Decellularized matrix transplantation has emerged as a promising therapeutic approach for repairing tissue defects, with numerous studies assessing its safety and efficacy in both animal models and clinical settings. The host immune response elicited by decellularized matrix grafts of natural biological origin plays a crucial role in determining the success of tissue repair, influenced by matrix heterogeneity and the inflammatory microenvironment of the wound. However, the specific immunologic mechanisms underlying the interaction between decellularized matrix grafts and the host immune system remain elusive. This article reviews the sources of decellularized matrices, available decellularization techniques, and residual immunogenic components. It focuses on the host immune response following decellularized matrix transplantation, with emphasis on the key mechanisms of Toll-like receptor, T-cell receptor, and TGF-β/SMAD signaling in the stages of post-transplantation immunorecognition, immunomodulation, and tissue repair, respectively. Furthermore, it highlights the innovative roles of TLR10 and miR-29a-3p in improving transplantation outcomes. An in-depth understanding of the molecular mechanisms underlying the host immune response after decellularized matrix transplantation provides new directions for the repair of tissue defects.

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).

Objective To evaluate the feasibility and safety of supratotal resection of frontal or temporal lobe glioblastoma by the postoperative cognitive function and overall survival. Methods The clinical data of patients with frontal or temporal lobe glioblastoma and treated from January 2010 to January 2015 were analyzed retrospectively.The patients underwent supratotal resection of glioblastoma after March 2012(trial group, 33 cases). Before March 2012, the patients underwent total resection of glioblastoma(control group,28 cases).The Montreal cognitive assessment(MoCA)scores before operation and the 7th day after operation were used to evaluate the security, while overall survival was used to evaluate the feasibility. Variance analysis of repeated measurement quantitative data was used for the statistical analysis of the results. Multivariate Cox model was used as a method to estimate the independent association of a variable set with overall survival. Survival time observation was plotted by the Kaplan-Meier analysis,starting from the data of surgery.Results The MoCA scores in control group at the 7th day after operation were significantly lower than those before operation:(25.39 ± 3.04)scores vs.(26.67 ± 2.19)scores, t = 4.446,P < 0.05. The MoCA scores in trial group at the 7th day after operation were significantly lower than those before operation:(21.93 ± 4.46)scores vs.(25.39 ± 3.04) scores,t = 3.485,P < 0.05. The survival analysis of Kaplan-Meier method showed that age, surgical method and preoperative KPS scores were statistically significant (P < 0.05). Cox regression analysis showed that the choice of surgical method and preoperative KPS was 0.286 and 0.965,respectively.The risk of death in control group was 0.286 times of that in trial group.The survival time of trial group was better than that of control group.Conclusions The cognitive function of patients with frontal or temporal glioblastoma may have a certain degree of decline after tumor resection or supratotal resection.Supratotal resection could represent a promising strategy that can impact on outcome in glioblastoma patients. Supratotal resection could be a factor influencing survival.

