Objective:To reveal the evolutionary characteristics of tissue engineering strategies for spinal cord injury repair from basic research to clinical application, based on the core database of Web of Science.Methods:Key words such as ′′scaffold′′, ′′growth factors′′, ′′stem-cells′′ and ′′progenitors′′ were searched for in the core database of Web of Science before December 31, 2024, with different combinations of keywords used. The search range was set to ′′Topic′′, and the category was ′′Article′′. The original literature data were screened, sorted and formatted using Excel and self-made R program. High-frequency words and annual scientific output were analysed using the Bibliometrix software package. The literature bird online analysis tool was used to screen the high-impact team and draw the author relationship map.Results:A total of 62 142 articles were retrieved, involving multiple disciplines such as biology and medicine. scaffold (17 times), growth factors (9 times) and stem-cells (37 times) were the three most frequently occuring tissue engineering elements in the spinal cord injury. In terms of scientific output in the field of spinal cord injury mechanism research, the number of articles on stem cell-related research began to exceed that of biological scaffolds and growth factors in 2001 (7 articles campared to 1 and 5 articles), and this increase has continued. For over 20 years, the number of stem cell-related articles has consistently outnumbered those on biological scaffolds and growth factors, with the disparity widening over time. Since 2010, the number of articles on growth factor-related research has shown a downward trend, while the number of articles on biological scaffold-related research has increased steadily. Since 2012, the number of articles on biological scaffold-related research (33 articles) has consistently exceeded that of growth factors (22 articles). In the scientific output of clinical research in the field of spinal cord injury, the number of articles on stem cell-related research has gradually increased since 2002 (4 articles), and has consistently outnumbered those on biological scaffolds and growth factors. Since 2011, the number of articles on growth factor-related research has decreased, while the number of articles on biological scaffold-related research has increased. Since 2016, the number of articles on biological scaffold-related research (6 articles) has been higher than that of growth factors (3 articles). Before December 31, 2024, although the number of articles on stem cells was higher than those on growth factors and biological scaffolds (22 and 20 articles), the difference was far less significant than that for mechanism research (101 and 90 articles). The median scientific output of the three-element composite (48 articles) and its respective applications (37 stem cells articles, 33 growth factors articles, 17 biological scaffolds articles) in the field of tissue engineering all appeared in 2011. The scientific output of the three-element composite application in the field of spinal cord injury research was the highest in 2010 (9 articles). Taking 2010 as a boundary point, the research process can be divided into an early and a late stage. Early research focused on a single element, whereas late stage research turned to the composite application of all three elements. Related research results showed a rapid growth trend. Around 2010, the number of articles on the application of the three elements in the field of spinal cord injury was 2 445. The field entered a new period of rapid development around this time, with a growth rate of 9.15%, and has remained stable since then. Around 2010, the discovery and application of induced pluripotent stem cells also began to receive significant attention (496 articles), and related research has remained active ever since. The top five most influential researchers in the field of spinal cord injury neurorestoration were Dai JW (Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, China), Gage FH (Solke Institute of Biology, USA), G?tz M (Biomedical Center of the University of Munich, Germany), Song HJ (Johns Hopkins University School of Medicine, USA), and Shoichet MS (University of Toronto, Canada). Notably, only Dai JW team has published clinical studies exhibiting a head effect in the field.Conclusions:Based on the core database of Web of Science, the development of spinal cord injury was explored. Basic research into biological scaffolds, stem cells and growth factors has developed rapidly, with stem cells and biological scaffold material research being particularly active. The three elements are gradually tending towards multi-strategy combined application. Although research objectives in spinal cord injury have advanced from exploring the basic research of the three elements to clinical transformation, the efficiency with which research results are transformed into clinical practice remains low.

