Objective To compare the colonoscopy results of patients with positive fecal SDC2,ADHFE1,and PPP2R5C gene methylation tests to those with positive fecal occult blood tests,and analyze the effectiveness of colorectal cancer(CRC)screening.This study aims to provide a scientific basis for risk assessment in CRC screening.Methods From December 2023 to May 2024,9 284 combined test kits for SDC2,ADHFE1,and PPP2R5C gene methylation were distributed to high-risk individuals aged 40～80 years.Among them,841 patients(9.1％)tested positive.These patients were encouraged via telephone to undergo colonoscopy,with colonoscopy combined with pathological diagnosis as the gold standard,a total of 495 positive patients completed electronic colonoscopy.Among them,the 251 patients who tested positive for fecal SDC2,ADHFE1,and PPP2R5C gene methylation and completed electronic colonoscopy were the observation group;concurrently,244 patients who tested positive for fecal occult blood tests and underwent electronic colonoscopy were selected as the control group.Compare two groups of patients with polyp,number,shape,pathological changes and pathological types.Results There was no statistically significant difference in number and lesion location of polyps between the two groups of patients(P>0.05).The proportion of Yamada type Ⅰ in the observation group was lower than that in the control group,while the proportion of Yamada type Ⅱ was higher than that in the control group.The difference was statistically significant(P<0.05).In the observation group,1 case(0.4％)of CRC,62 cases(24.7％)of advanced adenomas,78 cases(31.1％)of non-advanced adenomas,20 cases(8.0％)of hyperplastic polyps,and 90 cases(35.9％)with no dysplastic lesions were identified.In the control group,6 cases(2.5％)of CRC,38 cases(15.6％)of advanced adenomas,53 cases(21.7％)of non-advanced adenomas,19 cases(7.8％)of hyperplastic polyps,and 128 cases(52.5％)with no dysplastic lesions were identified.The proportions of non-advanced adenomas and advanced adenomas were lower in the control group than those in the observation group,while the no dysplastic lesions rate was higher in the control group,the differences were statistically significant(P<0.05).Conclusion The detection rate of colorectal non-advanced adenomas and advanced adenomas is higher with fecal SDC2,ADHFE1,and PPP2R5C gene methylation testing compared to the fecal occult blood test.

BACKGROUND:The development of calcium phosphate bone cement is limited due to its poor mechanical properties and weak osteogenic ability.Silicate bioactive glass is highly favored due to its excellent biological activity and osteogenic ability.Simultaneously,fiber structures can enhance the mechanical strength of materials.OBJECTIVE:To investigate the mechanical properties,biocompatibility,and osteogenic effect of silicate bioactive glass fiber composite calcium phosphate bone cement.METHODS:Different mass percentages(0％,10％,and 20％)of silicate bioactive glass fiber were added to the solid phase of calcium phosphate bone cement,mixed with the liquid phase and cured for 48 hours to obtain silicate bioactive glass fiber composite calcium phosphate bone cement.The mechanical properties,setting time,and ion precipitation of the cement were characterized.The three groups of bone cement extracts were co-cultured with MC3T3-E1 cells.The cell compatibility of the materials was evaluated by CCK-8 assay,live/dead staining,and phalloidin staining.After osteogenic induction,the osteogenic induction ability of the materials was evaluated by alkaline phosphatase staining,alizarin red staining,RUNX2 immunofluorescence staining,and RT-PCR.RESULTS AND CONCLUSION:(1)With the increase of silicate bioactive glass fiber content,the compressive strength and flexural strength of bone cement increased,and the setting time was prolonged.When bone cement was immersed in simulated body fluid,the precipitation of silicon ions,calcium ions,and phosphorus ions could be detected.Moreover,with the increase of silicate bioactive glass fiber content,the mass concentration of silicon ions and phosphorus ions released by bone cement increased,and the mass concentration of calcium ions decreased.(2)Live/dead staining and phalloidin staining results exhibited that silicate bioactive glass fiber composite calcium phosphate bone cement had no toxic effect on MC3T3-E1 cells.CCK-8 assay results showed that silicate bioactive glass fiber composite calcium phosphate bone cement could promote the proliferation of MC3T3-E1 cells.(3)With the increase of silicate bioactive glass fiber content in bone cement,the alkaline phosphatase activity and extracellular calcium deposition of MC3T3-E1 cells increased,the expression of RUNX2 protein increased,and the expression of alkaline phosphatase,osteocalcin,osteopontin,and RUNX2 mRNA expression increased.(4)The results indicate that silicate bioactive glass fibers can enhance the mechanical properties and osteogenic induction ability of calcium phosphate bone cement,among which 20％silicate bioactive glass fibers have a more obvious effect.

