In recent years, studies have shown that exosomes can replace mesenchymal stem cell for chronic wound repair. However, exosomes have some problems such as poor targeting, low availability and low yield, so it has limited effect in the treatment of chronic wound. Maximizing the therapeutic benefits of exosomes is the primary challenge that needs to be overcome when used for chronic wound repair. Studies have shown that the treatment potential of exosomes can be further developed by pretreatment and engineering modification of exosomes. This article reviewed the research progress of exosome pretreatment and engineering modification in chronic wound repair, and provided reference for subsequent research and clinical application.

In recent years, studies have shown that exosomes can replace mesenchymal stem cell for chronic wound repair. However, exosomes have some problems such as poor targeting, low availability and low yield, so it has limited effect in the treatment of chronic wound. Maximizing the therapeutic benefits of exosomes is the primary challenge that needs to be overcome when used for chronic wound repair. Studies have shown that the treatment potential of exosomes can be further developed by pretreatment and engineering modification of exosomes. This article reviewed the research progress of exosome pretreatment and engineering modification in chronic wound repair, and provided reference for subsequent research and clinical application.

Atrial fibrillation (AF) is one of the most common arrhythmias, associated with high morbidity, mortality, and healthcare costs, and it places a significant burden on both individuals and society. Anti-arrhythmic drugs are the most commonly used strategy for treating AF. However, drug therapy faces challenges because of its limited efficacy and potential side effects. Catheter ablation is widely used as an alternative treatment for AF. Nevertheless, because the mechanism of AF is not fully understood, the recurrence rate after ablation remains high. In addition, the outcomes of ablation can vary significantly between medical institutions and patients, especially for persistent AF. Therefore, the issue of which ablation strategy is optimal is still far from settled. Computational modeling has the advantages of repeatable operation, low cost, freedom from risk, and complete control, and is a useful tool for not only predicting the results of different ablation strategies on the same model but also finding optimal personalized ablation targets for clinical reference and even guidance. This review summarizes three-dimensional computational modeling simulations of catheter ablation for AF, from the early-stage attempts such as Maze III or circumferential pulmonary vein isolation to the latest advances based on personalized substrate-guided ablation. Finally, we summarize current developments and challenges and provide our perspectives and suggestions for future directions.

Objective:To investigate the application of therapeutic grade ionization chamber to rapid measurement of short pulsed and high-dose-rate X-ray.Methods:The half-value layer of pulsed X-ray caused by an electron accelerator was measured by interpolation method and its equivalent energy was estimated. The cumulative doses from a certain amount of pulsed radiation at different distances in the same direction around the equipment were compared using the therapeutic grade ionization chamber and thermoluminescence measurement method . The relationship between the measurement result by using ionization chamber dosimeter and the distances away from source was analyzed. The cumulative doses from a certain amount of pulsed radiation at the same location at different frequencies were compared.Results:In working condition, 100 pulses of radiation were received accumulatively at 1 to 12 meters away from the outer wall of the equipment. The range of air Kerma was 0.08-9.65 mGy measured by using thermoluminescence dometers and 0.08 - 9.85 mGy using the ionization chamber dosimeters, respectively. The difference between both is within 10%. At different frequencies (1-10 Hz), there was no significant difference in X-ray air Kerma from 100 pulses measured by ionization chamber dosimeter at 2 m away from the front of the equipment ( P>0.05). Conclusions:The therapeutic grade ionization chamber dosimeter can be used for the rapid measurement of short pulsed X-ray radiation dose in the range of dose rates and pulse frequencies involved in the experimental accelerator device.

In recent years, the number of interventions for valvular heart disease has been increasing day by day, and it has become a hot topic in the field of cardiovascular surgery. Given the aging global population and trends in the prevalence of valvular disease and the broadening of indications for transcatheter aortic valve replacement (TAVR), a breakthrough of 130 000 TAVR procedures is expected by 2026. In the new technology development period, the development potential and technical advantages of heart valve interventional therapy should be faced squarely. This paper focuses on key issues such as comparison of outcomes after TAVR versus surgical aortic valve replacement (SAVR), prosthetic valve endocarditis after TAVR, and broadening of indications for TAVR, as well as recommendations on how surgeons face the era of TAVR. We hope that this article will help and attract the attention of cardiac surgeons.