Objective:To explore the coverage of influenza and pneumonia vaccination and factors influencing the vaccination in children.Methods:A cross-sectional questionnaire survey was conducted in children's parents in Beijing and Gansu by using two-stage cluster-sampling to investigate the influenza and pneumonia vaccination rates and influencing factors in children.Results:A total of 2 377 parents were included in the study, and the results indicated that the influenza vaccination coverage was 35.93% and the pneumonia vaccination coverage was 16.58% in children in survey areas, the vaccination rate of both vaccines was 11.65%. The top three reasons for vaccination for both vaccines were being aware of severity of the diseases (influenza vaccine: 36.02%; pneumonia vaccine: 49.61%), being required by school or organization (influenza vaccine: 28.76%; pneumonia vaccine: 25.45%) and being aware of the susceptibility of the diseases (influenza vaccine: 26.41%; pneumonia vaccine: 13.88%). The top three reasons for having no vaccinations were personal unwillingness, concern about vaccine and vaccine accessibility. Families with multi children, living in rural areas and lower family income were the negative factors for both types of vaccinations.Conclusions:The influenza and pneumonia vaccination coverage in children need further improvement, and rural families and families with multi children are the key concern groups for expanding vaccination coverage. Health education about influenza and pneumonia vaccinations, coordinating vaccine supply and decreasing vaccine prices play an important role in improving influenza and pneumonia vaccination coverage.

Objective:To investigate the clinical significance of the transforming growth factor-β receptor I (TGF-βRⅠ) expression in na?ve CD4 + T cells from patients with systemic lupus erythematosus (SLE). Methods:Na?ve CD4 + T cells were purified using magnetic microbeads from peripheral blood mononuclear cells of SLE patients and healthy controls. Real-time quantitative PCR was used to detect TGF-βRⅠ mRNA level, and flow cytometry was used to detect the percentage of CD69 +CD4 + T cells. Data were analyzed by t test and Pearson correlation analysis. Results:The level of TGF-βR Ⅰ mRNA in na?ve CD4 + T cells from SLE patients was significantly lower than that in healthy controls [(0.674±0.873) vs (1.445±1.112), t=2.301, P<0.05]. The TGF-βR Ⅰ mRNA level was negatively correlated with systemic lupus erythematosus disease activity index (SLEDAI) ( r=-0.376, P<0.05), erythrocyte sedimentation rate (ESR) ( r=-0.376, P<0.05), serum creatinine ( r=-0.323, P<0.05) and 24 h urine protein ( r=-0.331, P<0.05), and positively correlated with serum com-plement C3 ( r=0.528, P<0.01). The level of TGF-βRⅠ mRNA level in na?ve CD4 + T cells in SLE patients with renal involvement was lower than that in SLE patients without renal involvement [(0.525±0.536) vs (1.071±1.007), t=2.198, P<0.05]. The TGF-βR Ⅰ mRNA level in the na?ve CD4 + T cells in anti-dsDNA antibody positive group was lower than that in the anti-dsDNA antibody negative group [(0.344±0.315) vs (0.958±1.076), t=2.277, P<0.05]. The expression of TGF-βRⅠ mRNA in na?ve CD4 + T cells from SLE patients was reduced after 24 h stimulation with anti-CD3/CD28 beads [(0.047±0.013) vs (1.008±0.129), t=14.38, P<0.01], which was partially reversed by dexamethasone treatment [(0.240±0.042) vs (0.047±0.013), t=7.845, P<0.01]. Meanwhile, dexamethasone significantly decreased the expression of CD69 in CD4 + T cells [(15.0±2.1)% vs(34.9±2.0)%, t=32.57, P<0.01]. Conclusion:The abnormally low expression of TGF-βRⅠ in na?ve CD4 + T cells may be involved in the pathogenesis of SLE. Glucocorticoid treatment can upregulate the expression of TGF-βRI and inhibit the activation of T cells, This suggests suggesting that TGF-βRⅠ may be a potential target for SLE treatment.