Objective:To analyze the clinical efficacy and learning curve for robot-assisted cortical bone trajectory (CBT) screw fixation performed by surgeons with different seniority in the treatment of lumbar degenerative disease.Methods:The clinical data of 91 lumbar degenerative disease patients underwent robot-assisted CBT screw fixation from August 2020 to December 2022 in Beijing Shijitan Hospital, Capital Medical University were retrospectively analyzed. Among them, 48 patients underwent surgery performed by the same senior surgeon (senior group), with a total of 234 CBT screws were placed; while 43 patients underwent surgery performed by the same junior surgeon (junior group), with a total of 206 CBT screws were placed. The surgical related indexes, functional improvement score, lower back pain and lower limb radiation pain scores, acceptable nail insertion rate, non invasion rate of facet joints and incidence of postoperative complications were compared between two groups. The functional improvement score was evaluated using the Japanese Orthopaedic Association (JOA) score, the pain score was evaluated using visual analog score (VAS). The cumulative sum (CUSUM) method was used to depict the learning curve with "single screw placement time" as the observation index.Results:There were no statistical difference in incision length, operation time, intraoperative blood loss and postoperative hospital stay between two groups ( P>0.05). The least squares means of JOA scores 1, 3 and 6 months after surgery in both groups increased significantly compared to baseline, while the least squares means of lower back pain VAS and lower limb radiation pain VAS decreased significantly compared to baseline; there were no statistical differences between two groups ( P>0.05). There were no statistical difference in acceptable nail insertion rate, non invasion rate of facet joints and incidence of postoperative complications between two group ( P>0.05). The CUSUM learning curves were fitting well and the inflection point for senior surgeon corresponded to 18 cases, while it was reached after performing surgery on 21 cases for junior surgeon. Conclusions:Robot-assisted CBT screw fixation performed by surgeons with different seniority could achieve similar clinical outcomes for treating lumbar degenerative disease. The senior surgeons are able to complete the initial learning stage faster than the junior surgeons, but there is not much difference in the number of surgeries performed the learning curve.

Objective:To compare the effectiveness and safety between robot-assisted percutaneous kyphoplasty (PKP) and traditional fluoroscopy-assisted PKP in the treatment of dual-segment recurrent osteoporotic vertebral compression fracture (OVCF) including in situ vertebral fracture.Methods:The clinical data of 33 patients with dual-segment recurrent OVCF including in situ vertebral fracture from January 2016 to January 2023 in Beijing Shijitan Hospital Affiliated to Capital Medical University were retrospectively analyzed. All the patients were treated with PKP. Among them, 14 patients were treated with robot-assisted surgery (robot-assisted group), and 19 patients were treated with fluoroscopy-assisted surgery (fluoroscopy-assisted group). The total surgical time, preparation time and number of fluoroscopy were recorded. The in situ and other fracture vertebral operation time, number of punctures, amount of bone cement injection, bone cement filling effect, bone cement leakage, pedicle wall breakthrough and other special intraoperative situations were separately recorded. The visual analogue score (VAS) before surgery and 1 d, 3 months after surgery was recorded.Results:The preparation time in robot-assisted group was significantly longer than that in fluoroscopy-assisted group: (30.8 ± 6.9) min vs. (19.1 ± 4.5) min, the number of fluoroscopy was significantly lower than that in fluoroscopy-assisted group: (17.1 ± 4.1) times vs. (41.0 ± 6.3) times, and there were statistical differences ( P<0.01 and <0.05); there were no statistical differences in total surgical time and VAS at any time point between the two groups ( P>0.05). For the in situ fracture segment, the operation time and number of punctures in robot-assisted group were significantly lower than those in fluoroscopy-assisted group: (15.4 ± 2.8) min vs. (22.0 ± 5.5) min and (1.1 ± 0.4) times vs. (2.4 ± 1.2) times, the amount of bone cement injection was significantly higher than those in fluoroscopy-assisted group: (2.36 ± 0.75) ml vs. (1.79 ± 0.69) ml, the filling effect of bone cement was significantly better than that in fluoroscopy-assisted group, and there were statistical differences ( P<0.01 and <0.05); there were no statistical difference in bone cement leakage and pedicle wall breakthrough between the two groups ( P>0.05). For the other fracture segment, the operation time in robot-assisted group was significantly shorter than that in fluoroscopy-assisted group: (13.8 ± 3.8) min vs. (19.2 ± 6.4) min, and there was statistical difference ( P<0.01); there were no statistical difference in number of punctures, amount of bone cement injection, filling effect of bone cement, bone cement leakage and pedicle wall breakthrough between the two groups ( P>0.05). Conclusions:Robot-assisted PKP in the treatment of dual-segment OVCF including in situ vertebral fracture, could reduce operation time, minimize punctures and fluoroscopy numbers, and provide superior bone cement filling results.