Objective:To explore the clinical characteristics and predictors of severe acute pancreatitis complicated with acute respiratory distress syndrome (SAP-ARDS).Methods:Clinical data of consecutive 313 SAP patients hospitalized from January 2000 to January 2020 in Peking Union Medical College Hospital, were retrospectively analyzed, including 258 cases with ARDS (ARDS group) and 55 cases without ARDS (non-ARDS group). According to the severity of ARDS, ARDS group were further divided into mild ARDS group (165 cases) and moderate to severe ARDS group (93 cases). Clinical symptoms, laboratory examination and imaging results, ICU admission time and clinical outcome, as well as the local and systemic complications, acute physiology and chronic health evaluation (APACHEⅡ) within 24 h after admission, bedside index for severity in acute pancreatitis (BISAP), CT severity index (CTSI), sequential organ failure assessment (SOFA) and quick sequenctial organ failure assessment(qSOFA) score were recorded. Univariate and multivariate logistic regression were performed to analyze independent risk factors of SAP complicated with moderate to severe ARDS. Receiver operating characteristics curves (ROC) was drawn to calculate area under the ROC curve (area under curve, AUC) and evaluate the performance of WBC and hsCRP in predicting SAP complicated with moderate to severe ARDS, and assess the performance of APACHEⅡ, BISAP, CTSI, SOFA and qSOFA scores in predicting SAP-ARDS endotracheal intubation.Results:The ICU length of stay and mortality rate of SAP-ARDS patients were significantly higher than those without ARDS [(8.3±11.6 day vs 5.7±7.7 day, 12.4% vs 3.6%, all P value <0.05)]. Univariate analysis showed that elevated WBC ( OR 4.52, 95% CI 1.64-12.4) and hsCRP ( OR 3.69, 95% CI 1.29-10.48) on admission were independent risk factors for moderate to severe ARDS with SAP. The AUC of WBC and hsCRP for predicting SAP with moderate to severe ARDS at admission were 0.651(95% CI 0.532-0.770) and 0.615 (95% CI 0.500-0.730), respectively. The predicted cut-off values (Cut-off values) were 17.5×10 9/L and 159 mg/L, respectively, and the sensitivity was 53.1% and 78.1%, the specificity was 78.1% and 48.4% respectively. The area under the ROC curve for APACHEⅡ, BISAP, CTSI, SOFA, and qSOFA score 24 h after admission in the early prediction of endotracheal intubation were 0.739 (95% CI 0.626-0.840), 0.705 (95% CI 0.602-0.809), 0.753 (95% CI 0.650-0.849 ), 0.737 (95% CI 0.615-0.836) and 0.663 (95% CI 0.570-0.794), and the optimum Cut-off values were 14 points, 3 points, 5 points, 7 points, 2 points, and the sensitivity and specificity for these predictors were 58.8% and 81.4%, 79.4% and 60.0%, 73.5% and 67.1%, 38.2% and 98.6%, 45.5% and 83.3%, respectively. Conclusions::Elevated blood WBC and hsCRP on admission were independent risk factors for moderate to severe ARDS in SAP. APACHEⅡ≥14, BISAP≥3, CTSI≥5, SOFA≥7, or qSOFA≥2 within the 24 h admission indictaed that the risk of SAP patients to receive endotracheal intubation was high.

Objective: To investigate the effect of erythropoietin (EPO) on the expression of aquaporin 2-3 after the release of unilateral ureter obstruction in young rats. Methods: Twenty-four SD rats were randomly divided into 3 groups(CUUO-R group, CUUO-R+ EPO group and sham group, with 8 rats in each group). The CUUO-R model was built through unilateral ureteral ligation, after 48 h the obstruction was released.EPO was given to the CUUO-R+ EPO group at the time point of removing obstruction, and then repeated every other day for 1 week, and the same volume of saline was simultaneously given to the CUUO-R rats.The rats in sham group experienced the laparotomy and free dissection of left ureter but not ligation.The kidneys were harvested 7 d after the release of CUUO.The methods of Western blot and immunohistochemistry were used to examine the effects of erythropoietin on the expression of AQP2 and AQP3. Results: The osmotic pressure of CUUO-R+ EPO group was higher than those of CUUO-R group, but lower than that of sham group(P=0.007). The concentration of creatinine and urea in the CUUO-R group[(58.001±2.416) μmol/L and (9.025±1.158) mmol/L]were higher than those of CUUO-R+ EPO group [(57.072±2.286) μmol/L and (1.479±0.043) mmol/L] and sham group [(54.820±1.536) μmol/L and (6.929±0.604) mmol/L]. The differences of the concentration of creatinine and urea between CUUO-R group and sham group were statistically significant(P<0.05). There was no significant difference between CUUO-R+ EPO group and Sham group(P>0.05). The immunohistochemistry showed that the expressions of AQP2 and AQP3 in co-llecting duct in CUUO-R group were significantly weaker than those of in sham group, and the expression of those in CUUO-R+ EPO group were slightly weaker than sham group.These results were further confirmed by Western blot, as the relative quantity of AQP2 and AQP3 were also the lowest in CUUO-R group(AQP2 in 3 groups were 0.974±0.109, 1.923±0.097 and 2.002±0.044, F=392.4, P=0.000; AQP3 in 3 groups were 0.941±0.048, 1.497±0.043 and 1.863±0.043, F=735.8, P=0.000). Conclusions EPO treatment is beneficial for the recovery expre-ssion of AQP2 and AQP3 as well as renal function at the early period after the release of ureteral obstruction in young rats.