Objective:To explore the clinical efficacy of posterior short-segment internal fixation for the treatment of brucella spondylitis (BS).Methods:The medical records of 34 patients with BS admitted from January 2014 to June 2019 were retrospectively analyzed. There were 22 males and 12 females; the age was 52.3±10.6 years (range 35-72 years). On the basis of standardized use of antibacterial drugs, the lumbar spine posterior short-segment internal fixation was used. Twenty-nine cases underwent simple internal fixation, and posterolateral bone graft fusion, while 5 cases underwent primary debridement, autologous bone grafting and interbody fusion. Monitor erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and test tube agglutination test (SAT) were used to assess inflammation control. Imaging examinations of patients before operation, 1 month after operation, 3 months after operation, 6 months after operation, 1 year after operation to the last follow-up were analyzed to evaluate the condition of intervertebral fusion. The clinical efficacy evaluation was based on the pain visual analog scale (VAS), Japanese Orthopaedic Association (JOA) score, modified MacNab grading, and American Spinal Injury Association (ASIA) grading, as well as surgery-related complications.Results:The operation time of 34 patients was 104.64±16.72 min (range 65-145 min), the average hospital stay was 16.49±7.41 days (range 7-38 d), and the average postoperative follow-up time was 20.2 months (range 12-34 months). At the last follow-up, the ESR and CRP fell to the normal range, and the SAT was negative. At 3 months postoperatively, 11 cases (32.35%) reached Bridwell fusion criteria of grade II, 23 cases (67.65%) of grade III; 3 cases (8.82%) of grade I fusion at 6 months after surgery, 31 cases reached grade II fusion (91.18%); all reached grade I fusion at the last follow-up. After the operation, the symptoms of the waist or lower extremities were significantly relieved. The VAS score was 6.3±1.4 before the operation, 4.1±1.2 at 1 month after the operation, 2.7±1.4 at 3 months after the operation, 1.6±1.0 at 6 months after the operation, and 1.2±0.8 at the last follow-up. The JOA score before surgery was 13.8±2.4, 1 month after surgery 17.6±2.6, 3 months after surgery 21.7±3.1, 6 months after operation 4.9±2.7, and at the last follow-up 25.7±1.8. Compared with the preoperative time nodes of the above indicators, the differences were statistically significant. At the last follow-up, of the 12 patients (2 cases of grade C, 10 cases of grade D) with preoperative neurological dysfunction, 2 cases recovered from grade C to grade D, and 10 cases recovered from grade D to E; the excellent and good rate of modified MacNab grading reached 97.06% (33/34). No extradural hematoma, nerve damage, cerebrospinal fluid leakage and other surgical complications occurred. Only 1 case had wound infection complication, and the prognosis was good after active treatment. There were no recurrences during the follow-up period.Conclusion:On the basis of standardized antimicrobial treatment, posterior lumbar short-segment internal fixation is a safe and effective method for the treatment of BS, and good clinical effects can be obtained.

Objective:Network pharmacology was used to investigate the mechanism of the Sargassum treating thyroid nodule. Methods:The main active ingredients of Sargassum and the targets of active ingredients were obtained by TCMSP, and thyroid nodule disease targets were obtained through GeneCards and OMIM. The STRING database and Cytoscape 3.2.1 software were used to construct the active ingredients-disease-targets network and protein interaction network (PPI). The GO enrichment and KEGG pathway analysis of the targets were analyzed by using R version 4.0.0 software. Results:Two active ingredients were screened from Sargassum and 59 targets were related to thyroid nodule. Biological function analysis showed that the targets of Sargassum included DNA-binding transcription activator activity, RNA polymerase Ⅱ-specific, ubiquitin-like protein ligase binding. Sargassum played an important role in treating thyroid nodule by the gene targets such as RELA, CASP3, IL6, CASP9, EGFR, VEGFA and other targets mediating the signaling pathways such as PI3K-Akt signaling pathway, Kaposi sarcoma-associated herpesvirus infection and other pathways. Conclusion:The potential multi-target and multi-pathway network mechanism of Sargassum in the treatment of thyroid nodule provided theoretical basis for further research.