Objective To compare the colonoscopy results of patients with positive fecal SDC2,ADHFE1,and PPP2R5C gene methylation tests to those with positive fecal occult blood tests,and analyze the effectiveness of colorectal cancer(CRC)screening.This study aims to provide a scientific basis for risk assessment in CRC screening.Methods From December 2023 to May 2024,9 284 combined test kits for SDC2,ADHFE1,and PPP2R5C gene methylation were distributed to high-risk individuals aged 40～80 years.Among them,841 patients(9.1％)tested positive.These patients were encouraged via telephone to undergo colonoscopy,with colonoscopy combined with pathological diagnosis as the gold standard,a total of 495 positive patients completed electronic colonoscopy.Among them,the 251 patients who tested positive for fecal SDC2,ADHFE1,and PPP2R5C gene methylation and completed electronic colonoscopy were the observation group;concurrently,244 patients who tested positive for fecal occult blood tests and underwent electronic colonoscopy were selected as the control group.Compare two groups of patients with polyp,number,shape,pathological changes and pathological types.Results There was no statistically significant difference in number and lesion location of polyps between the two groups of patients(P>0.05).The proportion of Yamada type Ⅰ in the observation group was lower than that in the control group,while the proportion of Yamada type Ⅱ was higher than that in the control group.The difference was statistically significant(P<0.05).In the observation group,1 case(0.4％)of CRC,62 cases(24.7％)of advanced adenomas,78 cases(31.1％)of non-advanced adenomas,20 cases(8.0％)of hyperplastic polyps,and 90 cases(35.9％)with no dysplastic lesions were identified.In the control group,6 cases(2.5％)of CRC,38 cases(15.6％)of advanced adenomas,53 cases(21.7％)of non-advanced adenomas,19 cases(7.8％)of hyperplastic polyps,and 128 cases(52.5％)with no dysplastic lesions were identified.The proportions of non-advanced adenomas and advanced adenomas were lower in the control group than those in the observation group,while the no dysplastic lesions rate was higher in the control group,the differences were statistically significant(P<0.05).Conclusion The detection rate of colorectal non-advanced adenomas and advanced adenomas is higher with fecal SDC2,ADHFE1,and PPP2R5C gene methylation testing compared to the fecal occult blood test.

BACKGROUND:The development of calcium phosphate bone cement is limited due to its poor mechanical properties and weak osteogenic ability.Silicate bioactive glass is highly favored due to its excellent biological activity and osteogenic ability.Simultaneously,fiber structures can enhance the mechanical strength of materials.OBJECTIVE:To investigate the mechanical properties,biocompatibility,and osteogenic effect of silicate bioactive glass fiber composite calcium phosphate bone cement.METHODS:Different mass percentages(0％,10％,and 20％)of silicate bioactive glass fiber were added to the solid phase of calcium phosphate bone cement,mixed with the liquid phase and cured for 48 hours to obtain silicate bioactive glass fiber composite calcium phosphate bone cement.The mechanical properties,setting time,and ion precipitation of the cement were characterized.The three groups of bone cement extracts were co-cultured with MC3T3-E1 cells.The cell compatibility of the materials was evaluated by CCK-8 assay,live/dead staining,and phalloidin staining.After osteogenic induction,the osteogenic induction ability of the materials was evaluated by alkaline phosphatase staining,alizarin red staining,RUNX2 immunofluorescence staining,and RT-PCR.RESULTS AND CONCLUSION:(1)With the increase of silicate bioactive glass fiber content,the compressive strength and flexural strength of bone cement increased,and the setting time was prolonged.When bone cement was immersed in simulated body fluid,the precipitation of silicon ions,calcium ions,and phosphorus ions could be detected.Moreover,with the increase of silicate bioactive glass fiber content,the mass concentration of silicon ions and phosphorus ions released by bone cement increased,and the mass concentration of calcium ions decreased.(2)Live/dead staining and phalloidin staining results exhibited that silicate bioactive glass fiber composite calcium phosphate bone cement had no toxic effect on MC3T3-E1 cells.CCK-8 assay results showed that silicate bioactive glass fiber composite calcium phosphate bone cement could promote the proliferation of MC3T3-E1 cells.(3)With the increase of silicate bioactive glass fiber content in bone cement,the alkaline phosphatase activity and extracellular calcium deposition of MC3T3-E1 cells increased,the expression of RUNX2 protein increased,and the expression of alkaline phosphatase,osteocalcin,osteopontin,and RUNX2 mRNA expression increased.(4)The results indicate that silicate bioactive glass fibers can enhance the mechanical properties and osteogenic induction ability of calcium phosphate bone cement,among which 20％silicate bioactive glass fibers have a more obvious effect.

