BACKGROUND There is currently no effective treatment for osteoarthritis(OA),which is the most common joint disorder leading to disability.Although human umbilical cord mesenchymal stem cells(hUC-MSCs)are promising OA ...BACKGROUND There is currently no effective treatment for osteoarthritis(OA),which is the most common joint disorder leading to disability.Although human umbilical cord mesenchymal stem cells(hUC-MSCs)are promising OA treatments,their use is limited by the condition itself,and understanding of the underlying mechanisms of OA is lacking.AIM To explore the specific molecular mechanism by which hUC-MSC-derived exosomal miR-199a-3p improves OA.METHODS Sodium iodoacetate was injected into rat articulations to construct an animal model of OA.Interleukin(IL)-1βwas used to induce human chondrocytes(CHON-001)to construct an OA chondrocyte model.Exosomes in hUC-MSCs were isolated using Ribo™Exosome Isolation Reagent.Real-time reverse transcriptase-polymerase chain reaction and western blotting were used to detect the expression of related genes and proteins,and damage to CHON-001 cells and rat articular cartilage tissue was evaluated by enzyme-linked immunosorbent assay,terminal deoxynucleotidyl transferase-mediated deoxyuridine tripho-sphate-nick end labelling staining and hematoxylin and eosin staining.RESULTS hUC-MSC-derived exosomes(hUC-MSC-Exos)inhibited the expression of IL-1β-induced inflammatory cytokines,namely,IL-6,IL-8 and tumor necrosis factor-α.hUC-MSC-Exos also improved the viability but inhibited the apoptosis of CHON-001 cells,improved the pathological condition of articular cartilage tissue and alleviated the development of OA in vivo.Mechanistically,hUC-MSC-Exos downregulated the expression of mitogen-activated protein kinase 4 by delivering miR-199a-3p,thereby inhibiting the activation of the nuclear factor-kappaB signaling pathway,alleviating IL-1β-induced chondrocyte inflammation and apoptosis,and ultimately improving the development of OA.CONCLUSION hUC-MSC-derived exosomal miR-199a-3p alleviates OA by inhibiting the mitogen-activated protein kinase 4/nuclear factor-kappaB signaling pathway.The present findings suggest that miR-199a-3p delivery by hUC-MSCExos may be a novel strategy for the treatment of OA.展开更多
The present study assessed the efficacy and safety of thoracic radiotherapy(TRT)following first-line chemotherapy or chemoimmunotherapy in patients with extensive-stage small cell lung cancer(ES-SCLC),focusing on the ...The present study assessed the efficacy and safety of thoracic radiotherapy(TRT)following first-line chemotherapy or chemoimmunotherapy in patients with extensive-stage small cell lung cancer(ES-SCLC),focusing on the influence of different TRT timing strategies(consolidative vs.salvage)on survival rates.We retrospectively analyzed a total of 54 patients with ES-SCLC treated between January 2019 and July 2022.Patients receiving consolidative TRT(cTRT)within three months after completion of first-line treatment were compared with those receiving salvage TRT(sTRT)after disease progression.The primary endpoints were overall survival(OS),progression-free survival(PFS),locoregional-free survival(LRFS),and distant metastasis-free survival(DMFS);the secondary endpoint included safety.The cTRT group(n=41)showed significantly longer median OS(26.6 vs.14.8 months,P=0.048),PFS(12.9 vs.3.5 months,P<0.0001),and DMFS(10.7 vs.3.4 months,P=0.0044)than the sTRT group(n=13).Multivariate analysis revealed that cTRT was an independent,favorable prognostic factor.No significant differences in OS or LRFS were observed between high-dose(≥50 Gy)and low-dose(<50 Gy)TRT.Hematologic and respiratory toxicities were the most frequently reported adverse events,with acceptable tolerability.In conclusion,cTRT after chemoimmunotherapy significantly improves survival outcomes for ES-SCLC patients,and low-dose TRT may be a suitable option.展开更多
BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics...BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics of cancer stem cell markers CD24 and CD133 in GC pathological tissues,and to explore their association with patients’clinicopathological parameters and postoperative survival outcomes.METHODS A total of 304 GC patients who underwent surgical treatment in our hospital from January 2018 to January 2020 were retrospectively included.Immunohistochemistry was used to detect the protein expression of CD24 and CD133 in tumor tissues,adjacent tissues,and normal gastric mucosa tissues.Based on staining intensity and the proportion of positive cells,expression levels were classified into low and high expression,while clinicopathological parameters were recorded.