Objective: To evaluate the feasibility of intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DWI MRI) in the evaluation of tumor vascular normalization in a mouse model of colorectal cancer induced by recombinant human endostatin (rhES). Methods: The CT26 colorectal cancer xenograft model of BALB/c mice were established and divided into rhES group and control group, with 20 mice in each group. The mice of rhES group were intravenously injected with rhES 5 mg·kg^-1·d^-1 once daily for 12 days, while the mice of the control group were intravenously injected with the same volume of 0.9% saline. 5 mice of rhES group and control group were randomly selected to perform IVIM-DWI MRI as following times: before treatment and four, eight, twelve days after treatment. The parameters of IVIM-DWI were recorded, including true diffusion coefficient(D), pseudo-diffusion coefficient (D^*) and perfusion fraction (f). Meanwhile, microvessel density (MVD), pericyte coverage and tumor perfusion in tumor tissues were detected by immunofluorescence, respectively. Results: The tumor volumes of control group and rhES group before treatment were (154.42±24.65) mm³ and (174.24±28.27)mm^3, respectively, without statistically significant difference (P=0.440). From day 2 to day 12 after treatment, the tumor volume of rhES group was significantly smaller than that of control group (all P<0.05). There were no statistical significances of D value between the rhES group and control group before and after treatment (all P>0.05). The D^* values of the rhES group were (10.940±2.834)×10^-3mm²/s and (12.940±2.801)×10^-3mm²/s in day 4 and 8 after treatment respectively, significantly higher than (6.980±1.554)×10^-3mm²/s and (7.898±1.603)×10^-3mm²/s of control group (P<0.05). Moreover, compared with control group, the D^* value of rhES group was significantly lower in day 12 (6.848±1.460)×10^-3mm²/s vs (9.950±2.596)×10^-3mm²/s, (P<0.05). The f value of rhES group in day 8 was (0.226±0.021)%, significantly higher than (0.178±0.016)% of control group (P<0.01). The MVD of rhES group was significantly lower than that of control group (P<0.05), while the pericyte coverage and tumor perfusion of rhES group were significantly higher than those of control group in day 4 and 8 after treatment (all P<0.05). In addition, we found D^* value of IVIM-DWI in rhES group was significantly related with MVD, pericyte coverage and tumor perfusion (r=-0.354, r=0.555, r=0.559, all P<0.05). Meanwhile, the f value in rhES group was also significantly related with MVD, pericyte coverage and tumor perfusion (r=-0.391, r=0.538, r=0.315, all P<0.05). Conclusions IVIM-DWI MRI can effectively evaluate the vascular normalization in rhES-induced CT26 colorectal tumor.The parameters D^* and f are closely related to intratumorally microvessel density, pericyte coverage and perfusion, which can effectively monitor the occurrence of tumor vascular normalization time.