OBJECTIVE: To investigate the inhibitory effect of epidermal growth factor receptor tyrosine kinase inhibitor (EGFRTKI) HS-10296 on the proliferation of triple-negative breast cancer (TNBC) MDA-MB-231 cells and explore the possible molecular mechanism. METHODS: MDA-MB-231 cells were treated with HS-10296 for 24, 48, or 72 h, and CCK-8 assay was used to assess the changes in the cell viability. The inhibitory effect of HS-10296 on cell proliferation was determined by clonogenic assay. JC-1 and flow cytometry were employed for analyzing the cell apoptosis, and the ultrastructure of the cells was observed under electron microscope. After pretreatment with autophagy inhibitor chloroquine (CQ), MDA-MB-231 cells were divided into control group, CQ treatment group, HS-10296 (4 and 6 μmol/L) treatment groups and combined treatment groups, and the sensitivity of the treated cells to HS-10296 was determined using CCK-8 assay. The effects of HS-10296 on EGFR pathway and apoptosis- and autophagy-related proteins in MDA-MB-231 cells were investigated using Western blotting. RESULTS: HS-10296 significantly inhibited the proliferation of MDA-MB-231 cells with IC values at 24, 48 and 72 h of 8.393, 2.777 and 2.016 μmol/L, respectively. JC-1 and flow cytometry showed that HS-10296 induced obvious apoptosis of MDA-MB-231 cells, which showed an apoptosis rate of (21.63 ± 2.97)% following treatment with 8 μmol/L HS-10296. Autophagy vesicles were observed in the cells treated with HS-10296 under electron microscope. In MDA-MB-231 cells pretreated with CQ, inhibition of autophagy significantly enhanced HS-10296-induced cell death. Western blotting showed that the apoptosis-related protein caspase-3 was activated after HS-10296 treatment to cut its substrate PARP. The expression of autophagy-related protein light chain 3B (LC3B) was significantly enhanced after HS-10296 treatment ( < 0.01), which also resulted in inhibited phosphorylation of EGFR and AKT proteins in the cells. CONCLUSIONS HS-10296 can inhibit the proliferation and induce autophagy and apoptosis of MDA-MB-231 cells by inhibiting the EGFR/PI3K/AKT signaling pathway.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Autophagy ; drug effects ; Breast Neoplasms ; drug therapy ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; ErbB Receptors ; metabolism ; Humans ; Protein Kinase Inhibitors ; pharmacology ; Signal Transduction ; drug effects

OBJECTIVE: To investigate the inhibitory effect of epidermal growth factor receptor tyrosine kinase inhibitor (EGFRTKI) HS-10296 on the proliferation of triple-negative breast cancer (TNBC) MDA-MB-231 cells and explore the possible molecular mechanism. METHODS: MDA-MB-231 cells were treated with HS-10296 for 24, 48, or 72 h, and CCK-8 assay was used to assess the changes in the cell viability. The inhibitory effect of HS-10296 on cell proliferation was determined by clonogenic assay. JC-1 and flow cytometry were employed for analyzing the cell apoptosis, and the ultrastructure of the cells was observed under electron microscope. After pretreatment with autophagy inhibitor chloroquine (CQ), MDA-MB-231 cells were divided into control group, CQ treatment group, HS-10296 (4 and 6 μmol/L) treatment groups and combined treatment groups, and the sensitivity of the treated cells to HS-10296 was determined using CCK-8 assay. The effects of HS-10296 on EGFR pathway and apoptosis- and autophagy-related proteins in MDA-MB-231 cells were investigated using Western blotting. RESULTS: HS-10296 significantly inhibited the proliferation of MDA-MB-231 cells with IC values at 24, 48 and 72 h of 8.393, 2.777 and 2.016 μmol/L, respectively. JC-1 and flow cytometry showed that HS-10296 induced obvious apoptosis of MDA-MB-231 cells, which showed an apoptosis rate of (21.63 ± 2.97)% following treatment with 8 μmol/L HS-10296. Autophagy vesicles were observed in the cells treated with HS-10296 under electron microscope. In MDA-MB-231 cells pretreated with CQ, inhibition of autophagy significantly enhanced HS-10296-induced cell death. Western blotting showed that the apoptosis-related protein caspase-3 was activated after HS-10296 treatment to cut its substrate PARP. The expression of autophagy-related protein light chain 3B (LC3B) was significantly enhanced after HS-10296 treatment ( < 0.01), which also resulted in inhibited phosphorylation of EGFR and AKT proteins in the cells. CONCLUSIONS HS-10296 can inhibit the proliferation and induce autophagy and apoptosis of MDA-MB-231 cells by inhibiting the EGFR/PI3K/AKT signaling pathway.