χ2 test was used to evaluate the correlation between expression and categorical variables,Spearman rank correlation analysis was performed to assess the correlation between the expression intensities of the two markers,and multivariate regression models were applied to identify independent risk factors influencing co-expression.Kaplan-Meier survival curves and Log-rank test were used to compare survival differences among groups with different expression patterns.RESULTS Among the 304 patients,155 cases(50.99%)were CD24 positive,including 91 low-expression and 64 highexpression;133 cases(43.75%)were CD133 positive,including 81 low-expression and 52 high-expression.There were 74 cases(24.34%)with double positivity and 81 cases(26.64%)with double negativity.Compared with tumor tissues,the positive rates of CD24 and CD133 in normal gastric tissues and adjacent tissues were significantly lower(P<0.05).Univariate analysis showed that co-expression of CD24 and CD133 in GC tissues was significantly correlated with tumor size,Lauren classification,T stage,N stage,and vascular invasion(P<0.05),but not with patient age,gender,tumor site,World Health Organization histological classification,or M stage(P>0.05).Further multivariate regression analysis suggested that tumor size,T stage,N stage,and vascular invasion were independent risk factors promoting CD24 and CD133 double positivity.Spearman rank correlation analysis indicated a moderate positive correlation between their expression intensities(r=0.420,P<0.001).During follow-up,29 of 304 patients were lost(loss rate 9.54%);146 deaths occurred.According to expression combination,there were 89 cases of CD24 single positivity(39 deaths),68 cases of CD133 single positivity(31 deaths),81 cases of double negativity(25 deaths),and 66 cases of double positivity(51 deaths).Log-rank test showed significant differences in overall survival among the four groups(χ2=20.89,P<0.001),with CD24+/CD133+group showing the worst prognosis.CONCLUSION CD24 and CD133 exhibit high positive detection rates in GC tissues,and their co-positivity is closely associated with tumor stage progression and significantly indicates unfavorable survival outcomes.The co-expression of CD24/CD133 may reflect higher aggressiveness and metastatic potential of GC,serving as a potential prognostic marker and a direction for targeted therapeutic strategies.However,as this is a single-center retrospective study with limitations such as patient loss to follow-up and sample size,further prospective,multicenter,and mechanistic studies are required to validate its clinical applicability and biological role.展开更多
The dynamic responses of the Tsing Ma suspension bridge and the running behaviors of trains on the bridge under turbulent wind actions are analyzed by a three-dimensional wind-train-bridge interaction model. This mode...The dynamic responses of the Tsing Ma suspension bridge and the running behaviors of trains on the bridge under turbulent wind actions are analyzed by a three-dimensional wind-train-bridge interaction model. This model consists of a spatial finite element bridge model, a train model composed of eight 4-axle identical coaches of 27 degrees-of-freedom, and a turbulent wind model. The fluctuating wind forces, including the buffeting forces and the self-excited forces, act on the bridge only, since the train runs inside the bridge deck. The dynamic responses of the bridge are calculated and some results are compared with data measured from Typhoon York. The runnability of the train passing through the Tsing Ma suspension bridge at different speeds is researched under turbulent winds with different wind velocities. Then, the threshold curve of wind velocity for ensuring the running safety of the train in the bridge deck is proposed, from which the allowable train speed at different wind velocities can be determined. The numerical results show that rail traffic on the Tsing Ma suspension bridge should be closed as the mean wind velocity reaches 30 m/s.展开更多
In this paper, an FEM （Finite Element Method） model is established for the main span of the bridge, with the main box arch and suspender members modeled by beam elements, truss members by truss elements, and the ort...In this paper, an FEM （Finite Element Method） model is established for the main span of the bridge, with the main box arch and suspender members modeled by beam elements, truss members by truss elements, and the orthotropic steel deck by plate elements. The natural frequencies and mode shapes are acquired by the eigen-parameter analysis. By input of a typical earthquake excitation to the bridge system, the dynamic responses of the bridge, including the displacement and accelerations of the main joints of the structure, and the seismic forces and stresses of the key members, are calculated by the structural analysis program, based on which the main laws of the seismic responses of the bridge are summarized, and the safety of the structure is evaluated.展开更多
The traffic-induced vibrations of the new CCTV Headquarters building are studied stages. In the first stage when the through experiments in two 30th floor of the northwest tower and the 38th floor of the southeast tow...The traffic-induced vibrations of the new CCTV Headquarters building are studied stages. In the first stage when the through experiments in two 30th floor of the northwest tower and the 38th floor of the southeast tower were finished, the traffic flows on the roads surrounding the building were investigated, and 27 setups of accelerations were measured at the roadside, on the pile cap and on the 9th floor. In the second stage when the whole steel structure was completed, l 5 setups of accelerations were measured at the roadside, on the pile cap and on the 37th and the 48th floors. The accelerations of the building under different traffic flows, in different positions are analyzed in both time domain and frequency domain. The damping ratios are estimated by the upgraded half-power bandwidth method.展开更多
基金Supported by Basic Research Plan of Yunnan Province,No.202201AT070059National Natural Science Foundation of China,No.81760407Science and Technology Talent and Platform Plan of Yunnan Provincial Department of Science and Technology,No.202205AC160066.
