analyzed the data of 354 patients with AIDS-related malignant tumor. Univariate analysis was conducted by Log rank test and multivariate analysis was conducted by Cox proportional risk regression model. Results The average age of the patients was 54.10±12.96 years old. The ratio of male to female patients was 2.1:1. The number of patients with AIDS complicated with lymphoma was the most, accounting for 28.25%. The 1-, 3- and 5-year survival rates were 78.48%, 62.13% and 55.31%, respectively. Univariate analysis showed that there were statistical differences in prognosis of patients with different types of malignant tumor, age, gender, medical insurance type, number of admissions after diagnosis of AIDS, average length of stay, radiotherapy or not, leaving hospital according to medical advice. Multivariate analysis showed that gender, number of admissions after diagnosis of AIDS, average length of stay, proportion of out-of-pocket and leaving hospital according to medical advice were independent risk factors affecting the survival and prognosis of patients. Conclusion AIDS is easily complicated with lymphoma, lung cancer and cervical cancer. The patients received insufficient anti-tumor courses in hospital.

Objective:To explore the risk factors and prognosis of lymph node metastasis and residual cancer following additional surgery after endoscopic submucosal dissection (ESD) in early gastric cancer (EGC).Methods:Retrospective analysis was performed on the data of 42 patients with EGC who received additional surgery after ESD in General Surgery Department of Beijing Friendship Hospital, Capital Medical University from August 2012 to August 2019, including 35 males and 7 females, with a male to female ratio of 5∶1 and an average age of 62 (32 to 82 years old). The primary outcomes were lymph node metastasis risk and residual cancer risk, while the secondary outcomes were 3-year and 5-year overall survival. Logistic regression model was used to analyze the risk factors of lymph node metastasis and residual cancer, and Kaplan-Meier survival analysis was performed.Results:Multivariate analysis showed that gender ( OR: 45.3, 95% CI: 3.762-546.250, P=0.003), invasion depth ( OR: 3.965, 95% CI: 1.1019-15.432, P=0.047) and histological type ( OR: 9.455, 95% CI: 0.946-94.482, P=0.049) were independent risk factors for lymph node metastasis of early gastric cancer. The type of tumor invasion ( OR: 10.675, 95% CI: 1.840-61.932, P=0.008) and the horizontal resection margin ( OR: 9.341, 95% CI: 1.47-59.346, P=0.018) were independent risk factors affecting the occurrence of residual cancer. Stratified analysis showed that in men, the tumor invaded to T 1b-SM1, and the pathological type was undifferentiated; and in women, the tumor invaded to T 1b-SM2, regardless of the pathological type, lymph node metastasis occurred. When the horizontal margin was positive, regardless of the infiltration pattern; and the infiltration pattern is INF-c, regardless of the horizontal margin, residual cancer occurred. Survival analysis showed that the 3-year (100% vs 60%, P< 0.001) and 5-year overall survival rate (100% vs 25%, P< 0.001) were better than those with lymph node metastasis.The 3-year (100% vs 80%) and 5-year overall survival rates (100% vs 62.5%) of patients without residual cancer were significantly better than those with residual cancer, with statistically significant differences ( P<0.001). Conclusions:Gender, invasion depth and histological type are independent risk factors for lymph node metastasis of early gastric cancer, and tumor invasion form and horizontal incision margin are independent risk factors for the appearance of residual cancer. The long-term survival rate of patients with early gastric cancer without lymph node metastasis and residual cancer was significantly better than that of patients with lymph node metastasis and residual cancer. Therefore, ESD is one of the safe and effective treatment methods for patients with early gastric cancer, but some patients need additional surgery according to the specific situation in order to improve the prognosis.

Objective To analyze and explore the value of 3 T high resolution magnetic resonance vessel wall imaging for identifying the activity of Takayasu arteritis. Methods Twenty-six consecutive patients with Takayasu arteritis underwent 3.0 T high resolution MR vessel wall imaging on supraortic vessels (according to the classification of Lupi-Herrea , type Ⅰ and Ⅲ were included). Sixteen patients were in active phase and 10 in inactive phase based on the Kerr criteria. The MR vessel wall imaging appearances of Takayasu arteritis were compared between the active phase and inactive phase cases. Results Wall thickening was demonstrated in all involved arteries. There were statistically significant differences between active phase and inactive phase cases in MR appearances including multi-ring thickening of vessel wall (75/80 and 18/50), arterial inner wail enhancement (50/80 and 19/50), obscurity of perivascular fat (55/80 and 18/50,X<'2>=50.39,7.41,13.40,P<0.01). There was also a statistically significant difference in the thickness of carotid artery wall between the two groups [ (3.8±0.2) mm vs (2.5±0.8) mm]. Conclusion 3 T high resolution MR vessel wall imaging is valuable for identifying the activity of Takayasu arteritis.

Objective To examine the differences in the structure of brain white matter among deficit schizophrenia, nondeficit schizophrenia and healthy controls by using voxel-based morphometry (VBM). Methods Ten deficit schizophrenic patients, eleven nondeficit patients and fifteen healthy comparison subjects participated in the study. All the subjects were scanned by GE Twin Speed 1.5T MRI system. Whole brain, voxel-wise analyses of regional white matter volume were conducted by the VBM toolbox on the Matlab7.6 and SPM5. t -test was then used for the comparison between groups. Results Compared to the healthy controls, nondeficit schizophrenic patients significantly decreased the density of gray matter in the frontal, parietal, temporal, occipital lobe and basal ganglia , while the deficit patients showed the characteristically broad and significant decreasion in the frontal lobe, including left medial frontal gyrus, bilateral inferior frontal gyrus, left middle frontal gyrus, and left orbital gyrus (Cluster ≥ 30 mm3, P<0.01). Moreover, deficit patients showed the decreasion in the temporal cortex and the limbic lobe (right insula). Relative to the nondeficit schizophrenic patients, deficit patients had significant regional gray matter decreases in the left medial frontal gyrus, bilateral inferior frontal gyrus, right precentral gyrus, and right superior temporal gyrus (Cluster ≥ 30 mm3, P<0.01). Conclusion Structural heterogeneity in schizophrenia may relate to specific patterns of gray matter density reductions in deficit and nondeficit patient. However the two subtype of schizophremia patients share a common prefrontal-temperal pattern of structural brain alterations.

Due to the poor repair and regeneration capacity of articular cartilage, traditional treatment cannot get satisfactory curative effect on it. However, tissue engineering provides a new way for repairing articular cartilage defects. Present research focus has come down to the following issues: the stability of cell characters and phenotypes during mass amplification of seed cells, the control of directional differentiation, the combination of multi-scaffold materials, the synergistic effect of multi-growth factors, the gene transfer technology for maintaining the expression of growth factors, etc. This article reviews the advances in seed cells, scaffold materials, growth factors of articular cartilage tissue engineering, pointing out their advantages and disadvantages as well as the research direction in the future.

Objective To analyse the results of Zephir semiconstrained or Window dynamic cervical plates with autogenous cortical bone graft in treating the cervical spondylotic myelophathy(CSM). Methods A retrospective review was performed with 43 patients who underwent anterior cervical discectomy, autogenous cortical bone graft with endplate retaining, fixation with Zephir or Window cervical plates. Follow-up period ranged from 0.5 to 4.0 years (in average of 22 months). The clinical effect, the fusion rate, the intervertebral height and the degeneration of adjacent levels were observed. Results The JOA score after operation was significant higher than that before operation (P