Apoptosis ; Autophagy ; Breast Neoplasms ; Cell Line, Tumor ; Cell Proliferation ; ErbB Receptors ; Humans ; Phosphatidylinositol 3-Kinases ; Protein Kinase Inhibitors

Objective: To analyze the clinical pathology status of minor differentiated thyroid cancer (DTC). Methods: The clinical pathology data of 107 cases of DTC patients aging≤18 years old who accepted operations at Department of General Surgery, Peking Union Medical College Hospital from January 2000 to December 2016 were collected. There were 27 males and 80 females, aged (15.4±2.7) years (range: 6 to 18 years). And a randomly selected sample′s data was collected as control group, concluded 110 adult DTC patients. There were 35 males and 75 females, aged (43.2±11.8) years (range: 21 to 77 years). The clinical and pathological data of the two groups were retrospectively analyzed. The t test, Mann-Whitney U test, χ² test and Fisher exact test was used to analyze the data, respectively. Results: The minor patients had larger diameter of tumors ((16.5±9.9) mm vs. (8.7±5.1) mm, t=7.369, P=0.000), higher rate of lymph node metastasis (68.2% vs. 50.0%, χ²=7.446, P=0.006) and higher rate of lateral lymph node metastasis (36.4% vs. 11.8%, χ²=18.059, P=0.000) than adult patients. The rate of lateral lymph node metastasis was significantly higher when minor presented multiple fociin primary lesions (54.3% vs. 27.8%, χ²=7.144, P=0.008) than those with single foci lesions. Adult patients presented more capsular invasion than minor patients in primary lesions (55.6% vs. 19.2%, χ²=28.942, P=0.000). Conclusions The minor DTC patients present more progress disease status when they receive operations compared with the adult DTC patients. Minor DTC patients appeared as multiple foci should be alert to lateral lymph node metastasis.

Objective To establish and assess the new method of APTT assay based on the combinations of Mg2+and Ca2+for lupus anticoagulants(LA)measurements.Methods This prospective study included 309 trisodium citrate anticoagulated plasma samples from 244 random patients and 65 patients with different autoimmune diseases(AID)to establish and assess the method of LA measurement, respectively.Final concentrations of 0,2.0, 4.0, 8.0,16.0 mmol/L Mg2+were added into 25 mmol/L Ca2+solution, and Actin reagent was used to measured plasma APTT of 94 patients.The applied concentration of Mg2+-Ca2+solution was confirmed through the special and significant alteration of APTT from LA-positive and -negative plasma observed in the presence of Mg 2+(test solution).Based on Actin reagent use,the test solution and 25 mmol/L Ca2+solution were applied to measure APTT of patients and normal individuals, respectively, and the ratio of Mg2+-Ca2+-APTT to Ca2+-APTT(Mg2+-Ca2+-APTT indices)and normalized Mg2+-Ca2+-APTT indices(NAR)were calculated, respectively.Mixed plasma NAR was measured,and CV%was calculated to evaluate the repeatability and stability of Mg 2+-Ca2+-APTT method.APTT of 150 patients was measured with the test solution and Actin reagent to calculate Mg 2+-Ca2+-APTT indices, and normalized LA ratio was determined with dRVVT method.The applicability of Mg2+-Ca2+-APTT assay was assessed through comparisons of the results from the two methods.Finally, NAR and NLR of 65 patients with AID(including 26 SLE patients)were measured with Mg2+-Ca2+-APTT assay and dRVVT method, respectively, and ROC curve was also used to assess the efficacy of the two methods for LA measurements.Results In all LA-negative plasma,APTT increased from 28.1 ±4.5 s to 61.2 ±7.9 s in normal APTT group,47.2 ±8.9 s to 97.5 ±10.3 s in increased APTT group,and 27.6 ± 5.1 s to 61.2 ±7.9 s in ACA-positive group when Mg2+increased from 0 to 8 mmol/L in Mg2+-Ca2+solution(F=34.12, 38.9 and 28.35,P<0.01).Following increased Mg2+concentration, APTT shortened from 0 to 4.0 mmol/L, but simultaneously prolonged from 4.0 to 16.0 mmol/L in LA-positive plasma with prolonged or normal APTT(F=31.55 and 39.51, P<0.01), and APTT was significantly higher in 8.0 mmol/L than that in 4.0 mmol/L(P<0.001).The test concentration of Mg 2+/Ca2+solution was 4.0 mmol/L.The within, inter-day CV% of NAR was 1.39%,2.30%, and 3.44%, respectively. According to the judging criteria of <0.966 and >1.034 of Mg2+/Ca2+indices, there was 141 patients with increased indices and NLR <1.20, and 9 patients with decreased ones and NLR≥1.20 in all 150 patients.The area under ROC curve of NAR and NLR for LA detection was 0.913(95%CI:0.848-0.978) and 0.892(95%CI:0.817-0.966), respectively, and the cut-off value was 0.87 and 1.13, respectively. The sensitivity and specificity of NAR(85% and 77%)was higher than that of NLR(81% and 74%), respectively.The accordant rate of positive,negative,and total results between NAR and NLR was 94.4%, 98.5%,and 98%,respectively.Conclusion The method of APTT assay based on Mg2+combining Ca2+for LA measurements is feasible,and can be used to detect plasma LA of patients.