Objective: To explore the inhibitory effect of icotinib combined with cytokine induced killer (CIK) on various human lung adenocarcinoma cell lines in vitro. Methods: The inhibitory effect of icotinib alone or icotinib combined with CIK on HCC827 and A549 cells was detected by cell counting kit-8(CCK-8). The apoptosis was detected by flow cytometry via Annexin V/PI staining. The effect of icotinib on CIK phenotype was detected by flow cytometry. Results: The inhibitory rates of HCC827 cells treated with 1.5, 3, 6, 12 μmol/L icotinib were (5.64±0.05)%, (8.62±0.45)%, (14.57±0.65)% and (18.52±0.91)%, respectively. The inhibitory rates of A549 cells were (1.64±0.48)%, (2.09±0.28)%, (3.69±0.45)%, (4.41±0.58)%, respectively. At the same concentration, the inhibitory rate of HCC827 cells with icotinib treatment was significantly higher than that of A549 cells (P<0.05). When the effector/target ratio was 10∶1, 20∶1 or 40∶1, the inhibitory rates of HCC827 cells co-cultured with CIK were (15.17±2.33)%, (42.59±7.18)%, (62.59±8.95)%, respectively, and the inhibitory rates of A549 were(16.99±2.81)%, (46.31±1.89)%, (58.24±4.23)%, respectively. The inhibitory rate of HCC827 cells co-cultured with CIK was not significantly different from that of A549 cells at the same effector/target ratio (P_10∶1=0.299, P_20∶1=0.318, P_40∶1=0.366). When the effector/target ratio of CIK combined with 6 μmol/L icotinib was 10∶1, 20∶1 or 40∶1, the inhibitory rates of HCC827 cells were (37.07±3.50)%, (76.03±6.55)%, (80.34±10.69)%, respectively, and the inhibitory rates of A549 cells were(25.72±1.41)%, (52.76±3.82)%, (62.26±1.94)%, respectively. The inhibitory rates of 6 μmol/L icotinib combined with CIK were significantly higher than those of icotinib group and CIK group alone at the same effector/target ratio (P<0.05), except for the effector/target ratio at 40︰1 on A549 cells (P=0.089). Moreover, all of the combination index (CI) of combined group were <1 (P<0.05). The apoptotic rates of HCC827 and A549 cells induced by icotinib combined with CIK were significantly higher than those of icotinib group and blank control group (P<0.05), especially the proportion of late apoptotic or necrotic cells.Increasing effector/target ratio of CIK contributed to stronger inhibition(P<0.05). The expressional rate of CIK phenotype with or without icotinib treatment was not significantly different from each other(P>0.05). Conclusions EGFR mutant lung adenocarcinoma cells are more sensitive to icotinib, while the EGFR mutation status has no effect on the killing effect of CIK cells. icotinib combined with CIK has a synergistic effect on the inhibition of tumor growth, and icotinib has no any impact on the phenotype of CIK cells.

Objective To explore the efficiency of the ABC-HOME in the rapid identification and assessment of potential donors.Methods We developed a submit system and a rapid assessment method of ABC-HOME for potential donors at 2013.They were on trial in service area hospitals of Guangzou General Hospital Organ Procurement Organization (GHOPO) from February,2015.We reviewed medical records of potential donors occurring in the intensive unit at 2014,from February to December 2015 and 2016,respectively.We examined data on the number of potential donors,actual donors and beds of ICU,and calculated the number of potential donors and actual donors per bed per year.The reasons for donation failure were analyzed.Results 19,38 and 50 organ donations were realized in 243,474 and 513 potential donors in 2014,from February 2015 to December 2015 and 2016,respectively.The growth rate of organ donation and the number of actual donors per bed per year was 95.0%,8.2% and 0.45,0.89 and 0.96,respectively.The conversion rate in these potential donors was 8.92% from February 2015 to December 2016.The reasons for donation failure included the family and social factors,doctor-patient relationship and communication factor and illness condition of donors' factors.Conclusion ABC-HOME is a convenient assessment method for potential donors,which can help to promote the identification of potential donors and to increase the number of potential donor information.