文摘BACKGROUND There is currently no effective treatment for osteoarthritis(OA),which is the most common joint disorder leading to disability.Although human umbilical cord mesenchymal stem cells(hUC-MSCs)are promising OA treatments,their use is limited by the condition itself,and understanding of the underlying mechanisms of OA is lacking.AIM To explore the specific molecular mechanism by which hUC-MSC-derived exosomal miR-199a-3p improves OA.METHODS Sodium iodoacetate was injected into rat articulations to construct an animal model of OA.Interleukin(IL)-1βwas used to induce human chondrocytes(CHON-001)to construct an OA chondrocyte model.Exosomes in hUC-MSCs were isolated using Ribo™Exosome Isolation Reagent.Real-time reverse transcriptase-polymerase chain reaction and western blotting were used to detect the expression of related genes and proteins,and damage to CHON-001 cells and rat articular cartilage tissue was evaluated by enzyme-linked immunosorbent assay,terminal deoxynucleotidyl transferase-mediated deoxyuridine tripho-sphate-nick end labelling staining and hematoxylin and eosin staining.RESULTS hUC-MSC-derived exosomes(hUC-MSC-Exos)inhibited the expression of IL-1β-induced inflammatory cytokines,namely,IL-6,IL-8 and tumor necrosis factor-α.hUC-MSC-Exos also improved the viability but inhibited the apoptosis of CHON-001 cells,improved the pathological condition of articular cartilage tissue and alleviated the development of OA in vivo.Mechanistically,hUC-MSC-Exos downregulated the expression of mitogen-activated protein kinase 4 by delivering miR-199a-3p,thereby inhibiting the activation of the nuclear factor-kappaB signaling pathway,alleviating IL-1β-induced chondrocyte inflammation and apoptosis,and ultimately improving the development of OA.CONCLUSION hUC-MSC-derived exosomal miR-199a-3p alleviates OA by inhibiting the mitogen-activated protein kinase 4/nuclear factor-kappaB signaling pathway.The present findings suggest that miR-199a-3p delivery by hUC-MSCExos may be a novel strategy for the treatment of OA.
基金supported by the Young Talents Program of Jiangsu Cancer Hospital(Grant No.QL201802)the Science and Technology Development Fund of Jiangsu Cancer Hospital(Grant No.ZL202105).
文摘The present study assessed the efficacy and safety of thoracic radiotherapy(TRT)following first-line chemotherapy or chemoimmunotherapy in patients with extensive-stage small cell lung cancer(ES-SCLC),focusing on the influence of different TRT timing strategies(consolidative vs.salvage)on survival rates.We retrospectively analyzed a total of 54 patients with ES-SCLC treated between January 2019 and July 2022.Patients receiving consolidative TRT(cTRT)within three months after completion of first-line treatment were compared with those receiving salvage TRT(sTRT)after disease progression.The primary endpoints were overall survival(OS),progression-free survival(PFS),locoregional-free survival(LRFS),and distant metastasis-free survival(DMFS);the secondary endpoint included safety.The cTRT group(n=41)showed significantly longer median OS(26.6 vs.14.8 months,P=0.048),PFS(12.9 vs.3.5 months,P<0.0001),and DMFS(10.7 vs.3.4 months,P=0.0044)than the sTRT group(n=13).Multivariate analysis revealed that cTRT was an independent,favorable prognostic factor.No significant differences in OS or LRFS were observed between high-dose(≥50 Gy)and low-dose(<50 Gy)TRT.Hematologic and respiratory toxicities were the most frequently reported adverse events,with acceptable tolerability.In conclusion,cTRT after chemoimmunotherapy significantly improves survival outcomes for ES-SCLC patients,and low-dose TRT may be a suitable option.
基金National Natural Science Foundation of China,No.82003223and China Postdoctoral Science Foundation,No.2020M671398.