Objective To evaluate the feasibility of intravoxel incoherent motion diffusion?weighted magnetic resonance imaging (IVIM?DWI MRI) in the evaluation of tumor vascular normalization in a mouse model of colorectal cancer induced by recombinant human endostatin (rhES).Methods The CT26 colorectal cancer xenograft model of BALB／c mice were established and divided into rhES group and control group, with 20 mice in each group.The mice of rhES group were intravenously injected with rhES 5 mg·kg－1·d－1 once daily for 12 days, while the mice of the control group were intravenously injected with the same volume of 0.9%saline. 5 mice of rhES group and control group were randomly selected to perform IVIM?DWI MRI as following times: before treatment and four, eight, twelve days after treatment. The parameters of IVIM?DWI were recorded, including true diffusion coefficient( D), pseudo?diffusion coefficient ( D?) and perfusion fraction ( f).Meanwhile, microvessel density ( MVD), pericyte coverage and tumor perfusion in tumor tissues were detected by immunofluorescence, respectively. Results The tumor volumes of control group and rhES group before treatment were (154.42 ± 24.65) mm3 and (174.24 ± 28.27) mm3, respectively, without statistically significant difference ( P＝0.440). From day 2 to day 12 after treatment, the tumor volume of rhES group was significantly smaller than that of control group ( all P＜0.05).There were no statistical significances of D value between the rhES group and control group before and after treatment ( all P＞0.05).The D? values of the rhES group were (10.940±2.834)×10－3mm2／s and (12.940±2.801)×10－3 mm2／s in day 4 and 8 after treatment respectively, significantly higher than (6.980±1.554)×10－3mm2／s and (7.898±1.603)×10－3mm2／s of control group (P＜0.05). Moreover, compared with control group, the D?value of rhES group was significantly lower in day 12 (6.848±1.460)×10－3mm2／s vs (9.950±2.596)×10－3 mm2／s, (P＜0.05). The f value of rhES group in day 8 was (0.226± 0.021)%, significantly higher than (0.178±0.016)% of control group (P＜0.01). The MVD of rhES group was significantly lower than that of control group (P＜0.05), while the pericyte coverage and tumor perfusion of rhES group were significantly higher than those of control group in day 4 and 8 after treatment ( all P＜0.05).In addition, we found D?value of IVIM?DWI in rhES group was significantly related with MVD, pericyte coverage and tumor perfusion ( r＝－0.354, r＝0.555, r＝0.559, all P＜0.05). Meanwhile, the f value in rhES group was also significantly related with MVD, pericyte coverage and tumor perfusion ( r＝－0.391, r＝0.538, r＝0.315, all P＜0.05). Conclusions IVIM?DWI MRI can effectively evaluate the vascular normalization in rhES?induced CT26 colorectal tumor.The parameters D? and f are closely related to intratumorally microvessel density, pericyte coverage and perfusion, which can effectively monitor the occurrence of tumor vascular normalization time.[Subject words] Colorectal neoplasms; Intravoxel incoherent motion; Diffusion magnetic resonance imaging; Vascular normalization; Recombinant human endostatin; Angiogenesis

Objective To evaluate the feasibility of intravoxel incoherent motion diffusion?weighted magnetic resonance imaging (IVIM?DWI MRI) in the evaluation of tumor vascular normalization in a mouse model of colorectal cancer induced by recombinant human endostatin (rhES).Methods The CT26 colorectal cancer xenograft model of BALB／c mice were established and divided into rhES group and control group, with 20 mice in each group.The mice of rhES group were intravenously injected with rhES 5 mg·kg－1·d－1 once daily for 12 days, while the mice of the control group were intravenously injected with the same volume of 0.9%saline. 5 mice of rhES group and control group were randomly selected to perform IVIM?DWI MRI as following times: before treatment and four, eight, twelve days after treatment. The parameters of IVIM?DWI were recorded, including true diffusion coefficient( D), pseudo?diffusion coefficient ( D?) and perfusion fraction ( f).Meanwhile, microvessel density ( MVD), pericyte coverage and tumor perfusion in tumor tissues were detected by immunofluorescence, respectively. Results The tumor volumes of control group and rhES group before treatment were (154.42 ± 24.65) mm3 and (174.24 ± 28.27) mm3, respectively, without statistically significant difference ( P＝0.440). From day 2 to day 12 after treatment, the tumor volume of rhES group was significantly smaller than that of control group ( all P＜0.05).There were no statistical significances of D value between the rhES group and control group before and after treatment ( all P＞0.05).The D? values of the rhES group were (10.940±2.834)×10－3mm2／s and (12.940±2.801)×10－3 mm2／s in day 4 and 8 after treatment respectively, significantly higher than (6.980±1.554)×10－3mm2／s and (7.898±1.603)×10－3mm2／s of control group (P＜0.05). Moreover, compared with control group, the D?value of rhES group was significantly lower in day 12 (6.848±1.460)×10－3mm2／s vs (9.950±2.596)×10－3 mm2／s, (P＜0.05). The f value of rhES group in day 8 was (0.226± 0.021)%, significantly higher than (0.178±0.016)% of control group (P＜0.01). The MVD of rhES group was significantly lower than that of control group (P＜0.05), while the pericyte coverage and tumor perfusion of rhES group were significantly higher than those of control group in day 4 and 8 after treatment ( all P＜0.05).In addition, we found D?value of IVIM?DWI in rhES group was significantly related with MVD, pericyte coverage and tumor perfusion ( r＝－0.354, r＝0.555, r＝0.559, all P＜0.05). Meanwhile, the f value in rhES group was also significantly related with MVD, pericyte coverage and tumor perfusion ( r＝－0.391, r＝0.538, r＝0.315, all P＜0.05). Conclusions IVIM?DWI MRI can effectively evaluate the vascular normalization in rhES?induced CT26 colorectal tumor.The parameters D? and f are closely related to intratumorally microvessel density, pericyte coverage and perfusion, which can effectively monitor the occurrence of tumor vascular normalization time.[Subject words] Colorectal neoplasms; Intravoxel incoherent motion; Diffusion magnetic resonance imaging; Vascular normalization; Recombinant human endostatin; Angiogenesis