ObjectiveTo explore the changes of degree attribute values and its significance of post-concussion syndrome (PCS) patients with tinnitus by the brain network research method based on graph theory.Methods34 PCS patients were chosen,including 17 PCS patients with bilateral tinnitus (PCS tinnitus group) and 17 PCS patients without tinnitus (PCS non-tinnitus group).Meanwhile,17 healthy individuals with the matched age,gender and educational background were recruited as the control.Degree attribute values of PCS patients with tinnitus were figured out with the brain network research method based on graph theory.Results(1)The degree attribute values of PCS patients without tinnitus at left orbital middle frontal gyrus (3.13±1.07),left thalamus (2.51±1.03),left superior temporal gyrus (3.67±1.31),right anterior cingulate cortex (3.13±1.25),right posterior cingulate cortex (2.13±1.08) and right supramarginal gyrus (4.46±1.35) were reduced compared with the control group (4.41±1.47,3.71±1.08,5.27±2.13,5.51±0.67,5.63±2.16 and 5.64±1.30) (P<0.05).The degree attribute values of PCS patients without tinnitus at left posterior cingulate cortex (5.87±1.06) and left gyrus lingualis (4.67±1.48) increased compared with the control group (4.41±1.46,3.21±1.27) (P<0.05).(2) The degree attribute values of PCS patients with tinnitus at left posterior cingulate cortex (3.37±1.54),left parahippocampal gyrus (3.41±1.62),left amygdala (2.25±1.43),left angular gyrus (4.17±1.02),left superior temporal gyrus (3.25±1.02),right thalamus (2.35±1.34),right Heschl gyri (3.97±1.62),right superior temporal gyrus (3.26±1.22),right cuneus (3.18±1.32) and right lingular lobe (3.26±1.42) were decreased,compared with the control group (4.41±1.46,5.27±2.13,3.71±1.08,5.63±2.61,5.64±1.30,3.43±1.33,5.63±2.16,5.13±1.64,5.51±0.67,4.24±0.63) (P<0.05).The degree attribute values of PCS patients with tinnitus at right posterior cingulate cortex (5.76±1.83),left MPFC (6.08±1.62) and right precuneus (6.08±1.06) were increased,compared with the control group (4.47±1.26,4.41±1.47,4.81±0.62) (P<0.05).(3)The degree attribute values of PCS patients with tinnitus at left MPFC,left amygdale,left parahippocampal gyrus,right Heschl gyri,right superior temporal gyrus,right cuneus and right lingular lobe were decreased,compared with PCS patients without tinnitus (P<0.05).The degree attribute values of PCS patients with tinnitus at right posterior cingulate cortex and left insular lobe increased,compared with PCS patients without tinnitus (P<0.05).ConclusionsPCS patients with tinnitus present the alteration of degree attribute in related brain network structure.The alteration in degree attribute of relevant brain zones in auditory system,limbic system and default network system may be important factors which result in tinnitus of PCS patients.