文摘BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics of cancer stem cell markers CD24 and CD133 in GC pathological tissues,and to explore their association with patients’clinicopathological parameters and postoperative survival outcomes.METHODS A total of 304 GC patients who underwent surgical treatment in our hospital from January 2018 to January 2020 were retrospectively included.Immunohistochemistry was used to detect the protein expression of CD24 and CD133 in tumor tissues,adjacent tissues,and normal gastric mucosa tissues.Based on staining intensity and the proportion of positive cells,expression levels were classified into low and high expression,while clinicopathological parameters were recorded.χ2 test was used to evaluate the correlation between expression and categorical variables,Spearman rank correlation analysis was performed to assess the correlation between the expression intensities of the two markers,and multivariate regression models were applied to identify independent risk factors influencing co-expression.Kaplan-Meier survival curves and Log-rank test were used to compare survival differences among groups with different expression patterns.RESULTS Among the 304 patients,155 cases(50.99%)were CD24 positive,including 91 low-expression and 64 highexpression;133 cases(43.75%)were CD133 positive,including 81 low-expression and 52 high-expression.There were 74 cases(24.34%)with double positivity and 81 cases(26.64%)with double negativity.Compared with tumor tissues,the positive rates of CD24 and CD133 in normal gastric tissues and adjacent tissues were significantly lower(P<0.05).Univariate analysis showed that co-expression of CD24 and CD133 in GC tissues was significantly correlated with tumor size,Lauren classification,T stage,N stage,and vascular invasion(P<0.05),but not with patient age,gender,tumor site,World Health Organization histological classification,or M stage(P>0.05).Further multivariate regression analysis suggested that tumor size,T stage,N stage,and vascular invasion were independent risk factors promoting CD24 and CD133 double positivity.Spearman rank correlation analysis indicated a moderate positive correlation between their expression intensities(r=0.420,P<0.001).During follow-up,29 of 304 patients were lost(loss rate 9.54%);146 deaths occurred.According to expression combination,there were 89 cases of CD24 single positivity(39 deaths),68 cases of CD133 single positivity(31 deaths),81 cases of double negativity(25 deaths),and 66 cases of double positivity(51 deaths).Log-rank test showed significant differences in overall survival among the four groups(χ2=20.89,P<0.001),with CD24+/CD133+group showing the worst prognosis.CONCLUSION CD24 and CD133 exhibit high positive detection rates in GC tissues,and their co-positivity is closely associated with tumor stage progression and significantly indicates unfavorable survival outcomes.The co-expression of CD24/CD133 may reflect higher aggressiveness and metastatic potential of GC,serving as a potential prognostic marker and a direction for targeted therapeutic strategies.However,as this is a single-center retrospective study with limitations such as patient loss to follow-up and sample size,further prospective,multicenter,and mechanistic studies are required to validate its clinical applicability and biological role.
基金National Natural Science Foundation of China Under Grant No.90715008, 50838006The Fundamental Research Funds for the Central Universities Under Grant No 2009JBM078
文摘The dynamic responses of the Tsing Ma suspension bridge and the running behaviors of trains on the bridge under turbulent wind actions are analyzed by a three-dimensional wind-train-bridge interaction model. This model consists of a spatial finite element bridge model, a train model composed of eight 4-axle identical coaches of 27 degrees-of-freedom, and a turbulent wind model. The fluctuating wind forces, including the buffeting forces and the self-excited forces, act on the bridge only, since the train runs inside the bridge deck. The dynamic responses of the bridge are calculated and some results are compared with data measured from Typhoon York. The runnability of the train passing through the Tsing Ma suspension bridge at different speeds is researched under turbulent winds with different wind velocities. Then, the threshold curve of wind velocity for ensuring the running safety of the train in the bridge deck is proposed, from which the allowable train speed at different wind velocities can be determined. The numerical results show that rail traffic on the Tsing Ma suspension bridge should be closed as the mean wind velocity reaches 30 m/s.
基金Acknowledgments： This study is sponsored by the Natural Science Foundation of China （No. 90715008） and the Flander （Belgium）-China Bilateral Project （No. BIL07/07）.
文摘In this paper, an FEM （Finite Element Method） model is established for the main span of the bridge, with the main box arch and suspender members modeled by beam elements, truss members by truss elements, and the orthotropic steel deck by plate elements. The natural frequencies and mode shapes are acquired by the eigen-parameter analysis. By input of a typical earthquake excitation to the bridge system, the dynamic responses of the bridge, including the displacement and accelerations of the main joints of the structure, and the seismic forces and stresses of the key members, are calculated by the structural analysis program, based on which the main laws of the seismic responses of the bridge are summarized, and the safety of the structure is evaluated.
基金The study is sponsored by the National Natural Science Foundation of China （No. 50538010） and the Flander （Belgium）-China Bilateral Project （,No. BIL 07/07）.
文摘The traffic-induced vibrations of the new CCTV Headquarters building are studied stages. In the first stage when the through experiments in two 30th floor of the northwest tower and the 38th floor of the southeast tower were finished, the traffic flows on the roads surrounding the building were investigated, and 27 setups of accelerations were measured at the roadside, on the pile cap and on the 9th floor. In the second stage when the whole steel structure was completed, l 5 setups of accelerations were measured at the roadside, on the pile cap and on the 37th and the 48th floors. The accelerations of the building under different traffic flows, in different positions are analyzed in both time domain and frequency domain. The damping ratios are estimated by the upgraded half-power bandwidth method.