Objective To explore the safety and feasibility of guiding catheter passing through spasmodic vessels in patients undergoing percutaneous coronary intervention (PCI) via radial artery access by the aid of PCI guiding wire and balloon .Methods The clinical data of 33 coronary artery disease (CAD) patients undergoing PCI via radial artery access with radial artery or (and) brachial artery spasm ( group A ) were retrospectively analyzed .Among all these patients , guiding catheters were delivered through the spasmodic vessels successfully by the aid of PCI guiding wires and balloons .The clinical data of other 38 CAD patients having PCI during the same period performed by other operators via radial artery or ( and ) brachial artery approach and experienced vessel spasm were anlysed as the control ( group B ) .All patients in group B received conventional anti-spasm management during PCI .All vessel spasm was identified by angiography.For patients in group A , a diameter of 0.014 inch guiding wire was chosen to pass through the spasmodic vessel segment carefully and gently .The diameter of balloon should be chosen according to the diameter of guiding catheter .A balloon diameter of 2.0 mm and 2.5 mm was corresponded to 6F and 7F guiding catheter respectively .The balloon was advanced to the tip of guiding catheter , keeping a half in catheter and a half in vessel followed by inflating the balloon with a pressure of 8 atm.The balloon was kept inflated the guiding catheter was pushed in vitro carefully and slowly until the catheter passed through the spasmodic vessel segment .Then the balloon was deflated and pulled out together with PCI guiding wire . Exchanged a diameter of 0.035 inch wire and completed the positioning of guiding catheter .After finishing the PCI, radial or ( and) brachial angiography was performed again to observe if spasm disappeared and to determine if there any contrast medium exudation .For patients in group B , routine approach was applied including administration of nitroglycerine , diltiazem or nitroprusside etc . to relieve vessel spasm. Results The location of vessel spasm was similar in group A and group B ( P=0.150 ) , and the incidence rate of spasm in brachial artery was higher than that in radial artery in both groups .The chance of guiding catheter crossing the spasmodic vessel segment was significantly higher in group A than in group B ( 100%vs.39.5%, P=0.00).In patients whose guiding catheter could pass through the spasmodic vessel segment successfully , time spent in group A was shorter than in group B ( P=0.000 ) .The patient number which time spent was less than five minutes , five to 15 minutes and more than 15 minutes was 30 and 2 ( 90.1%vs.13.3%) , 3 and 7 ( 9.9% vs.46.7%) and 0 and 6 ( 0% vs.40.0%) in group A and in group B respectively.The incidence of forearm hematoma was lower in group A than in group B without statistical difference [6.1%(2/33) vs.18.4%(7/38), P =0.113].Conclusions It is safe and feasible for passing guiding catheter through spasmodic vessels during PCI via radial artery access by the aid of PCI guiding wire and balloon .

Objective Using abandoned white cells separated from preparation of blood products to cultivate NK cells in vitro, and to optimize the method of cultivation of allogeneic NK cells for clinical application.Methods Abandoned white cells separated from blood production were collected from 15 healthy donors.PBMCs were isolated from the abandoned white cells and cultured for 17 days using culture bottles as previously coated antibodies (group CD3 mAb was coated with CD3 mAb, group CD 16mAb was coated with CD16mAb, and group CD3mAb +CD16 mAb was coated with CD3 mAb and CD16 mAb).Flow cytometry was used to determine the ratio of CD3-CD56+cells, expression of activated cell surface receptors, and secretion of IFN-γ.The anti-tumor cytotoxicity against K562 and Raji cells was determined using LDH cytotoxicity assay and flow cytometry.Results After expansion for 17 days, the proportions of CD3-CD56+cells was (15.19±12.22)% in the group CD3 mAb, (83.63±10.63)% in the group CD16 mAb, (49.40± 12.64)% in the group CD3mAb +CD16 mAb, and it was (16.34±10.51)% before expansion.The total number of NK cells was more than 10 9 .The expression ratios of NK cell surface activated receptors NKp30 and NKp46 were significantly increased, while that of the NKG2D was not significantly changed.The NK cells after expansion showed high cytotoxicity activity against K562 cells, reaching up to(76.97±3.16)%when effector-cell-to-target-cell ratio (E ∶T ratio) was 40 ∶1.Conclusions NK cells can be obtained from abandoned white cells after cultivation for 17 days, with a purity up to 90% and total cell number of more than 10 9 .Their activity was reinforced, the anti-tumor cytotoxicity activity was increased, and may meet the standard of clinical therapeutic application.