Objective:To analyze the clinical efficacy and learning curve for robot-assisted cortical bone trajectory (CBT) screw fixation performed by surgeons with different seniority in the treatment of lumbar degenerative disease.Methods:The clinical data of 91 lumbar degenerative disease patients underwent robot-assisted CBT screw fixation from August 2020 to December 2022 in Beijing Shijitan Hospital, Capital Medical University were retrospectively analyzed. Among them, 48 patients underwent surgery performed by the same senior surgeon (senior group), with a total of 234 CBT screws were placed; while 43 patients underwent surgery performed by the same junior surgeon (junior group), with a total of 206 CBT screws were placed. The surgical related indexes, functional improvement score, lower back pain and lower limb radiation pain scores, acceptable nail insertion rate, non invasion rate of facet joints and incidence of postoperative complications were compared between two groups. The functional improvement score was evaluated using the Japanese Orthopaedic Association (JOA) score, the pain score was evaluated using visual analog score (VAS). The cumulative sum (CUSUM) method was used to depict the learning curve with "single screw placement time" as the observation index.Results:There were no statistical difference in incision length, operation time, intraoperative blood loss and postoperative hospital stay between two groups ( P>0.05). The least squares means of JOA scores 1, 3 and 6 months after surgery in both groups increased significantly compared to baseline, while the least squares means of lower back pain VAS and lower limb radiation pain VAS decreased significantly compared to baseline; there were no statistical differences between two groups ( P>0.05). There were no statistical difference in acceptable nail insertion rate, non invasion rate of facet joints and incidence of postoperative complications between two group ( P>0.05). The CUSUM learning curves were fitting well and the inflection point for senior surgeon corresponded to 18 cases, while it was reached after performing surgery on 21 cases for junior surgeon. Conclusions:Robot-assisted CBT screw fixation performed by surgeons with different seniority could achieve similar clinical outcomes for treating lumbar degenerative disease. The senior surgeons are able to complete the initial learning stage faster than the junior surgeons, but there is not much difference in the number of surgeries performed the learning curve.

Objective:To compare the effectiveness and safety between robot-assisted percutaneous kyphoplasty (PKP) and traditional fluoroscopy-assisted PKP in the treatment of dual-segment recurrent osteoporotic vertebral compression fracture (OVCF) including in situ vertebral fracture.Methods:The clinical data of 33 patients with dual-segment recurrent OVCF including in situ vertebral fracture from January 2016 to January 2023 in Beijing Shijitan Hospital Affiliated to Capital Medical University were retrospectively analyzed. All the patients were treated with PKP. Among them, 14 patients were treated with robot-assisted surgery (robot-assisted group), and 19 patients were treated with fluoroscopy-assisted surgery (fluoroscopy-assisted group). The total surgical time, preparation time and number of fluoroscopy were recorded. The in situ and other fracture vertebral operation time, number of punctures, amount of bone cement injection, bone cement filling effect, bone cement leakage, pedicle wall breakthrough and other special intraoperative situations were separately recorded. The visual analogue score (VAS) before surgery and 1 d, 3 months after surgery was recorded.Results:The preparation time in robot-assisted group was significantly longer than that in fluoroscopy-assisted group: (30.8 ± 6.9) min vs. (19.1 ± 4.5) min, the number of fluoroscopy was significantly lower than that in fluoroscopy-assisted group: (17.1 ± 4.1) times vs. (41.0 ± 6.3) times, and there were statistical differences ( P<0.01 and <0.05); there were no statistical differences in total surgical time and VAS at any time point between the two groups ( P>0.05). For the in situ fracture segment, the operation time and number of punctures in robot-assisted group were significantly lower than those in fluoroscopy-assisted group: (15.4 ± 2.8) min vs. (22.0 ± 5.5) min and (1.1 ± 0.4) times vs. (2.4 ± 1.2) times, the amount of bone cement injection was significantly higher than those in fluoroscopy-assisted group: (2.36 ± 0.75) ml vs. (1.79 ± 0.69) ml, the filling effect of bone cement was significantly better than that in fluoroscopy-assisted group, and there were statistical differences ( P<0.01 and <0.05); there were no statistical difference in bone cement leakage and pedicle wall breakthrough between the two groups ( P>0.05). For the other fracture segment, the operation time in robot-assisted group was significantly shorter than that in fluoroscopy-assisted group: (13.8 ± 3.8) min vs. (19.2 ± 6.4) min, and there was statistical difference ( P<0.01); there were no statistical difference in number of punctures, amount of bone cement injection, filling effect of bone cement, bone cement leakage and pedicle wall breakthrough between the two groups ( P>0.05). Conclusions:Robot-assisted PKP in the treatment of dual-segment OVCF including in situ vertebral fracture, could reduce operation time, minimize punctures and fluoroscopy numbers, and provide superior bone cement filling results.

Antioxidant enzymes fused with cell-penetrating peptides could enter cells and protect cells from irradiation damage. However, the unselective transmembrane ability of cell-penetrating peptide may also bring antioxidant enzymes into tumor cells, thus protecting tumor cells and consequently reducing the efficacy of radiotherapy. There are active matrix metalloproteinase (MMP)-2 or MMP-9 in most tumor cellular microenvironments. Therefore, a fusion protein containing an MMP-2/9 cleavable substrate peptide X, a cell-penetrating peptide R9, a glutathione S-transferase (GST), and a human Cu, Zn superoxide dismutase (SOD1), was designed and named GST-SOD1-X-R9. In the tumor microenvironment, GST-SOD1-X-R9 would lose its cell-penetrating peptide and could not enter tumor cells due to the cleavage of substrate X by active MMP-2/9, thereby achieving selected entering normal cells. The complete nucleotide sequence of SOD1-X-R9 was synthesized and inserted into the prokaryotic expression vector pGEX-4T-1. The pGEX4T-1-SOD1-X-R9 recombinant plasmid was obtained, and soluble expression of the fusion protein was achieved. GST-SOD1-X-R9 was purified by ammonium sulfate precipitation and GST affinity chromatography. The molecular weight of the fusion protein was approximately 47 kDa, consistent with the theoretical value. The SOD and GST activities were 2 954 U/mg and 328 U/mg, respectively. Stability test suggested that almost no change in either SOD activity or GST activity of GST-SOD1-X-R9 was observed under physiological conditions. The fusion protein could be partially digested by collagenase Ⅳ in solution. Subsequently, the effect of MMP-2/9 activity on transmembrane ability of the fusion protein was tested using 2D and 3D cultured HepG2 cells. Little extracellular MMP-2 activity of HepG2 cells was observed under 2D culture condition. While under the 3D culture model, the size and the MMP-2 activity of the HepG2 tumor spheroid increased daily. GST-SOD1-R9 proteins showed the same transmembrane efficiency in 2D cultured HepG2 cells, but the transmembrane efficiency of GST-SOD1-X-R9 in 3D cultured HepG2 spheres was reduced remarkably. This study provided a basis for further investigating the selectively protective effect of GST-SOD1-X-R9 against oxidative damage in normal cells.
Ammonium Sulfate ; Antioxidants ; Cell-Penetrating Peptides/pharmacology* ; Endopeptidases ; Glutathione Transferase/metabolism* ; Humans ; Matrix Metalloproteinase 2/genetics* ; Matrix Metalloproteinase 9/genetics* ; Recombinant Fusion Proteins ; Recombinant Proteins ; Superoxide Dismutase/metabolism* ; Superoxide Dismutase-1

Huntington's disease (HD) is a deadly neurodegenerative disease with abnormal expansion of CAG repeats in the huntingtin gene. Mutant Huntingtin protein (mHTT) forms abnormal aggregates and intranuclear inclusions in specific neurons, resulting in cell death. Here, we tested the ability of a natural heat-shock protein 90 inhibitor, Gedunin, to degrade transfected mHTT in Neuro-2a cells and endogenous mHTT aggregates and intranuclear inclusions in both fibroblasts from HD patients and neurons derived from induced pluripotent stem cells from patients. Our data showed that Gedunin treatment degraded transfected mHTT in Neuro-2a cells, endogenous mHTT aggregates and intranuclear inclusions in fibroblasts from HD patients, and in neurons derived from induced pluripotent stem cells from patients in a dose- and time-dependent manner, and its activity depended on the proteasomal pathway rather than the autophagy route. These findings also showed that although Gedunin degraded abnormal mHTT aggregates and intranuclear inclusions in cells from HD patient, it did not affect normal cells, thus providing a new perspective for using Gedunin to treat HD.