Objective To compare the effects of septal ablation (SA) versus conservative medication (CM) on the hemodynamic,clinical status and survival in patients with hypertrophic obstructive cardiomyopathy (HOCM).Methods This retrospective study included 350 consecutive patients with HOCM (mean age (51.3 ± 13.5) years old) hospitalized in Anzhen Hospital between September 2002 to September 2014.The patients were followed up to 14 years and the follow up rate was 99.4％ (348/350).Overall and cardiac-related mortalities were compared between SA group (n =184) and CM group (n =184).Moreover,SA related cardiac function and hemodynamics improvement were also evaluated,predictors for clinical events were evaluated by Cox regression analysis and Kaplan-Meier survival analysis was used to compare the total mortality between the two groups.The log-rank test was used to compare the survival curve differences between the two groups.Results The median follow-up period was 4 years (1-14 years).The annual mortalities of SA and CM were 2.4％ and 0.6％ respectively (P ＜ 0.001) and cumulative sudden cardiac death (SCD) rates were 3.61％ (6/166) and 0.54％ (1/184) respectively (P =0.031).Multivariate regression analysis demonstrated that the age was the most important independent predictor for overall mortality(HR =1.259,95％ CI 1.101-1.438,P =0.001).In addition,left ventricular outflow tract (LVOT) gradient was significantly reduced post SA (peak velocity of LVOT:baseline (4.23:± 1.05) m/s,post SA:(1.83 ±0.79) m/s,P ＜0.01) and heart function was also significantly improved post SA (NYHA at baseline:2.97 ±0.29,post SA:1.74 ±0.53,P ＜0.001).Conclusion SA could significantly improve the hemodynamics and clinical status in drug-resistant patients with HOCM.In comparison to patients received CM,overall survival rate was significantly higher in SA group without extra risk of SCD.

Objective Using abandoned white cells separated from preparation of blood products to cultivate NK cells in vitro, and to optimize the method of cultivation of allogeneic NK cells for clinical application.Methods Abandoned white cells separated from blood production were collected from 15 healthy donors.PBMCs were isolated from the abandoned white cells and cultured for 17 days using culture bottles as previously coated antibodies (group CD3 mAb was coated with CD3 mAb, group CD 16mAb was coated with CD16mAb, and group CD3mAb +CD16 mAb was coated with CD3 mAb and CD16 mAb).Flow cytometry was used to determine the ratio of CD3-CD56+cells, expression of activated cell surface receptors, and secretion of IFN-γ.The anti-tumor cytotoxicity against K562 and Raji cells was determined using LDH cytotoxicity assay and flow cytometry.Results After expansion for 17 days, the proportions of CD3-CD56+cells was (15.19±12.22)% in the group CD3 mAb, (83.63±10.63)% in the group CD16 mAb, (49.40± 12.64)% in the group CD3mAb +CD16 mAb, and it was (16.34±10.51)% before expansion.The total number of NK cells was more than 10 9 .The expression ratios of NK cell surface activated receptors NKp30 and NKp46 were significantly increased, while that of the NKG2D was not significantly changed.The NK cells after expansion showed high cytotoxicity activity against K562 cells, reaching up to(76.97±3.16)%when effector-cell-to-target-cell ratio (E ∶T ratio) was 40 ∶1.Conclusions NK cells can be obtained from abandoned white cells after cultivation for 17 days, with a purity up to 90% and total cell number of more than 10 9 .Their activity was reinforced, the anti-tumor cytotoxicity activity was increased, and may meet the standard of clinical therapeutic application.

Objective To explore how to improve the sensitivity and specificity of CT cisternography (CTC) examination.Methods The clinical data of 20 cases of CTC in detecting cerebrospinal fluid rhinorrhea were analyzed,and the influence of continuous dripping of fluid and the filling time of subarachnoid space upon the image quality were observed.Results Nineteen cases of active cerebrospinal fluid rhinorrhea were found with CTC,and the fistula sites were determined by CTC.Eighteen cases received operation which confirmed the fistula sites.One case was found with no active fistula site.According to the image of ethmoid sinus leaks results,7 cases had better image quality in 9 cases whose subarachnoid space filling time was longer than or equal to 10 min.One case had better image quality in 6 cases whose subarachnoid space filling time was shorter than 10 min.There was significant difference (P =0.0406).Conclusion To raise the positive rate of CTC,the position of active fistula should be maintained and keep the time between the injection and scan longer than or equal to 10 min,which help to get better image quality.